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Increasing evidence indicates that gut microbiota can influence cognition via the gut–brain axis, and brain networks play a critical role during the process. However, little is known about how brain network topology and structural–functional connectivity (SC–FC) coupling contribute to gut microbiota-related cognition. Fecal samples were collected from 157 healthy young adults, and 16S amplicon sequencing was used to assess gut diversity and enterotypes. Topological properties of brain structural and functional networks were acquired by diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI data), and SC–FC coupling was further calculated. 3-Back, digit span, and Go/No-Go tasks were employed to assess cognition. Then, we tested for potential associations between gut microbiota, complex brain networks, and cognition. The results showed that gut microbiota could affect the global and regional topological properties of structural networks as well as node properties of functional networks. It is worthy of note that causal mediation analysis further validated that gut microbial diversity and enterotypes indirectly influence cognitive performance by mediating the small-worldness (Gamma and Sigma) of structural networks and some nodal metrics of functional networks (mainly distributed in the cingulate gyri and temporal lobe). Moreover, gut microbes could affect the degree of SC–FC coupling in the inferior occipital gyrus, fusiform gyrus, and medial superior frontal gyrus, which in turn influence cognition. Our findings revealed novel insights, which are essential to provide the foundation for previously unexplored network mechanisms in understanding cognitive impairment, particularly with respect to how brain connectivity participates in the complex crosstalk between gut microbiota and cognition. [ABSTRACT FROM AUTHOR]

Network neuroscience has broadly conceptualized the functions of the brain as complex communication within and between large‐scale neural networks. Nevertheless, whether and how the gut microbiota influence functional network connectivity that in turn impact human behaviors has yet to be determined. We collected fecal samples from 157 healthy young adults and used 16S sequencing to assess gut microbial diversity and enterotypes. Large‐scale inter‐ and intranetwork functional connectivity was measured using a combination of resting‐state functional MRI data and independent component analysis. Sleep quality and core executive functions were also evaluated. Then, we tested for potential associations between gut microbiota, functional network connectivity and behaviors. We found significant associations of gut microbial diversity with internetwork functional connectivity between the executive control, default mode and sensorimotor systems, and intranetwork connectivity of the executive control system. Moreover, some internetwork functional connectivity mediated the relations of microbial diversity with sleep quality, working memory, and attention. In addition, there was a significant effect of enterotypes on intranetwork connectivity of the executive control system, which could mediate the link between enterotypes and executive function. Our findings not only may expand existing biological knowledge of the gut microbiota‐brain‐behavior relationships from the perspective of large‐scale functional network organization, but also may ultimately inform a translational conceptualization of how to improve sleep quality and executive functions through the regulation of gut microbiota. [ABSTRACT FROM AUTHOR]

Background The field of microbiota-gut-brain research in animals has progressed, while the exact nature of gut microbiota-brain-cognition relationship in humans is not completely elucidated, likely due to small sample sizes and single neuroimaging modality utilized to delineate limited aspects of the brain. We aimed to comprehensively investigate such association in a large sample using multimodal MRI. Methods Fecal samples were collected from 157 healthy young adults and 16S sequencing was used to assess gut microbial diversity and enterotypes. Five brain imaging measures, including regional homogeneity (ReHo) and functional connectivity density (FCD) from resting-state functional MRI, cerebral blood flow (CBF) from arterial spin labeling, gray matter volume (GMV) from structural MRI, and fractional anisotropy (FA) from diffusion tensor imaging, were jointly analyzed with a data-driven multivariate fusion method. Cognition was evaluated by 3-back and digit span tasks. Results We found significant associations of gut microbial diversity with ReHo, FCD, CBF, and GMV within the frontoparietal, default mode and visual networks, as well as with FA in a distributed set of juxtacortical white matter regions. In addition, there were FCD, CBF, GMV, and FA differences between Prevotella- versus Bacteroides-enterotypes in females and between Prevotella- versus Ruminococcaceae-enterotypes in males. Moreover, the identified neuroimaging fusion biomarkers could mediate the associations between microbial diversity and cognition. Conclusions Our findings not only expand existing knowledge of the microbiota-gut-brain axis, but also have potential clinical and translational implications by exposing the gut microbiota as a promising treatment and prevention target for cognitive impairment and related brain disorders. • Gut microbiota-brain-cognition association was assessed using multimodal MRI. • Multimodal MRI measures were jointly analyzed with a multivariate fusion method. • Gut microbial diversity was correlated with multiple neuroimaging fusion measures. • There were differences in multiple neuroimaging fusion measures between enterotypes. • Fusion biomarkers mediated the relations between microbial diversity and cognition. [ABSTRACT FROM AUTHOR]