New Study Links Single Gene in Gut Bacteria to Obesity and Metabolic Syndrome

A Summary of Selective Gut Bacterial Bile Salt Hydrolase Alters Host Metabolism by Yao,

The gut microbiome is quickly emerging as an important research focus to better understand it’s integral role in human health and disease. The scientific community is discovering how the interaction between intestinal microbial communities and their human host impacts the development of varied human diseases, including obesity and metabolic-related disorders. Research has shown, for example, that when the microbiome from obese subjects (which differs from lean subjects) is transplanted into germ free mice, the mice develop obesity-associated phenotypes. The mechanism through which microbial communities influence host metabolism, however, is still unknown.

In this recently published paper, Yao uncovers one such mechanism. The investigators focused on bile salt hydrolases, produced by a common colonic bacteria, and found this specific enzyme had a significant impact on metabolic processes. To provide a brief background, bile acids are produced by the liver and gallbladder, and released into the intestine to help digest food and release nutrients. While some of these acids are recycled back to the liver, some of the bile acids continue their journey through the intestine, are modified by the resident bacteria, and subsequently influence how we metabolize and store ingested fats and carbohydrates. The authors identified selective Bacteroides strains that generated bile salt hydrolases (BSH), and engineered bacterial strains missing the necessary gene to produce the enzyme. They then colonized germ-free mice with both the control strains as well as the mutant strains of bacteria. They fed both groups of mice a high fat diet, and compared differences in metabolism.

The investigators noted several important differences when they compared the two groups of mice. First, the mice colonized with bacteria that lacked the ability to make BSH gained less weight, had lower levels of fat in the blood and liver, and were more likely to burn fat (instead of carbohydrates) for energy. In addition to these metabolic differences, they also noted alterations in circadian rhythms and immune responses in the mice with decreased levels of BSH. These groundbreaking results demonstrate, for the first time, how a specific bacterial gene from the gut microbiota may have a significant impact on host metabolic pathways, ultimately manifesting in human disease.