Prebiotic fructan chain length influences enteric microbiota-host GABAergic signaling and intestinal motility

Dietary fiber ingestion serves as a critical regulator of intestinal motility and the structure and function of the enteric microbiome. Yet, the extent to which subtle structural differences among fibers modulate motility via microbiota-host interactions remains undefined. GABA is a microbial metabolite intimately related to microbial fructan fermentation and host intestinal motility. The purpose of this study was to investigate how fructan chain length influenced microbiota-host signaling underlying ileal and colonic contractions. Male and female mice were pair-fed diets containing no fiber (fiber-free diet, FFD) or the same diet containing cellulose (CELL, fiber control), short-chain fructooligosaccharides (scFOS), or inulin (INU) for 2 weeks. scFOS and INU similarly enhanced total microbial load (fluorescence in situ hybridization), relative abundances of GABA-synthesizing bacteria (16S rRNA sequencing), and luminal GABA concentrations (ELISA) in the ileum and colon versus FFD. Conversely, scFOS altered expression (Fluidigm qPCR) of more motility- and GABA-related genes than INU in the ileum, whereas INU altered expression of more motility and GABA-related genes than scFOS in the colon. Incubation of ileal segments with GABA potentiated contraction force in INU but not scFOS ex vivo. Conversely, incubation of colon segments with GABA repressed contraction force in scFOS, reducing them to levels observed in INU with or without GABA. Notably, GABA altered contraction forces only in female mice. Our study highlights dietary fructan chain length as a determinant of segment- and sex-specific GABA-mediated intestinal motility and creates a rationale and framework for investigation of how prebiotic fiber structures influence microbiota-host interactions and physiology.