The researchers have investigated colon biopsies in Ussing chambers. Photo credit Karin Söderlund Leifler
IBS, or irritable bowel syndrome, disturbs bowel function. The condition leads to repeated episodes of abdominal pain, and usually gives rise to constipation or diarrhoea. Around 10% of people in Sweden suffer from IBS, and it is twice as common among women as among men.
Åsa Keita. Photo credit Thor Balkhed
“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,” says Åsa Keita, researcher at the Department of Clinical and Experimental Medicine (IKE). She has led the study together with Susanna Walter, specialist in gastrointestinal diseases at Linköping University Hospital and also a researcher at IKE.
Barrier against bacteria
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. The large intestine has a layer of mucous, which constitutes the first line of defence against the bacteria in the intestine. Behind this, there is a layer of epithelial cells known as enterocytes, and behind these is tissue that contains immune cells. The present study has looked at this layer of epithelial cells, and examined how permeable it is to bacteria.
The researchers 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 a Ussing chamber, in which it is possible to measure the transport of substances and bacteria through living tissue.Salmonella bacterium interacting with microvilli in human colon. Photo credit: Maria Vicario, Universitat Autonoma de Barcelona
Infection with the pathogenic bacterium Salmonella typhimurium is a risk factor for developing IBS, and this led the researchers to investigate how this Salmonella strain interacts with the intestinal membrane. They also studied a strain of E. coli (Escherichia coli HS), which is usually present in the intestine. Both bacteria passed through the intestinal mucosa of patients with IBS around twice as rapidly as was the case for healthy subjects.
“Patients with IBS in our study had a higher passage of bacteria in the model system. But we cannot transfer this result directly to clinical practice, and further research is needed. What we can say, however, is that there is something that makes one layer of the intestinal mucosa of patients with IBS more sensitive to bacteria than in healthy subjects,” says Åsa Keita.
Immune system involved?
The researchers also looked at mast cells, a type of immune cell that is an important component of the innate immune defence, which protects against micro-organisms. They 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.The researchers measure transport of bacteria across the colon biopsy in a Ussing chamber. Photo credit Karin Söderlund Leifler
The study has been carried out in collaboration with scientists at the Universitat Autònoma de Barcelona in Spain and at the David Geffen School of Medicine at UCLA in the US. Funding for the research has been provided by, among other sources, Stiftelsen Hälsofonden and Diarrheal Disease Research Centre (Region Östergötland, Linköping University), AFA Insurance and Bengt-Ihre Research Fellowship.
The article: Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome, Olga Bednarska,
Susanna A. Walter, Maite Casado-Bedmar, Magnus Ström, Eloísa Salvo-Romero, Maria Vicario, Emeran A. Mayer, Åsa V. Keita, published online 13 July 2017, doi: 10.1053/j.gastro.2017.06.051