Gut Microbiome-Host Metabolome Homeostasis upon Exposure to PFOS and GenX in Male Mice

Faizan Rashid; Veronika Dubinkina; Saeed Ahmad; Sergei Maslov; Joseph Maria Kumar Irudayaraj

doi:10.3390/toxics11030281

Gut Microbiome-Host Metabolome Homeostasis upon Exposure to PFOS and GenX in Male Mice

Toxics. 2023 Mar 19;11(3):281. doi: 10.3390/toxics11030281.

Authors

Faizan Rashid^{1

2}, Veronika Dubinkina^{3

4}, Saeed Ahmad^{1

3}, Sergei Maslov^{3

4}, Joseph Maria Kumar Irudayaraj^{1

2

3

5

6}

Affiliations

¹ Biomedical Research Center, Mills Breast Cancer Institute, Carle Foundation Hospital, Urbana, IL 61801, USA.
² Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
³ Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
⁴ Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
⁵ Micro and Nanotechnology Laboratory, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
⁶ Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.

Abstract

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.

Keywords: GenX; PFOS; colon; gut microbiota–host metabolome homeostasis; metabolome; microbiome; small intestine.

Grants and funding

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.