Science behind Akkermansia Muciniphila

Latin for “mucus lover,” A. muciniphila possesses a distinctive ability to feed off the mucus lining within the gastrointestinal tract. This microbe is typically found along the large intestine, constituting approximately 0.5-5% of a healthy human's microbiome. Remarkably, A. muciniphila's primary function revolves around the degradation of mucin proteins, serving as a gatekeeper of intestinal permeability, and thus, influencing the integrity of the gut-brain axis.

In contrast to the majority of gut bacteria, which rely on fiber as their dietary source, A. muciniphila assumes a pivotal role within the microbiota ecosystem, not only by consuming mucins to maintain the intestinal mucus lining, but also by producing nutrients, such as short chain fatty acids. These byproducts serve a purpose of nourishing other bacteria and fostering the development of a robust and health-promoting commensal microbiota environment.

Even before A. muciniphila’s discovery in 2004, the important connection between gut permeability and inflammatory and neurological diseases, or the gut-brain axis, was well known. Consequently, researchers at the Wageningen University of the Netherlands initially posited that bacteria engaged in metabolizing the gut lining would play a substantial role in interacting with human intestinal cells and shaping various health outcomes. These researchers soon isolated and discovered A. muciniphila as the exclusive mucin-degrading bacteria in the human intestines. Further investigation found A. muciniphila strains in infants and throughout diverse human populations, along with genetically similar strains in a range of wild animal populations. These finding suggest the evolutionary importance and pivotal role of mucus-consuming bacteriain the well-being and growth of animals. Moreover, since its discovery, Akkermansia has garnered over 2,000 mentions in PubMed articles in just two decades. Extensive research has revealed robust links between its presence and various health advantages, establishing it as a next-gen probiotics with numerous potential targets for therapeutic applications.

Although this is not an exhaustive summary of A. muciniphila research, the following information provides an overview of important scientific research around A. muciniphila and why it has emerged as one of the most promising, naturally occurring, next-gen probiotics to treat metabolic disorders and help with weight loss.

A. muciniphila Abundance is associated with Healthy Lifestyle Factors in Humans

Healthy levels of A. muciniphila in the gut align with a balanced diet, regular exercise, and favorable eating habits in humans. Individuals who maintain consistent exercise regimens and incorporate polyphenol-rich foods into their diets, such as dark berries, chocolate, coffee, and tea, tend to exhibit healthy levels of this bacterium. Interestingly, as a mucus-consuming bacterium that does not need starch or sugar to survive, A. muciniphila has been observed to flourish in the presence of calorie restriction and resiliency during periods of starvation or fasting, demonstrating potential insight to its ubiquity and widespread presence among humans and animals globally.

Another significant factor linked to the presence of A. muciniphila is longer food transit time, meaning digestion takes longer in the intestines. This results in heightened nutrient absorption and an extended feeling of satiation after eating. Remarkably, extended food transit time, leading to decreased appetite is also a noteworthy effect observed in one of the world's most widely used pharmaceuticals for diabetes management and weight loss—semaglutide, available under brand names Ozempic, Wegovy, and Rybelsus. This phenomenon may be attributed to the natural activation of glucagon-like peptide-1 (GLP-1) by A. muciniphila. Semaglutide, in essence, emulates the effects of GLP-1—a hormone typically released in the small intestine, responsible for slowing gastric emptying and increasing satiety

In contrast to the presence of A. muciniphila at healthy levels, mounting evidence underscores its lack of presence as a risk factor for metabolic conditions such as obesity, type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disorders. These associations with metabolic health not only suggest that A. muciniphila in humans may act as a preventive measure against metabolic and cardiovascular conditions linked to high body-mass index, but also offer indications of its therapeutic potential in treating and enhancing outcomes for 2 individuals affected by these conditions. One study, which examined the abundance of A. muciniphila in a group of 11 overweight and 38 obese individuals, revealed positive correlations with improved overall metabolic profiles and heightened clinical success following caloric restriction. This, in turn, has the potential to enhance the quality of life for overweight individuals and increase the likelihood of successful weight loss treatments.

Studies conducted on rodents have strongly supported the connection between A. muciniphila and the reduction of metabolic diseases. In these studies, daily administration of live A. muciniphila reversed metabolic conditions induced by a high-fat diet in mice. Improved conditions included decreased fat mass, metabolic endotoxemia, inflammation in adipose tissue, and insulin resistance. Pasteurized A. muciniphila also contributed to reducing the development of fat mass, insulin resistance, and dyslipidemia in mice.

Furthermore, research on rodents has demonstrated that A. muciniphila supplementation leads to a decrease in cholesterol and serum triglyceride levels in metabolic disease models. It has been effective in preventing nonalcoholic fatty liver disease by regulating the expression of genes related to fat synthesis and inflammatory markers in the liver of mice. Additionally, in mouse models of atherosclerosis, it has been shown to reduce the severity of atherosclerotic lesions. A. muciniphila has also shown promise in mitigating diabetes in both type 2 and type 1 diabetes mouse models by lowering gut permeability and reducing inflammation. Other studies have indicated that A. muciniphila supplementation reduces the severity of inflammatory bowel disease, alcoholic liver disease, colitis-associated tumorigenesis, and progeria in mice. Currently, human clinical studies are underway to validate the promising results on metabolic disorder treatments observed in rodent studies.

Ashrafian F, Keshavarz Azizi Raftar S, Shahryari A, Behrouzi A, Yaghoubfar R, et al. 2021. Comparative effects of alive and pasteurized Akkermansia muciniphila on normal diet-fed mice. Scientific Reports 2021 11:1. 11(1):1–13

Asnicar F, Leeming ER, Dimidi E, Mazidi M, Franks PW, et al. 2021. Blue poo: impact of gut transit time on the gut microbiome using a novel marker. Gut. 70(9):1665–74

Bárcena C, Valdés-Mas R, Mayoral P, Garabaya C, Durand S, et al. 2019. Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice. Nature Medicine 2019 25:8. 25(8):1234–42

Becken B, Davey L, Middleton DR, Mueller KD, Sharma A, et al. 2021. Genotypic and phenotypic diversity among human isolates of akkermansia muciniphila. mBio. 12(3)

Belzer C, De Vos WM. 2012. Microbes inside—from diversity to function: the case of Akkermansia. The ISME Journal 2012 6:8. 6(8):1449–58

Berer K, Gerdes LA, Cekanaviciute E, Jia X, Xiao L, et al. 2017. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A. 114(40):10719–24

Bian X, Wu W, Yang L, Lv L, Wang Q, et al. 2019. Administration of Akkermansia muciniphila Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice. Front Microbiol. 10:471824

Cani PD, Depommier C, Derrien M, Everard A, de Vos WM. 2022. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. Nature Reviews Gastroenterology & Hepatology 2022 19:10. 19(10):625–37

Carabotti M, Scirocco A, Maselli MA, Severi C. 2015. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of Gastroenterology : Quarterly Publication of the Hellenic Society of Gastroenterology. 28(2):203

Cekanaviciute E, Yoo BB, Runia TF, Debelius JW, Singh S, et al. 2017. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci U S A. 114(40):10713–18

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