Assistant Professor of Immunology Weill Cornell Med., United States
Introduction/Rationale: With global rise in obesity, there is a growing urgency to shift our focus from obesity treatment to prevention. Dietary fiber is a promising non-pharmacologic intervention that has potential to limit tissue adiposity, but its mechanisms remain poorly defined. This study aims to determine the role of dietary fiber-induced microbial metabolites in adipose tissue homeostasis.
Methods: Untargeted metabolomic profiling of adipose tissue was performed to assess the metabolic effects of a high fiber diet. Metagenomic sequencing characterized changes in microbial pathways. Confocal imaging was used to analyze adipose tissue architecture. Finally, chemogenetic silencing determined the role of sympathetic neurons in mediating fiber-induced metabolic responses.
Results: We show that a high fiber diet significantly alters microbial metabolism of several metabolites including bile acids, elevating their levels in adipose tissue. These diet-induced changes were associated with beiging of white adipose tissue, reduced visceral adiposity, and improved glucose tolerance. Dietary regulation of adiposity was absent in germ-free mice and could be restored by a defined human Bacteroidota consortium. A subset of microbiota-derived secondary bile acids mimicked the effects of high fiber diet on adipose tissue via the liver X receptor. Notably, high fiber diet increased the density of sympathetic neurons in the adipose tissue and disrupting their signaling abolished the effects of high fiber diet on adiposity. Mechanistically, secondary bile acids increased the expression of IL-33 in adipose stem and progenitor cells and recruited eosinophils in the adipose tissue which were required for promoting neuronal density and beiging of white adipocytes.
Conclusion: Together, these data indicate that dietary fiber alters microbial metabolism and tissue distribution of bile acid derivatives, regulating adiposity via a neuroimmune axis with implications for prevention of obesity and associated metabolic syndromes.
