Alterations in intestinal barrier facilitate the entry of bacteria in Irritable Bowel Syndrome patients

A study carried out by the group of Physiology and Pathophysiology of the Digestive Tract of Vall d'Hebron Institut de Recerca (VHIR) has determined the existence of changes in the permeability of intestinal barrier in Irritable Bowel Syndrome (IBS) patients which facilitate the bacterial passage from the intestinal lumen into the organism.

The study, published in Gastroenterology, has been led by Linköping University in Sweden in collaboration with VHIR and the Center for Neurobiology of Stress and Resilence in Los Angeles.

The defensive function carried out by the intestine is governed by the central nervous system and by the enteric nervous system. Both psychosocial stress and local infection can lead to intestinal barrier alterations that can compromise health. The group of Physiology and Pathophysiology of the Digestive Tract had already identified that chronic psychosocial stress determines the functionality of the intestinal barrier and that the epithelium of IBS patients is more permeable to the intestinal contents, which favors exposure to ingested antigens and facilitates local inflammatory processes.

On the basis of this knowledge, this study is the first of its characteristics that works with live bacteria, specifically with enteroinvasive bacteria. "We have quantified, for the first time, the passage of live bacteria through intestinal colon epithelium of IBS patients. This bacterial passage is significantly higher in tissues from patients than from healthy controls" says Dr. Maria Vicario, principal investigator of Translational Mucosa Immunology, from the Physiology and Pathophysiology of the Digestive Tract group

Bacterial traffic in IBS patients

Two bacterial strains were used in the study: E. coli, a commensal bacteria normally found in the intestine, and Salmonella typhimurium, a pathogenic bacterium with a great enteroinvasive ability. They decided to study Salmonella due to the high prevalence of infectious gastroenteritis in a large number of IBS patients.

This bacterial pathway is regulated by immune cells present in the digestive mucosa, including mast cells, and by molecules such as the vasoactive intestinal peptide (VIP), a hormone produced in different tissues and found in both mast cells and enteric neurons responsible for innervating the gastrointestinal tract. This work showed increased activation of mast cells in the mucosa of the colon from ISB patients compared to healthy individuals. The pharmacological inhibition of these cells and VIP was able to decrease the passage of bacteria through the intestinal epithelium.

The contribution of VHIR to the study

The team of Dr. María Vicario has performed the morphological and the cellular ultrastructure analysis, using different microscopy techniques. In addition to quantifying mast cell degranulation, indicative of this cell type activation, they have also demonstrated the interaction between the epithelium and the luminal bacteria to gain access to the organism through the transcellular pathway.

The next objective: to identify the causes of changes in intestinal permeability

Ongoing experiments are designed to identify epithelial defense mechanisms and the immunological factors that facilitate bacterial passage across the epithelium. "In our laboratory, we are analyzing the adaptive immune response to assess whether an underlying infectious process is present in all IBS patients and how psychosocial stress contributes to intestinal dysfunction in this scenario," Dr. Vicario concludes.

Irritable Bowel Syndrome

Irritable Bowel Syndrome affects 10% - 15% of the population in industrialized countries and is more prevalent in women than in men. However, the causes are unknown. Its development has been related to psychosocial stress and to a microbial imbalance in the intestine. In post-infectious IBS, symptoms develop after an infectious gastroenteritis.