"Walking While Black": Impacts of Inequities in Nature Access and Belongingness.

Cerebral small vessel disease (CSVD) represents a common age-related cerebral degeneration, frequently accompanied by structural brain changes and cognitive decline [], with MRI serving as the fundamental diagnostic tool []. Brain atrophy, reflected by cortical thinning, is one of the most important MRI biomarkers for CSVD, progressing at approximately twice the annual rate than age-matched healthy individuals [,] and is closely related to cognitive impairment in CSVD [,]. However, the systemic affecting factors contributing to the cortical thinning in CSVD are unclear. Recent studies have considered microbiota dysbiosis as a risk factor detrimental to brain health [,], demonstrating connections between the oral microbiota and brain atrophy [] and cognitive function [], both of which are core features of CSVD. The alterations of microbiota components, such as the enrichment of , have been implicated in cognitive impairment and cortical pathology in neurodegenerative diseases [,,,], and the depletion of and was directly linked to brain atrophy []. Despite existing studies exploring the interactions between the microbiota and brain atrophy, most studies have focused on the reduction of global brain volume or cortical thinning in the specific regions, such as hippocampal and entorhinal, which may not reflect the characteristic brain atrophy patterns of CSVD []. Besides, while previous studies link oral microbiota to cognitive function, they rarely illustrate how the microbiota can impact cognition. Consequently, robust approaches are still needed to detect the specific contributions of microbial dysbiosis to the progress of cortical thinning in CSVD, as well as the underlying effects of microbiota dysbiosis on cognitive function. As brain atrophy is a robust index that has clear relationships with cognitive function, we hypothesize that CSVD patients harbor distinct oral microbiota alterations that are associated with cortical thinning, which is an indirect pathway that further mediates cognitive decline. We employed a longitudinal design and integrated metagenomic sequencing with MRI-based morphology modeling, which quantified the regional cortical thinning in each individual by referring to a large-scale normalized cohort [,]. This study aims to elucidate the role of oral microbiota dysbiosis in CSVD patients, thus providing insights into the predictive value of microbial abundance on the progress of cortical thinning and cognitive impairment in CSVD patients.