Commensal Bacteria in the Gut Microbiome Encode Previously Unrecognized Aromatic Hydrocarbon Catabolic Machinery

Authors

Nwike, C. P., Shittu, O. P., Andrews, M. E., Roos, E. C., Relangi, T. R., Wright, A. T.

Abstract

Introduction. Polycyclic aromatic hydrocarbon (PAH) toxicology has been primarily defined by host metabolic bioactivation to reactive intermediates. Yet ingested PAHs and biliary-delivered metabolites also enter the intestinal lumen, where they encounter the gut microbiota, an additional but understudied metabolic compartment that may alter toxicant fate. Although PAH interactions are well characterized in environmental microbes, resulting in defined enzymatic pathways for their catabolism, whether gut commensal organisms express related machinery in vivo remains poorly understood. To address this gap, we used an oral murine-exposure model of naphthalene and integrated compartment-resolved 16S rRNA gene profiling, global metaproteomics, and chemoproteomics to resolve the PAH-processing repertoire of the gut microbiota and its spatial distribution. Results. Naphthalene, a common environmental toxicant and representative PAH, elicited a compartment-dependent functional response that was most pronounced in the large intestine. Distally, exposure was associated with 2,386 differential proteins and accounted for 48.4% of metaproteomic variation, compared with 7.9% of 16S rRNA gene compositional variation. The small intestine showed a reduced proteomic response, with 994 differentially abundant proteins. Hydrocarbon catabolic markers showed a 4.8-fold distal expansion (36 to 172 proteins), including the naphthalene-catabolic nahE, proteins associated with phenylacetate, {beta}-ketoadipate, catechol/TOL, and anaerobic CoA-linked redox machinery. The small-intestinal repertoire decreased from 19 to 14 proteins, though aromatic-catabolic markers doubled, indicating a selective expansion. Critically, these homologs concentrated in Lachnospiraceae, a gut family that is prevalent in humans, primarily known for anaerobic fermentation, with no priorly described PAH-processing capacity. An uncultured Acetatifactor showed the largest hydrocarbon hits (14 to 82 protein increase), with additional contributions from Kineothrix, Eisenbergiella, and Petralouisia. Chemoproteomics, using a naphthalene-based probe, revealed enrichment of an orthogonal proteome of proteins interacting with naphthalene, capturing 171 small-intestinal and 67 large-intestinal proteins that were undetected in the global metaproteomes. Conclusions. Gut commensals express homologs of aromatic-hydrocarbon catabolic enzymes characterized in environmental microorganisms, and naphthalene amplifies this repertoire most strongly in the large intestine. The decoupling of taxonomic structure, expressed-protein representation, and probe engagement identifies a functional dimension of PAH exposure that composition-based profiling does not resolve and positions microbiome variation as a candidate modifier of PAH metabolic fate.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 12 Oct 2026.

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