Bile Acids: A Communication Channel in the Gut-Brain Axis
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Bile Acids: A Communication Channel in the Gut‑Brain Axis Vera F. Monteiro‑Cardoso1,2 · Maria Corlianò1,2 · Roshni R. Singaraja1,2 Received: 1 August 2020 / Accepted: 8 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Bile acids are signalling hormones involved in the regulation of several metabolic pathways. The ability of bile acids to bind and signal through their receptors is modulated by the gut microbiome, since the microbiome contributes to the regulation and synthesis of bile acids as well to their physiochemical properties. From the gut, bacteria have been shown to send signals to the central nervous system via their metabolites, thus affecting the behaviour and brain function of the host organism. In the last years it has become increasingly evident that bile acids affect brain function, during normal physiological and pathological conditions. Although bile acids may be synthesized locally in the brain, the majority of brain bile acids are taken up from the systemic circulation. Since the composition of the brain bile acid pool may be regulated by the action of intestinal bacteria, it is possible that bile acids function as a communication bridge between the gut microbiome and the brain. However, little is known about the molecular mechanisms and the physiological roles of bile acids in the central nervous system. The possibility that bile acids may be a direct link between the intestinal microbiome and the brain is also an understudied subject. Here we review the influence of gut bacteria on the bile acid pool composition and properties, as well as striking evidence showing the role of bile acids as neuroactive molecules. Keywords Bile acids · Gut microbiome · Neurodegenerative disorders · Gut-brain axis
Introduction In the past years it has become increasingly evident that the gut microbiome and the brain communicate, and that this gut-brain communication plays a key role in maintaining brain health. The human gut contains approximately 1 013 to 1014 microorganisms that are estimated to weigh over 1 kg, about the same weight as the human brain (Dinan et al. 2015). It is estimated that the human gut microbiome harbors over 100 times as many genes as the human genome, thus increasing the functional genome contributing to human physiology (Stilling et al. 2014). Increasing evidence suggests that the gut microbiome not only modulates intestinal Vera F. Monteiro-Cardoso and Maria Corlianò contributed equally to the manuscript. * Roshni R. Singaraja [email protected]‑star.edu.sg 1
Translational Laboratories in Genetic Medicine, Agency for Science, Technology and Research, 8A Biomedical Grove, Singapore 138648, Singapore
Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
2
health, but also modulates the normal physiological functions of other organs, including the brain. Indeed, the gut microbiome has a significant impact on neurophysiology and behavior (Sampson and Mazmanian 2015). The principal
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