A diet high in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) (HFM) induces gastrointestinal symptoms in patients with irritable bowel syndrome (IBS) and a diet low in FODMAPs (LFM) improves symptoms in up to 60% of IBS patients. However, the mechanism by which FODMAPs affect IBS symptoms is unclear. We showed that mice fed on an HFM diet have mast cell activation and colonic barrier loss. Using mast cell-deficient mice with/without mast cell reconstitution, we showed that HFM-mediated colonic barrier loss is dependent on TLR4-dependent mast cell activation. In in vitro studies, we demonstrated IBS fecal supernatant stimulates mast cell significantly more compared to fecal supernatant from healthy controls. This effect of IBS fecal supernatant on mast cell stimulation is ameliorated in absence of TLR4 receptor and after an LFM diet. Translating these findings into IBS patients, we found an LFM diet improves colonic barrier function and reduces mast cell activation while decreasing fecal LPS levels. Our findings indicate that a HFM diet causes mast cell activation via LPS which in turn leads to colonic barrier loss and an LFM diet reverses these pathophysiologic mucosal changes.
Prashant Singh, Gintautas Grabauskas, Shi-Yi Zhou, Jun Gao, Yawen Zhang, Chung Owyang