Akkermansia

Akkermansia muciniphila, a key element in the gut microbiome. plays a crucial role in both longevity and metabolism. Studies have revealed that Akkermansia not only contributes to longevity by promoting gut health and immune resilience but also plays an important role in optimizing metabolism.'-2·3 The primary manner in which Akkermansia is involved in longevity is the role it plays in creating an ideal environment in the gut. This, ultimately, lends to its impact on metabolism. specifically the production of glucagon-like peptide 1 (GLP-1), a specialized hormone which serves as a central player in metabolic health.4 At its core. the role of Akkermansia in promoting longevity is driven by this optimization of metabolism via GLP-1. 

GUT HEALTH AND LONGEVITY 

Akkermansia muciniphila has been shown to play an important role in promoting gut health, and thus, longevity through multiple mechanisms. First, Akkermansia muciniphila thrives on mucin and utilizes it as a source of energy. As Akkermansia consumes mucin. it stimulates the production of additional mucin by epithelial cells. This process of "mucin making" leads to the reinforcement of the intestinal wall. which is essential for maintaining gut health and overall well-being.5 Additionally. Akkermansia has been shown to promote short chain fatty acids. which further support the gut's immune defenses by inhibiting the invasion of potentially harmful bacteria.6 These combined effects create an environment conducive to a balanced gut microbiota and optimal gut function. which are key factors in supporting longevity and overall well-being. 

METABOLISM AND GLP-1 PRODUCTION 

In terms of metabolic optimization. Akkermansia muciniphila demonstrates remarkable capabilities, particularly in increasing the production of glucagon-like peptide 1 (GLP-1). GLP-1 is an incretin hormone that plays a crucial role in regulating glucose metabolism and insulin secretion.• Akkermansia promotes GLP-1 production through several pathways. First, it stimulates enteroendocrine cells in the gut to release GLP-1 in response to nutrient intake. Second. when Akkermansia provides aid to gut barrier function. it can reduce metabolic endotoxemia. which can further stimulate GLP-1 secretion. Finally. as mentioned previously. Akkermansia produces short-chain fatty acids (SCFAs) like acetate. propionate. and butyrate during fermentation. which have been shown to increase GLP-1 levels.6 The collective impact of these mechanisms results in the body's ability to support glucose tolerance. insulin sensitivity·7•8 and metabolic regulation. ultimately allowing for more efficient fat metabolism and more effective means to achieving lean body composition and browning white fat. 

1. Ou yang J, Lin J, lsnard S, Fombuena B, Peng X, Marette A, Routy B, Messaoudene M, Chen Y, Routy JP. The Bacterium Akkermansia muciniphila: A Sentinel for Gut Permeability and Its Relevance to HIV-Related Inflammation. Front lmmunol. 2020 Apr 9;11:645. 

2.     Chelakkot c .. Choi Y .. Kim D.-K .. Park H.T .. Ghim J .. Kwon Y .. Jeon J .. Kim M.-s .. Jee Y.-K .. Gho Y.S .. et al. Akkermansia muciniphi/a-derived extracellular vesicles influence gut permeability through the regulation of tight junctions. Exp. Mo/. Med. 2018;50:e450. 

3.     Bae M .. Cassilly G.D .. Liu x .. Park s.-M., Tusi B.K.. Chen x .. Kwon J .. Filipcfk P .. Bolze A.S .. Liu z .. et al. Akkermansia muciniphi/a phospholipid induces homeostatic immune responses. Nature. 2022;608:168-173. 

4.     Yoon H.S .. Cho C.H .. Yun M.S .. Jang SJ .. You HJ .. Kim J.-H .. Han D .. Cha K.H .. Moon S.H .. Lee K., et al. Akkermansia muciniphi/a secretes a g/ucagon-like peptide-I-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat Microbiol. 2021;6:563-573. 

5.     Kim S .. Shin Y.-c .. Kim T.-Y .. Kim Y .. Lee Y.-s .. Lee S.-H., Kim M.-N., OE., Kim K.S .. Kweon M.-N. Mucin degrader accelerates intestinal stem cell-mediated epithelial development Gut Microbes. 2021;13:1892441. 

6.     Rodrigues VF, Elias-Oliveira J, Pereira fs. Pereira JA. Barbosa SC, Machado MSG, Carlos D. Akkermansia muciniphi/a and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes. Front lmmunol. 2022 Jul 7;13:934695. 

7.     Depommier C., Everard A., Druart C .. Plovier H .. Van Hui M .. Vieira-Silva S., Fa/ony G .. Raes J., Maiter D., Delzenne N.M .. et al. Supplementation with Akkermansia muciniphi/a in overweight and obese human volunteers: A proof-of-concept exploratory study. Nat. Med. 2019;25:1096-1103. 

8.     Wang z. Cui S, Zhang T. Wang W, Li J, Chen YQ. Zhu SI. Akkermansia muciniphila supplementation improves glucose tolerance in intestinal Ffar4 knockout mice during the daily light to dark transition. mSystems. 2023 Oct 26;8(5):e0057323. 

9.     Everard A., Belzer C., Geurts L, Ouwerkerk J.P., Druart C., Binde/s LB., Guiot Y., Derrien M., Muccioli G.G., Delzenne N.M., et al. Cross-talk between Akkermansia muciniphi/a and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA. 2013;110:9066-9071. 

10.     Deng L. Ou z .. Huang D .. Li c .. Luz .. Liu W .. Wu F .. Nong c .. Gao J .. Peng Y. Diverse effects of different Akkermansia muciniphila genotypes on Brown adipose tissue inflammation and whitening in a high-fat-diet murine model. Microb. Pathog. 2020;147:104353.