New Study Reveals Genetic Modification in Gut Bacteria Alters Host Metabolism

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Researchers from Harvard Medical School suggest that bile acid in gut bacteria cause changes in metabolism and reduced weight gain in mice.

Microbiome in the human body influences the development of obesity and metabolic diseases such as diabetes. However, the mechanism of the microbiome that affects metabolism is hard to decipher due to the presence of several species of bacteria in the gut that produce many different kinds of metabolites. Furthermore, understanding the individual effects of these metabolites is a significant challenge. Now, a research led by Sloan Devlin, assistant professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School used a variety of genetic modifications to isolate a particular gene from the microbiome, to investigate its effects on host metabolism. The researchers focused on bile acids, which are a group of naturally occurring substances in the human gut. Imbalances in the bile acid pool causes diet-induced obesity. However, it is unclear which specific bile acids cause these effects. In previous research by the team, it was observed that salt hydrolases significantly affect regulations of host metabolism. The researchers observed that a certain bacterial species with a bile salt hydrolase metabolizes certain types of bile salts and they generated two strains of bacteria — one with the hydrolase and one without hydrolase. Both the strains were introduced into germ-free mice. It was observed that mice colonized with the hydrolase-deficient strain contained higher amounts of certain unmetabolised bile salts in their intestine. The research was published online in the journal eLife on July 17, 2018.

In next stage of the experiment, the researchers investigated the downstream effects of modifying the levels of specific bile salts on mouse metabolism. Surprisingly, the mice colonized with bacteria lacking the hydrolase gained less weight than the mice colonized with the normal bacteria. Furthermore, the mice had lower levels of fats and cholesterol in the blood and liver than those with the hydrolase, and the mice metabolized fats rather than carbohydrates for energy. Further genetic analysis revealed changes in genes controlling circadian rhythm and immune response suggesting the border role of bile acid in alterations caused by bacteria.

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