The gut microbiome is a dynamic ecosystem formed by thousands of diverse bacterial species. This bacterial diversity is acquired early in life and shaped over time by a combination of multiple factors, including dietary exposure to distinct nutrients and xenobiotics. Alterations of the gut microbiota composition and associated metabolic activities in the gut are linked to various immune and metabolic diseases. The microbiota could potentially interact with xenobiotics in the gut environment as a result of their board enzymatic capacities and thereby affect the bioavailability and toxicity of the xenobiotics in enterohepatic circulation. Consequently, microbiome-xenobiotic interactions might affect host health. Here, we aimed to investigate the effects of dietary perfluorooctane sulfonic acid (PFOS) exposure on gut microbiota in adult mice and examine the induced changes in animal metabolic functions. In mice exposed to dietary PFOS for 7 weeks, body PFOS and lipid contents were measured, and to elucidate the effects of PFOS exposure, the metabolic functions of the animals were assessed using oral glucose-tolerance test and intraperitoneal insulin-tolerance and pyruvate-tolerance tests; moreover, on Day 50, cecal bacterial DNA was isolated and subject to 16S rDNA sequencing. Our results demonstrated that PFOS exposure caused metabolic disturbances in the animals, particularly in lipid and glucose metabolism, but did not substantially affect the diversity of gut bacterial species. However, marked modulations were detected in the abundance of metabolism-associated bacteria belonging to the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Cyanobacteria, including, at different taxonomic levels, Turicibacteraceae, Turicibacterales, Turicibacter, Dehalobacteriaceae, Dehalobacterium, Allobaculum, Bacteroides acidifaciens, Alphaproteobacteria, and 4Cod-2/YS2. The results of PICRUSt analysis further indicated that PFOS exposure perturbed gut metabolism, inducing notable changes in the metabolism of amino acids (arginine, proline, lysine), methane, and a short-chain fatty acid (butanoate), all of which are metabolites widely recognized to be associated with inflammation and metabolic functions. Collectively, our study findings provide key information regarding the biological relevance of microbiome–xenobiotic interactions associated with the ecology of gut microbiota and animal energy metabolism.
Transcriptomic and LC-MS/MS-based targeted lipidomic analyses were conducted to identify the effects of in utero PFOS exposure on neonatal testes and its relation to testicular dysfunction in adult offspring. Pregnant mice were orally administered 0.3 and 3 μg PFOS/g body weight until term. Neonatal testes (P1) were collected for the detection of PFOS, and were subjected to omics study. Integrated pathway analyses using DAVID, KEGG, and IPA underlined the effects of PFOS exposure on lipid metabolism, oxidative stress and cell junction signaling in testes. LC-MS/MS analysis showed that the levels of adrenic acid and docosahexaenoic acid (DHA) in testes were significantly reduced in the PFOS treatment groups. A significant linear decreasing trend in eicosapentaenoic acid and DHA with PFOS concentrations was observed. Moreover, LOX-mediated 5-hydroxyeicosatetraenoic acids (HETE) and 15-HETE from arachidonic acid in the testes were significantly elevated and a linear increasing trend of 15-HETE concentrations was detected with doses of PFOS. The perturbations of lipid mediators suggested that PFOS has potential negative impacts on testicular functions. Postnatal analysis of male offspring at P63 showed significant reductions in serum testosterone and epididymal sperm count. This study sheds light into the as yet unrevealed action of PFOS on lipid mediators in affecting testicular functions.
Perfluorooctane sulfonate (PFOS) is a metabolic-disrupting chemical. There is a strong association between maternal and cord blood PFOS concentrations, affecting metabolism in early life. However, the underlying effects have not been fully elucidated. In this study, using the maternal−fetal model, we investigated the impact of gestational PFOS exposure on the placental structure and nutrient transport. Pregnant mice were oral gavaged with PFOS (1 or 3 μg PFOS/g body weight) from gestational day (GD) 4.5 until GD 17.5. Our data showed a significant reduction in fetal body weight at high dose exposure. There were no noticeable changes in placental weights and the relative areas of junctional and labyrinth zones among the control and exposed groups. However, a placental nutrient transport assay showed a significant reduction in maternal−fetal transport of the glucose and amino acid analogues. Western blot analysis showed a significant decrease in the expression levels of placental SNAT4 upon PFOS exposure. Moreover, in the highdose exposed group, placenta and fetal livers were found to have significantly higher corticosterone levels, a negative regulator of fetal growth. The perturbation in the placental transport function and corticosterone levels accounted for the PFOS-induced reduction of fetal body weights.
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