Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate

Abstract

Alterations of intestinal microflora may significantly contribute to the pathogenesis of different inflammatory and autoimmune disorders. There is emerging interest on the role of selective modulation of microflora in inducing benefits in inflammatory intestinal disorders, by as probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). To summarize recent evidences on microflora modulation in main intestinal inflammatory disorders, PubMed was searched using terms microbiota, intestinal flora, probiotics, prebiotics, fecal transplantation. More than three hundred articles published up to 2015 were selected and reviewed. Randomized placebo-controlled trials and meta-analysis were firstly included, mainly for probiotics. A meta-analysis was not performed because of the heterogeneity of these studies. Most of relevant data derived from studies on probiotics, reporting some efficacy in ulcerative colitis and in pouchitis, while disappointing results are available for Crohn's disease. Probiotic supplementation may significantly reduce rates of rotavirus diarrhea. Efficacy of probiotics in NSAID enteropathy and irritable bowel syndrome is still controversial. Finally, FMT has been recently recognized as an efficacious treatment for recurrent Clostridium difficile infection. Modulation of intestinal flora represents a very interesting therapeutic target, although it still deserves some doubts and limitations. Future studies should be encouraged to provide new understanding about its therapeutical role.

Keywords: Gut; Inflammation; Microbiota; Prebiotic; Probiotic.

Figure 1

Interactions between luminal bacteria and intestine. The interaction between luminal bacteria and EC causes the production of cytokines, such as TGF-β, TSLP, IL-10 that may induce inflammatory cytokines synthesis from DC and mononuclear cells. These substances, together with retinoic acid produced by DC, can also promote the IgA switch in B cells. In Peyer’s patches DC and macrophages uptake bacterial antigens. The TSLP produced by TLR signaling, enhance APRIL and BAFF production from DC. Anti-inflammatory response is mainly mediated by TGF-β production by epithelial cells and IL-10 from mononuclear cells. Moreover, the interaction with commensal bacteria can result in T-cell expansion and regulation of Th-cells. Probiotics may modulate intestinal function, and in particular mucosal immunity, by secreted factors and by direct interactions with immune cells and the intestinal epithelium. EC: Enterocytes; MC: M cells; Tj: Tight junctions; TGF: Transforming growth factor; TNF: Tumor necrosis factor; TSLP: Thymic stromal lymphopoietin; DC: Dendritic cells; TLR: Toll-like receptors; APRIL: A proliferation-inducing factor; BAFF: B-cell activating factor; IL-10: Interleukin-10; MAMPs: Microbial Associated Molecular Patterns; LPS: Lipopolysaccharide; PRRs: Pattern Recognition Receptors; FPRs: Formylated peptide receptors; NODs: Nucleotide-binding oligomerization domain-like receptors.