Functional Impact of IBS-D Microbiota on the Gut-Brain Axis

Irritable Bowel Syndrome (IBS) is a common disorder characterized by altered gut function and frequent psychiatric co-morbidity. Although altered intestinal microbiome profiles have been documented, their relevance to the clinical expression of IBS is unknown. To assess the functional role of the microbiota, we colonized germ-free mice with fecal microbiota from healthy controls or from IBS patients with diarrhea (IBS-D) with or without accompanying anxiety, and monitored gut function (gastrointestinal transit, expression of several genes related to inflammation, and barrier function) and behavior. Specific microbial profiles were transferred from the human donors into mouse recipients. Despite having taxonomically similar composition as controls, mice with IBS-D microbiota had distinct serum metabolomic profiles related to neuro- and immunomodulation. Mice with IBS-D, but not control microbiota, exhibited faster gastrointestinal transit, intestinal barrier dysfunction, innate immune activation and anxiety-like behavior. Our study thus supports the notion that gut microbiota contributes to both intestinal and behavioral manifestations of IBS-D and supports the use of microbiota-directed therapies in ameliorating this condition.