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Akkermansia muciniphila: Next-Gen Bacteria for Metabolic Health

A unique, mucin-loving keystone species

The gut mucus layer forms a natural defense barrier, and its integrity is vital for maintaining the intestinal health of the host.1 Akkermansia muciniphila, unlike many of the known probiotic species, is a unique commensal microbe inhabiting the mucus layer, where it can interact closely with host intestinal epithelial cells and immune cells. Akkermansia muciniphila is known to utilize mucins (key components of mucus) as nutrient and energy sources and produce beneficial short-chain fatty acids (SCFAs).2 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.3

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Research Highlights

Akkermansia muciniphila is a keystone species inhabiting host intestinal mucus layer and contributes to the maintenance of a healthy gut barrier.

A lower abundance of Akkermansia muciniphila is associated with poor metabolic health, whereas a higher abundance is linked to better metabolic health.

Its membrane protein Amuc_1100 can help maintain host gut barrier integrity, support immune homeostasis, and improve metabolic functions via TLR2 signaling. Amuc_1100 remains active after pasteurization.

A human clinical trial demonstrated that pasteurized Akkermansia muciniphila is more effective than the live bacterium in improving metabolic health-related parameters.

Clinical relevance of Akkermansia muciniphila

The presence and abundance of Akkermansia muciniphila in the gut may be indicative of the host’s metabolic health:4

  • In multiple human cohort studies, the abundance of Akkermansia muciniphila is reduced in the microbiomes of individuals with obesity, type 2 diabetes (T2DM), impaired glucose control, high blood pressure, inflammatory bowel diseases, and liver diseases (Figure 1).5-10
  • Conversely, greater abundance of Akkermansia muciniphila is linked with a leaner body weight, lower body fat mass, and greater improvement in insulin sensitivity (Figure 1).5,11

Proposed mechanisms of actions of Akkermansia muciniphila

Recent intervention studies in animals demonstrated Akkermansia muciniphila administration reversed high-fat diet-induced metabolic disorders, fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance.12

As seen in Figure 2, Akkermansia muciniphila has been demonstrated to exert several mechanisms of action such as:

  • Enhance mucin production by increasing the number and density of goblet cells (mucin-producing cells), which helps restore the thickness of the mucus layer.13
  • Increase the expression of tight-junction proteins within the intestinal epithelium to augment the integrity of tight junctions.14
  • Its membrane protein Amuc_1100 binding to Toll-like receptor 2 (TLR2), leading to activation of anti-inflammatory pathways, prevention of lipopolysaccharides (LPS) translocation, and improvement in mucin secretion and gut barrier.15
Akkermansia muciniphila
Figure 2

More important, researchers discovered that mice receiving pasteurized Akkermansia muciniphila had a greater reduction in body weight, fat-mass gain, plasma lipids, and insulin-resistance markers than mice receiving the live bacterium.15 Research found that the protein Amuc_1100 remained heat-stable after pasteurization, and its administration alone recapitulated most of the observed metabolic benefits in vivo. This suggests that pasteurization enhances the effects of Akkermansia muciniphila by increasing accessibility of Amuc_1100 to the host.15

Human clinical trial of Akkermansia muciniphila

The metabolic benefits seen in animal studies led to the first human clinical trial investigating the health-promoting potential of Akkermansia muciniphila (both alive and pasteurized) in people who were overweight or obese and insulin-resistant.

Thirty-two volunteers received either placebo, live Akkermansia muciniphila (10 billion CFU/day), or pasteurized Akkermansia muciniphila [30 billion total fluorescent units (TFU)/day]  for three months and were asked not to change their diet and exercise habits. The study found:16

The supplementation of pasteurized form but not of live form markedly improved insulin sensitivity and reduced insulinemia and plasma total cholesterol levels compared with volunteers supplemented with placebo.

  • Compared with placebo, pasteurized Akkermansia muciniphila decreased body weight, hip circumference, and waist circumference by an average of 5.0 lb., 1.0 in., and 0.6 in., respectively.
  • Compared with placebo, pasteurized Akkermansia muciniphila decreased plasma LPS levels (metabolic endotoxemia) by an average of 117%.
  • Both live and pasteurized Akkermansia muciniphila for three months were safe and well-tolerated.
Summary

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, berberine),17,18 supplementing selected probiotic strains,19,20 and exercise.21 Today, daily supplementation of Akkermansia muciniphila has become a reality. 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.

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