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Effects of Perfluorooctanoic Acid on Gut Microbiota and Microbial Metabolites in C57BL/6J Mice.

ABSTRACT: Perfluorooctanoic acid (PFOA) represents an increasing public health concern due to its persistence in the environment and its toxic effects. The gut microbiota is known to produce various metabolites that assist the host to maintain metabolic homeostasis. However, few studies have explored the effects of PFOA on gut-microbiota-related metabolites. In the present study, male C57BL/6J mice were exposed to 1 ppm of PFOA in drinking water for four weeks and integrative analysis of the gut microbiome and metabolome was performed to reveal the health effects of PFOA. Our results showed that PFOA disturbed both the gut microbiota composition and the metabolic profiles of the feces, serum, and liver in mice. A correlation was found between Lachnospiraceae UCG004, Turicibacter, Ruminococcaceae, and different fecal metabolites. Significant alterations of gut-microbiota-related metabolites were induced by PFOA exposure, including bile acids and tryptophan metabolites such as 3-indoleacrylic acid and 3-indoleacetic acid. The findings of this study are helpful to improve the understanding of the health effects of PFOA, which might be mediated through the gut microbiota and its related metabolites.

SUBMITTER: Gao B

PROVIDER: S-EPMC10305235 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Effects of Perfluorooctanoic Acid on Gut Microbiota and Microbial Metabolites in C57BL/6J Mice.

Gao Bei B Chen Lixia L Xu Weichen W Shan Jinjun J Shen Weishou W Gao Nan N

Metabolites 20230530 6

Perfluorooctanoic acid (PFOA) represents an increasing public health concern due to its persistence in the environment and its toxic effects. The gut microbiota is known to produce various metabolites that assist the host to maintain metabolic homeostasis. However, few studies have explored the effects of PFOA on gut-microbiota-related metabolites. In the present study, male C57BL/6J mice were exposed to 1 ppm of PFOA in drinking water for four weeks and integrative analysis of the gut microbiom ...[more]

PMID: 37367865

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Project description:IntroductionNeurological diseases can stem from environmental influences such as antecedent viral infections or exposure to potential toxicants, some of which can trigger immune responses leading to neurological symptoms. Theiler's murine encephalomyelitis virus (TMEV) is used to model human neurological conditions associated with prior viral infections, with outcomes partly attributable to improper induction and regulation of the immune response. Perfluorooctanoic acid (PFOA) can alter pathologies known to influence neurological disease such as inflammatory responses, cytokine expression, and glial activation. Co-exposure to TMEV and PFOA was used to test the hypothesis that early life exposure to the potential immunotoxicant PFOA would affect immune responses so as to render TMEV-resistant C57BL/6J (B6) mice susceptible to viral-induced neurological disease.MethodsNeonate B6 mice were exposed to different treatments: non-injected, sham-infected with PBS, and TMEV-infected, with the drinking water of each group including either 70 ppt PFOA or filtered water. The effects of PFOA were evaluated by comparing neurological symptoms and changes in immune-related cytokine and chemokine production induced by viral infection. Immune responses of 23 cytokines and chemokines were measured before and after infection to determine the effects of PFOA exposure on immune response.ResultsPrior to infection, an imbalance between Th1, Th2, and Treg cytokines was observed in PFOA-exposed mice, suppressing IL-4 and IL-13 production. However, the balance was restored and characterized by an increase in pro-inflammatory cytokines in the non-infected group, and a decrease in IL-10 in the PFOA + TMEV group. Furthermore, the PFOA + TMEV group experienced an increase in seizure frequency and severity.DiscussionOverall, these findings provide insight into the complex roles of immune responses in the pathogenesis of virus-associated neurological diseases influenced by co-exposures to viruses and immunotoxic compounds.

Dataset Information

Effects of Perfluorooctanoic Acid on Gut Microbiota and Microbial Metabolites in C57BL/6J Mice.

Publications

Effects of Perfluorooctanoic Acid on Gut Microbiota and Microbial Metabolites in C57BL/6J Mice.

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