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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 Klebsiella aerogenes , carrying a histidine decarboxylase gene variant, as a major producer of this histamine. This bacterial strain was highly abundant in the fecal microbiota of three independent cohorts of patients with IBS compared with healthy individuals. Pharmacological blockade of the histamine 4 receptor in vivo inhibited visceral hypersensitivity and decreased mast cell accumulation in the colon of germ-free mice colonized with the high histamine-producing IBS fecal microbiota. These results suggest that therapeutic strategies directed against bacterial histamine could help treat visceral hyperalgesia in a subset of patients with IBS with chronic abdominal pain.

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Mississippi summers are hot. When you pick up a camera you are instantly drenched with sweat from the exertion. Three thousand watts of quartz light and two hundred people crammed into a little church add to the effect. It was the first day's shoot and I was nervous; they weren't getting audio in the recording van and already the deacon was starting the revival. My collaborator, folklorist Worth Long, had briefed me on the order of the service and what to expect. I thought over what he said as I waited. The two men in the front row were seekers who expected to accept religion; the preaching, singing, and praying would focus on them. If all went well, they would cross over to the mourner's bench which faced the congregation. "Tape's rolling." Director Alan Lomax' voice came across the intercom. I swung the Ikegami HL-77 onto my shoulder and looked across the room to Ludwig Goon who would be shooting concurrently with a TKP-45. He smiled and gestured thumbs up as the congregation eased into the galvanizing moan of a lining hymn. Things moved fast for the next three hours. Alan coordinated the coverage by intercom from the van where he would watch both monitors. Much of the interaction consisted of rapid alternation between song leader and congregation or preacher and congregation, so each camera fed a separate recorder for greatest flexibility in editing. The experience was more intense that I had expected. There was poetry in the songs and sermon, tender community support of the parishioners in trance, and the resolution of an essential conflict of group membership when the two seekers cross over. I was swept into the excitement; the camera became part of me, the heat ceased to be noticeable, and I moved as part of the congregation. This revival service was the start of a month of shooting that would culminate in a one-hour program for PBS, THE LAND WHERE THE BLUES BEGAN.