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

The microbiota-gut-brain axis is a key conduit linking metabolism, mood, and cognition; however, its position within the continuous functional hierarchy of the cortex and the underlying mechanisms are unclear. In this study, a cross-modal brain-gut dataset from 88 healthy male participants was utilized. By integrating functional magnetic resonance imaging (fMRI) gradient analysis, microbiome sequencing, and dietary behavioral information, this study systematically evaluated the relationships between the abundance of unclassified Ruminococcaceae (Ruminococcaceae_unc), cerebral functional hierarchy, network topology, and emotional symptoms. The results demonstrated that increased abundance of this bacterial group was associated with a functional shift in the brain from unimodal to transmodal hubs, accompanied by a drift of the small-world network toward randomization. Functional gradient values were significantly negatively correlated with depression and anxiety scores and were tightly coupled with latent components in the dietary behavioral dimension, including education, physical activity, and nutrient intake. Transcriptomic analysis further revealed that the GPCR-Rho/integrin-vesicular trafficking pathway may serve as the key molecular mechanism. In conclusion, this study proposes a multiscale coupling framework encompassing the gut microbiota, functional gradients, and emotional health, thereby providing a theoretical basis for the development of microbiota-targeted intervention strategies for modulating transmodal emotions and cognition.