Therapeutic strategies of small molecules in the microbiota-gut-brain axis for alcohol use disorder

Lushuang Xie; Wiramon Rungratanawanich; Qiang Yang; Guoqiang Tong; Eric Fu; Shiguang Lu; Yuancai Liu; Mohammed Akbar; Byoung-Joon Song; Xin Wang

doi:10.1016/j.drudis.2023.103552

Therapeutic strategies of small molecules in the microbiota-gut-brain axis for alcohol use disorder

Drug Discov Today. 2023 May;28(5):103552. doi: 10.1016/j.drudis.2023.103552. Epub 2023 Mar 11.

Authors

Affiliations

¹ Departments of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China.
² Section of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20892, USA.
³ Hubei Provincial Key Lab for Quality and Safety of Traditional Chinese Medicine Health Food, Jing Brand Research Institute, Daye, Hubei 435100, China.
⁴ Departments of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁵ Division of Neuroscience & Behavior, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20892, USA.
⁶ Section of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20892, USA. Electronic address: bj.song@nih.gov.
⁷ Departments of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: xwang@rics.bwh.harvard.edu.

PMID: 36907319
PMCID: PMC10298843 (available on 2024-05-01)
DOI: 10.1016/j.drudis.2023.103552

Abstract

The microbiota-gut-brain axis (MGBA) is important in maintaining the structure and function of the central nervous system (CNS) and is regulated by the CNS environment and signals from the peripheral tissues. However, the mechanism and function of the MGBA in alcohol use disorder (AUD) are still not completely understood. In this review, we investigate the underlying mechanisms involved in the onset of AUD and/or associated neuronal deficits and create a foundation for better treatment (and prevention) strategies. We summarize recent reports focusing on the alteration of the MGBA in AUD. Importantly, we highlight the properties of small-molecule short-chain fatty acids (SCFAs), neurotransmitters, hormones, and peptides in the MGBA and discusses their usage as therapeutic agents against AUD.

Keywords: AUD; MGBA; SCFAs; hormones; neurotransmitters; peptides; therapeutic targets and interventions.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Alcoholism* / drug therapy
Brain
Brain-Gut Axis
Central Nervous System
Humans

Substances

methylglyoxal bis(3-aminopropylamidinohydrazone)

Grants and funding

Z01 AA000036/ImNIH/Intramural NIH HHS/United States