Brain–Gut–Microbe Communication in Health and Disease

By S. Grenham, G. Clarke, J. Cryan, Ted G. Dinan. Front. Physio., 2011

904 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Pharmacy, Plant Science

View Paper: https://www.semanticscholar.org/paper/c056784a5d5715771ebcd31d6ad614906e1a278c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. J. Cryan
2. Ted G. Dinan
3. G. Clarke
4. C. Stanton
5. P. Kennedy
6. R. Stilling
7. J. R. Kelly
8. M. Conlon

In Pharmacy

1. J. Cryan
2. Ted G. Dinan
3. G. Clarke
4. C. Stanton
5. P. Kennedy
6. R. Stilling
7. S. Mazmanian
8. J. Foster

In Plant Science

1. J. Cryan
2. Ted G. Dinan
3. M. Conlon

Citations in the corpus

• Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders (2015, background): “These pathways are under the influence of the gut microbiota and together, they comprise the brain-gut-microbiota axis (Grenham et al., 2011).”
• Psychobiotics: a novel class of psychotropic. (2013, background): “Colonization of the infant gut commences at birth when delivery exposes the infant to a complex microbiota and its initial microbiome has a maternal signature (23,24).”
• Minireview: Gut microbiota: the neglected endocrine organ. (2014, background): “Although this cross-talk can occur via a number of mechanisms that take advantage of gut-brain axis scaffolding, including neural routes (see Figure 4), humoral options also exist (3).”
• Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration (2017, background): “The mechanisms of communication are complex and are slowly being unravelled; they include immune, neural, endocrine and metabolic pathways (Grenham et al. 2011; Mayer et al. 2014a; El Aidy et al. 2015; Koh et al. 2016; Sommer & Backhed, 2016).”
• Stress & the gut-brain axis: Regulation by the microbiome (2017, neutral): “However, the key question remains: through what mechanisms do the gut microbiota influence the CNS, and vice-versa? A complex communication network exists between the gut and the CNS, which includes the enteric nervous system (ENS), sympathetic and parasympathetic branches of the autonomic nervous s”
• Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis (2014, background): “Indeed, it is becoming clear that certain pathologies, which are associated with an altered microbiome, are connected to mood, stress, behaviour and/or cognition (for review see Grenham et al. 2011; Shanahan 2012).”
• Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications (2019, background): “Gut microbiota affects the brain through three routes, including neural, endocrine, and immune pathways [142,144,145].”
• Role of intestinal microbiota and metabolites on gut homeostasis and human diseases (2017, background): “In addition to bacterial biosynthesis and sensing of similar neurohormones found in the mammals, it is postulated that the bacterial symbiosis with the intestine plays a predominant role in the postnatal development and maturation of the host immune and endocrine system, which underpins CNS function”
• The Impact of Diet and Lifestyle on Gut Microbiota and Human Health (2014, background): “The gut-brain axis is bi-directional, involving both hormonal and neuronal pathways [41], and so changes in the gut microbiota may influence brain activity, including mood [42].”