Akkermansia muciniphila: Your Next-Generation Bacteria for Metabolic Health

by Lewis Chang, PhD
Not all heroes are muscle-bound and wear capes. There is a tiny, almost invisible, hero that lives in our gut and promotes our health and wellbeing. Its name, Akkermansia muciniphila, may be a mouthful, but it’s time to get to know this hero better, as its health-promoting effects have earned it the reputation as a next-generation beneficial bacteria.1

​Gut health is intricately connected to human health in ways that surprise us. Our gut is home to trillions of bacteria, fungi, and other microorganisms that form a complex ecosystem known as the gut microbiome. A healthy gut microbiome promotes proper digestion, strengthens our immune system to fight off infections and diseases, helps regulate our metabolism and weight, and influences our mood and brain function. On the other hand, an imbalance in the gut microbiome can lead to various health issues, including digestive problems like bloating, diarrhea, and constipation. It can also weaken our immune system, making us more susceptible to infections and inflammation.2 Additionally, an imbalanced gut microbiome has been linked to conditions such as obesity, metabolic disorders, mental health disorders, and autoimmune diseases.

Enter Akkermansia muciniphila and why it’s a guardian of our gut
The layer of mucus in our gut acts as a natural defence barrier, crucial for keeping our intestines healthy. Akkermansia muciniphila, unlike many of the known probiotic species in the gut, is unique for living inside the mucus layer, where it can interact closely with intestinal epithelial and immune cells. It feeds on mucins (key components of mucus) and produces beneficial substances called short-chain fatty acids (SCFAs), which have anti-inflammatory and antioxidant properties, improve insulin sensitivity, and help regulate appetite.3 Numerous studies have uncovered actions of Akkermansia muciniphila in the gut. For example:

• It enhances mucin production by increasing the number and density of goblet cells (mucin-producing cells), which helps restore the thickness of the mucus layer.4
• It enhances the integrity of the intestinal lining by boosting the expression of proteins that strengthen the tight junctions between cells.5
• One of its membrane proteins, Amuc_1100, interacts with toll-like receptor 2 (TLR2), triggering anti-inflammatory pathways and preventing the passage of harmful substances (such as lipopolysaccharides (LPS)).6
• The short-chain fatty acid (SCFA) acetate produced by Akkermansia muciniphila supports the growth of other beneficial bacteria, such as Faecalibacterium prausnitzii, which is known for producing another beneficial SCFA, butyrate.7 

It is believed that through reinforcing gut barrier function, Akkermansia muciniphila supports various bodily functions, such as energy, lipid and glucose metabolism, as well as immune responses.1

The connection between Akkermansia muciniphila and metabolic health
Akkermansia muciniphilia, has garnered significant attention due to its relative abundance.  The reason behind this growing interest lies in the compelling links observed between low levels of this species and various health conditions, including obesity, type 2 diabetes, high blood pressure, and liver diseases.9-14

Conversely, when Akkermansia muciniphila is more abundant in the gut, it tends to be associated with a healthier body weight, less body fat, and better insulin sensitivity.9,15 Furthermore, animal studies have shown Akkermansia muciniphila reverses metabolic disorders, weight gain caused by a high-fat diet, metabolic endotoxemia, inflammation in fat tissues, and insulin resistance.8

Given the correlation between abundance of Akkermansia muciniphila and health status, efforts have been made to restore and promote abundance of Akkermansia muciniphila, such as increasing intake of polyphenol-rich foods (e.g., EGCG),16,17 supplementing selected probiotic strains,18,19 and exercise.20 This unique species is now available in supplemental form, allowing a direct route to augment Akkermansia muciniphila abundance.

In a clinical study conducted by Patrice Cani, PhD, Willam de Vos, PhD and their colleagues, they examined the health-promoting potential of this microbe in people who were overweight or obese and had insulin-resistance.21 Thirty-two volunteers received either placebo (inactive medicine), live Akkermansia muciniphila (10 billion CFU/day), or pasteurized Akkermansia muciniphila (30 billion total fluorescent unit (TFU)/day) for three months and were asked not to change their diet and exercise habits. At the end of study, researchers found supplementation with Akkermansia muciniphila to be safe and well-tolerated and demonstrated improvements in metabolic syndrome risk factors, such as total cholesterol and insulin resistance, as well as body weight, fat mass, and hip circumference. Importantly, the pasteurized (heat-inactivated) form of Akkermansia muciniphila, not the live form, improved insulin resistance and reduced insulinemia and total cholesterol, as well as parameters elevated in obesity and glucose intolerance (i.e., white blood cell counts) and inflammation (i.e., LPS). These findings suggest the pasteurized form of Akkermansia muciniphila is more effective for addressing metabolic syndrome risk factors.21

Who can benefit from Akkermansia muciniphila supplementation?
The unique attributes of this tiny hero, Akkermansia muciniphila, has gained its recognition as a valuable player in gut and metabolic health.1 While a balanced diet and regular exercise are the cornerstones for maintaining healthy weight and minimizing metabolic syndrome risks, this next-generation bacteria, pasteurized Akkermansia muciniphila, offers a novel solution to support metabolic health in those who are overweight or obese.

Citations

1. Cani PD et al. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. Nat Rev Gastroenterol Hepatol. 2022;19:625-637.
2. Cani PD. Gut microbiota – at the intersection of everything? Nat Rev Gastroenterol Hepatol. 2017;14(6):321-322.
3. Derrien M et al. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004;54(Pt 5):1469-1476.
4. Zhu L et al. Akkermansia muciniphila protects intestinal mucosa from damage caused by S. pullorum by initiating proliferation of intestinal epithelium. Vet Res. 2020;51(1):34.
5. Ottman N et al. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS One. 2017;12(3):e0173004.
6. Plovier H et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017;23(1):107-113.
7. Lopez-Siles M et al. Alterations in the abundance and co-occurrence of Akkermansia muciniphila and Faecalibacterium prausnitzii in the colonic mucosa of inflammatory bowel disease subjects. Front Cell Infect Microbiol. 2018;8:281.
8. Everard A et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013;110(22):9066-9071.
9. Dao MC et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016;65(3):426-436.
10. Yassour M et al. Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. Genome Med. 2016;8(1):17.
11. Zhang X et al. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One. 2013;8(8):e71108.
12. Li J et al. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017;5(1):14.
13. Grander C et al. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut. 2018;67(5):891-901.
14. Png CW et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol. 2010;105(11):2420-2428.
15. Fruge AD et al. Fecal Akkermansia muciniphila is associated with body composition and microbiota diversity in overweight and obese women with breast cancer participating in a presurgical weight loss trial. J Acad Nutr Diet. 2020;120(4):650-659.
16. Zhu L et al. Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe(-/-) mice. Atherosclerosis. 2018;268:117-126.
17. Jeong HW et al. Green tea encourages growth of Akkermansia muciniphila. J Med Food. 2020;23(8):841-851.
18. Ryan JJ et al. Short-term tolerability, safety, and gut microbial composition responses to a multi-strain probiotic supplement: an open-label study in healthy adults. Integr Med (Encinitas). 2021;20(1):24-34.
19. Hibberd AA et al. Probiotic or synbiotic alters the gut microbiota and metabolism in a randomised controlled trial of weight management in overweight adults. Benef Microbes. 2018:1-16.
20. Munukka E et al. Six-week endurance exercise alters gut metagenome that is not reflected in systemic metabolism in over-weight women. Front Microbiol. 2018;9:2323.
21. Depommier C et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019;25(7):1096-1103.