Laccase-mediated biotransformation potential for fluorinated compounds by geographically diverse human gut microbiota
4 affiliations
- 1Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
- 2Department of Environmental Microbiology, Swiss Federal Institute of Aquatic Science and Technology, Dübendorf, Switzerland
- 3Department of Chemistry and Biochemistry, Bethel University, St. Paul, Minnesota, USA
- 4Institute of Biogeochemistry and Pollutant Dynamics, Department of Environmental Systems Science, ETH Zurich, Zurich, Switzerland
Abstract
The growing prevalence of synthetic organofluorine substances in agrochemicals, food packaging, and consumer products has led to increasing gastrointestinal exposure, with potential consequences for human health. Despite the extreme stability of fluorinated compounds, several microbial pathways for their transformation are known, including those involving laccases, a type of multicopper oxidase. However, the functionality of laccases in the gut microbiome, a natural contact point between food-associated chemicals and microbial biotransformation pathways, is poorly defined. Through a multi-study analysis of 1,578 human gut metagenomes spanning a global gradient from hunter-gatherer societies to industrialized urban populations, we found that laccase-coding gene homologs are widely distributed in the human gut microbiome. We identified a significant association between both the abundance and phylogenetic diversity of laccase homologs and the degree of urbanization. As human gut microbial laccase activity has not been experimentally demonstrated, eight gut metagenome-derived laccases were heterologously expressed and screened for activity with a redox mediator system. Six of the eight laccases demonstrated activity. One of these gut microbial laccases, derived from Veillonella, and three previously characterized laccases were then tested for their capacity to deplete 11 different food-associated chemicals. The Veillonella laccase depleted the agrochemicals cyflumetofen and fluazinam, as well as the industrial chemical bisphenol AF, to a lesser extent. By linking global gut metagenomes with activity assays, this work demonstrates the untapped potential of mining human gut metagenomes for laccases and other microbial enzymes that can actively modify various agricultural and industrial chemicals.
IMPORTANCE: As adverse effects of fluorinated compounds on human health are emerging, the responsible enzymes from the human gut microbiome of geographically diverse human cohorts mediating interactions with fluorinated compounds in the gastrointestinal tract remain poorly characterized. In a multi-study analysis of publicly available microbiome sequencing data, we linked the abundance, diversity, and phylogeny of laccases within the gut microbiome to the degree of urbanization of human cohorts and experimentally demonstrated the ability of these laccases to deplete a range of food-associated fluorochemicals. Another significant contribution of our study is in the integration of rural catchment areas as a quantitative metric of urbanization in gut microbiome metagenomics and enzyme activity surveys.
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BibTeX
@article{scharer2026laccasemediated,
title = {{Laccase-mediated biotransformation potential for fluorinated compounds by geographically diverse human gut microbiota}},
author = {Milo R. Schärer and Yaochun Yu and Aaron Grawe and James K. Christenson and Serina L. Robinson and Nicholas A. Bokulich},
journal = {mBio},
year = {2026},
month = aug,
doi = {10.1128/mbio.01026-26},
url = {https://doi.org/10.1128/mbio.01026-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Laccase-mediated biotransformation potential for fluorinated compounds by geographically diverse human gut microbiota
AU - Milo R. Schärer
AU - Yaochun Yu
AU - Aaron Grawe
AU - James K. Christenson
AU - Serina L. Robinson
AU - Nicholas A. Bokulich
PY - 2026
DA - 2026/08/31
JO - mBio
DO - 10.1128/mbio.01026-26
UR - https://doi.org/10.1128/mbio.01026-26
AB - The growing prevalence of synthetic organofluorine substances in agrochemicals, food packaging, and consumer products has led to increasing gastrointestinal exposure, with potential consequences for human health. Despite the extreme stability of fluorinated compounds, several microbial pathways for their transformation are known, including those involving laccases, a type of multicopper oxidase. However, the functionality of laccases in the gut microbiome, a natural contact point between food-associated chemicals and microbial biotransformation pathways, is poorly defined. Through a multi-study analysis of 1,578 human gut metagenomes spanning a global gradient from hunter-gatherer societies to industrialized urban populations, we found that laccase-coding gene homologs are widely distributed in the human gut microbiome. We identified a significant association between both the abundance and phylogenetic diversity of laccase homologs and the degree of urbanization. As human gut microbial laccase activity has not been experimentally demonstrated, eight gut metagenome-derived laccases were heterologously expressed and screened for activity with a redox mediator system. Six of the eight laccases demonstrated activity. One of these gut microbial laccases, derived from Veillonella, and three previously characterized laccases were then tested for their capacity to deplete 11 different food-associated chemicals. The Veillonella laccase depleted the agrochemicals cyflumetofen and fluazinam, as well as the industrial chemical bisphenol AF, to a lesser extent. By linking global gut metagenomes with activity assays, this work demonstrates the untapped potential of mining human gut metagenomes for laccases and other microbial enzymes that can actively modify various agricultural and industrial chemicals. IMPORTANCE: As adverse effects of fluorinated compounds on human health are emerging, the responsible enzymes from the human gut microbiome of geographically diverse human cohorts mediating interactions with fluorinated compounds in the gastrointestinal tract remain poorly characterized. In a multi-study analysis of publicly available microbiome sequencing data, we linked the abundance, diversity, and phylogeny of laccases within the gut microbiome to the degree of urbanization of human cohorts and experimentally demonstrated the ability of these laccases to deplete a range of food-associated fluorochemicals. Another significant contribution of our study is in the integration of rural catchment areas as a quantitative metric of urbanization in gut microbiome metagenomics and enzyme activity surveys.
SN - 2150-7511
ER -