Culture-independent antibiotic resistance gene analyses enable broad explorations of microbial communities but often fail to link such genes to bacterial hosts and genetic contexts. This makes assessing prevalence of resistant pathogens and likelihood of further transmission or resistance evolution uncertain.
References
Larsson, D. G. J. & Flach, C.-F. Antibiotic resistance in the environment. Nat. Rev. Microbiol. 20, 257–269 (2022).
Ouyang, B. et al. Recent advances in environmental antibiotic resistance genes detection and research focus: from genes to ecosystems. Environ. Int. 191, 108989 (2024).
Knight, M. E. et al. National-scale antimicrobial resistance surveillance in wastewater: a comparative analysis of HT qPCR and metagenomic approaches. Water Res. 262, 121989 (2024).
Inda-Díaz, J. S. et al. Latent antibiotic resistance genes are abundant, diverse, and mobile in human, animal, and environmental microbiomes. Microbiome 11, 44 (2023).
Abramova, A., Karkman, A. & Bengtsson-Palme, J. Metagenomic assemblies tend to break around antibiotic resistance genes. BMC Genom. 25, 959 (2024).
Trigodet, F., Sachdeva, R., Banfield, J. F. & Eren, A. M. Troubleshooting common errors in assemblies of long-read metagenomes. Nat. Biotechnol. https://doi.org/10.1038/s41587-025-02971-8 (2026).
Mao, X. et al. Longitudinal metagenomic analysis on antibiotic resistome, mobilome, and microbiome of river ecosystems in a sub-tropical metropolitan city. Water Res. 274, 123102 (2025).
Liu, S. et al. Long-read epicPCR enhances species-level host identification of clinically relevant antibiotic resistance genes in environmental microbial communities. Environ. Int. 197, 109337 (2025).
Kent, A. G., Vill, A. C., Shi, Q., Satlin, M. J. & Brito, I. L. Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C. Nat. Commun. 11, 4379 (2020).
Zou, Y. et al. Deciphering the extracellular and intracellular antibiotic resistance genes in multiple environments reveals the persistence of extracellular ones. J. Hazard. Mater. 429, 128275 (2022).
Peek, J. et al. Environmental resistome–guided development of resistance-tolerant antibiotics. Proc. Natl. Acad. Sci. USA 122, e2504781122 (2025).
Böhm, M.-E., Razavi, M., Marathe, N. P., Flach, C.-F. & Larsson, D. G. J. Discovery of a novel integron-borne aminoglycoside resistance gene present in clinical pathogens by screening environmental bacterial communities. Microbiome 8, https://doi.org/10.1186/s40168-020-00814-z (2020).
Pei, Y. et al. ARGNet: using deep neural networks for robust identification and classification of antibiotic resistance genes from sequences. Microbiome 12, 84 (2024).
Pereira, M. B., Wallroth, M., Jonsson, V. & Kristiansson, E. Comparison of normalization methods for the analysis of metagenomic gene abundance data. BMC Genom. 19, 274 (2018).
Jonsson, V., Österlund, T., Nerman, O. & Kristiansson, E. Modelling of zero-inflation improves inference of metagenomic gene count data. Stat. Methods Med. Res. 28, 3712–3728 (2019).
Larsson, D. G. J., Flach, C.-F. & Laxminarayan, R. Sewage surveillance of antibiotic resistance holds both opportunities and challenges. Nat. Rev. Microbiol. 21, 213–214 (2022).
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D.G.J.L., C.F.F. and E.K. contributed to the disposition and content the article. D.G.J.L. drafted the manuscript and E.K., C.F.F. and D.G.J.L. worked together on revising and finalising the text.
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Larsson, D.G.J., Flach, CF. & Kristiansson, E. Antibiotic resistance gene analyses in microbial communities: challenges and opportunities. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71462-4
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DOI: https://doi.org/10.1038/s41467-026-71462-4
