Shenjun AKK, has the mechanism for weight loss and blood sugar control been found?

The star bacteria in the intestinal microorganisms has a very resounding name: Akkermansia muciniphila. This bacterium has been popular and can be called a "magic bacterium". It has a good improvement effect on host metabolism, immunity and intestinal barrier, cancer and neurological diseases.

Akk is an oval Gram-negative bacterium that is a resident of the human intestine, accounting for 3-5% of the human microbiome. It can grow in the intestinal mucus layer and use mucin secreted by the host as a "feed", thereby settling in the intestine and protecting the intestine from pathogens through competitive exclusion.

Many research results show that Akk bacteria can help lose weight, but it is still unknown how Akk bacteria works.

A team from Seoul National University in South Korea revealed the weight loss mechanism for the first time. They published important research results on the mechanism of Akk bacteria improving host obesity and glucose homeostasis in the journal Nature Microbiology. They found the key to the many benefits of Akk bacteria, a protein P9.

There are several findings:

1. Live bacteria can help you lose weight. When mice are fed Akk bacteria, it affects brown fat, increases the heat production of the interscapular BAT (iBAT) of mice, causes the skin temperature and rectal temperature of mice to rise, "burns" the calories of mice, and causes the mice to lose weight!

2. Akk bacteria also activated the secretion of the gastrointestinal hormone glucagon-like peptide 1 (GLP-1) in the intestine, regulated the host energy balance, and improved the glucose homeostasis of mice.

3. During the mechanism analysis, it was found that only the supernatant of live bacteria fermentation can promote the secretion of GLP-1.

4. We also compared 47 other commonly used probiotics, including the most commonly used lactic acid bacteria or bifidobacteria, and found that these bacteria did not have a similar effect in promoting GLP-1, indicating that this effect is unique to Akk bacteria.

5. Through a series of separations of Akk bacterial secretions, the researchers found that some proteins with a molecular weight of 100-300 kDa can promote the secretion of GLP-1, among which the P9 protein with a molecular weight of 84 kDa has the strongest effect.

6. Amuc_1100, another "star" protein of Akk bacteria, plays an important role in the process of Akk exerting beneficial effects on the host. Although Amuc_1100 can also promote the secretion of GLP-1, the effect of Amuc_1100 on GLP-1 is almost "not worth mentioning" in front of P9 protein!

7. How effective is this protein? They administered the same dose of P1, P5 and P9 proteins to obese mice and found that these proteins, like Amuc_1100, could improve obesity and glucose homeostasis in mice. P9 performed best.

8. The mechanism of action of P9 protein in improving host obesity and glucose homeostasis: After binding to its ligand ICAM-2, P9 protein activates the GLP-1R signaling pathway and IL-6, promoting the body's heat production and thus improving obesity and glucose homeostasis in HFD mice.

This research result explained for the first time the mechanism by which Akk bacteria improve obesity from the perspective of brown adipose tissue, and discovered that a protein P9 secreted by Akk bacteria is the core of the action, providing a new target for the development of therapeutic drugs for metabolic diseases.

However, these studies are only animal experiments and cannot be used on humans, nor have they been made into drugs.

Yoon HS, Cho CH, Yun MS, et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice[J]. Nat Microbiol, 2021, 6(5): 563-573.