Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids

TLDR

Gut microbiota modulates diet‑derived polyunsaturated fatty acids, influencing host metabolism and obesity risk, yet the physiological impact of these microbial pathways remains poorly understood. The study aims to show that gut microbiota protects against high‑fat diet‑induced obesity by altering dietary PUFA metabolism. They demonstrated that the gut‑derived metabolite HYA, elevated by Lactobacillus colonization, reduces HFD‑induced obesity in mice via free fatty acid receptors while avoiding inflammation. The results reveal that gut microbiota, through HYA production, protects against obesity and suggests targeting microbial metabolites could prevent metabolic disorders.

Abstract

Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy-cis-12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus-colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites.