Sub‑chronic PFOA exposure at human‑relevant increasing doses in male mice: Role of stress‑induced gut barrier disruption in shaping intestinal and hepatic responses under high-dose conditions
Abstract
In humans, dietary intake is thought to be the main route of exposure to perfluorooctanoic acid (PFOA). The gastrointestinal tract is the primary entry point for this highly persistent and bioaccumulative environmental pollutant; however, its fate and effects within the digestive system remain largely unknown. Combining biology-based approaches with mass-spectrometry chemical imaging, our study investigated the impact of 90-day oral exposure to PFOA at a dose relevant to highly exposed human populations on an intact versus stress-impaired gut barrier in adult male mice. A ten-day corticosterone treatment was used to develop an intestinal hyperpermeability model. Unlike this model, exposure to PFOA at 15,000 ng/kg body weight/day did not impair gut barrier integrity nor gut microbiota composition or metabolic functions, when considered separately. However, integrating the 16S metabarcoding and metabolomic datasets revealed subtle yet significant effects of PFOA exposure including a decrease in Lactobacillus, Orodobacter and Ligilactobacillus, as well as changes in short-chain fatty acids (acetate, propionate) and cholic acid. The impact on the liver was determined by simultaneously assessing functional enzymatic activity and mRNA expression of xenobiotic metabolising enzymes. Notably, CYP2C37 activity was inhibited by PFOA exposure under both control and corticosterone conditions. Hepatic homeostasis was also assessed, revealing changes at the transcriptional level in cholesterol transport and biosynthesis pathways, though with no major downstream functional effects. PFOA was found to accumulate in the hepatocyte cytosol as well as in intestinal goblet cells. This work, conducted at human-relevant doses, paves the way for future health risk assessments of PFOA and other substances belonging to the extremely large PFAS family.
Related
- Disruption of Mitochondrial Bioenergetics Links Oxidative Stress-Mediated Apoptosis to Hepatorenal Injury Following Sub-Chronic Exposure to Titanium Dioxide Nanoparticles.
- From Food Structure to L-Cell Exposure: How Processing and Digestion Shape Endogenous GLP-1 Responses
- Microplastic Release from Drinking Water Contact Materials: Material-Specific Responses to Chlorination and Implications for Consumer Exposure
- Assessment of grape exposure and UV radiation effects on rotundone in Vitis vinifera L. cv. Tardif under warm and dry vintage conditions
- Volatile Metabolic Signatures Reveal Early Pulmonary Responses to PFAS Exposure
BibTeX
@article{bodon2026subchronic,
title = {{Sub‑chronic PFOA exposure at human‑relevant increasing doses in male mice: Role of stress‑induced gut barrier disruption in shaping intestinal and hepatic responses under high-dose conditions}},
author = {Anaïs Bodon and Rémi Dagès and Valérie Bézirard and Elodie Person and Charlotte B.A. Stoffels and Núria Solà Tapias and Sandrine Bruel and Cécile Canlet and Marie Tremblay-Franco and Bruno Sovran and Laila Mselli-Lakhal and Jean-Nicolas Audinot and Nicolas Cabaton and Hervé Robert and Muriel Mercier-Bonin},
journal = {Environment International},
year = {2026},
month = oct,
doi = {10.1016/j.envint.2026.110551},
url = {https://hal.science/hal-05784126v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sub‑chronic PFOA exposure at human‑relevant increasing doses in male mice: Role of stress‑induced gut barrier disruption in shaping intestinal and hepatic responses under high-dose conditions
AU - Anaïs Bodon
AU - Rémi Dagès
AU - Valérie Bézirard
AU - Elodie Person
AU - Charlotte B.A. Stoffels
AU - Núria Solà Tapias
AU - Sandrine Bruel
AU - Cécile Canlet
AU - Marie Tremblay-Franco
AU - Bruno Sovran
AU - Laila Mselli-Lakhal
AU - Jean-Nicolas Audinot
AU - Nicolas Cabaton
AU - Hervé Robert
AU - Muriel Mercier-Bonin
PY - 2026
DA - 2026/10/07
JO - Environment International
DO - 10.1016/j.envint.2026.110551
UR - https://hal.science/hal-05784126v1
AB - In humans, dietary intake is thought to be the main route of exposure to perfluorooctanoic acid (PFOA). The gastrointestinal tract is the primary entry point for this highly persistent and bioaccumulative environmental pollutant; however, its fate and effects within the digestive system remain largely unknown. Combining biology-based approaches with mass-spectrometry chemical imaging, our study investigated the impact of 90-day oral exposure to PFOA at a dose relevant to highly exposed human populations on an intact versus stress-impaired gut barrier in adult male mice. A ten-day corticosterone treatment was used to develop an intestinal hyperpermeability model. Unlike this model, exposure to PFOA at 15,000 ng/kg body weight/day did not impair gut barrier integrity nor gut microbiota composition or metabolic functions, when considered separately. However, integrating the 16S metabarcoding and metabolomic datasets revealed subtle yet significant effects of PFOA exposure including a decrease in Lactobacillus, Orodobacter and Ligilactobacillus, as well as changes in short-chain fatty acids (acetate, propionate) and cholic acid. The impact on the liver was determined by simultaneously assessing functional enzymatic activity and mRNA expression of xenobiotic metabolising enzymes. Notably, CYP2C37 activity was inhibited by PFOA exposure under both control and corticosterone conditions. Hepatic homeostasis was also assessed, revealing changes at the transcriptional level in cholesterol transport and biosynthesis pathways, though with no major downstream functional effects. PFOA was found to accumulate in the hepatocyte cytosol as well as in intestinal goblet cells. This work, conducted at human-relevant doses, paves the way for future health risk assessments of PFOA and other substances belonging to the extremely large PFAS family.
SN - 0160-4120
ER -