Presentation Information
[3EMT-05]Physicochemical gradients govern microbiome-mediated transformation of per- and polyfluorosubstances (PFAS) in the human gut
○Amy A Rand1, Sierra Peskett1, Jillian Rohonczy1, Daniel Gregoire1 (1. Carleton University (Canada))
Keywords:
PFAS biotransformation,PFAS exposure pathways,Fluorotelomer precursors (diPAP),Gut microbiome,Metagenomics
Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industrial and consumer applications and are routinely detected in human biological matrices. PFAS exposure has been linked to adverse health outcomes, yet a key knowledge gap in PFAS toxicology is understanding how host-associated processes, particularly the gut microbiome, influence PFAS transformation and resulting toxicity.
Microbial PFAS biotransformation has been demonstrated in environmental systems, where physicochemical variables such as pH, redox conditions, and carbon availability govern transformation pathways. However, whether analogous gradients within the human gastrointestinal tract exert similar controls remains poorly understood. This is particularly important for fluorotelomer-based precursors such as 6:2 polyfluoroalkyl phosphate diester (6:2 diPAP), which can be transformed into intermediate products (e.g., fluorotelomer alcohols, FTOHs; fluorotelomer acids, FTCAs/FTUCAs) that may exhibit greater toxicity than terminal perfluoroalkyl carboxylic acids (PFCAs).
Here, we investigated how physicochemical gradients relevant to the human gut (pH, oxygen availability, and carbon source) influence microbial PFAS biotransformation and community structure. Anaerobic enrichment cultures derived from human gut microbiota were amended with perfluorooctanoic acid (PFOA) and 6:2 diPAP. Targeted PFAS analysis was coupled with 16S rRNA gene sequencing and long-read metagenomics to link metabolite profiles with taxonomic and functional shifts.
No measurable degradation of PFOA was observed, confirming its recalcitrance under the tested conditions. In contrast, 6:2 diPAP underwent significant biotransformation, with product distributions strongly influenced by pH, incubation time, and interindividual microbiome composition, but not by oxygen or carbon source. Neutral pH conditions promoted hydrolysis of diPAP to 6:2 FTOH, whereas acidic conditions suppressed transformation. Microbial community analyses showed that the same variables (pH and time) structured community composition, with enrichment of Enterobacteriaceae, Enterococcaceae, and Leuconostocaceae associated with shifts in PFAS metabolites.
Metagenomic analyses identified candidate functional genes linked to PFAS transformation. Notably, homologs of the benD gene were detected exclusively in PFAS-exposed communities and in taxa enriched under these conditions, suggesting a role for broadly conserved oxidoreductases in PFAS metabolism. These reactions are consistent with observed transformations of diPAP-derived intermediates.
Collectively, these results demonstrate that physicochemical gradients characteristic of the human gut govern microbial PFAS biotransformation pathways and community structure. This work provides new mechanistic insight into microbiome-mediated PFAS metabolism and highlights the importance of host-associated microbial processes in shaping PFAS exposure and toxicity.
Microbial PFAS biotransformation has been demonstrated in environmental systems, where physicochemical variables such as pH, redox conditions, and carbon availability govern transformation pathways. However, whether analogous gradients within the human gastrointestinal tract exert similar controls remains poorly understood. This is particularly important for fluorotelomer-based precursors such as 6:2 polyfluoroalkyl phosphate diester (6:2 diPAP), which can be transformed into intermediate products (e.g., fluorotelomer alcohols, FTOHs; fluorotelomer acids, FTCAs/FTUCAs) that may exhibit greater toxicity than terminal perfluoroalkyl carboxylic acids (PFCAs).
Here, we investigated how physicochemical gradients relevant to the human gut (pH, oxygen availability, and carbon source) influence microbial PFAS biotransformation and community structure. Anaerobic enrichment cultures derived from human gut microbiota were amended with perfluorooctanoic acid (PFOA) and 6:2 diPAP. Targeted PFAS analysis was coupled with 16S rRNA gene sequencing and long-read metagenomics to link metabolite profiles with taxonomic and functional shifts.
No measurable degradation of PFOA was observed, confirming its recalcitrance under the tested conditions. In contrast, 6:2 diPAP underwent significant biotransformation, with product distributions strongly influenced by pH, incubation time, and interindividual microbiome composition, but not by oxygen or carbon source. Neutral pH conditions promoted hydrolysis of diPAP to 6:2 FTOH, whereas acidic conditions suppressed transformation. Microbial community analyses showed that the same variables (pH and time) structured community composition, with enrichment of Enterobacteriaceae, Enterococcaceae, and Leuconostocaceae associated with shifts in PFAS metabolites.
Metagenomic analyses identified candidate functional genes linked to PFAS transformation. Notably, homologs of the benD gene were detected exclusively in PFAS-exposed communities and in taxa enriched under these conditions, suggesting a role for broadly conserved oxidoreductases in PFAS metabolism. These reactions are consistent with observed transformations of diPAP-derived intermediates.
Collectively, these results demonstrate that physicochemical gradients characteristic of the human gut govern microbial PFAS biotransformation pathways and community structure. This work provides new mechanistic insight into microbiome-mediated PFAS metabolism and highlights the importance of host-associated microbial processes in shaping PFAS exposure and toxicity.
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