Elsevier

Clinical Therapeutics

Volume 37, Issue 5, 1 May 2015, Pages 954-967
Clinical Therapeutics

Review Article
Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

https://doi.org/10.1016/j.clinthera.2015.03.002Get rights and content

Abstract

Purpose

It is well established that mammals are so-called super-organisms that coexist with a complex microbiota. Growing evidence points to the delicacy of this host–microbe interplay and how disruptive interventions could have lifelong consequences. The goal of this article was to provide insights into the potential role of the gut microbiota in coordinating the immune–neuroendocrine cross-talk.

Methods

Literature from a range of sources, including PubMed, Google Scholar, and MEDLINE, was searched to identify recent reports regarding the impact of the gut microbiota on the host immune and neuroendocrine systems in health and disease.

Findings

The immune system and nervous system are in continuous communication to maintain a state of homeostasis. Significant gaps in knowledge remain regarding the effect of the gut microbiota in coordinating the immune–nervous systems dialogue. Recent evidence from experimental animal models found that stimulation of subsets of immune cells by the gut microbiota, and the subsequent cross-talk between the immune cells and enteric neurons, may have a major impact on the host in health and disease.

Implications

Data from rodent models, as well as from a few human studies, suggest that the gut microbiota may have a major role in coordinating the communication between the immune and neuroendocrine systems to develop and maintain homeostasis. However, the underlying mechanisms remain unclear. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, the immune system, and the neuroendocrine system in a network of communication to eventually translate these findings to the human situation, both in health and disease.

Introduction

Our knowledge of the host–microbe interrelationship is accelerating because of the availability of rapidly expanding molecular techniques, especially in combination with the use of reductionist in vivo host models. A growing body of research continues to show that the normal mammalian structure and function are significantly dependent on their constant engagement in complex interactions with microbes.1 For example, the intestinal microbiota with its components and metabolites affects the host physiology in various ways to control energy homeostasis, gut barrier function, mucosal inflammation, and behavior.2, 3, 4 Subsequently, the host modifies many of the microbial activities, which suggests a feedback mechanism that could influence the microbiota and drive a further cycle of biological changes to host physiology.5 This multidirectional interactive dialogue seems to strongly influence an expanding repertoire of human disorders, including obesity, depression, and irritable bowel syndrome; the goal is to decipher the tête-à-tête between the host and its commensal organisms.6, 7

The present review highlights emerging evidence, which provides a framework for appreciating the impact of the host–microbiota interplay on health that is undoubtedly much broader than previously thought. This review outlines the impact of the gut microbiota on the immune system as well as the neuroendocrine system, both of which point to a potential role of the microbiota as crucial coordinators in the cross-talk between these systems.

Section snippets

Materials and Methods

Literature from a range of sources, including PubMed, Google Scholar, and MEDLINE, was searched to identify recent reports on the impact of the gut microbiota on the host immune and neuroendocrine systems in health and disease. All data were gathered for the latest available years.

The Host–Microbiota Dialogue

Over the past decade, remarkable advances toward a better understanding of how the host–microbe interactome is linked with most pathways that affect health, disease, and aging were made possible with novel technologies; these include high-throughput DNA sequencing, bioinformatics, and gnotobiotic animal models.1 The intimate interactions between the host and its microbes that outnumber the host’s cells by 10 to 1 are required to stimulate the complete maturation of an efficient intestinal

Conclusions

Over the past decade, preclinical trials, as well as a few clinical studies, have highlighted the crucial role of the gut microbiota in maintaining host homeostasis. Analogously, microbiota dysbiosis has been associated with a wide range of host disorders, including inflammatory bowel disorders, neuroendocrine disorders, and behavioral disorders. This growing body of research illustrates the significant direct effect that microbes have on the host immune and neuroendocrine systems. Nonetheless,

Conflicts of Interest

The authors’ research at the Alimentary Pharmabiotic Centre is funded by Science Foundation Ireland, through the Irish Government’s National Development Plan in collaboration with a variety of pharmaceutical and food industries. The authors have indicated that they have no other conflicts of interest regarding the content of this article.

Acknowledgments

Drs. Dinan and Cryan are supported by Science Foundation Ireland (grant no. 07/CE/B1368 and 12/RC/2273) and by the Irish Health Research Board, Health Research Awards (HRA_POR/2011/23) and (HRA_POR/2012/32). Sahar El Aidy contribution: literature search, figure creation, writing. Timothy G. Dinan and John Cryan: critical reviewing.

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