Exposure to environmentally relevant concentration of sodium p-perfluorous nonenoxybenzene sulfonate is associated with aberrant barbering behavior in diabetic mice

This study originated from an incidental behavioral observation. We found that exposure to environmentally relevant concentration of sodium p-perfluorous nonenoxybenzene sulfonate (OBS; 3 μg/L), as reported in a previous field measurement study, was associated with aberrant barbering behavior in diabetic mice. To investigate the underlying mechanisms, sixteen 8-week-old male db/db mice were administered OBS at 3 μg/L for 91 days. Biochemical assays of endothelial- and barrier-related markers, hippocampal OBS quantification, stereotaxic hippocampal OBS administration, and metagenomic sequencing of the colonic contents and hippocampal tissues were performed. Based on the metagenomic results, computational biology analyses, including molecular docking, molecular dynamics simulations, and protein functional annotation, were conducted to assess potential OBS-bacterial protein interactions. The results showed that exposure to environmentally relevant concentration of OBS was associated with aberrant barbering behavior in the experimental mice (100 % prevalence). Circulating markers of endothelial activation and basal lamina injury were significantly elevated. Metagenomic analysis revealed that the abundance of Salmonella enterica subsp. diarizonae was significantly increased in both the colonic contents and hippocampal tissues, with hippocampal abundance positively correlated with colonic abundance. Molecular docking and molecular dynamics simulations indicated that OBS binds effectively to two bacterial proteins. Functional annotation suggested that these proteins are associated with central metabolic and biosynthetic processes relevant to bacterial proliferation. Together, these findings suggest that exposure to environmentally relevant concentration of OBS is associated with aberrant barbering behavior in diabetic mice and may be associated with increased colonic S. enterica subsp. diarizonae abundance and its presence in the hippocampus.