Pathophysiology of IBD associated diarrhea

Abstract

Inflammatory bowel diseases broadly categorized into Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the gastrointestinal tract with increasing prevalence worldwide. The etiology of the disease is complex and involves a combination of genetic, environmental, immunological and gut microbial factors. Recurring and bloody diarrhea is the most prevalent and debilitating symptom in IBD. The pathogenesis of IBD-associated diarrhea is multifactorial and is essentially an outcome of mucosal damage caused by persistent inflammation resulting in dysregulated intestinal ion transport, impaired epithelial barrier function and increased accessibility of the pathogens to the intestinal mucosa. Altered expression and/or function of epithelial ion transporters and channels is the principle cause of electrolyte retention and water accumulation in the intestinal lumen leading to diarrhea in IBD. Aberrant barrier function further contributes to diarrhea via leak-flux mechanism. Mucosal penetration of enteric pathogens promotes dysbiosis and exacerbates the underlying immune system further perpetuating IBD associated-tissue damage and diarrhea. Here, we review the mechanisms of impaired ion transport and loss of epithelial barrier function contributing to diarrhea associated with IBD.

Establishment and evaluation of specific antibiotic-induced Inflammatory bowel disease (IBD) model in rats

“…IBD often is associated with diarrhea [33,34] .The present study showed that diarrhea appeared in treated groups and the severity depended on the dose and method of administration. This potentially suggested the feasibility of antibiotic-induced IBD rat models.…”

Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases

“…The expression of TJs in the gut varies according to the localization, such as villus vs. crypt and small bowel vs. colon 155 . The paracellular trafficking and intestinal epithelial permeability are essentially controlled by the TJs along with claudins, occludins, JAM, and tricellulin 16 . The extracellular domains of TJs connect to adjacent cells, thereby forming networks of linking strands.…”

Slc26a3 deletion alters pH‐microclimate, mucin biosynthesis, microbiome composition and increases the TNFα expression in murine colon

“…Disturbances in luminal pH, in mucin synthesis and composition, mucus layer properties and secretory rate, and the luminal microbiome have also been described in patients with inflammatory bowel disease. [20][21][22][23][24] The first aim of the present study was an investigation into the consequences of lost Slc26a3 expression on the colonic mucus-bicarbonate "barrier," including the measurement of the colonic surface pH-microclimate and mucus output in vivo, and on the development of spontaneous intestinal inflammation. When we observed the striking goblet cell thecae depletion in the slc26a3 −/− colon, we also performed a microbiome analysis at the genera level, to obtain a first glimpse into the potential alterations of the colonic luminal microclimate to explain in part the reduced mucus content and development of mucosal inflammation.…”