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Gut microbiota, gut microbiome, or gut flora, are the
microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in old ...
s, including
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
,
archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaeba ...
,
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
, and
viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's ...
that live in the digestive tracts of animals. The gastrointestinal
metagenome Metagenomics is the study of genetic material recovered directly from environmental or clinical samples by a method called sequencing. The broad field may also be referred to as environmental genomics, ecogenomics, community genomics or microb ...
is the aggregate of all the
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...
s of the gut
microbiota Microbiota are the range of microorganisms that may be commensal, symbiotic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found ...
. The gut is the main location of the
human microbiome The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, seminal fluid, uterus, ovarian ...
. The gut microbiota has broad impacts, including effects on
colonization Colonization, or colonisation, constitutes large-scale population movements wherein migrants maintain strong links with their, or their ancestors', former country – by such links, gain advantage over other inhabitants of the territory. When ...
, resistance to
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
s, maintaining the
intestinal epithelium The intestinal epithelium is the single cell layer that form the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelial cells, it serves two main functi ...
, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut–brain axis. The microbial composition of the gut microbiota varies across regions of the digestive tract. The colon contains the highest microbial density recorded in any habitat on Earth, representing between 300 and 1000 different
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriat ...
. Bacteria are the largest and to date, best studied component and 99% of gut bacteria come from about 30 or 40 species. Up to 60% of the dry mass of
feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a rela ...
is bacteria. Over 99% of the bacteria in the gut are
anaerobe An anaerobic organism or anaerobe is any organism that does not require molecular oxygen for growth. It may react negatively or even die if free oxygen is present. In contrast, an aerobic organism (aerobe) is an organism that requires an oxygenate ...
s, but in the
cecum The cecum or caecum is a pouch within the peritoneum that is considered to be the beginning of the large intestine. It is typically located on the right side of the body (the same side of the body as the appendix, to which it is joined). The wo ...
, aerobic bacteria reach high densities. It is estimated that the human gut microbiota have around a hundred times as many
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s as there are in the
human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the ...
.


Overview

In humans, the gut microbiota has the largest numbers and species of bacteria compared to other areas of the body. In humans, the gut flora is established at one to two years after birth, by which time the
intestinal epithelium The intestinal epithelium is the single cell layer that form the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelial cells, it serves two main functi ...
and the intestinal mucosal barrier that it secretes have co-developed in a way that is tolerant to, and even supportive of, the gut flora and that also provides a barrier to pathogenic organisms. The relationship between some gut microbiota and humans is not merely
commensal Commensalism is a long-term biological interaction (symbiosis) in which members of one species gain benefits while those of the other species neither benefit nor are harmed. This is in contrast with mutualism, in which both organisms benefit fro ...
(a non-harmful coexistence), but rather a mutualistic relationship. Some human gut microorganisms benefit the host by
fermenting Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food p ...
dietary fiber Dietary fiber (in British English fibre) or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical composition, and can be grouped generally by t ...
into short-chain fatty acids (SCFAs), such as
acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main componen ...
and
butyric acid Butyric acid (; from grc, βούτῡρον, meaning "butter"), also known under the systematic name butanoic acid, is a straight-chain alkyl carboxylic acid with the chemical formula CH3CH2CH2CO2H. It is an oily, colorless liquid with an unp ...
, which are then absorbed by the host. Intestinal
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
also play a role in synthesizing vitamin B and
vitamin K Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation ...
as well as metabolizing
bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primar ...
s,
sterol Sterol is an organic compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the go ...
s, and
xenobiotic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...
s. The systemic importance of the SCFAs and other compounds they produce are like
hormones A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
and the gut flora itself appears to function like an endocrine organ, and dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions. The composition of human gut microbiota changes over time, when the diet changes, and as overall health changes. A
systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...
from 2016 examined the preclinical and small human trials that have been conducted with certain commercially available strains of probiotic bacteria and identified those that had the most potential to be useful for certain
central nervous system disorder Central nervous system diseases, also known as central nervous system disorders, are a group of neurological disorders that affect the structure or function of the brain or spinal cord, which collectively form the central nervous system (CNS). T ...
s.


Classifications

The microbial composition of the gut microbiota varies across the digestive tract. In the
stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...
and
small intestine The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...
, relatively few species of bacteria are generally present. The colon, in contrast, contains the highest microbial density recorded in any habitat on Earth with up to 1012 cells per gram of intestinal content. These bacteria represent between 300 and 1000 different
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriat ...
. However, 99% of the bacteria come from about 30 or 40 species. As a consequence of their abundance in the intestine, bacteria also make up to 60% of the dry mass of
feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a rela ...
.
Fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
,
protist A protist () is any eukaryotic organism (that is, an organism whose cells contain a cell nucleus) that is not an animal, plant, or fungus. While it is likely that protists share a common ancestor (the last eukaryotic common ancestor), the e ...
s,
archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaeba ...
, and
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsk ...
es are also present in the gut flora, but less is known about their activities. Over 99% of the bacteria in the gut are
anaerobe An anaerobic organism or anaerobe is any organism that does not require molecular oxygen for growth. It may react negatively or even die if free oxygen is present. In contrast, an aerobic organism (aerobe) is an organism that requires an oxygenate ...
s, but in the
cecum The cecum or caecum is a pouch within the peritoneum that is considered to be the beginning of the large intestine. It is typically located on the right side of the body (the same side of the body as the appendix, to which it is joined). The wo ...
, aerobic bacteria reach high densities. It is estimated that these gut flora have around a hundred times as many
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s in total as there are in the
human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the ...
. Many species in the gut have not been studied outside of their hosts because they cannot be cultured. While there are a small number of core microbial species shared by most individuals, populations of microbes can vary widely. Within an individual, their microbial populations stay fairly constant over time, with some alterations occurring due to changes in lifestyle, diet and age. The Human Microbiome Project has set out to better describe the
microbiota Microbiota are the range of microorganisms that may be commensal, symbiotic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found ...
of the human gut and other body locations. The four dominant
bacterial phyla Bacterial phyla constitute the major lineages of the domain ''Bacteria''. While the exact definition of a bacterial phylum is debated, a popular definition is that a bacterial phylum is a monophyletic lineage of bacteria whose 16S rRNA genes s ...
in the human gut are
Bacillota The Bacillota (synonym Firmicutes) are a phylum of bacteria, most of which have gram-positive cell wall structure. The renaming of phyla such as Firmicutes in 2021 remains controversial among microbiologists, many of whom continue to use the earl ...
(Firmicutes),
Bacteroidota The phylum Bacteroidota (synonym Bacteroidetes) is composed of three large classes of Gram-negative, nonsporeforming, anaerobic or aerobic, and rod-shaped bacteria that are widely distributed in the environment, including in soil, sediments, and ...
,
Actinomycetota The ''Actinomycetota'' (or ''Actinobacteria'') are a phylum of all gram-positive bacteria. They can be terrestrial or aquatic. They are of great economic importance to humans because agriculture and forests depend on their contributions to s ...
, and
Pseudomonadota Pseudomonadota (synonym Proteobacteria) is a major phylum of Gram-negative bacteria. The renaming of phyla in 2021 remains controversial among microbiologists, many of whom continue to use the earlier names of long standing in the literature. Th ...
. Most bacteria belong to the genera ''
Bacteroides ''Bacteroides'' is a genus of Gram-negative, obligate anaerobic bacteria. ''Bacteroides'' species are non endospore-forming bacilli, and may be either motile or nonmotile, depending on the species. The DNA base composition is 40–48% GC. Unus ...
'', ''
Clostridium ''Clostridium'' is a genus of anaerobic, Gram-positive bacteria. Species of ''Clostridium'' inhabit soils and the intestinal tract of animals, including humans. This genus includes several significant human pathogens, including the causative a ...
'', ''
Faecalibacterium ''Faecalibacterium'' is a genus of bacteria. Its sole known species, ''Faecalibacterium prausnitzii'' is gram-positive, mesophilic, rod-shaped, anaerobic and is one of the most abundant and important commensal bacteria of the human gut microbiota ...
'', ''
Eubacterium ''Eubacterium'' is a genus of Gram-positive bacteria in the family Eubacteriaceae. These bacteria are characterised by a rigid cell wall A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It ...
'', ''
Ruminococcus ''Ruminococcus'' is a genus of bacteria in the class Clostridia. They are anaerobic, Gram-positive gut microbes. One or more species in this genus are found in significant numbers in the human gut microbiota. The type species is ''R. flavefacien ...
'', '' Peptococcus'', ''
Peptostreptococcus ''Peptostreptococcus'' is a genus of anaerobic, Gram-positive, non-spore forming bacteria. The cells are small, spherical, and can occur in short chains, in pairs or individually. They typically move using cilia. ''Peptostreptococcus'' are slow-g ...
'', and '' Bifidobacterium''. Other genera, such as ''
Escherichia ''Escherichia'' () is a genus of Gram-negative, non- spore-forming, facultatively anaerobic, rod-shaped bacteria from the family Enterobacteriaceae. In those species which are inhabitants of the gastrointestinal tracts of warm-blooded animals, ...
'' and ''
Lactobacillus ''Lactobacillus'' is a genus of Gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus ''Lactobacillus'' comprised over 260 phylogenetically, ecologically, and metabolically div ...
'', are present to a lesser extent. Species from the genus ''Bacteroides'' alone constitute about 30% of all bacteria in the gut, suggesting that this genus is especially important in the functioning of the host. Fungal genera that have been detected in the gut include '' Candida'', ''
Saccharomyces ''Saccharomyces'' is a genus of fungi that includes many species of yeasts. ''Saccharomyces'' is from Greek σάκχαρον (sugar) and μύκης (fungus) and means ''sugar fungus''. Many members of this genus are considered very important in f ...
'', ''
Aspergillus ' () is a genus consisting of several hundred mold species found in various climates worldwide. ''Aspergillus'' was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli. Viewing the fungi under a microscope, Mic ...
'', ''
Penicillium ''Penicillium'' () is a genus of ascomycetous fungi that is part of the mycobiome of many species and is of major importance in the natural environment, in food spoilage, and in food and drug production. Some members of the genus produce pe ...
'', '' Rhodotorula'', '' Trametes'', '' Pleospora'', '' Sclerotinia'', ''
Bullera ''Bullera'' is a genus of fungi in the family (biology), family Bulleraceae. The genus, which comprises both Teleomorph, anamorph and holomorph, anamorphic and Teleomorph, anamorph and holomorph, teleomorphic forms, formerly contained some 35 spe ...
'', and '' Galactomyces'', among others. ''Rhodotorula'' is most frequently found in individuals with
inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine and large intestine, as well ...
while ''Candida'' is most frequently found in individuals with hepatitis B cirrhosis and chronic hepatitis B.
Archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaeba ...
constitute another large class of gut flora which are important in the metabolism of the bacterial products of fermentation. Industralization is associated with changes in the microbiota and the reduction of diversity could drive certain species to extinction; in 2018, researchers proposed a
biobank A biobank is a type of biorepository that stores biological samples (usually human) for use in research. Biobanks have become an important resource in medical research, supporting many types of contemporary research like genomics and personalize ...
repository of human microbiota.


Enterotype

An enterotype is a classification of living organisms based on its bacteriological
ecosystem An ecosystem (or ecological system) consists of all the organisms and the physical environment with which they interact. These biotic and abiotic components are linked together through nutrient cycles and energy flows. Energy enters the syst ...
in the human gut microbiome not dictated by age, gender, body weight, or national divisions. There are indications that long-term diet influences enterotype. Three human enterotypes have been proposed, but their value has been questioned.


Composition


Bacteriome


Stomach

Due to the high acidity of the stomach, most microorganisms cannot survive there. The main bacterial inhabitants of the stomach include: '' Streptococcus'', ''
Staphylococcus ''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical ( cocci), and form in grape-like clusters. ''Staphylococcus'' species are faculta ...
'', ''Lactobacillus'', ''Peptostreptococcus''. ''
Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...
'' is a
gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...
spiral bacterium that establishes on
gastric mucosa The gastric mucosa is the mucous membrane layer of the stomach, which contains the glands and the gastric pits. In humans, it is about 1 mm thick, and its surface is smooth, soft, and velvety. It consists of simple columnar epithelium, lamin ...
causing chronic
gastritis Gastritis is inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain (see dyspepsia). Other possi ...
, and
peptic ulcer disease Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines ...
, and is a
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive sub ...
for
gastric cancer Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lym ...
.


Intestines

The small intestine contains a trace amount of microorganisms due to the proximity and influence of the stomach.
Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...
cocci and
rod-shaped bacteria A bacillus (), also called a bacilliform bacterium or often just a rod (when the context makes the sense clear), is a rod-shaped bacterium or archaeon. Bacilli are found in many different taxonomic groups of bacteria. However, the name ''Bacillu ...
are the predominant microorganisms found in the small intestine. However, in the distal portion of the small intestine alkaline conditions support gram-negative bacteria of the ''Enterobacteriaceae''. The bacterial flora of the small intestine aid in a wide range of intestinal functions. The bacterial flora provide regulatory signals that enable the development and utility of the gut. Overgrowth of bacteria in the small intestine can lead to intestinal failure. In addition the large intestine contains the largest bacterial ecosystem in the human body. About 99% of the large intestine and feces flora are made up of obligate anaerobes such as ''Bacteroides'' and ''Bifidobacterium.'' Factors that disrupt the microorganism population of the large intestine include antibiotics, stress, and parasites. Bacteria make up most of the flora in the colonUniversity of Glasgow. 2005
The normal gut flora.
Available through web archive. Accessed May 22, 2008
and 60% of the dry mass of
feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a rela ...
. This fact makes feces an ideal source of gut flora for any tests and experiments by extracting the nucleic acid from fecal specimens, and bacterial 16S rRNA gene sequences are generated with bacterial primers. This form of testing is also often preferable to more invasive techniques, such as biopsies. Five
phyla Phyla, the plural of ''phylum'', may refer to: * Phylum, a biological taxon between Kingdom and Class * by analogy, in linguistics, a large division of possibly related languages, or a major language family which is not subordinate to another Phy ...
dominate the intestinal microbiota:
Bacteroidota The phylum Bacteroidota (synonym Bacteroidetes) is composed of three large classes of Gram-negative, nonsporeforming, anaerobic or aerobic, and rod-shaped bacteria that are widely distributed in the environment, including in soil, sediments, and ...
,
Bacillota The Bacillota (synonym Firmicutes) are a phylum of bacteria, most of which have gram-positive cell wall structure. The renaming of phyla such as Firmicutes in 2021 remains controversial among microbiologists, many of whom continue to use the earl ...
(Firmicutes),
Actinomycetota The ''Actinomycetota'' (or ''Actinobacteria'') are a phylum of all gram-positive bacteria. They can be terrestrial or aquatic. They are of great economic importance to humans because agriculture and forests depend on their contributions to s ...
,
Pseudomonadota Pseudomonadota (synonym Proteobacteria) is a major phylum of Gram-negative bacteria. The renaming of phyla in 2021 remains controversial among microbiologists, many of whom continue to use the earlier names of long standing in the literature. Th ...
, and
Verrucomicrobiota Verrucomicrobiota is a phylum of Gram-negative bacteria that contains only a few described species. The species identified have been isolated from fresh water, marine and soil environments and human faeces. A number of as-yet uncultivated speci ...
—with Bacteroidota and Bacillota constituting 90% of the composition. Somewhere between 300 and 1000 different
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriat ...
live in the gut, with most estimates at about 500. However, it is probable that 99% of the bacteria come from about 30 or 40 species, with ''
Faecalibacterium prausnitzii ''Faecalibacterium'' is a genus of bacteria. Its sole known species, ''Faecalibacterium prausnitzii'' is gram-positive, mesophilic, rod-shaped, anaerobic and is one of the most abundant and important commensal bacteria of the human gut microbiota ...
'' (phylum firmicutes) being the most common species in healthy adults. Research suggests that the relationship between gut
flora Flora is all the plant life present in a particular region or time, generally the naturally occurring ( indigenous) native plants. Sometimes bacteria and fungi are also referred to as flora, as in the terms '' gut flora'' or '' skin flora''. ...
and humans is not merely
commensal Commensalism is a long-term biological interaction (symbiosis) in which members of one species gain benefits while those of the other species neither benefit nor are harmed. This is in contrast with mutualism, in which both organisms benefit fro ...
(a non-harmful coexistence), but rather is a mutualistic,
symbiotic Symbiosis (from Greek , , "living together", from , , "together", and , bíōsis, "living") is any type of a close and long-term biological interaction between two different biological organisms, be it mutualistic, commensalistic, or para ...
relationship. Though people can survive with no gut flora, the microorganisms perform a host of useful functions, such as
fermenting Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food p ...
unused energy substrates, training the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
via end products of metabolism like propionate and
acetate An acetate is a salt formed by the combination of acetic acid with a base (e.g. alkaline, earthy, metallic, nonmetallic or radical base). "Acetate" also describes the conjugate base or ion (specifically, the negatively charged ion called ...
, preventing growth of harmful species, regulating the development of the gut, producing vitamins for the host (such as
biotin Biotin (or vitamin B7) is one of the B vitamins. It is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. The name ''biotin'', bo ...
and
vitamin K Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation ...
), and producing hormones to direct the host to store fats. Extensive modification and imbalances of the gut microbiota and its microbiome or gene collection are associated with obesity. However, in certain conditions, some species are thought to be capable of causing
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
by causing
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
or increasing
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
risk for the host.


Mycobiome

Fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
and
protist A protist () is any eukaryotic organism (that is, an organism whose cells contain a cell nucleus) that is not an animal, plant, or fungus. While it is likely that protists share a common ancestor (the last eukaryotic common ancestor), the e ...
s also make up a part of the gut flora, but less is known about their activities.


Virome

The human virome is mostly
bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bac ...
s.


Variation


Age

It has been demonstrated that there are common patterns of microbiome composition evolution during life. In general, the diversity of microbiota composition of fecal samples is significantly higher in adults than in children, although interpersonal differences are higher in children than in adults. Much of the maturation of microbiota into an adult-like configuration happens during the three first years of life. As the microbiome composition changes, so does the composition of bacterial proteins produced in the gut. In adult microbiomes, a high prevalence of enzymes involved in fermentation, methanogenesis and the metabolism of arginine, glutamate, aspartate and lysine have been found. In contrast, in infant microbiomes the dominant enzymes are involved in cysteine metabolism and fermentation pathways.


Geography

Gut microbiome composition depends on the geographic origin of populations. Variations in a trade-off of ''
Prevotella ''Prevotella'' is a genus of Gram-negative bacteria. ''Prevotella'' spp. are members of the oral, vaginal, and gut microbiota and are often recovered from anaerobic infections of the respiratory tract. These infections include aspiration pn ...
'', the representation of the
urease Ureases (), functionally, belong to the superfamily of amidohydrolases and phosphotriesterases. Ureases are found in numerous bacteria, fungi, algae, plants, and some invertebrates, as well as in soils, as a soil enzyme. They are nickel-contai ...
gene, and the representation of genes encoding glutamate synthase/degradation or other enzymes involved in amino acids degradation or vitamin biosynthesis show significant differences between populations from the US,
Malawi Malawi (; or aláwi Tumbuka: ''Malaŵi''), officially the Republic of Malawi, is a landlocked country in Southeastern Africa that was formerly known as Nyasaland. It is bordered by Zambia to the west, Tanzania to the north and northe ...
, or Amerindian origin. The US population has a high representation of enzymes encoding the degradation of
glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...
and enzymes involved in vitamin and
lipoic acid Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA) and thioctic acid, is an organosulfur compound derived from caprylic acid (octanoic acid). ALA is made in animals normally, and is essential for aerobic metabolism. It i ...
biosynthesis; whereas Malawi and Amerindian populations have a high representation of enzymes encoding glutamate synthase and they also have an overrepresentation of α-amylase in their microbiomes. As the US population has a diet richer in fats than Amerindian or Malawian populations which have a corn-rich diet, the diet is probably the main determinant of the gut bacterial composition. Further studies have indicated a large difference in the composition of microbiota between European and rural African children. The fecal bacteria of children from
Florence Florence ( ; it, Firenze ) is a city in Central Italy and the capital city of the Tuscany region. It is the most populated city in Tuscany, with 383,083 inhabitants in 2016, and over 1,520,000 in its metropolitan area.Bilancio demografico ...
were compared to that of children from the small rural village of Boulpon in
Burkina Faso Burkina Faso (, ; , ff, 𞤄𞤵𞤪𞤳𞤭𞤲𞤢 𞤊𞤢𞤧𞤮, italic=no) is a landlocked country in West Africa with an area of , bordered by Mali to the northwest, Niger to the northeast, Benin to the southeast, Togo and Ghana t ...
. The diet of a typical child living in this village is largely lacking in fats and animal proteins and rich in polysaccharides and plant proteins. The fecal bacteria of European children were dominated by ''Firmicutes'' and showed a marked reduction in biodiversity, while the fecal bacteria of the Boulpon children was dominated by ''Bacteroidetes''. The increased biodiversity and different composition of the gut microbiome in African populations may aid in the digestion of normally indigestible plant polysaccharides and also may result in a reduced incidence of non-infectious colonic diseases. On a smaller scale, it has been shown that sharing numerous common environmental exposures in a family is a strong determinant of individual microbiome composition. This effect has no genetic influence and it is consistently observed in culturally different populations.


Malnourishment

Malnourished children have less mature and less diverse gut microbiota than healthy children, and changes in the microbiome associated with nutrient scarcity can in turn be a pathophysiological cause of malnutrition. Malnourished children also typically have more potentially pathogenic gut flora, and more
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...
in their mouths and throats. Altering diet may lead to changes in gut microbiota composition and diversity.


Race and ethnicity

Researchers with the American Gut Project and Human Microbiome Project found that twelve microbe families varied in abundance based on the race or ethnicity of the individual. The strength of these associations is limited by the small sample size: the American Gut Project collected data from 1,375 individuals, 90% of whom were white. The Healthy Life in an Urban Setting (HELIUS) study in Amsterdam found that those of Dutch ancestry had the highest level of gut microbiota diversity, while those of South Asian and Surinamese descent had the lowest diversity. The study results suggested that individuals of the same race or ethnicity have more similar microbiomes than individuals of different racial backgrounds.


Socioeconomic status

As of 2020, at least two studies have demonstrated a link between an individual's
socioeconomic status Socioeconomic status (SES) is an economic and sociological combined total measure of a person's work experience and of an individual's or family's economic access to resources and social position in relation to others. When analyzing a family's ...
(SES) and their gut microbiota. A study in
Chicago (''City in a Garden''); I Will , image_map = , map_caption = Interactive Map of Chicago , coordinates = , coordinates_footnotes = , subdivision_type = List of sovereign states, Count ...
found that individuals in higher SES neighborhoods had greater microbiota diversity. People from higher SES neighborhoods also had more abundant ''Bacteroides'' bacteria. Similarly, a study of
twin Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two em ...
s in the United Kingdom found that higher SES was also linked with a greater gut diversity.


Acquisition in human infants

The establishment of a gut flora is crucial to the health of an adult, as well as the functioning of the gastrointestinal tract. In humans, a gut flora similar to an adult's is formed within one to two years of birth as microbiota are acquired through parent-to-child transmission and transfer from food, water, and other environmental sources. The traditional view of the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
of a normal
fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal dev ...
is that it is sterile, although this view has been challenged in the past few years. Multiple lines of evidence have begun to emerge that suggest there may be bacteria in the intrauterine environment. In humans, research has shown that microbial colonization may occur in the fetus with one study showing ''Lactobacillus'' and ''Bifidobacterium'' species were present in placental biopsies. Several rodent studies have demonstrated the presence of bacteria in the amniotic fluid and placenta, as well as in the meconium of babies born by sterile cesarean section. In another study, researchers administered a culture of bacteria orally to a pregnant dam, and detected the bacteria in the offspring, likely resulting from transmission between the digestive tract and amniotic fluid via the blood stream. However, researchers caution that the source of these intrauterine bacteria, whether they are alive, and their role, is not yet understood. During birth and rapidly thereafter, bacteria from the mother and the surrounding environment colonize the infant's gut. The exact sources of bacteria is not fully understood, but may include the birth canal, other people (parents, siblings, hospital workers), breastmilk, food, and the general environment with which the infant interacts. Research has shown that the microbiome of babies born vaginally differ significantly from those of babies delivered by
caesarean section Caesarean section, also known as C-section or caesarean delivery, is the surgical procedure by which one or more babies are delivered through an incision in the mother's abdomen, often performed because vaginal delivery would put the baby or m ...
and that vaginally born babies got most of their gut bacteria from their mother, while the microbiota of caesarean babies had more bacteria associated with hospital environments. During the first year of life, the composition of the gut flora is generally simple and changes a great deal with time and is not the same across individuals. The initial bacterial population are generally
facultative anaerobic organism A facultative anaerobic organism is an organism that makes ATP by aerobic respiration if oxygen is present, but is capable of switching to fermentation if oxygen is absent. Some examples of facultatively anaerobic bacteria are ''Staphylococcus' ...
s; investigators believe that these initial colonizers decrease the oxygen concentration in the gut, which in turn allows obligately anaerobic bacteria like ''Bacteroidota'', ''Actinomycetota'', and ''Bacillota'' to become established and thrive. Breast-fed babies become dominated by
bifidobacteria ''Bifidobacterium'' is a genus of gram-positive, nonmotile, often branched anaerobic bacteria. They are ubiquitous inhabitants of the gastrointestinal tract though strains have been isolated from the vagina and mouth ('' B. dentium'') of ma ...
, possibly due to the contents of bifidobacterial growth factors in breast milk, and by the fact that breast milk carries prebiotic components, allowing for healthy bacterial growth. In contrast, the microbiota of formula-fed infants is more diverse, with high numbers of ''
Enterobacteriaceae Enterobacteriaceae is a large family of Gram-negative bacteria. It was first proposed by Rahn in 1936, and now includes over 30 genera and more than 100 species. Its classification above the level of family is still a subject of debate, but o ...
'', enterococci,
bifidobacteria ''Bifidobacterium'' is a genus of gram-positive, nonmotile, often branched anaerobic bacteria. They are ubiquitous inhabitants of the gastrointestinal tract though strains have been isolated from the vagina and mouth ('' B. dentium'') of ma ...
, ''Bacteroides'', and clostridia. Caesarean section,
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
s, and formula feeding may alter the gut microbiome composition. Children treated with antibiotics have less stable, and less diverse floral communities. Caesarean sections have been shown to be disruptive to mother-offspring transmission of bacteria, which impacts the overall health of the offspring by raising risks of disease such as celiacs, asthma, and type 1 diabetes. This further evidences the importance of a healthy gut microbiome. Various methods of microbiome restoration are being explored, typically involving exposing the infant to maternal vaginal contents, and oral probiotics.


Functions

When the study of gut flora began in 1995, it was thought to have three key roles: direct defense against
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
s, fortification of host defense by its role in developing and maintaining the
intestinal epithelium The intestinal epithelium is the single cell layer that form the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelial cells, it serves two main functi ...
and inducing antibody production there, and metabolizing otherwise indigestible compounds in food; subsequent work discovered its role in training the developing immune system, and yet further work focused on its role in the gut-brain axis.


Direct inhibition of pathogens

The gut flora community plays a direct role in defending against pathogens by fully colonising the space, making use of all available nutrients, and by secreting compounds that kill or inhibit unwelcome organisms that would compete for nutrients with it, these compounds are known as
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...
s. Different strains of gut bacteria cause the production of different cytokines. Cytokines are chemical compounds produced by our immune system for initiating the inflammatory response against infections. Disruption of the gut flora allows competing organisms like '' Clostridium difficile'' to become established that otherwise are kept in abeyance.


Development of enteric protection and immune system

In humans, a gut flora similar to an adult's is formed within one to two years of birth. As the gut flora gets established, the lining of the intestines – the intestinal epithelium and the intestinal mucosal barrier that it secretes – develop as well, in a way that is tolerant to, and even supportive of, commensalistic microorganisms to a certain extent and also provides a barrier to pathogenic ones. Specifically,
goblet cell Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 5AC. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use apocrine methods, budding off their s ...
s that produce the mucosa proliferate, and the mucosa layer thickens, providing an outside mucosal layer in which "friendly" microorganisms can anchor and feed, and an inner layer that even these organisms cannot penetrate. Additionally, the development of
gut-associated lymphoid tissue Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut. Owing to its physiological function in food absorption, the mucosa ...
(GALT), which forms part of the intestinal epithelium and which detects and reacts to pathogens, appears and develops during the time that the gut flora develops and established. The GALT that develops is tolerant to gut flora species, but not to other microorganisms. GALT also normally becomes tolerant to food to which the infant is exposed, as well as digestive products of food, and gut flora's
metabolites In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...
(molecules formed from metabolism) produced from food. The human
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
creates
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...
s that can drive the immune system to produce inflammation in order to protect itself, and that can tamp down the immune response to maintain
homeostasis In biology, homeostasis ( British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
and allow healing after insult or injury. Different bacterial species that appear in gut flora have been shown to be able to drive the immune system to create cytokines selectively; for example ''
Bacteroides fragilis ''Bacteroides fragilis'' is an anaerobic, Gram-negative, pleomorphic to rod-shaped bacterium. It is part of the normal microbiota of the human colon and is generally commensal, but can cause infection if displaced into the bloodstream or surrou ...
'' and some ''
Clostridia The Clostridia are a highly polyphyletic class of Bacillota, including ''Clostridium'' and other similar genera. They are distinguished from the Bacilli by lacking aerobic respiration. They are obligate anaerobes and oxygen is toxic to them. S ...
'' species appear to drive an anti-inflammatory response, while some
segmented filamentous bacteria Segmented filamentous bacteria or ''Candidatus'' Savagella are members of the gut microbiota of rodents, fish and chickens, and have been shown to potently induce immune responses in mice. They form a distinct lineage within the Clostridiaceae a ...
drive the production of inflammatory cytokines. Gut flora can also regulate the production of
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
by the immune system. One function of this regulation is to cause
B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...
to class switch to
IgA Iga may refer to: Arts and entertainment * Ambush at Iga Pass, a 1958 Japanese film * Iga no Kagemaru, Japanese manga series * Iga, a set of characters from the Japanese novel '' The Kouga Ninja Scrolls'' Biology * ''Iga'' (beetle), a g ...
. In most cases B cells need activation from T helper cells to induce
class switching Immunoglobulin class switching, also known as isotype switching, isotypic commutation or class-switch recombination (CSR), is a biological mechanism that changes a B cell's production of immunoglobulin from one type to another, such as from the ...
; however, in another pathway, gut flora cause NF-kB signaling by intestinal epithelial cells which results in further signaling molecules being secreted. These signaling molecules interact with B cells to induce class switching to IgA. IgA is an important type of antibody that is used in mucosal environments like the gut. It has been shown that IgA can help diversify the gut community and helps in getting rid of bacteria that cause inflammatory responses. Ultimately, IgA maintains a healthy environment between the host and gut bacteria. These cytokines and antibodies can have effects outside the gut, in the lungs and other tissues. The immune system can also be altered due to the gut bacteria's ability to produce
metabolites In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...
that can affect cells in the immune system. For example short-chain fatty acids (SCFA) can be produced by some gut bacteria through
fermentation Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food p ...
. SCFAs stimulate a rapid increase in the production of innate immune cells like
neutrophils Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
,
basophils Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
and
eosinophils Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...
. These cells are part of the innate immune system that try to limit the spread of infection.


Metabolism

Without gut flora, the human body would be unable to utilize some of the undigested
carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may o ...
s it consumes, because some types of gut flora have
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s that human cells lack for breaking down certain
polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with w ...
s. Rodents raised in a
sterile Sterile or sterility may refer to: *Asepsis Asepsis is the state of being free from disease-causing micro-organisms (such as pathogenic bacteria, viruses, pathogenic fungi, and parasites). There are two categories of asepsis: medical and surgi ...
environment and lacking in gut flora need to eat 30% more
calories The calorie is a unit of energy. For historical reasons, two main definitions of "calorie" are in wide use. The large calorie, food calorie, or kilogram calorie was originally defined as the amount of heat needed to raise the temperature of ...
just to remain the same weight as their normal counterparts. Carbohydrates that humans cannot
digest Digest may refer to: Biology *Digestion of food *Restriction digest Literature and publications *'' The Digest'', formerly the English and Empire Digest *Digest size magazine format * ''Digest'' (Roman law), also known as ''Pandects'', a digest ...
without bacterial help include certain
starches Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human diets, ...
,
fiber Fiber or fibre (from la, fibra, links=no) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often incorporate ...
,
oligosaccharides An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide polymer containing a small number (typically two to ten) of monosaccharides (simple suga ...
, and
sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or do ...
s that the body failed to digest and absorb like
lactose Lactose is a disaccharide sugar synthesized by galactose and glucose subunits and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by mass). The name comes from ' (gen. '), the Latin word for milk, plus the suffix ' ...
in the case of
lactose intolerance Lactose intolerance is a common condition caused by a decreased ability to digest lactose, a sugar found in dairy products. Those affected vary in the amount of lactose they can tolerate before symptoms develop. Symptoms may include abdominal pai ...
and
sugar alcohol Sugar alcohols (also called polyhydric alcohols, polyalcohols, alditols or glycitols) are organic compounds, typically derived from sugars, containing one hydroxyl group (–OH) attached to each carbon atom. They are white, water-soluble solids ...
s,
mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It ...
produced by the gut, and proteins. Bacteria turn carbohydrates they ferment into short-chain fatty acids by a form of fermentation called
saccharolytic fermentation {{Short pages monitor The gut-brain axis is the biochemical signaling that takes place between the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
and the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
. That term has been expanded to include the role of the gut flora in the interplay; the term "microbiome-gut-brain axis" is sometimes used to describe paradigms explicitly including the gut flora. Broadly defined, the gut-brain axis includes the central nervous system,
neuroendocrine Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bri ...
and neuroimmune systems including the hypothalamic–pituitary–adrenal axis (HPA axis), sympathetic and parasympathetic arms of the
autonomic nervous system The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that supplies internal organs, smooth muscle and glands. The autonomic nervous system is a control system t ...
including the enteric nervous system, the
vagus nerve The vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or simply CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and righ ...
, and the gut
microbiota Microbiota are the range of microorganisms that may be commensal, symbiotic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found ...
. A
systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on t ...
from 2016 examined the preclinical and small human trials that have been conducted with certain commercially available strains of
probiotic Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut microbiota. Probiotics are considered generally safe to consume, but may cause bacteria-host i ...
bacteria and found that among those tested, '' Bifidobacterium'' and ''Lactobacillus''
genera Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial nomenclat ...
('' B. longum'', '' B. breve'', '' B. infantis'', ''
L. helveticus ''Lactobacillus helveticus'' is a lactic-acid producing, rod-shaped bacterium of the genus ''Lactobacillus''. It is most commonly used in the production of American Swiss cheese and Emmental cheese, but is also sometimes used in making other st ...
'', '' L. rhamnosus'', '' L. plantarum'', and '' L. casei''), had the most potential to be useful for certain
central nervous system disorder Central nervous system diseases, also known as central nervous system disorders, are a group of neurological disorders that affect the structure or function of the brain or spinal cord, which collectively form the central nervous system (CNS). T ...
s.


Alterations in microbiota balance


Effects of antibiotic use

Altering the numbers of gut bacteria, for example by taking
broad-spectrum antibiotic A broad-spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial ...
s, may affect the host's health and ability to digest food. Antibiotics can cause antibiotic-associated diarrhea by irritating the
bowel The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
directly, changing the levels of microbiota, or allowing
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
ic bacteria to grow. Another harmful effect of antibiotics is the increase in numbers of antibiotic-resistant bacteria found after their use, which, when they invade the host, cause illnesses that are difficult to treat with antibiotics. Changing the numbers and species of gut microbiota can reduce the body's ability to ferment carbohydrates and metabolize
bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bi ...
acids and may cause
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
. Carbohydrates that are not broken down may absorb too much water and cause runny stools, or lack of SCFAs produced by gut microbiota could cause diarrhea. A reduction in levels of native bacterial species also disrupts their ability to inhibit the growth of harmful species such as ''C. difficile'' and ''
Salmonella kedougou ''Salmonella'' is a genus of rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' is the type species and is furt ...
'', and these species can get out of hand, though their overgrowth may be incidental and not be the true cause of diarrhea. Emerging treatment protocols for C. difficile infections involve fecal microbiota transplantation of donor feces (see Fecal transplant). Initial reports of treatment describe success rates of 90%, with few side effects. Efficacy is speculated to result from restoring bacterial balances of bacteroides and firmicutes classes of bacteria. The composition of the gut microbiome also changes in severe illnesses, due not only to antibiotic use but also to such factors as
ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...
of the gut, failure to eat, and immune compromise. Negative effects from this have led to interest in
selective digestive tract decontamination Selective may refer to: * Selective school, a school that admits students on the basis of some sort of selection criteria ** Selective school (New South Wales) Selective strength: the human body transitions between being weak and strong. This ran ...
, a treatment to kill only pathogenic bacteria and allow the re-establishment of healthy ones. Antibiotics alter the population of the microbiota in the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
, and this may change the intra-community metabolic interactions, modify caloric intake by using carbohydrates, and globally affects host metabolic, hormonal and immune homeostasis. There is reasonable evidence that taking probiotics containing ''Lactobacillus'' species may help prevent antibiotic-associated diarrhea and that taking probiotics with ''Saccharomyces'' (e.g., '' Saccharomyces boulardii '') may help to prevent ''Clostridium difficile'' infection following systemic antibiotic treatment.


Pregnancy

The gut microbiota of a woman changes as
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...
advances, with the changes similar to those seen in metabolic syndromes such as diabetes. The change in gut microbiota causes no ill effects. The newborn's gut microbiota resemble the mother's first-trimester samples. The diversity of the microbiome decreases from the first to third trimester, as the numbers of certain species go up.


Probiotics, prebiotics, synbiotics, and pharmabiotics

Probiotics Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut microbiota. Probiotics are considered generally safe to consume, but may cause bacteria- host i ...
are
microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in old ...
s that are believed to provide health benefits when consumed. With regard to gut microbiota, prebiotics are typically non-digestible,
fiber Fiber or fibre (from la, fibra, links=no) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often incorporate ...
compounds that pass undigested through the upper part of the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
and stimulate the growth or activity of advantageous gut flora by acting as substrate for them. Synbiotics refers to
food ingredient An ingredient is a substance that forms part of a mixture (in a general sense). For example, in cooking, recipes specify which ingredients are used to prepare a specific dish. Many commercial products contain secret ingredients that are purpor ...
s or
dietary supplements A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
combining probiotics and prebiotics in a form of synergism. The term "pharmabiotics" is used in various ways, to mean:
pharmaceutical formulation Pharmaceutical formulation, in pharmaceutics, is the process in which different chemical substances, including the active drug, are combined to produce a final medicinal product. The word ''formulation'' is often used in a way that includes dosage ...
s (standardized manufacturing that can obtain regulatory approval as a drug) of probiotics, prebiotics, or synbiotics; probiotics that have been genetically engineered or otherwise optimized for best performance (shelf life, survival in the digestive tract, etc.); and the natural products of gut flora metabolism (vitamins, etc.). There is some evidence that treatment with some probiotic strains of bacteria may be effective in
irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...
and
chronic idiopathic constipation Functional constipation, known as chronic idiopathic constipation (CIC), is constipation that does not have a physical (anatomical) or physiological (hormonal or other body chemistry) cause. It may have a neurological, psychological or psychosoma ...
. Those organisms most likely to result in a decrease of symptoms have included: * '' Bifidobacterium breve'' * '' Bifidobacterium infantis'' * ''
Enterococcus faecium ''Enterococcus faecium'' is a Gram-positive, gamma-hemolytic or non- hemolytic bacterium in the genus '' Enterococcus''. It can be commensal (innocuous, coexisting organism) in the gastrointestinal tract of humans and animals, but it may also ...
'' * '' Lactobacillus plantarum'' * ''
Lactobacillus reuteri ''Limosilactobacillus reuteri'' is a lactic acid bacterium found in a variety of natural environments, including the gastrointestinal tract of humans and other animals. It does not appear to be pathogenic and may have health effects. Discove ...
'' * '' Lactobacillus rhamnosus'' * ''
Lactobacillus salivarius ''Ligilactobacillus salivarius'' is a probiotic bacteria species that has been found to live in the gastrointestinal tract and exert a range of therapeutic properties including suppression of pathogenic bacteria. Therapeutic research Irrita ...
'' * '' Propionibacterium freudenreichii'' * '' Streptococcus thermophilus'' The most clinically researched multi-strain probiotic formulation for the treatment of microbiota imbalances including irritible bowel syndrome, antibiotic-associated diarrhea,
inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine and large intestine, as well ...
s including
ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and ...
and pouchitis, and for babies that are bottle-fed is the De Simone Formulation named after the gastroenterologist medical doctor that invented it in the 1990s, Professor Claudio De Simone. The De Simone Formulation was researched and sold under the brand name VSL#3 until 2016 when the makers of VSL#3 changed their formulation. Since, the original De Simone Formulation has been researched and sold under various regional brand names including Visbiome in the United States and Vivomixx in Europe.


Fecal floatation

Feces of about 10-15% of people consistently floats in toilet water ('floaters'), while the rest produce feces that sinks ('sinkers') and production of gas causes feces to float. While conventional mice often produce 'floaters', gnotobiotic germfree mice no gut microbiota (bred in germfree isolator) produce 'sinkers', and gut microbiota colonization in germfree mice leads to food transformation to microbial biomass and enrichment of multiple gasogenic bacterial species that turns the 'sinkers' into 'floaters'.


Research

Tests for whether non-antibiotic drugs may impact human gut-associated bacteria were performed by ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
'' analysis on more than 1000 marketed drugs against 40 gut bacterial strains, demonstrating that 24% of the drugs inhibited the growth of at least one of the bacterial strains.


Effects of exercise

Gut microbiota and exercise have recently been shown to be interconnected. Both moderate and intense exercise are typically part of the training regimen of endurance athletes, but they exert different effects on health. The interconnection between gut microbiota and endurance sports depends upon exercise intensity and training status.


Role in disease

Bacteria in the digestive tract can contribute to and be affected by disease in various ways. The presence or overabundance of some kinds of bacteria may contribute to inflammatory disorders such as
inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine and large intestine, as well ...
. Additionally, metabolites from certain members of the gut flora may influence host signalling pathways, contributing to disorders such as
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
and
colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowe ...
. Alternatively, in the event of a breakdown of the gut
epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
, the intrusion of gut flora components into other host compartments can lead to
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
.


Ulcers

''
Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...
'' infection can initiate formation of stomach ulcers when the bacteria penetrate the stomach epithelial lining, then causing an inflammatory phagocytotic response. In turn, the inflammation damages parietal cells which release excessive hydrochloric acid into the stomach and produce less of the protective mucus. Injury to the stomach lining, leading to ulcers, develops when gastric acid overwhelms the defensive properties of cells and inhibits endogenous
prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deriv ...
synthesis, reduces mucus and bicarbonate secretion, reduces mucosal blood flow, and lowers resistance to injury. Reduced protective properties of the stomach lining increase vulnerability to further injury and ulcer formation by stomach acid, pepsin, and bile salts.


Bowel perforation

Normally- commensal bacteria can harm the host if they extrude from the intestinal tract. Translocation, which occurs when bacteria leave the gut through its
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It i ...
l lining, can occur in a number of different diseases. If the gut is perforated, bacteria invade the
interstitium The interstitium is a contiguous fluid-filled space existing between a structural barrier, such as a cell membrane or the skin, and internal structures, such as organs, including muscles and the circulatory system. The fluid in this space is ...
, causing a potentially fatal
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
.


Inflammatory bowel diseases

The two main types of
inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine and large intestine, as well ...
s,
Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distensi ...
and
ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and ...
, are chronic inflammatory disorders of the gut; the causes of these diseases are unknown and issues with the gut flora and its relationship with the host have been implicated in these conditions. Additionally, it appears that interactions of gut flora with the gut-brain axis have a role in IBD, with physiological stress mediated through the hypothalamic–pituitary–adrenal axis driving changes to intestinal epithelium and the gut flora in turn releasing factors and metabolites that trigger signaling in the enteric nervous system and the
vagus nerve The vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or simply CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and righ ...
. The diversity of gut flora appears to be significantly diminished in people with inflammatory bowel diseases compared to healthy people; additionally, in people with ulcerative colitis, Proteobacteria and Actinobacteria appear to dominate; in people with Crohn's, ''
Enterococcus faecium ''Enterococcus faecium'' is a Gram-positive, gamma-hemolytic or non- hemolytic bacterium in the genus '' Enterococcus''. It can be commensal (innocuous, coexisting organism) in the gastrointestinal tract of humans and animals, but it may also ...
'' and several Proteobacteria appear to be over-represented. There is reasonable evidence that correcting gut flora imbalances by taking probiotics with ''
Lactobacilli The ''Lactobacillaceae'' are a family of lactic acid bacteria. It is the only family in the lactic acid bacteria which includes homofermentative and heterofermentative organisms; in the ''Lactobacillaceae,'' the pathway used for hexose fermentati ...
'' and ''Bifidobacteria'' can reduce visceral pain and gut inflammation in IBD.


Irritable bowel syndrome

Irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...
is a result of stress and chronic activation of the HPA axis; its symptoms include abdominal pain, changes in bowel movements, and an increase in proinflammatory cytokines. Overall, studies have found that the luminal and mucosal microbiota are changed in irritable bowel syndrome individuals, and these changes can relate to the type of irritation such as diarrhea or
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel moveme ...
. Also, there is a decrease in the diversity of the microbiome with low levels of fecal Lactobacilli and Bifidobacteria, high levels of facultative
anaerobic bacteria An anaerobic organism or anaerobe is any organism that does not require molecular oxygen for growth. It may react negatively or even die if free oxygen is present. In contrast, an aerobic organism (aerobe) is an organism that requires an oxygenat ...
such as ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'', and increased ratios of Firmicutes: Bacteroidetes.


Other inflammatory or autoimmune conditions

Allergy Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...
,
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
, and
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
are
autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
and
inflammatory disorders Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
of unknown cause, but have been linked to imbalances in the gut flora and its relationship with the host. As of 2016 it was not clear if changes to the gut flora cause these auto-immune and inflammatory disorders or are a product of or adaptation to them.


Asthma

With asthma, two hypotheses have been posed to explain its rising prevalence in the developed world. The
hygiene hypothesis In medicine, the hygiene hypothesis states that early childhood exposure to particular microorganisms (such as the gut flora and helminth parasites) protects against allergic diseases by contributing to the development of the immune system. In pa ...
posits that children in the developed world are not exposed to enough microbes and thus may contain lower prevalence of specific bacterial taxa that play protective roles. The second hypothesis focuses on the Western pattern diet, which lacks
whole grain A whole grain is a grain of any cereal and pseudocereal that contains the endosperm, germ, and bran, in contrast to refined grains, which retain only the endosperm. As part of a general healthy diet, consumption of whole grains is associated ...
s and
fiber Fiber or fibre (from la, fibra, links=no) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often incorporate ...
and has an overabundance of simple sugars. Both hypotheses converge on the role of short-chain fatty acids (SCFAs) in
immunomodulation Immunomodulation is modulation (regulatory adjustment) of the immune system. It has natural and human-induced forms, and thus the word can refer to the following: * Homeostasis in the immune system, whereby the system self-regulates to adjust immun ...
. These bacterial fermentation metabolites are involved in immune signalling that prevents the triggering of asthma and lower SCFA levels are associated with the disease. Lacking protective genera such as ''Lachnospira'', '' Veillonella'', '' Rothia'' and ''
Faecalibacterium ''Faecalibacterium'' is a genus of bacteria. Its sole known species, ''Faecalibacterium prausnitzii'' is gram-positive, mesophilic, rod-shaped, anaerobic and is one of the most abundant and important commensal bacteria of the human gut microbiota ...
'' has been linked to reduced SCFA levels. Further, SCFAs are the product of bacterial fermentation of fiber, which is low in the Western pattern diet. SCFAs offer a link between gut flora and immune disorders, and as of 2016, this was an active area of research. Similar hypotheses have also been posited for the rise of food and other allergies.


Diabetes mellitus type 1

The connection between the gut microbiota and
diabetes mellitus type 1 Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...
has also been linked to SCFAs, such as
butyrate The conjugate acids are in :Carboxylic acids. {{Commons category, Carboxylate ions, Carboxylate anions Carbon compounds Oxyanions ...
and acetate. Diets yielding butyrate and acetate from bacterial fermentation show increased Treg expression. Treg cells
downregulate In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pr ...
effector T cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
, which in turn reduces the inflammatory response in the gut. Butyrate is an energy source for colon cells. butyrate-yielding diets thus decrease
gut permeability Intestinal permeability is a term describing the control of material passing from inside the gastrointestinal tract through the cells lining the gut wall, into the rest of the body. The intestine normally exhibits some permeability, which allows ...
by providing sufficient energy for the formation of
tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...
s.SÄEMANN, M. D., BÖHMIG, G. A., ÖSTERREICHER, C. H., BURTSCHER, H., PAROLINI, O., DIAKOS, C., STÖCKL, J., HÖRL, W. H., & ZLABINGER, G. J. (2000). Anti-inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL-12 and up-regulation of IL-10 production. The FASEB Journal, 14(15), 2380–2382. https://doi.org/10.1096/fj.00-0359fje Additionally, butyrate has also been shown to decrease insulin resistance, suggesting gut communities low in butyrate-producing microbes may increase chances of acquiring
diabetes mellitus type 2 Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinati ...
. Butyrate-yielding diets may also have potential
colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...
suppression effects.


Obesity and metabolic syndrome

The gut flora has also been implicated in obesity and
metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndro ...
due to the key role it plays in the digestive process; the Western pattern diet appears to drive and maintain changes in the gut flora that in turn change how much energy is derived from food and how that energy is used. One aspect of a
healthy diet A healthy diet is a diet that maintains or improves overall health. A healthy diet provides the body with essential nutrition: fluid, macronutrients such as protein, micronutrients such as vitamins, and adequate fibre and food energy. A hea ...
that is often lacking in the Western-pattern diet is fiber and other complex carbohydrates that a healthy gut flora require flourishing; changes to gut flora in response to a Western-pattern diet appear to increase the amount of energy generated by the gut flora which may contribute to obesity and metabolic syndrome. There is also evidence that microbiota influence eating behaviours based on the preferences of the microbiota, which can lead to the host consuming more food eventually resulting in obesity. It has generally been observed that with higher gut microbiome diversity, the microbiota will spend energy and resources on competing with other microbiota and less on manipulating the host. The opposite is seen with lower gut microbiome diversity, and these microbiotas may work together to create host food cravings. Additionally, the liver plays a dominant role in
blood glucose Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the b ...
homeostasis by maintaining a balance between the uptake and storage of glucose through the metabolic pathways of
glycogenesis Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in ...
and
gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non- carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In verteb ...
. Intestinal lipids regulate glucose homeostasis involving a gut-brain-liver axis. The direct administration of lipids into the upper intestine increases the long chain fatty
acyl-coenzyme A Acyl-CoA is a group of coenzymes that metabolize fatty acids. Acyl-CoA's are susceptible to beta oxidation, forming, ultimately, acetyl-CoA. The acetyl-CoA enters the citric acid cycle, eventually forming several equivalents of ATP. In this wa ...
(LCFA-CoA) levels in the upper intestines and suppresses glucose production even under subdiaphragmatic vagotomy or gut vagal
deafferentation Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
. This interrupts the neural connection between the brain and the gut and blocks the upper intestinal lipids' ability to inhibit glucose production. The gut-brain-liver axis and gut microbiota composition can regulate the glucose homeostasis in the liver and provide potential therapeutic methods to treat obesity and diabetes. Just as gut flora can function in a feedback loop that can drive the development of obesity, there is evidence that restricting intake of calories (i.e.,
dieting Dieting is the practice of eating food in a regulated way to decrease, maintain, or increase body weight, or to prevent and treat diseases such as diabetes and obesity. As weight loss depends on calorie intake, different kinds of calorie-red ...
) can drive changes to the composition of the gut flora.


Liver disease

As the liver is fed directly by the
portal vein The portal vein or hepatic portal vein (HPV) is a blood vessel that carries blood from the gastrointestinal tract, gallbladder, pancreas and spleen to the liver. This blood contains nutrients and toxins extracted from digested contents. Approx ...
, whatever crosses the intestinal epithelium and the intestinal mucosal barrier enters the liver, as do cytokines generated there.
Dysbiosis Dysbiosis (also called dysbacteriosis) is characterized by a disruption to the microbiome resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, or a shift in their local distribution. For e ...
in the gut flora has been linked with the development of
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
and
non-alcoholic fatty liver disease Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic ...
.


Cancer

Some genera of bacteria, such as ''Bacteroides'' and ''Clostridium'', have been associated with an increase in
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
growth rate, while other genera, such as ''Lactobacillus'' and ''
Bifidobacteria ''Bifidobacterium'' is a genus of gram-positive, nonmotile, often branched anaerobic bacteria. They are ubiquitous inhabitants of the gastrointestinal tract though strains have been isolated from the vagina and mouth ('' B. dentium'') of ma ...
'', are known to prevent tumor formation. As of December 2017 there was preliminary and indirect evidence that gut microbiota might mediate response to PD-1 inhibitors; the mechanism was unknown. Obese people are at a higher risk for several types of cancer including
hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...
. This increased risk may be related to the increased production of
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive sub ...
ic bile acids by gut microorganisms in such individuals.Devkota S, Turnbaugh PJ. Cancer: An acidic link. Nature. 2013 Jul 4;499(7456):37-8. doi: 10.1038/nature12404. Epub 2013 Jun 26. PMID 23803768Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Iwakura Y, Oshima K, Morita H, Hattori M, Honda K, Ishikawa Y, Hara E, Ohtani N. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013 Jul 4;499(7456):97-101. doi: 10.1038/nature12347. Epub 2013 Jun 26. Erratum in: Nature. 2014 Feb Obesity caused by diet or genetic factors is associated with alterations of gut microbiota that increase the level of the
bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primar ...
deoxycholic acid, a metabolite that causes
DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...
.


Neuropsychiatric

Interest in the relationship between gut flora and neuropsychiatric issues was sparked by a 2014 study showing that germ-free mice showed an exaggerated HPA axis response to stress compared to non-GF laboratory mice. As of January 2016, most of the work that has been done on the role of gut flora in the gut-brain axis had been conducted in animals, or characterizing the various neuroactive compounds that gut flora can produce, and studies with humans measuring differences between people with various psychiatric and neurological differences, or changes to gut flora in response to stress, or measuring effects of various probiotics (dubbed " psychobiotics in this context), had generally been small and could not be generalized; whether changes to gut flora are a result of disease, a cause of disease, or both in any number of possible feedback loops in the gut-brain axis, remained unclear. The gut-brain axis is a dynamic relationship that can also impact mental health. The gut microbiome is responsible for the production of some neurotransmitters, metabolism of tryptophan (an amino acid), and short-chain fatty acids. There are several reasons that the gut microbiome can become imbalanced including, diet, geography, stress (HPA axis),and pharmaceuticals. An imbalance can cause dysbiosis and inflammation, which can lead to depression and anxiety. A systematic review from 2016 examined the preclinical and small human trials that have been conducted with certain commercially available strains of probiotic bacteria and found that among those tested, the genera ''Bifidobacterium'' and ''Lactobacillus'' (''B. longum'', ''B. breve'', ''B. infantis'', ''
L. helveticus ''Lactobacillus helveticus'' is a lactic-acid producing, rod-shaped bacterium of the genus ''Lactobacillus''. It is most commonly used in the production of American Swiss cheese and Emmental cheese, but is also sometimes used in making other st ...
'', ''L. rhamnosus'', ''L. plantarum'', and ''L. casei'') had the most potential to be useful for certain central nervous system disorders.


Other animals

The composition of the human gut microbiome is similar to that of the other great apes. However, humans’ gut biota has decreased in diversity and changed in composition since our evolutionary split from ''Pan''. Humans display increases in Bacteroidetes, a bacterial phylum associated with diets high in animal protein and fat, and decreases in Methanobrevibacter and Fibrobacter, groups that ferment complex plant polysaccharides. These changes are the result of the combined dietary, genetic, and cultural changes humans have undergone since evolutionary divergence from ''Pan''. In addition to humans and vertebrates, some insects also possess complex and diverse gut microbiota that play key nutritional roles. Microbial communities associated with termites can constitute a majority of the weight of the individuals and perform important roles in the digestion of lignocellulose and
nitrogen fixation Nitrogen fixation is a chemical process by which molecular nitrogen (), with a strong triple covalent bond, in the air is converted into ammonia () or related nitrogenous compounds, typically in soil or aquatic systems but also in industry. Atmo ...
. These communities are host-specific, and closely related insect species share comparable similarities in gut microbiota composition. In
cockroach Cockroaches (or roaches) are a paraphyletic group of insects belonging to Blattodea, containing all members of the group except termites. About 30 cockroach species out of 4,600 are associated with human habitats. Some species are well-known ...
es, gut microbiota have been shown to assemble in a deterministic fashion, irrespective of the inoculum; the reason for this host-specific assembly remains unclear. Bacterial communities associated with insects like termites and cockroaches are determined by a combination of forces, primarily diet, but there is some indication that host
phylogeny A phylogenetic tree (also phylogeny or evolutionary tree Felsenstein J. (2004). ''Inferring Phylogenies'' Sinauer Associates: Sunderland, MA.) is a branching diagram or a tree showing the evolutionary relationships among various biological s ...
may also be playing a role in the selection of lineages. For more than 51 years it has been known that the administration of low doses of antibacterial agents promotes the growth of farm animals to increase weight gain. In a study carried out on
mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus'' ...
the ratio of ''Firmicutes'' and ''
Lachnospiraceae The Lachnospiraceae are a family of obligately anaerobic, variably spore-forming bacteria in the order Eubacteriales that ferment diverse plant polysaccharides to short-chain fatty acids (butyrate, acetate) and alcohols (ethanol). These bacteria ...
'' was significantly elevated in animals treated with subtherapeutic doses of different antibiotics. By analyzing the caloric content of faeces and the concentration of small chain fatty acids (SCFAs) in the GI tract, it was concluded that the changes in the composition of microbiota lead to an increased capacity to extract calories from otherwise indigestible constituents, and to an increased production of SCFAs. These findings provide evidence that antibiotics perturb not only the composition of the GI microbiome but also its metabolic capabilities, specifically with respect to SCFAs.


See also

* Colonisation resistance *
List of human flora This article lists some of the species recognized as belonging to the human microbiome. Whole-body distributed *''Acinetobacter calcoaceticus'' *''Burkholderia cepacia'' *'' Pseudomonas pseudoalcaligenes'' *''Peptostreptococcus spp'' Natur ...
*
List of microbiota species of the lower reproductive tract of women This is the list of healthy vaginal microbiota (VMB), which is defined as the group of species and genera that generally are found to have lack of symptoms, absence of various infections, and result in good pregnancy outcomes. VMB is dominated ...
*
Skin flora Skin flora, also called skin microbiota, refers to microbiota ( communities of microorganisms) that reside on the skin, typically human skin. Many of them are bacteria of which there are around 1,000 species upon human skin from nineteen phyla.P ...
* Verotoxin-producing ''Escherichia coli''


Notes


References


Further reading

; Review articles * * * * {{DEFAULTSORT:Gut Flora Bacteriology Digestive system Bacillota Environmental microbiology Microbiomes