Gut unclassified Ruminococcaceae reweights cortical functional gradients and small-world topology with links to mood and diet.

Increased abundance of unclassified Ruminococcaceae (Ruminococcaceae_unc) was associated with a functional shift in the brain from unimodal to transmodal hubs.

• The study used a cross-modal brain-gut dataset from 88 healthy male participants.
• Integration of fMRI gradient analysis, microbiome sequencing, and dietary behavioral information was used to evaluate these relationships.
• The functional shift reflected a reweighting of cortical functional gradients toward transmodal regions.

Increased Ruminococcaceae_unc abundance was accompanied by a drift of the small-world network topology toward randomization.

• Small-world network topology was assessed alongside functional gradient analysis.
• The drift toward randomization was concurrent with the unimodal-to-transmodal functional shift.
• This finding suggests that gut microbiota composition is linked to global brain network organization.

Functional gradient values were significantly negatively correlated with depression and anxiety scores.

• Depression and anxiety scores were measured as part of the emotional symptom assessment.
• The negative correlation indicates that higher transmodal gradient values were associated with lower depression and anxiety.
• This relationship was observed across the 88 healthy male participants.

Functional gradient values were tightly coupled with latent components in the dietary behavioral dimension, including education, physical activity, and nutrient intake.

• Dietary behavioral information was integrated into the multimodal analysis framework.
• Latent components identified included education, physical activity, and nutrient intake as key dietary behavioral factors.
• These couplings suggest that lifestyle and dietary factors modulate the gut-brain functional hierarchy relationship.

Transcriptomic analysis revealed that the GPCR-Rho/integrin-vesicular trafficking pathway may serve as the key molecular mechanism underlying the Ruminococcaceae_unc–brain relationship.

• Transcriptomic analysis was used to investigate potential molecular mechanisms.
• The GPCR-Rho/integrin-vesicular trafficking pathway was identified as a candidate mediating mechanism.
• This pathway may link gut microbial signals to cortical functional reorganization.

The study proposes a multiscale coupling framework encompassing the gut microbiota, functional gradients, and emotional health.

• The framework provides a theoretical basis for development of microbiota-targeted intervention strategies.
• The interventions are proposed for modulating transmodal emotions and cognition.
• The framework integrates microbiome, neuroimaging, and behavioral data across multiple scales.