The role of gut microbiota in modulating brain structure and psychiatric disorders: A Mendelian randomization study (May 2025) Causation 

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https://www.sciencedirect.com/science/article/pii/S1053811925002952

Highlights​

  • Bidirectional gut - brain axis: Using Mendelian randomization, the study shows bidirectional causality between gut microbiota and brain structure. Some gut bacteria affect brain activity, and brain structures influence gut microbiota, highlighting the dynamic gut - brain axis.
  • Gut microbiota - psychiatric disorder associations: The research finds significant links between gut microbiota genera and psychiatric disorders. For example, Prevotellaceae is linked to a higher risk of Autism Spectrum Disorder, and Ruminococcaceae UCG005 may be protective.
  • Brain structures as mediators: Mediation analysis reveals that brain structures mediate the relationship between gut microbiota and some psychiatric disorders like bipolar disorder. The impact of gut microbiota on these disorders is transmitted via brain structure changes.

Abstract​

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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