Diet is a key determinant of gut microbial composition and mucosal immune function, yet the microbial mechanisms linking diet-mediated metabolic changes to immune regulation remain incompletely understood. T helper 17 (Th17) cells play central roles in both protective mucosal immunity and inflammatory pathology, making them a critical target of immunometabolic regulation. In this study, we show that 1,3-butanediol (BD) treatment, which leads to elevated circulating β-hydroxybutyrate (BHB) independently of diet, is associated with suppression of intestinal Th17 responses, remodeling of the gut microbiota, and reduced levels of segmented filamentous bacteria (SFB). We further demonstrate that BHB-associated microbiota changes are linked to increased susceptibility to enteric infection. This work provides a mechanistic framework illustrating how metabolic state can influence host immunity through selective effects on commensal microbes. These findings inform future studies of microbiota-mediated immune regulation.

I cannot wipe this dirt from beneath my fingernails. The porcelain has been stained like a slaughterhouse. Mama, I cannot get rid of this dirt beneath my fingernails, I fear it may be etched into my marrow. Mama, yes, I understand that God put me on this earth for a reason, But I am ready to strip my clothes at the altar and bare it all for Him.