Integrated Metagenomic and Metabolomic Analysis of In Vitro Murine Gut Microbial Cultures upon Bisphenol S Exposure

Background: The gut microbiota are an important interface between the host and the environment, mediating the host’s interactions with nutritive and non-nutritive substances. Dietary contaminants like Bisphenol A (BPA) may disrupt the microbial community, leaving the host susceptible to additional exposures and pathogens. BPA has long been a controversial and well-studied contaminant, so its structural analogues like Bisphenol S (BPS) are replacing it in consumer products, but have not been well studied. Methods: This study aimed to determine the impact of BPS on C57BL/6 murine gut microbiota using shotgun metagenomic sequencing and the metabolomic profiling of in vitro anaerobic cultures. Results: The results demonstrated that a supraphysiologic BPS dose did not overtly distort the metagenomic or metabolomic profiles of exposed cultures compared to controls. A distinct BPS-associated metabolite profile was not observed, but several metabolites, including saturated fatty acids, were enriched in the BPS-exposed cultures. In the absence of a BPS-associated enterotype, Lactobacillus species specifically were associated with BPS exposure in a discriminant model. Conclusions: Our study provides evidence contrasting the effects of BPS in the gut microbiome to its predecessor, BPA, but also emphasizes the role of inter-animal variation in microbiome composition, indicating that further study is needed to characterize BPS in this context.