+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Intestinal Immune Imbalance is an Alarm in the Development of IBD

      , , , ,
      Mediators of Inflammation

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Immune regulation plays a crucial role in human health and disease. Inflammatory bowel disease (IBD) is a chronic relapse bowel disease with an increasing incidence worldwide. Clinical treatments for IBD are limited and inefficient. However, the pathogenesis of immune-mediated IBD remains unclear. This review describes the activation of innate and adaptive immune functions by intestinal immune cells to regulate intestinal immune balance and maintain intestinal mucosal integrity. Changes in susceptible genes, autophagy, energy metabolism, and other factors interact in a complex manner with the immune system, eventually leading to intestinal immune imbalance and the onset of IBD. These events indicate that intestinal immune imbalance is an alarm for IBD development, further opening new possibilities for the unprecedented development of immunotherapy for IBD.

          Related collections

          Most cited references245

          • Record: found
          • Abstract: found
          • Article: not found

          Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.

          Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.
            • Record: found
            • Abstract: found
            • Article: not found

            The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

            Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases

              Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.

                Author and article information

                Mediators Inflamm
                Mediators Inflamm
                Mediators of Inflammation
                31 July 2023
                : 2023
                : 1073984
                Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
                Author notes

                Academic Editor: Veedamali S. Subramanian

                Author information
                Copyright © 2023 Chunli Hu et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 15 April 2023
                : 6 July 2023
                : 8 July 2023
                Funded by: National Natural Science Foundation of China
                Award ID: 82103206
                Award ID: 82173360
                Funded by: Natural Science Foundation of Chongqing
                Award ID: cstc2021jcyj-msxmX0018
                Funded by: Special Support for Chongqing Postdoctoral Research Project
                Award ID: 2021XM3027
                Funded by: Chongqing Medical University
                Award ID: kryc-yq-2224
                Award ID: 13-003-023
                Funded by: Senior Medical Talents Program of Chongqing for Young and Middle-aged
                Award ID: 11-020
                Funded by: Joint project of Chongqing Health Commission and Science and Technology Bureau
                Award ID: 2020GDRC014
                Review Article



                Comment on this article