Metabolomic, Lipidomic, Transcriptomic, and Metagenomic Analyses in Mice Exposed to PFOS and Fed Soluble and Insoluble Dietary Fibers

Background: Perfluorooctane sulfonate (PFOS) is a persistent environmental pollutant that has become a significant concern around the world. Exposure to PFOS may alter gut microbiota and liver metabolic homeostasis in mammals, thereby increasing the risk of cardiometabolic diseases. Diets high in soluble fibers can ameliorate metabolic disease risks. Objectives: We aimed to test the hypothesis that soluble fibers (inulin or pectin) could modulate the adverse metabolic effects of PFOS by affecting microbe-liver metabolism and interactions. Methods: Male C57BL/6J mice were fed an isocaloric diet containing different fibers: a) inulin (soluble), b) pectin (soluble), or c) cellulose (control, insoluble). The mice were exposed to PFOS in drinking water (3μg/g per day) for 7 wk. Multi-omics was used to analyze mouse liver and cecum contents. Results: In PFOS-exposed mice, the number of differentially expressed genes associated with atherogenesis and hepatic hyperlipidemia were lower in those that were fed soluble fiber than those fed insoluble fiber. Shotgun metagenomics showed that inulin and pectin protected against differences in microbiome community in PFOS-exposed vs. control mice. It was found that the plasma PFOS levels were lower in inulin-fed mice, and there was a trend of lower liver accumulation of PFOS in soluble fiber-fed mice compared with the control group. Soluble fiber intake ameliorated the effects of PFOS on host hepatic metabolism gene expression and cecal content microbiome structure. Discussions: Results from metabolomic, lipidomic, and transcriptomic studies suggest that inulin- and pectin-fed mice were less susceptible to PFOS-induced liver metabolic disturbance, hepatic lipid accumulation, and transcriptional changes compared with control diet-fed mice. Our study advances the understanding of interaction between microbes and host under the influences of environmental pollutants and nutrients. The results provide new insights into the microbe-liver metabolic network and the protection against environmental pollutant-induced metabolic diseases by high-fiber diets. https://doi.org/10.1289/EHP11360