Pathways from inequality to health: Social determinants of health shape the gut microbiome in low-resource U.S. communities

The gut microbiome influences cardiovascular and gastrointestinal disease risk, yet the indirect pathways through which structural social determinants of health (SDoH) shape microbial composition remain understudied. We investigated causal pathways linking SDoH - systemic conditions that shape health opportunities - to the gut microbiome in two low-resource, flood-prone U.S. communities. We collected questionnaires, dried blood spots, and fecal samples (n=131; ages 3-79) in Mississippi and Illinois (2022-2023) as part of a longitudinal project on infrastructure and health, identifying bacterial composition via 16S rRNA sequencing. Controlling for covariates, structural equation modeling showed education positively predicted microbiome richness and evenness, partially mediated through income and diet. This suggests that structural inequities in education, food access, and income significantly influence the microbiome. Notably, contrary to established literature, greater consumption of processed and fried foods was associated with increased alpha diversity. Therefore, in this context, diet may covary with environmental vulnerability, such as opportunistic pathogen exposure from frequent flooding. Analysis of beta diversity showed direct effects from education, diet, and CRP; income and homeownership had indirect effects mediated through diet. The taxa driving these relationships likely include Tannerellaceae for diet and a subgroup of Firmicutes for income, based on our differential abundance analysis. These findings indicate that pathways linking SDoH to the microbiome may vary by local infrastructure and environmental context. This research highlights how structural inequality may be biologically embedded, suggesting that public health interventions should target infrastructural inequities linked with environmental racism, rather than individual behavioral change.