Gut Bacteria in the Control of Obesity and Type 2 Diabetes

The bacteria (microbiota) that reside in our intestines were once thought to be of little consequence except for their role in vitamin synthesis. However, very recently a new area of study has begun to focus on the role of the bacterial complement of the gut and the role these microorganisms play in altering dietary and metabolic processes. Of particular significance is the now recognized alteration in gut microbiota associated with obesity, type 2 diabetes, and the associated increase in intestinal inflammation and gut barrier disruption this causes.

For more information on the correlation between obesity and gut bacteria visit the Obesity: Metabolic and Clinical Consequences page of my website.

A recent paper in this field, published in the Proceedings of the National Academy of Sciences, has demonstrated that a particular strain of gut bacteria, Akkermansia muciniphila, is directly involved in the control of diet-induced obesity. A. muciniphila is a Gram-negative bacteria (i.e., it contains LPS) that constitutes 3–5% of the gut microbiota. 

Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity

A. muciniphila is a mucin-degrading bacterium that resides in the mucus layer of the intestinal tract. Strikingly, there is an inverse correlation in humans between the levels of this bacterium and body weight.

Earlier studies by this same group examined the changes in gene expression within the gut of germ-free mice inoculated with A. muciniphila. What they discovered was that genes involved in pathways that regulate lipid metabolism, cell signaling, and molecular transport activated by this bacterium

This most recent study utilized mouse models of obesity and diabetes to define the role of A. muciniphila in these disorders. They found that the levels of A. muciniphila were decreased in obese and type 2 diabetic mice. Of potential clinical significance was their finding that prebiotic feeding normalized A. muciniphila levels and this change could be correlated with an improved metabolic profile in these animals. Prebiotics are non-digestible food ingredients (primarily carbohydrates) that stimulate the growth and/or activity of beneficial bacteria in the gut.  Another result of this study was that A. muciniphila treatment reversed many of the metabolic dysfunctions that result from a high-fat diet including fat-mass gain, adipose tissue inflammation, and insulin resistance. 

The administration of A. muciniphila to these mice was also shown to result in increased intestinal levels of endocannabinoids. Gut endocanabinoids control intestinal inflammation, stimulate gut barrier functions, and increase gut peptide secretion. Important gut peptides stimulated to be released by endocannabinoids are glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2). GLP-1 is involved in glucose homeostasis via its actions on the pancreas and it is involved in the control of appetite via actions within the brain. GLP-2 is involved in the regulation of gut barrier function.

More information on the roles of the endocanabinoids

More information on the functions of GLP-1

The results of this research provide a strong rationale for the use of prebiotics that stimulate the density of A. muciniphila in the gut, and/or for treatments that utilize this strain of bacteria for the prevention or treatment of obesity and its associated metabolic disorders.