Image: Scientists measured the transport of bacteria across the colon biopsy in an Ussing chamber (Photo courtesy of Karin Söderlund Leifler).
Irritable bowel syndrome disturbs bowel function and the condition leads to repeated episodes of abdominal pain, and usually gives rise to constipation or diarrhea. Around 10% of people in Sweden suffer from IBS, and it is twice as common among women as among men.
Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis and symptoms of IBS develop following gastroenteritis. It is still unclear why the condition arises, but there is increasing evidence that changes in the way in which the brain interacts with the bacterial flora in the gut play a role.
Scientists at Linköping University (Linköping, Sweden) investigated small samples of tissue taken from the large intestine of 37 women with IBS, and compared them with samples from women with no intestinal symptoms. They studied the membranes in an instrument known as an Ussing chamber, in which it is possible to measure the transport of substances and bacteria through living tissue. They measured numbers of fluorescently labeled Escherichia coli HS and Salmonella typhimurium that passed through from the mucosal side to the serosal side of the tissue. Some biopsies were exposed to agents that block the vasoactive intestinal peptide (VIP) receptors (VPAC1 and VPAC2) or mast cells (MCs). Levels of VIP and tryptase were measured in plasma and biopsy lysates. The number of MCs and MCs that express VIP or VIP receptors were quantified by immunofluorescence.
The investigators found that in colon biopsies from patients with IBS, larger numbers of E coli HS and Salmonella passed through the epithelium than in biopsies from controls. In transmission electron microscopy analyses, bacteria were found to cross the epithelium via only the transcellular route. Bacterial passage was reduced in biopsies from patients with IBS and controls after addition of antibodies against VPACs or ketotifen, which inhibits MCs. Plasma samples from patients with IBS, had higher levels of VIP than plasma samples from controls. Biopsies from patients with IBS had higher levels of tryptase, larger numbers of MCs, and a higher percentage of MCs that express VPAC1 than biopsies from controls. In biopsies from patients with IBS, addition of Salmonella significantly reduced levels of occludin; subsequent addition of ketotifen significantly reversed this effect.
The team found that mast cells appear to play a significant role in regulating the passage of bacteria across the intestinal membrane, in both healthy subjects and in people with IBS. The mechanism seems, however, to be more active in those with IBS. Åsa V. Keita, PhD, the senior investigator of the study, said, “People affected by IBS have been regarded as a rather diffuse group. Our study has shown that people with IBS are clearly different from healthy people in the way in which the part of the intestine known as the colon (or large intestine) reacts to bacteria.” The study was originally published online in July 2017 in the journal Gastroenterology.