Manipulation of Visceral Hypersensitivity With Probiotic Bacteria in Irritable Bowel Syndrome

Background

An incomplete understanding of the mechanisms underlying irritable bowel syndrome (IBS) has hampered the development of an effective therapy for this condition. This is long overdue for a condition that affects at least 20 percent of the population (1), and has a major impact on patient's quality of life (QOL) (2).Current understanding of the underlying aetiology and pathogenesis of IBS is centered on two levels: the brain-gut axis which provides concept of how stress, emotion and psychological conditions all alter the perception of IBS symptoms. Within the intestinal wall, the patho-physiological mechanisms that are implicated in IBS include infection, immune activation, dysmotility, abnormal fermentation and visceral hypersensitivity. Studies have shown that visceral pain thresholds in response to stress are lower in patients with IBS compared to healthy volunteers (3). This hypersensitivity is apparent in response to both a physical and chemical stimulus but the triggers to visceral hypersensitivity remain largely unknown. intestinal bacteria play a significant role in inducing IBS. For instance post-infectious IBS developed in a subgroup of patients following a bout of gastroenteritis (4). Manipulation of the commensal microbiota can alleviate IBS symptoms and there is some evidence that probiotic preparations containing certain Bifidobacteria may be particularly effective (5). This proposal will focus on further exploration of the mechanisms underlying visceral hypersensitivity to direct future targeting of therapy with probiotic preparation.

Aims The aims of this study are (i) to identify IBS-associated changes in intestinal microbiota; (ii) to study SERT expression and genotyping, and their relationship with the gut microbiota, and (iii) to determine whether probiotic therapy alters visceral sensitivity in IBS patients and whether probiotic-induced changes in visceral hypersensitivity are associated with changes in the intestinal microbiota.

Hypothesis The investigators postulate that bacteria modulate sensory afferent signalling and serotonin signalling, necessary for visceral sensation and that these pathways can be targeted for therapy of IBS using probiotic bacteria.

RESEARCH PLAN This study consists of two parts. The first part will be a cross-sectional study comparing the colonic microbiota and SERT expression in IBS patients and healthy controls. The second part will involve a pilot open-label study to assess the effects of oral probiotic bacteria in visceral hypersensitivity, SERT expression and mucosal microbiota in patients with IBS.