Perfluorooctanoic acid (PFOA) alters the structure of gut microbial community and colonoid transcription

Authors: Liu, Lin; Narrowe, Adrienne; Firrman, Jenni; Mahalak, Karley; Jaganatha Chetty, Venkateswari; Scarino Lemons, Johanna; BAUDOT, AURELIEN - Cryptobiotix; VAN DEN ABBEELE, PIETER - Cryptobiotix

Submitted to: Current Issues in Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/19/2026
Publication Date: 5/22/2026
Citation: Liu, L.S., Narrowe, A.B., Firrman, J., Mahalak, K.K., Jaganatha Chetty, V., Scarino Lemons, J.M., Baudot, A., Van den Abbeele, P. 2026. Perfluorooctanoic acid (PFOA) alters the structure of gut microbial community and colonoid transcription. Current Issues in Molecular Biology. https://doi.org/10.3390/cimb48060542.
DOI: https://doi.org/10.3390/cimb48060542

Interpretive Summary: The “forever chemical” perfluorooctanoic acid (PFOA) has been detected in the organs and blood of nearly all age groups across the U.S. population and poses serious health issues, and has attracted huge resources on research to resolve this crisis. Although remarkable progress has been achieved, many unknown or blind points remain, partly due to most current studies focusing on the direct effects of PFOA on cells directly, or bacteria within the gut microbiome separately. Little attention has been paid to their combinational effect. In the present study, ARS scientists in Wyndmoor, Pennsylvania, in collaboration with Belgian scientists, cultured human fecal samples with PFOA at higher dosage to capture long-term exposure effects within a short period experiment. PFOA-induced bacterial metabolites (PIBM) were used to challenge an in vitro culture of colon epithelial cells. It was found that PFOA induced a sharp shift in gut microbial structure, suppressed short chain fatty acid production; and that it is the PIBM or its combination with PFOA that strongly influenced the gut’s protective functions. In contrast, PFOA alone showed less effect under our experimental conditions. The findings highlight a new approach to explore the mechanism of PFOA-induced health issues.

Technical Abstract: Perfluorooctanoic acid (PFOA) is an environmentally persistent chemical that is recognized as a pollutant harmful to health and environments. PFOA enters the food-chain, reaching the human digestive tract. Because of this challenge to human health, PFOA’s impact on the gut microbiome is an area of active research interest. Many studies of PFOA consider its direct effects on cells of the human gastrointestinal tract (GIT), or on the members of the microbiome without combining these systems. Here we co-cultured fecal samples from healthy adults aged 25 - 70 in the in vivo SIFR® technology, adding PFOA at 10mg/L to represent the accumulated effects of long-term exposure. The supernatants from this experiment were used in human colonoid cell cultures to assess the effects of PFOA-impacted microbiomes on the cells of the GIT. Results obtained from bacterial cell counting by flow cytometer and shotgun metagenomic sequencing revealed PFOA was broadly disruptive to the microbiome and that Pseudomonadota emerged as a dominating phylum by replacing Bacteriodota and Bacillota, including key members of short chain fatty acid producing groups. The culture of colonoid cells with bacterial free supernatants showed that the combination of PFOA-impacted microbiomes had stronger effects on the cells than either untreated bacterial supernatants or PFOA alone. Reduced TEER measurements and transcriptomics indicated effects on epithelial integrity and shifts to other key processes. These results highlight the importance of integrating microbiome and human cells in studies of the effects of PFOA on human GIT health.