Complex carbohydrate utilization by gut bacteria modulates host food consumption

Kristie B. Yu (), Celine Son, Ezgi Özcan, Anisha Chandra, Jorge Paramo, Andrew Varghese, Alicia Roice, Delanie Finnigan, Franciscus Chandra, Anna Novoselov, Sabeen A. Kazmi, Gregory R. Lum, Arlene Lopez-Romero, Jonathan B. Lynch and Elaine Y. Hsiao ()
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Kristie B. Yu: University of California, Los Angeles
Celine Son: University of California, Los Angeles
Ezgi Özcan: University of California, Los Angeles
Anisha Chandra: University of California, Los Angeles
Jorge Paramo: David Geffen School of Medicine
Andrew Varghese: University of California, Los Angeles
Alicia Roice: University of California, Los Angeles
Delanie Finnigan: University of California, Los Angeles
Franciscus Chandra: University of California, Los Angeles
Anna Novoselov: University of California, Los Angeles
Sabeen A. Kazmi: University of California, Los Angeles
Gregory R. Lum: University of California, Los Angeles
Arlene Lopez-Romero: David Geffen School of Medicine
Jonathan B. Lynch: University of California, Los Angeles
Elaine Y. Hsiao: University of California, Los Angeles

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract The gut microbiota interacts with dietary nutrients and can modify host feeding behavior, but underlying mechanisms remain poorly understood. Gut bacteria digest complex carbohydrates that the host cannot digest and liberate metabolites that serve as energy sources and signaling molecules. Here, we use a gnotobiotic mouse model to examine how gut bacterial fructose polysaccharide metabolism influences host intake of diets containing these carbohydrates. Two Bacteroides species ferment fructans with different glycosidic linkages: B. thetaiotaomicron ferments levan with β2-6 linkages, whereas B. ovatus ferments inulin with β2-1 linkages. We find that mice eat relatively more diet containing the carbohydrate that their gut bacteria cannot ferment compared to the fermentable ones: mice colonized with B. thetaiotaomicron consume more inulin diet, while mice colonized with B. ovatus consume more levan diet. Knockout of bacterial fructan utilization genes attenuates this difference, whereas swapping the fermentation ability of B. thetaiotaomicron to inulin confers increased consumption of levan diet. Bacterial fructan fermentation and host feeding behavior are associated with neuronal activation in the arcuate nucleus of the hypothalamus. These results reveal that bacteria nutrient metabolism modulates host food consumption through sensing of differential energy extraction, which contributes to our understanding of determinants of food choice.

Date: 2025
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DOI: 10.1038/s41467-025-63372-8

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