Authors: Giada De Palma, Chiko Shimbori, David E. Reed, Yang Yu, Virginia Rabbia, Jun Lu, Nestor Jimenez-Vargas, Jessica Sessenwein, Cintya Lopez-Lopez, Marc Pigrau, Josue Jaramillo-Polanco, Yong Zhang, Lauren Baerg, Ahmad Manzar, Julien Pujo, Xiaopeng Bai, Maria Ines Pinto-Sanchez, Alberto Caminero, Karen Madsen, Michael G. Surette, Michael Beyak, Alan E. Lomax, Elena F. Verdu, Stephen M. Collins, Stephen J. Vanner, Premysl Bercik
Published: 2022-07-27
DOI: 10.1126/scitranslmed.abj1895
Source: Full article
The gut microbiota has been implicated in chronic pain disorders, including irritable bowel syndrome (IBS), yet specific pathophysiological mechanisms remain unclear. We showed that decreasing intake of fermentable carbohydrates improved abdominal pain in patients with IBS, and this was accompanied by changes in the gut microbiota and decreased urinary histamine concentrations. Here, we used germ-free mice colonized with fecal microbiota from patients with IBS to investigate the role of gut bacteria and the neuroactive mediator histamine in visceral hypersensitivity. Germ-free mice colonized with the fecal microbiota of patients with IBS who had high but not low urinary histamine developed visceral hyperalgesia and mast cell activation. When these mice were fed a diet with reduced fermentable carbohydrates, the animals showed a decrease in visceral hypersensitivity and mast cell accumulation in the colon. We observed that the fecal microbiota from patients with IBS with high but not low urinary histamine produced large amounts of histamine in vitro. We identified