Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders
By J. R. Kelly, P. Kennedy, J. Cryan, Ted G. Dinan, G. Clarke, N. Hyland. Frontiers in Cellular Neuroscience, 2015
1,012 citations recorded by the source corpus.
The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a “leaky gut” may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function.
Subfields: Biological Psychiatry, Gastroenterology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/57a262590e053b9b0cfed924676d3d8d9e4267ab
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Citations in the corpus
- Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. (2016, background): “We then assessed gut permeability as a potential mechanism by which gut bacteria may influence brain function (Julio-Pieper et al., 2014; Kelly et al., 2015).”
- Human gut microbiota/microbiome in health and diseases: a review (2020, background): “…2018), controlling epithelial cell proliferation and differentiation (Wiley et al. 2017), modifying insulin resistance and affecting its secretion (Kelly et al. 2015a, b), influencing brain–gut communication and thus affecting the mental and neurological functions of the host (Zheng et al. 2019),…”
- The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? (2016, background): “the gut epithelium and the blood brain barrier, and permeability through both of these barriers has been shown to be affected by the microbiome (Kelly et al., 2015).”
- Kynurenine pathway metabolism and the microbiota‐gut‐brain axis (2017, background): “…et al., 2016) Alternatively, microbial metabolites such as SCFAs can impact on intestinal barrier integrity and the systemic inflammation arising from increased intestinal permeability could also lead to alterations in kynurenine pathway metabolism (Kelly et al., 2015b; Tilg and Moschen, 2015).”
- Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration (2017, background): “…and its mucous layer have many functions, including the regulation of nutrient and fluid absorption from the gut lumen in addition to serving as a physical barrier from invading pathogens or harmful substances (Farhadi et al. 2003; Scaldaferri et al. 2012; Johansson et al. 2013; Kelly et al. 2015).”