Abstract # 3094 Microbiota-neuroimmune interactions in a humanized mouse model of IBS: The role of diet and mast cells

Gut immune system, microbiota and diet appear to play important roles in irritable bowel syndrome (IBS). Increased levels of colonic mast cell (MC) located in close proximity to mucosal nerves were reported in IBS patients, correlating with increased abdominal pain. We showed recently that IBS patients’ beneficial response to a low-fermentable diet was associated with changes in gut microbiota and urinary histamine. Here we investigated the interaction between microbiota, diet and MC in a humanized IBS mouse model. Germ-free mice, receiving custom-made low (LF) or high (HF) fermentable diets, were colonized with fecal microbiota from two IBS patients, with high (HH) or low (LH) urinary histamine (n = 24 mice/patient), and one healthy control (n = 8). HH mice on HF-diet (HHHF) had increased c-kit + MCs in both jejunum and colon compared to HH mice on LF-diet (HHLF), which was associated with increased visceral sensitivity assessed by electrophysiology. Colonic MC number in HHHF mice negatively correlated with the relative abundance of several bacterial genera. Tryptase + area and MCs were higher in the jejunum of HHHF compared to HHLF mice. Furthermore, most MCs were in close proximity to PGP9.5 + nerve fibers. In the jejunum, the density of PGP9.5 + and substance P + nerves was higher in HHHF mice. In summary, MCs may play a key role in host-microbiota-diet interactions in a subset of IBS patients, contributing to increased abdominal pain perception.