The Gut-Brain Axis and the Microbiome: Mechanisms and Clinical Implications

Abstract

Background & aims: Based largely on results from preclinical studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the gut, its microbiome, and the nervous system. Limited data obtained in human beings suggest that alterations in these interactions may play a role in several brain gut disorders.

Methods: We reviewed the preclinical and clinical literature related to the topic of brain gut microbiome interactions.

Results: Well-characterized bidirectional communication channels, involving neural, endocrine, and inflammatory mechanisms, exist between the gut and the brain. Communication through these channels may be modulated by variations in the permeability of the intestinal wall and the blood-brain barrier. Brain gut microbiome interactions are programmed during the first 3 years of life, including the prenatal period, but can be modulated by diet, medications, and stress throughout life. Based on correlational studies, alterations in these interactions have been implicated in the regulation of food intake, obesity, and in irritable bowel syndrome, even though causality remains to be established.

Conclusions: Targets within the brain gut microbiome axis have the potential to become targets for novel drug development for brain gut disorders.

Keywords: Diet; Early Life Influences; Irritable Bowel Syndrome.

Conflict of interest statement

Conflicts of interest

This author discloses the following: Emeran A. Mayer is a member of the scientific advisory boards of Danone, Viome, Amare, Prolacta, Pharmavite, Axial Biotherapeutics, Bloom Science, Whole Biome, Ubiome, and Mahana, and a consultant for General Mills, Host Therabiotics, Kelloggs, Nestle, and Kevita. The remaining authors disclose no conflicts.

Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Early life events and the development of the infant gut microbiota. Early life represents a particularly vulnerable period for the infant gut microbiome because it is highly responsive to numerous factors. In addition to genetics, prenatal influences (maternal nutrition, stress, overall health), mode of delivery, early life nutrition (breastfeeding, formula feeding), physical and psychological environment, and antibiotic use all influence the infant gut microbiome. Modified from Borre et al.

Figure 2.

The developing gut microbiome and brain. Gut microbiota and brain development begins during the prenatal period and continues throughout adulthood, with the first 3 years of life representing a particularly important developmental period. Disruptions in development can influence communication between these 2 systems and may contribute to the pathogenesis of neurodevelopmental disorders such as IBS, autism, anxiety, attention-deficit hyperactivity disorder (ADHD), and obesity. Modified from Borre et al.