Highlights d Ketogenic diets (KDs) alter the gut microbiota in a manner distinct from high-fat diets d Gut microbial shifts on KDs are driven in part through host production of ketone bodies d b-hydroxybutyrate selectively inhibits bifidobacterial growth d The KD-associated gut microbiota reduces levels of intestinal Th17 cells
Highlights d A generalizable approach is presented for meta-analysis of microbiome datasets d High-fat diets induce reproducible shifts in the mouse gut microbiome d Nonviable Lactococcus contamination is widespread in experimental diets d Phylogenetic and gene signatures translate to human microbiomes
The microbiota plays a critical, weight-promoting role in diet-induced obesity (DIO), but the pathways that cause the microbiota to induce weight gain are unknown. We report that mice deficient in lymphotoxin (LT), a key molecule in gut immunity, were resistant to DIO. Ltbr−/− mice differed in microbial community composition compared to their heterozygous littermates, including an overgrowth of segmented filamentous bacteria (SFB). Furthermore, cecal transplantation conferred leanness to germ-free recipients. Housing Ltbr−/− mice with their obese siblings rescued weight gain, demonstrating the communicability of the obese phenotype. Ltbr−/− animals lacked interleukin 23 (IL-23) and IL-22 that can regulate SFB. Mice deficient in these pathways also resisted DIO, demonstrating that intact mucosal immunity guides diet-induced changes to the microbiota to enable obesity.
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