The role of gut microbiota in modulating brain structure and psychiatric disorders: A Mendelian randomization study

May 27, 2025NeuroImage

How gut bacteria may influence brain structure and mental health disorders

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Abstract

Genetic data from large-scale studies indicated that 196 gut microbiota taxa influence ten psychiatric disorders via changes in 3143 brain structures.

Significant bidirectional causal relationships exist between gut microbiota and brain structures.
Certain gut microbiota taxa, such as Bacteroides, are associated with changes in brain activity.
The composition of gut microbiota can be influenced by specific brain structures, including the right hippocampus.
The genus Prevotellaceae is linked to an increased risk of Autism Spectrum Disorder, while Ruminococcaceae UCG005 may provide a protective effect.
Alistipes is positively associated with Panic Disorder, and both protective (Barnesiella) and risk-associated (Phascolarctobacterium) genera are identified in Schizophrenia.
Mediation analysis suggests that changes in brain structure fully transmit the effects of gut microbiota on five psychiatric disorders.

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The influence of the gut microbiome on the human brain, especially its associations with psychiatric disorders, has emerged as a focal area in contemporary neuroscience and psychiatry research. In this study, we employed a mediation Mendelian randomization approach to delve into the potential causal relationships between gut microbiota and psychiatric disorders, with a focus on the mediating role of brain structural changes. We harnessed genetic data from large - scale genome - wide association studies to analyze how 196 gut microbiota taxa affect ten psychiatric disorders via alterations in 3143 brain structures. Our key findings revealed significant bidirectional causal relationships. In the gut microbiota - brain structure relationship, certain gut microbiota taxa, such as Bacteroides and Marvinbryantia, were associated with changes in brain activity and white matter integrity respectively. Conversely, brain structures like the right hippocampus and left superior cerebellar peduncle influenced gut microbiota composition. Regarding gut microbiota and psychiatric disorders, we identified numerous associations. For example, the genus Prevotellaceae was significantly associated with an increased risk of Autism Spectrum Disorder, while Ruminococcaceae UCG005 showed a protective effect. In Panic Disorder, Alistipes was positively associated, and for Schizophrenia, both protective (Barnesiella) and risk - associated (Phascolarctobacterium) genera were found. Moreover, through mediation analysis, we found that brain structures mediated the effects of gut microbiota on five psychiatric disorders, including bipolar disorder and anorexia nervosa. In these cases, the influence of gut microbiota on the disorders was fully transmitted through changes in brain structure. Overall, our research clarifies the role of the microbiota - gut - brain axis in mental health. It offers a new perspective on how intestinal microbes impact brain physiology and psychiatric pathology. These findings not only deepen our understanding of the biological interactions between the gut and brain but also suggest that targeted gut microbiota modifications could be novel therapeutic strategies for mental health disorders.

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The role of gut microbiota in modulating brain structure and psychiatric disorders: A Mendelian randomization study

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