Akkermansia muciniphila

Akkermansia muciniphila is a Gram-negative, strictly anaerobic, non-motile, non-spore-forming, oval bacterium. == Structure of LOS ==

The lipopolysaccharide (LPS) of A. muciniphila has been found to lack the O-antigen unit, making it a lipooligosaccharide (LOS), also known as rough-type LPS. The LOS of A. muciniphila has been found to consist of two core oligosaccharides: an undeca- and a hexadecasaccharide chain. Both core oligosaccharides contain three 2-keto-3-deoxy-D-manno-octulosonic acid (Kdo) residues that attach to the lipid A moiety of LOS. In addition, N-acetylgalactosamine and N-acetyl-D-glucosamine residues are present in both chains. and antigen A on red blood cells, while N-acetyl-D-glucosamine is present in human hyaluronic acid. The presence of these residues on A. muciniphila LOS may thus mediate host molecular mimicry, inhibiting potential pro-inflammatory responses. A blend of mono- and bis-phosphorylated lipid A moieties has also been observed. The presence of monophosphorylated lipid A may weaken interactions with host TLR4 receptors, which could potentially compensate for the pro-inflammatory TLR4 activation of A. muciniphila LOS. == Activation of TLR signaling ==

Akkermansia muciniphila LOS has been found to induce moderately strong TLR4 activation in vitro. The lipid A moiety of A. muciniphila has been shown to strongly induce TLR2 activation, likely through the TLR2/6 heterodimer. It has been hypothesized that activation of anti-inflammatory TLR2 signaling partly explains the beneficial immunomodulatory activities of A. muciniphila Injection of A. muciniphila LOS has been found to trigger the expression of TLR2 mRNA in mice. Interestingly, the expression of TLR4 mRNA was also shown to increase after LOS injection, although to a much lower level compared to TLR2 mRNA. == Ecology and metabolism ==

It colonizes the gastrointestinal tract of humans and animals. It can be found within the intestinal mucosal layer of the epithelial crypts as well as in the cecum. 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. Akkermansia muciniphila can use mucin as its sole source of carbon, nitrogen, and energy, and is hence considered a specialist. A. muciniphila can then get access to the de-capped O-glycans and the mucin peptide chain, both of which it can utilize as an energy source. The released monosaccharides are distributed to the environment, where other mucus-associated gut bacteria can utilize them. This way, A. muciniphila contributes to nutrient-sharing in gut-associated microbial communities. Mucin degradation can also lead to the production of beneficial products such as short chain fatty acids, which aid in the growth of other bacteria and maintain healthy mucus turnover. ==Genomics==

The circular chromosome of the type strain contains 2,664,102 base pairs and its proteome contains 5,644 unique proteins. ==Human consumption==

Oral Akkermansia muciniphila, either live or pasteurized, "are safe and well tolerated in overweight and obese individuals." With clinical research increasingly underscoring the power of the gut microbiome to human health in general, probiotics companies globally were keen to harness Akkermansia muciniphila. But, because it is an anaerobic strain (i.e., it cannot tolerate oxygen), it was a problematic challenge. San Francisco-based company Pendulum Therapeutics eventually invented a proprietary manufacturing environment and process that replicated the gut's oxygen-free environment, as well as acid-resistant capsules that could transport the Akkermansia muciniphila strain through the highly acidic stomach, through the small intestine, and into the large intestine, where it could get to work. == Diet ==

Consumption of galacto-oligosaccharides increases the relative abundance of Akkermansia muciniphila in the human gut. == Research ==

Akkermansia muciniphila is under preliminary research for its potential to affect various disorders, such as in gut barrier function, obesity, type 2 diabetes, immune system dysfunction, colorectal cancer, and inflammatory bowel disease. Daily administration of live A. muciniphila MucThas been found to decrease adipose tissue inflammation, insulin resistance and metabolic endotoxemia in mice that were fed a high-fat diet. ==References==