Bilophila wadsworthia is linked to basal ganglia atrophy in the general population.

Bilophila wadsworthia, a sulfite-reducing bacterium stimulated by bile acids and enriched under high-fat diets, has been linked to several neurological disorders involving disturbances of motor function and basal ganglia circuitry. However, its potential association with alterations of brain structure remains unclear. Here, we investigated relationships between Bilophila (wadsworthia) abundance and basal ganglia volumes in two independent population-based cohorts combining gut microbiome profiling and brain MRI data. Genus-level Bilophila abundance was assessed using 16S rRNA gene sequencing and complemented by species-level analyses of B. wadsworthia using whole-genome shotgun sequencing. Higher abundance of Bilophila (wadsworthia) was consistently associated with reduced volumes of basal ganglia regions, particularly the globus pallidus and nucleus accumbens. These associations were largely specific to basal ganglia regions when compared across a broad set of cortical thickness and other volumetric brain measures. Additionally, Bilophila (wadsworthia) was linked to elevated liver enzymes, elevated triglycerides, and pro-inflammatory states, confirming prior evidence from animal models while revealing novel associations in the general population. Constraint-based community modeling revealed that B. wadsworthia-enriched microbiomes exhibit increased functional redundancy for bile acid and sulfur metabolism and may modulate trimethylamine pathways. Together, these findings link variation in B. wadsworthia abundance to structural differences within basal ganglia regions and to unfavorable metabolic and inflammatory profiles in the general population, suggesting a potential role of this microbial species in gut-brain axis alterations relevant to neurodegenerative disease progression.