Gut-Brain Connection: Deciphering Causal Pathways Between Gut Microbiota and Neuroimaging Profiles Through Mendelian...

Area of Science:

• Neuroscience
• Microbiology
• Genetics

Background:

• The gut-brain axis (GBA) links gut microbiome activity to brain function, but causal links to brain connectivity are unclear.
• Understanding how gut microbiota impacts mood and cognition is crucial for GBA research.

Purpose of the Study:

• To investigate the causal relationship between the gut microbiome and brain imaging-derived phenotypes (IDPs) of functional and structural connectivity.
• To explore the bidirectional interactions within the gut-brain axis using a Mendelian randomization approach.

Main Methods:

• Utilized large-scale genome-wide association studies (GWAS) data.
• Employed a bidirectional Mendelian randomization (MR) approach.
• Analyzed 196 gut microbiome taxa and seven resting-state networks (RSNs) from UK Biobank (UKB) data.

Main Results:

• Forward MR identified specific bacteria (e.g., Ruminococcus torques, Terrisporobacter) influencing default mode network (DMN) and dorsal attention network (DAN) connectivity.
• Reverse MR showed associations between functional connectivity of DAN/ventral attention network (VAN) and specific bacterial abundances (e.g., Alloprevotella).
• Structural connectivity of frontoparietal network (FPN) and somatomotor network (SMN) were linked to reduced abundance of certain bacterial groups (e.g., Bacilli).

Conclusions:

• Established causal evidence for gut microbiome's influence on brain network connectivity.
• Supported a bidirectional regulatory pattern in the gut-brain axis.
• Provided a theoretical basis for microbiome-based interventions targeting emotional regulation, cognition, and neurodevelopment.