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.

The Impact of Early-Life Cecal Microbiota Transplantation on Social Stress and Injurious Behaviors in Egg-Laying Chickens

“…Normally, it prompts chickens’ ability to adapt to their rearing environments, while abnormally, an overload of stress challenge (too much exposure to a stressor or combined stressors causing a long-term activation of the stress response systems) reduces gut microbiota diversity, composition, or both [ 131 ]. The gut microbiota is functionally like an endocrine organ, releasing numerous bioactive factors to activate the HPA and SAM stress systems in response to stimulations, consequently affecting host physiological and behavioral homeostasis via the bidirectional communication of the MGB and MGI axes [ 63 , 64 ]. Healthy intestinal microbial communities and functions are essential for animals to fit their living environments [ 132 , 133 ].…”

“…Several probiotics, as psychobiotics, for example, Bifidobacterium and Lactobacillus , deliver mental health benefits with neurobehavioral effects, which have been used in humans for improving cognitive function and for preventing and treating patients with behavioral impairment in neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, and in diseases with neuropsychiatric disorders, such as anxiety, depression, and impulsively and compulsively disrupted social behavior [ 75 , 77 , 78 , 79 , 83 , 84 ]. Based on findings, targeting the gut microbiota has been recognized as a novel therapeutic option for patients with neuropsychiatric disorders [ 63 , 73 , 74 ]. Current studies have evidenced that the influence of the gut microbiota on the host behavior as seen in mammals is shared in chickens [ 173 ].…”

“…The gut microbiota plays a critical role in early programming and later activity of the central stress systems, i.e., the hypothalamic–pituitary–adrenal (HPA) and the sympathetic–adrenal–medullary (SAM) axes [ 52 , 53 , 54 ]. Like an endocrine organ, the gut microbiota is sensitive and reactive to various exogenous stimuli, functioning as an environmental sensor linked to the pathogenesis of stress-related illnesses through the bidirectional communication of the MGB axis [ 55 , 56 , 57 , 58 , 59 ] and the microbiota–gut–immune (MGI) axis [ 60 , 61 ] in various animals including chickens [ 62 , 63 , 64 ]. Maintaining gut microbiota balance and health is essential for animals (including chickens) to maintain their optimal physiological and behavioral functions of growth, reproduction, and welfare.…”

Multiomics and blood-based biomarkers of moyamoya disease: protocol of Moyamoya Omics Atlas (MOYAOMICS)

“…This phenomenon compromised the integrity of both the gut epithelial barrier and the blood-brain barrier, resulting in increased permeability. Intriguingly, a noteworthy discovery emerged when fecal transplantation from specific-pathogen-free mice was employed, successfully reversing the changes in the blood-brain barrier [ 32 ]. A wealth of compelling evidence suggests a strong link between alterations in the gut microbiota and a spectrum of central nervous system diseases.…”

Epigenetic Aberrations in Major Psychiatric Diseases Related to Diet and Gut Microbiome Alterations

“…A variety of serious diseases especially mental disorders are linked to differences in gut microbiome composition and function [88,89]. For example, a significantly reduced abundance of the phylum Bacteroidetes and an increased abundance of the Actinobacteria and Firmicutes have been found in bipolar disorder with current major depressive episodes [90].…”