Brain-gut-microbe communication in health and disease - PubMed (original) (raw)

Brain-gut-microbe communication in health and disease

Sue Grenham et al. Front Physiol. 2011.

Abstract

Bidirectional signalling between the gastrointestinal tract and the brain is regulated at neural, hormonal, and immunological levels. This construct is known as the brain-gut axis and is vital for maintaining homeostasis. Bacterial colonization of the intestine plays a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signaling. Recent research advances have seen a tremendous improvement in our understanding of the scale, diversity, and importance of the gut microbiome. This has been reflected in the form of a revised nomenclature to the more inclusive brain-gut-enteric microbiota axis and a sustained research effort to establish how communication along this axis contributes to both normal and pathological conditions. In this review, we will briefly discuss the critical components of this axis and the methodological challenges that have been presented in attempts to define what constitutes a normal microbiota and chart its temporal development. Emphasis is placed on the new research narrative that confirms the critical influence of the microbiota on mood and behavior. Mechanistic insights are provided with examples of both neural and humoral routes through which these effects can be mediated. The evidence supporting a role for the enteric flora in brain-gut axis disorders is explored with the spotlight on the clinical relevance for irritable bowel syndrome, a stress-related functional gastrointestinal disorder. We also critically evaluate the therapeutic opportunities arising from this research and consider in particular whether targeting the microbiome might represent a valid strategy for the management of CNS disorders and ponder the pitfalls inherent in such an approach. Despite the considerable challenges that lie ahead, this is an exciting area of research and one that is destined to remain the center of focus for some time to come.

Keywords: central nervous system; dysbiosis; enteric nervous system; inflammation; irritable bowel syndrome; microbiota; probiotic; vagus nerve.

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Figures

Figure 1

Figure 1

Development of the microbiome in early life. Subsequent to the sterile uterine environment, colonization begins at birth with facultative bacteria (blue) colonizing the GIT immediately. The anaerobic bacteria colonize later (orange). By 1 year of age the microbiome has a stable adult-like signature. Rodents follow a similar colonization pattern to humans and this forms the rationale for the use of germ free animals to study the impact of the microbiota.

Figure 2

Figure 2

Function of the intestinal microbiome. Commensal bacteria exert a miscellany of protective, structural, and metabolic effects on the intestinal mucosa.

Figure 3

Figure 3

Proposed mechanisms of action. There are a variety of proposed mechanisms, including both humoral and neural routes, through which the microbiota can modulate signaling along the brain–gut axis. For example, recent studies suggest a role for both the vagus nerve and modulation of systemic tryptophan levels in relaying the influence of both resident and exogenous microflora along this bidirectional communication axis.

Figure 4

Figure 4

Brain–gut–microbe communication in health and disease. A stable gut microbiota is essential for normal gut physiology and contributes to appropriate signaling along the brain–gut axis and to the healthy status of the individual as shown on the left hand side of the diagram. Conversely, as shown on the right hand side of the diagram, intestinal dysbiosis can adversely influence gut physiology leading to inappropriate brain–gut axis signaling and associated consequences for CNS functions and disease states. Stress at the level of the CNS can also impact on gut function and lead to perturbations of the microbiota.

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