Bacteroides uniformis degrades beta-glucan to promote Lactobacillus johnsonii improving ILA levels in alleviating colitis

The gut microbiota plays a crucial role in the onset and progression of inflammatory bowel disease (IBD). beta-glucan (BG), a soluble dietary fiber widely present in oats, barley, fungi, yeast, and some bacteria, has multiple bioactive properties such as mitigating intestinal inflammation; however, the underlying mechanisms remain unclear. Here, we demonstrate that BG protects against colitis by increasing the abundance of Lactobacillus johnsonii in the gut, which promotes the production of indole-3-lactic acid (ILA) to activate the aryl hydrocarbon receptor (AhR) and increase the secretion of IL-22. Interestingly, L. johnsonii can not utilize BG but requires a cross-feeding interaction with Bacteroides uniformis. B. uniformis-derived nicotinamide (NAM) via the cobB gene promotes the growth of L. johnsonii. Deletion of cobB from B. uniformis results in inefficacy in L. johnsonii growth and fighting against colitis. In support of our findings, we conducted a clinical trial of the BG intervention, which demonstrated that BG increases the abundance of B. uniformis and L. johnsonii in the human gut along with increasing ILA levels. Our findings reveal the mechanism by which BG ameliorates colitis via L. johnsonii-ILA-AhR axis and provide new insights into cross-feeding between bacteria.