TY - JOUR
T1 - Gut Microbiome-Host Metabolome Homeostasis upon Exposure to PFOS and GenX in Male Mice
AU - Rashid, Faizan
AU - Dubinkina, Veronika
AU - Ahmad, Saeed
AU - Maslov, Sergei
AU - Irudayaraj, Joseph Maria Kumar
N1 - Funding Information:
This research was funded by the Startup Funds and the Planning Grant Award from the Cancer Center at Illinois at the University of Illinois at Urbana-Champaign.
Funding Information:
The authors would like to acknowledge support from Jodi Flaws and Daryl Meling from the Department of Comparative Biosciences and Tauseef Shah from the Department of Molecular and Integrative Physiology in sample collection, as well the support from the DNA Services and the Metabolomics Facility in the Roy J. Carver Biotechnology Center at the University of Illinois Urbana-Champaign.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/3
Y1 - 2023/3
N2 - Alterations of the normal gut microbiota can cause various human health concerns. Environmental chemicals are one of the drivers of such disturbances. The aim of our study was to examine the effects of exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS)—specifically, perfluorooctane sulfonate (PFOS) and 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy) propanoic acid (GenX)—on the microbiome of the small intestine and colon, as well as on liver metabolism. Male CD-1 mice were exposed to PFOS and GenX in different concentrations and compared to controls. GenX and PFOS were found to have different effects on the bacterial community in both the small intestine and colon based on 16S rRNA profiles. High GenX doses predominantly led to increases in the abundance of Clostridium sensu stricto, Alistipes, and Ruminococcus, while PFOS generally altered Lactobacillus, Limosilactobacillus, Parabacteroides, Staphylococcus, and Ligilactobacillus. These treatments were associated with alterations in several important microbial metabolic pathways in both the small intestine and colon. Untargeted LC-MS/MS metabolomic analysis of the liver, small intestine, and colon yielded a set of compounds significantly altered by PFOS and GenX. In the liver, these metabolites were associated with the important host metabolic pathways implicated in the synthesis of lipids, steroidogenesis, and in the metabolism of amino acids, nitrogen, and bile acids. Collectively, our results suggest that PFOS and GenX exposure can cause major perturbations in the gastrointestinal tract, aggravating microbiome toxicity, hepatotoxicity, and metabolic disorders.
AB - Alterations of the normal gut microbiota can cause various human health concerns. Environmental chemicals are one of the drivers of such disturbances. The aim of our study was to examine the effects of exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS)—specifically, perfluorooctane sulfonate (PFOS) and 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy) propanoic acid (GenX)—on the microbiome of the small intestine and colon, as well as on liver metabolism. Male CD-1 mice were exposed to PFOS and GenX in different concentrations and compared to controls. GenX and PFOS were found to have different effects on the bacterial community in both the small intestine and colon based on 16S rRNA profiles. High GenX doses predominantly led to increases in the abundance of Clostridium sensu stricto, Alistipes, and Ruminococcus, while PFOS generally altered Lactobacillus, Limosilactobacillus, Parabacteroides, Staphylococcus, and Ligilactobacillus. These treatments were associated with alterations in several important microbial metabolic pathways in both the small intestine and colon. Untargeted LC-MS/MS metabolomic analysis of the liver, small intestine, and colon yielded a set of compounds significantly altered by PFOS and GenX. In the liver, these metabolites were associated with the important host metabolic pathways implicated in the synthesis of lipids, steroidogenesis, and in the metabolism of amino acids, nitrogen, and bile acids. Collectively, our results suggest that PFOS and GenX exposure can cause major perturbations in the gastrointestinal tract, aggravating microbiome toxicity, hepatotoxicity, and metabolic disorders.
KW - colon
KW - GenX
KW - gut microbiota–host metabolome homeostasis
KW - metabolome
KW - microbiome
KW - PFOS
KW - small intestine
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U2 - 10.3390/toxics11030281
DO - 10.3390/toxics11030281
M3 - Article
C2 - 36977046
SN - 2305-6304
VL - 11
JO - Toxics
JF - Toxics
IS - 3
M1 - 281
ER -