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Cited by 6Antibiotic Resistance in BacteriaPharmaceutical and Antibiotic Environmental ImpactsAntibiotic Use and Resistance

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Global landscape of antibiotic resistance genes in the human gut microbiome metagenome-assembled genomes

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Wang, Chenjie, Wang, Cancan, Chen, Si, Shi, Kai, Yu, Juanjuan, Ding, Yiping, Yue, Yujie, Hua, Yi, Wang, Hong, Chen, Jianwei·2025·BMC Microbiology
DOI 10.1186/s12866-025-04586-0PMC PMC12817740

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Abstract

Antibiotic resistance poses a significant threat to human health, and the human gut microbiota serves as a major reservoir of antibiotic resistance genes (ARGs). In this study, we analyzed 149,515 metagenome-assembled genomes (MAGs) from human gut microbiomes and revealed marked geographic variations in the global distribution of gut-associated ARGs. Asia exhibits the highest diversity of ARGs. At the phylum level, Pseudomonadota was identified as the predominant ARG host among pathogenic bacteria, with its pathogenic strains frequently exhibiting high levels of multidrug resistant strains harboring ≥ 5 ARGs accounting for up to 88.5% and 79.1% in Africa and South America, respectively. Campylobacterota was also recognized as a potential high-risk ARG host phylum. Horizontal gene transfer (HGT) analysis revealed that ARG transmission predominantly occurred within the same phylum, with Bacillota being the most active donor, which was likely influenced by antibiotic selection pressure. Actinomycetota and Bacteroidota were identified as major recipients of interphylum HGT, indicating their greater capacity to acquire exogenous ARGs. Through the integration of deep learning and structural calculation, we also identified a potentially novel class of β-lactam resistance genes. This study provides a comprehensive global landscape of gut-associated resistomes, underscores the critical roles of public health infrastructure, antibiotic misuse, and HGT in shaping antimicrobial resistance (AMR), and offers methodological insights for the discovery of novel ARGs. Our findings highlight urgent challenges and provide a scientific basis for developing global AMR mitigation strategies.

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Fig. 1 Global patterns of metagenome-assembled genomes (MAGs) and antibiotic resistance genes (ARGs) distribution. A Geographic distribution of MAGs. Each point represents a country; the point size indicates the number of samples, and the point color reflects the range of MAG counts. Samples without specific country information are grouped under “not provided.” B Distribution of identified ARGs across continents. The colors of the central sectors represent different ARG types. The presence of an outer ring indicates the detection of corresponding ARG subtypes, and the color of the ring denotes the continent. C Distribution of ARG types across continents, showing only the top 10 most prevalent ARG types within each continent. D Distribution of ARG subtypes across continents, showing only the top 10 most prevalent ARG subtypes within each continent
Fig. 1 Global patterns of metagenome-assembled genomes (MAGs) and antibiotic resistance genes (ARGs) distribution. A Geographic distribution of MAGs. Each point represents a country; the point size indicates the number of samples, and the point color reflects the range of MAG counts. Samples without specific country information are grouped under “not provided.” B Distribution of identified ARGs across continents. The colors of the central sectors represent different ARG types. The presence of an outer ring indicates the detection of corresponding ARG subtypes, and the color of the ring denotes the continent. C Distribution of ARG types across continents, showing only the top 10 most prevalent ARG types within each continent. D Distribution of ARG subtypes across continents, showing only the top 10 most prevalent ARG subtypes within each continentCC BY-NC-ND · PubMed Central
Fig. 2 Phylogenetic and taxonomic distribution of ARG-hosting species in Europe and Asia. A Circular phylogenetic tree showing the taxonomic classification of ARG-hosting species in Europe. From the innermost to the outermost rings, the layers represent phylum, class, order, family, genus, and species. The colors of the lines and nodes indicate different phyla. The outer symbols denote human pathogenic bacteria (HPB): circles represent non-HPB, and triangles represent HPB. The accompanying bar chart indicates the proportion of pathogenic species within each phylum in Europe. B The same representations as in panel A but for ARG-hosting species identified in Asia
Fig. 2 Phylogenetic and taxonomic distribution of ARG-hosting species in Europe and Asia. A Circular phylogenetic tree showing the taxonomic classification of ARG-hosting species in Europe. From the innermost to the outermost rings, the layers represent phylum, class, order, family, genus, and species. The colors of the lines and nodes indicate different phyla. The outer symbols denote human pathogenic bacteria (HPB): circles represent non-HPB, and triangles represent HPB. The accompanying bar chart indicates the proportion of pathogenic species within each phylum in Europe. B The same representations as in panel A but for ARG-hosting species identified in AsiaCC BY-NC-ND · PubMed Central
Fig. 3 Global distribution and ARG burden of HPB. A Phylum-level composition of HPB across different continents. B Genus-level composition of HPB across continents. C Distribution of HPB according to the number of ARG subtypes they carry on each continent. D Phylum-level distribution of ARG subtype combinations carried by HPB. The labels “2-ARGs,” “3-ARGs,” “4-ARGs,” and “ > 5-ARGs” represent combinations involving 2, 3, 4, and more than 5 ARG subtypes, respectively
Fig. 3 Global distribution and ARG burden of HPB. A Phylum-level composition of HPB across different continents. B Genus-level composition of HPB across continents. C Distribution of HPB according to the number of ARG subtypes they carry on each continent. D Phylum-level distribution of ARG subtype combinations carried by HPB. The labels “2-ARGs,” “3-ARGs,” “4-ARGs,” and “ > 5-ARGs” represent combinations involving 2, 3, 4, and more than 5 ARG subtypes, respectivelyCC BY-NC-ND · PubMed Central
Fig. 4 Intergenus horizontal transfer of ARGs. Each connected pair of nodes represents two different bacterial genera. The shape of each node indicates the bacterial phylum, whereas the color of the arrows represents the type of ARG involved in the transfer
Fig. 4 Intergenus horizontal transfer of ARGs. Each connected pair of nodes represents two different bacterial genera. The shape of each node indicates the bacterial phylum, whereas the color of the arrows represents the type of ARG involved in the transferCC BY-NC-ND · PubMed Central
Fig. 5 Structural comparison and docking analysis of Ppbp and PBP1A Proteins. A Predicted 3D structure of the candidate Ppbp protein generated by AlphaFold2. The predicted domain architecture is shown below the structure. B Predicted 3D structure of a known PBP1A protein generated by AlphaFold2. C Structural alignment of the predicted models of Ppbp and PBP1A. D Molecular docking model of PBP1A with cefotaxime. E Molecular docking model of Ppbp with cefotaxime
Fig. 5 Structural comparison and docking analysis of Ppbp and PBP1A Proteins. A Predicted 3D structure of the candidate Ppbp protein generated by AlphaFold2. The predicted domain architecture is shown below the structure. B Predicted 3D structure of a known PBP1A protein generated by AlphaFold2. C Structural alignment of the predicted models of Ppbp and PBP1A. D Molecular docking model of PBP1A with cefotaxime. E Molecular docking model of Ppbp with cefotaximeCC BY-NC-ND · PubMed Central

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References 56 · Cited by 6

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Metadata

Authors
Wang, C., Wang, C., Chen, S., Shi, K., Yu, J., Ding, Y., Yue, Y., Hua, Y., Wang, H., & Chen, J.
Affiliations
  • Bozhou University (CN)
  • Zhejiang University of Technology (CN)
Corresponding author
Chen, Jianwei
ORCID
Venue
BMC Microbiology
Publisher
Springer Science and Business Media LLC
Published
2025-12-09
Volume
26
Issue
1
Pages
33-33
ISSN
1471-2180 (ISSN-L)
DOI
10.1186/s12866-025-04586-0
PMC
PMC12817740
OpenAlex
W4417184105
Cited by
6
References
56
Citations by year
2026: 6
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Microbiology (publishedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
Funders
  • the Scientific Research Program of the Bozhou University (No.202524)
  • International Cooperation and Exchanges NSFC-ASRT (No. W2412100)
  • National Natural Science Foundation of China (No. 42276137)
  • National Key Research and Development Program of China (No. 2022YFC2804205, No. 2022YFC2804104)
Topics
  • Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
  • Physical Sciences › Environmental Science › Pollution › Pharmaceutical and Antibiotic Environmental Impacts
  • Health Sciences › Medicine › Infectious Diseases › Antibiotic Use and Resistance
Keywords
antibiotic resistance genes, human gut microbiome, metagenome-assembled genomes, horizontal gene transfer, multidrug resistance, Proteobacteria, Campylobacterota, Firmicutes, actinobacteria, Bacteroidetes, beta-lactam resistance genes, antibiotic misuse, antimicrobial resistance mitigation
MeSH terms
Gastrointestinal Microbiome, Anti-Bacterial Agents, Bacteria, Drug Resistance, Microbial, Genes, Bacterial, Humans, Phylogeny, Genome, Bacterial, Gene Transfer, Horizontal, Drug Resistance, Bacterial, Metagenome

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Wang, C., Wang, C., Chen, S., Shi, K., Yu, J., Ding, Y., Yue, Y., Hua, Y., Wang, H., & Chen, J. (2025). Global landscape of antibiotic resistance genes in the human gut microbiome metagenome-assembled genomes. BMC Microbiology. https://doi.org/10.1186/s12866-025-04586-0