The Molecular Gut-Brain Axis in Early Brain Development

Int J Mol Sci. 2022 Dec 6;23(23):15389. doi: 10.3390/ijms232315389.

Abstract

Millions of nerves, immune factors, and hormones in the circulatory system connect the gut and the brain. In bidirectional communication, the gut microbiota play a crucial role in the gut-brain axis (GBA), wherein microbial metabolites of the gut microbiota regulate intestinal homeostasis, thereby influencing brain activity. Dynamic changes are observed in gut microbiota as well as during brain development. Altering the gut microbiota could serve as a therapeutic target for treating abnormalities associated with brain development. Neurophysiological development and immune regulatory disorders are affected by changes that occur in gut microbiota composition and function. The molecular aspects relevant to the GBA could help develop targeted therapies for neurodevelopmental diseases. Herein, we review the findings of recent studies on the role of the GBA in its underlying molecular mechanisms in the early stages of brain development. Furthermore, we discuss the bidirectional regulation of gut microbiota from mother to infant and the potential signaling pathways and roles of posttranscriptional modifications in brain functions. Our review summarizes the role of molecular GBA in early brain development and related disorders, providing cues for novel therapeutic targets.

Keywords: epigenetics; gut-brain axis; molecules; neurodevelopment; vagus nerve.

Publication types

  • Review

MeSH terms

  • Brain / metabolism
  • Brain-Gut Axis
  • Gastrointestinal Microbiome* / physiology
  • Humans
  • Neurodevelopmental Disorders* / metabolism

Grants and funding

This work was funded in part by the financial support from Shenzhen Science and Technology Program (KCXFZ20211020163549011, XL & BF); the “Nutrition and Care of Maternal & Child Research Fund Project” of Biostime Institute of Nutrition & Care (2020BINCMCF058, XL); National Natural Science Foundation of China (NSFC) (31900728, XL, 32000710, ZC, U20A2016, ZC); CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024, XL); Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2017B030301017, XL); Guangdong Basic and Applied Basic Research Foundation (2019A1515110190, ZC); Shenzhen Key Basic Research Project (JCYJ20200109115641762, ZC); Shenzhen governmental grant (ZDSYS20190902093601675, ZC).