Akkermansia muciniphila

''Akkermansia muciniphila'' is a human intestinal symbiont, isolated from human feces. It is a mucin-degrading bacterium belonging to the genus, ''Akkermansia'', discovered in 2004 by Muriel Derrien and Willem de Vos at Wageningen University of the Netherlands. It belongs to the phylum Verrucomicrobiota and its type strain is Muc^T (=ATCC BAA-835^T =CIP 107961^T). There is growing evidence to suggest that the prevalence of this bacteria is associated with intestinal homeostasis, immunity and a healthy gut. Extensive research is being undertaken to also understand its association with obesity, type 2 diabetes, and inflammation. It is also being developed as a next-generation probiotic. There are also studies showing that excessive enrichment of ''A. muciniphila'' in some cases may exacerbate intestinal inflammation.

Recently, ''A. muciniphila'' strain Urmite became the first (evidently) unculturable bacterial strain to be sequenced in its entirety entirely from a human stool sample.

Morphology, Colonization and Metabolism

''A. muciniphila'' is a Gram-negative, strictly anaerobic, non-motile, non-spore-forming, oval-shaped bacterium. Its circular chromosome contains 2,664,102 base pairs and its proteome contains 5644 unique proteins. It colonizes the gastrointestinal tract of humans and other animals and can be found within the intestinal mucosal layer of the epithelial crypts as well as in the caecum. ''A. muciniphila'' is found in about 90% of healthy humans, makes up about 1% to 3% of the fecal microbiota and colonizes the gut during the first year of life. Its prevalence can decrease with age or in disease states

''A. muciniphila'' is able to use mucin as its sole source of carbon, nitrogen and energy, and is hence considered a specialist. It degrades mucin to produce beneficial products such as short chain fatty acids which aid in growth of other bacteria and maintain healthy mucus turnover. It also maintains microbial balance by competing with and inhibiting the over growth of other mucin degrading bacteria. ''A. muciniphila'' is culturable under anaerobic conditions on medium containing porcine gastric mucin or synthetic medium containing protein source with glucose, N-acetylglucosamine and N-acetylgalactosamine.

Effects on metabolic disorders

In a study conducted on mice, researchers showed that ''A. muciniphila'' could be used to combat obesity and type 2 diabetes. In this study obese mice were then fed the bacteria, which reduce the fat burden of the mice by half without any change to diet. This effect was associated with restoration of a proper gut barrier function. Interestingly, in the same study, the authors found that heat killed version of this bacteria was unable to improve the metabolic response. A study published in June 2015 showed a positive association between increased ''A. muciniphila'' abundance, insulin sensitivity, and a healthier metabolic status in overweight/obese adults. In addition, this study showed that a higher abundance of ''A. muciniphila'' at baseline was associated with greater clinical benefits after weight loss.

Another study demonstrated that dietary fats influence the growth of ''Akkermansia muciniphilia'' relative to other bacterium in the dietary tract. Researchers conducted a study in which mice were fed diets which varied in fat composition but were otherwise identical: one group received lard, while the other received fish oil. After 11 weeks, the group receiving a fish oil diet had increased levels of ''A. muciniphila'' and bacterium of genus ''Lactobacillus'', while the group receiving a lard diet had decreased levels of ''A. muciniphila'' and ''Lactobacillus''. Fecal material from mice on the fish oil diet or the lard based diet was transplanted into a new group of mice which had their native gut flora removed by antibiotic treatment. All of these mice were then fed a lard based diet. Despite receiving the same lard-based diet for 3 weeks, recipients of transplants from lard-fed donor mice showed increased levels of ''Lactobacillus'' and increased levels of inflammation, while recipients of transplants from fish oil-fed donors showed increased levels of ''A. muciniphila'' and decreased levels of inflammation. Researchers concluded that the increase in ''A. muciniphila'' corresponded to a reduction in inflammation, indicating a link between dietary fats, gut flora composition, and inflammation levels.

Effects on inflammatory gut disorders

According to some studies there is an inverse relationship between ''A. muciniphila'' colonization and inflammatory conditions such as appendicitis or inflammatory bowel disease (IBD). In one study, reduced levels of ''A. muciniphila'' correlated with increased severity of appendicitis. In a separate study, IBD patients were found to have lower levels ''A. muciniphila'' in their intestinal tract than individuals without IBD.

Effects on cancer immunotherapy treatment

One study looked at 249 patients with lung or kidney cancer, ''A. muciniphila'' was in 69% of patients that did respond compared with just a third of those who did not. Boosting levels of ''A. muciniphila'' in mice seemed to also boost their response to immunotherapy.

Effects on ALS in a mouse model

Researchers discovered that a mouse model of Amyotrophic lateral sclerosis suffers from an abnormal gut microbiome, and that supplementing these mice with ''Akkermansia muciniphila'' improved their symptoms, slowed the progression of their disease, and increased their survival. Moreover, they found that ''A. muciniphila'' produce the vitamin nicotinamide, which when injected into the diseased mice improved their motor symptoms, although it did not increase their lifespan as the bacteria had. They also found lower levels of nicotinamide in the circulation and the cerebrospinal fluid (CSF) of a small sample human ALS patients compared to their family members, and lower levels of ''A. muciniphila'' in their stool. In addition, ALS patients with lower levels of nicotinamide in their blood tended to have worse symptoms than patients with higher levels.

Antibiotic Resistance

The MucT strain of ''Akkermansia muciniphila'' is resistant to several antibiotics including chloramphenicol, clindamycin, streptomycin, erythromycin, vancomycin, and metronidazole and it is found enriched in the gastrointestinal tracts of people treated with antibiotics.

Development as a Probiotic

In 2017, it was discovered that pasteurizing (70 °C 30min) the bacteria increased the beneficial effects of the bacteria by a mechanism likely associated with the presence of a protein present on the outer membrane of ''Akkermansia muciniphila'' and called Amuc_1100. Then in 2019, the same team of Belgian researchers from the UCLouvain tested for the first time in humans the impact of an oral supplementation with either ''A. muciniphila'' alive or pasteurized versus a placebo for 3 months. In this double-blind placebo-controlled proof-of-concept study, they found that the overweight or obese insulin resistant subjects displayed an improved metabolism with lower blood insulin, lower insulin resistance, lower inflammation and better cardiometabolic profile. More recently, they have linked this effect with the possible increased production of some endocannabinoids acting on the receptor PPAR-a.

Recent studies have shown that pasteurized ''Akkermansia muciniphila'' can be consumed without any negative effects and the European Union has recognized pasteurized ''Akkermansia muciniphila'' as a novel food. However, the safety of ''Akkermansia muciniphila'' use as a treatment during disease states is not yet established.

References

Further reading

*

External links

*
Type strain of ''Akkermansia muciniphila'' at Bac''Dive'' - the Bacterial Diversity Metadatabase

{{DEFAULTSORT:Akkermansia muciniphila
Verrucomicrobiota
Bacteria described in 2004
Gram-negative bacteria