Irritable bowel syndrome, gut microbiota and probiotics

Abstract

Irritable bowel syndrome (IBS) is a complex disorder characterized by abdominal symptoms including chronic abdominal pain or discomfort and altered bowel habits. The etiology of IBS is multifactorial, as abnormal gut motility, visceral hypersensitivity, disturbed neural function of the brain-gut axis and an abnormal autonomic nervous system are all implicated in disease progression. Based on recent experimental and clinical studies, it has been suggested that additional etiological factors including low-grade inflammation, altered gut microbiota and alteration in the gut immune system play important roles in the pathogenesis of IBS. Therefore, therapeutic restoration of altered intestinal microbiota may be an ideal treatment for IBS. Probiotics are live organisms that are believed to cause no harm and result in health benefits for the host. Clinical efficacy of probiotics has been shown in the treatment or prevention of some gastrointestinal inflammation-associated disorders including traveler's diarrhea, antibiotics-associated diarrhea, pouchitis of the restorative ileal pouch and necrotizing enterocolitis. The molecular mechanisms, as cause of IBS pathogenesis, affected by altered gut microbiota and gut inflammation-immunity are reviewed. The effect of probiotics on the gut inflammation-immune systems and the results from clinical trials of probiotics for the treatment of IBS are also summarized.

Keywords: Immunity; Inflammation; Irritable bowel syndrome; Microbiota; Probiotics.

Figure

Mechanisms for preserving mucosal barrier function. To protect intestinal epithelium from noxious inflammatory process, there are several mechanisms to preserve mucosal barrier function; ① mucous layer, ② production of antimicrobial peptides by paneth cell, ③ secretary IgA and ④ epithelial-cell tight junction complex (eg, ZO-1 and occludin 1). Specialized intestinal epithelial cells which overlie Peyer's patches facilitate luminal sampling and transport of microbiota. ⑤ Mucosal mast cells are increased in small and large bowel. Their localization, number and mediators are correlated with generation of irritable bowel syndrome (IBS) symptom. Increased mast cells close to ending of nerve fiber are associated with perception of pain in IBS patients. ⑥ Dendritic cells (DC) interact with gut microbiota and other stimuli to determine if immune response or tolerance will be induced. Microbial factors interact with different DC cell surface pattern recognition receptors to determine DC maturation that produce IL-1β, IL-6 and IL-23. Activated DCs subsequently regulate the differentiation of naïve T cells into Th1, Th2, Th17 or Treg. In IBS patients infiltration of CD3+ and CD25+ T cells are increased in colonic mucosa and blood T cell are activated with expression CD 69 and HLA-DR/integrin β7. The proinflammatory cytokines from Th1 induce switching to IgG producing cell. Frequency of ⑦ IgG+ B cells are increased in the blood of IBS patients with increased expression of CD80/86.