Inflammation and the intestine

Abstract

Inflammatory bowel diseases : Crohn's disease (CD) and ulcerative colitis (UC) affect more than one person in a thousand. Their etiology is multifactorial, including genetic and environmental factors. Numerous genetic risk factors with low individual impact have been identified, but alone they account for only a small proportion of the risk. Their analysis nevertheless contributes to understanding the physiology of these effectors and the involvement of cytokine signalling pathways such as TNF, IL-12 and IL-23. Associated gene expression profiling studies carried out on intestinal biopsies show the involvement of certain metabolic pathways (CD) or extracellular matrix biology (UC). The main environmental factor concerns variations in the intestinal flora, whose diversity and composition are greatly disturbed during chronic inflammatory bowel disease. The flora is poor in bacteria producing anti-inflammatory molecules - such as certain short-chain fatty acids - and, on the contrary, rich in bacteria producing pro-inflammatory products.

In UC, this is compounded by quantitative and qualitative defects in the synthesis of the mucins that make up the protective mucus of the intestinal epithelium, which is damaged as a result. This leads to increased permeability of the intestinal barrier to bacterial products that promote inflammation. During CD, there appears to be a defect in intracellular bacterial clearance, notably due to a deficiency in autophagy, which promotes the production of pro-inflammatory cytokines such as IL-1, IL-23 and TNF, resulting in a pathological T immune response of the TH17 type directed against microbiota antigens. This contributes to intestinal damage through the formation of granulomas. This information has led to the development of new therapies based on the neutralization of pro-inflammatory cytokines - primarily TNF ( ), but also anti-IL-12/IL-23. Blocking lymphocyte migration towards the intestinal mucosa by inhibiting the adhesion molecule α4β7 provides an interesting alternative. Other therapeutic avenues, including intestinal flora transplantation, are under study. However, to date, no curative treatment is available.