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Front. Immunol. | doi: 10.3389/fimmu.2019.02429

Dietary SCFAs, IL-22 and GFAP: the three musketeers in the gut-neuro-immune network in type 1 diabetes

  • 1Monash University, Australia
  • 2Biomedicine Discovery Institute, Monash University, Australia
  • 3Monash Univeristy, Australia
  • 4Department of Immunology and Pathology, Monash University, Australia

Microbial metabolites have a profound effect on the development of type 1 diabetes (T1D). The crosstalk between the gut microbiota the nervous and immune system is necessary to establish and maintain immune and gut tolerance. As quoted by Hippocrates, “All disease begins in the gut.” Although this has been recognized for 2000 years, the connection between the gut and autoimmune T1D is not yet well understood. Here we outline new advances supported by our research and others that have contributed to elucidate the impact of microbial metabolites on the physiology of the pancreas and the gut through their remarkable effect on the immune and nervous system. Amongst many of the mechanisms involved in the gut-beta cell-immune crosstalk, Glial Fibrillary Acidic Protein (GFAP)- expressing cells are critical players in the development of invasive insulitis. Besides, this review reveals a novel mechanism for microbial metabolites by stimulating IL-22, an essential cytokine for gut homeostasis and beta cell survival. The close connections between the gut and the pancreas are highlighted through our review as microbial metabolites recirculate through the whole body and intimately react with the nervous system, which controls essential disorders associated with diabetes. As such, we discuss the mechanisms of action of microbial metabolites or short chain fatty acids (SCFAs) on immune cells, beta cells, gut epithelial cells, neurons, and glial cells via metabolite sensing receptors or through epigenetic effects. The fine-tuned gut-neuro-immune network may be profoundly affected by SCFAs deficiency related to dysbiosis and diet alterations at very early stages of the initiation of the disease. Thus, dampening the initial​ immune response or preventing the perpetuation of the immune response by maintaining the integrity of the gut is among alternative approaches to prevent T1D.

Keywords: SCFA (short chain fatty acids), GFAP - Glial fibrillary acidic protein, Gut Microbiota, Glial cell, interleukin 22 (IL-22), ILC3s, Beta cells, diabetes mellitus

Received: 10 Jul 2019; Accepted: 30 Sep 2019.

Copyright: © 2019 Mariño and Jayasimhan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Eliana Mariño, Monash University, Melbourne, Australia, eliana.marino@monash.edu