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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]

Functional stability is a newly developed dynamic functional connectivity approach. The objective of this study was to adopt functional stability to investigate diagnosis-associated abnormalities (patients vs. controls) and status-related changes (acute vs. remitted status) in brain function in major depressive disorder (MDD). 132 MDD patients and 102 healthy controls underwent resting-state functional MRI as well as clinical and cognitive assessment at baseline, with 48 patients completing follow-up examinations at an average of 7 months. Results showed no group differences in baseline functional stability and no longitudinal functional stability changes from acute to remitted status in patients. However, we found that baseline functional stability in the dorsal and ventral anterior cingulate cortex, calcarine sulcus, and middle occipital gyrus could predict improvement in depressive symptoms from acute to remitted status in MDD patients, with longitudinal functional stability changes in these regions related to the degree of symptom improvement. In addition, lower baseline functional stability in the inferior temporal gyrus could predict a greater improvement in sustained attention, which was associated with a greater functional stability increase in this region. Our findings highlight functional stability as a potential prognostic biomarker to predict and track disease progression or stratify MDD patients for optimizing disease management and treatment strategies. • Baseline functional stability could predict clinical improvement in MDD patients. • Longitudinal functional stability changes related to clinical improvement degree. • Baseline functional stability could predict cognitive improvement in MDD patients. • Longitudinal functional stability changes related to cognitive improvement degree. [ABSTRACT FROM AUTHOR]