Gut microbiome at the crossroad of genetic variants and behavior disorders

ABSTRACT

Genetic variants are traditionally known to shape the susceptibility to neuropsychiatric disorders. An increasing number of studies indicate that remodeling of the gut microbiome by genetic variance serves as a versatile regulator of gut-brain crosstalk and behavior. Evidence also emerges that certain behavioral symptoms are specifically attributed to gut microbial remodeling and gut-to-brain signals, which necessitates rethinking of neuropsychiatric disease etiology and treatment from a systems perspective of reciprocal gene-microbe interactions. Here, we present an emerging picture of how gut microbes and host genetics interactively shape complex psychiatric phenotypes. We illustrate the growing understanding of how the gut microbiome is shaped by genetic changes and its connection to behavioral outcome. We also discuss working strategies and open questions in translating associative gene-microbiome-behavior findings into causal links and novel targets for neurobehavioral disorders. Dual targeting of the genetic and microbial factors may expand the space of drug discovery for neuropsychiatric diseases.

KEYWORDS:

• Gut dysbiosis
• microbiome-gut-brain axis
• neuropsychological disorder
• genetic risk
• microbial metabolites

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Conceptualization was made by X. Z. and H.P.H.; L.S.C., H.Q.W., Z. C., and X. Z. wrote the manuscript; figures and tables were prepared by L.S.C. and H.Q.W.

Availability of data and material

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Additional information

Funding

The work is financially supported by the National Natural Science Foundation of China under grant [81973556, 82274009], “Double-first” Discipline funding of China Pharmaceutical University under grant [CPUQNJC22_09], the National Key Research and Development Programme of China under grant [2021YFA1301300] and Sanming Project of Medicine in Shenzhen under grant [SZSM201801060].