Opinion Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Feb 26, 2022; 10(6): 1754-1763
Published online Feb 26, 2022. doi: 10.12998/wjcc.v10.i6.1754
Gut-brain axis: Focus on gut metabolites short-chain fatty acids
Cen Guo, Ya-Jing Huo, Yu Li, Yan Han, Da Zhou
Cen Guo, Ya-Jing Huo, Yan Han, Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
Yu Li, Da Zhou, Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai Institute of Liver Disease, Shanghai 200032, China
Author contributions: Guo C and Huo YJ are involved in drafting and writing the manuscript; Li Y and Han Y are involved in editing the manuscript; Zhou D are involved in critical revision and editing the manuscript; all authors read and approved the final version of this manuscript.
Supported by the National Natural Science Foundation of China, No. 81800510; and Shanghai Sailing Program, No. 18YF1415900.
Conflict-of-interest statement: All authors confirmed no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Da Zhou, MD, PhD, Attending Doctor, Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai Institute of Liver Disease, No. 180 Fenglin Road, Shanghai 200032, China. zhou.da@zs-hospital.sh.cn
Received: August 24, 2021
Peer-review started: August 24, 2021
First decision: November 17, 2021
Revised: November 25, 2021
Accepted: January 19, 2022
Article in press: January 19, 2022
Published online: February 26, 2022
Abstract

Emerging evidence supports that the gut microbiome, reconsidered as a new organ in the human body, can not only affect the local gut, but also communicate with the brain via multiple pathways related to neuroendocrine, immune, and neural pathways, thereby proposing the new concept of the microbiome-gut-brain (MGB) axis. Recently, the role of short-chain fatty acids (SCFAs), which are the main anaerobic fermented metabolites of the gut microbiota in the MGB axis, has garnered significant attention. SCFAs are involved in a broad range of central neurological diseases, including neurodegenerative diseases, cerebral vascular diseases, epilepsy, neuroimmune inflammatory diseases, and mood disorders. However, the underlying mechanism of SCFA-related distant organ crosstalk is yet to be elucidated. Herein, we summarize current knowledge regarding interactions between SCFAs and the MGB axis, as well as their protective effects against central neurological diseases.

Keywords: Gut-brain axis, Short-chain fatty acids, Neurological disease, Microbiome-gut-brain

Core Tip: Recently, emerging evidence suggests that short-chain fatty acids (SCFAs) exert crucial functions on the brain. The levels of SCFAs can change in many neurological disorders such as Parkinson’s disease, Alzheimer’s disease, autism spectrum disorder, major depressive disorder, stroke, epilepsy, multiple sclerosis, and so on. Meanwhile, SCFAs might play a role in the pathogenesis of these diseases. In this review, we outline possible pathways of microbiota–gut–brain (MGB) axis, the interactions between SCFAs and MGB axis, as well as their relationships with different central neurological diseases, which helps to better understand the biological roles of SCFAs in neurological disorders via MGB axis and shed light on potential therapeutic approaches for these neurological disorders.