Pasteurized Akkermansia Muciniphila Supplementation: Exploring Potential Benefits in Overweight and Obese Individuals

Akkermansia muciniphila is a unique mucin-loving keystone species residing in the human gastrointestinal tract, purportedly offering health benefits, especially in the realms of metabolic health and obesity.¹

Clinical investigations exploring A. muciniphila supplementation in overweight and obese cohorts seek to elucidate its potential impact on metabolic parameters, adiposity, and other health metrics. Studies consistently show reduced abundance in obesity, type 2 diabetes, high blood pressure, and other metabolic conditions.²

Intervention studies in animals demonstrated A. muciniphila administration reversed high-fat diet-induced metabolic disorders, fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. ³

The inaugural human clinical trial, examining the health-promoting potential of both live and pasteurized A. muciniphila, targeted individuals characterized by overweight or obesity and insulin resistance. Employing a randomized, double-blind, placebo-controlled design with primary endpoints centered on safety, tolerability, and metabolic parameters—including insulin resistance, circulating lipids, visceral adiposity, and body mass—the study enrolled 40 overweight/obese insulin-resistant participants, of whom 32 completed the trial.⁴

The findings indicated that daily oral supplementation of 10¹⁰ bacteria, whether alive or pasteurized A. muciniphila over 3 months, was deemed safe and well-tolerated. Pasteurized A. muciniphila demonstrated statistically significant improvements in insulin sensitivity (p=0.002), reduced insulinemia (p=0.006), and lowered plasma total cholesterol (p=0.02) compared to placebo. Additionally, there were marginal reductions in body weight (p=0.091) compared to the placebo group, and fat mass (p=0.092) and hip circumference (p=0.091) as compared to baseline. Following 3 months of supplementation, A. muciniphila contributed to decreased levels of pertinent blood markers associated with liver dysfunction and inflammation, with no discernible impact on the overall gut microbiome structure. Live A. muciniphila slightly improved insulin sensitivity (p=0.095), reduced insulinemia (p=0.056) and cholesterol levels (p=0.088) as compared to placebo, but the results were not statistically significant.

In the light of established link between A. muciniphila abundance and overall health, strategies to enhance its presence include consuming polyphenol-rich foods with compounds like epigallocatechin gallate (EGCG) and berberine,^5,6 known for their impact on gut microbiota. Targeted supplementation with probiotic strains supporting A. muciniphila proliferation and regular physical activity are also recognized interventions to modify A. muciniphila abundance in the gut. ^7,8

The recent development of daily supplementation with A. muciniphila, particularly in its pasteurized form, stands as a contemporary intervention aimed at supporting metabolic health, especially in individuals suffering from overweight or obesity. This innovative approach is positioned at the forefront of advancing metabolic health support. It is essential to underscore that, while maintaining a well-balanced diet and regular exercise regimen remains foundational for weight management and mitigating risks associated with metabolic syndrome, the inclusion of pasteurized A. muciniphila introduces a novel dimension to this evolving landscape of metabolic health interventions.

Why is this Clinically Relevant?

1. Pasteurized A. muciniphila improved insulin sensitivity, lowered insulinemia and plasma total cholesterol, with slight reductions in body weight, fat mass, and hip circumference. It also reduced blood markers of liver dysfunction and inflammation without affecting the overall gut microbiome structure.
2. This proof-of-concept study illustrates that the administration of a daily dose as high as 10¹⁰ cells of pasteurized A. muciniphila is safe and well-tolerated and improves several metabolic parameters. Therefore, it can be a part of a patient’s daily regimen and can be a viable option for improving metabolic health.

Citations

1. 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.
2. Roshanravan N et al. A comprehensive systematic review of the effectiveness of Akkermansia muciniphila, a member of the gut microbiome, for the management of obesity and associated metabolic disorders. Arch Physiol Biochem. 2023;129(3):741-751
3. 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.
4.  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.
5. 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.
6. Jeong HW et al. Green tea encourages growth of Akkermansia muciniphila. J Med Food. 2020;23(8):841-851.
7. Hibberd AA et al. Probiotic or symbiotic alters the gut microbiota and metabolism in a randomized controlled trial of weight management in overweight adults. Benef Microbes. 2018:1-16.
8. 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.