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Metformin drives the antibiotic resistome in activated sludge by reshaping microbial communities and promoting horizontal gene transfer.

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Title: Metformin drives the antibiotic resistome in activated sludge by reshaping microbial communities and promoting horizontal gene transfer.
Authors: Yi, Jiaming1 (AUTHOR), Li, Zhengtao1 (AUTHOR), Han, Xuezhu1 (AUTHOR), Li, Jingpeng1 (AUTHOR), Liu, Haotian1 (AUTHOR), Zhu, Lin1 (AUTHOR) lzhu@zjgsu.edu.cn, Wang, Meizhen1 (AUTHOR) wmz@zjgsu.edu.cn
Source: Journal of Hazardous Materials. Jan2026, Vol. 501, pN.PAG-N.PAG. 1p.
Subjects: Metformin, Drug resistance in bacteria, Wastewater treatment, Activated sludge process, Horizontal gene transfer, Pathogenic bacteria, Metagenomics, Microbial communities
Abstract: Aerobic granular sludge (AGS) serves as a major reservoir and dissemination hotspot for human bacterial pathogens (HBPs) and antibiotic resistance genes (ARGs). Metformin (MET) as an emerging contaminant, which exacerbates antibiotic resistance and poses a problem for the stable operation of the activated sludge process in wastewater treatment plants. However, the specific mechanisms underlying the effects of MET stress on microbial communities and ARGs propagation in activated sludge remain poorly understood. In this study, we employed metagenomic analysis to investigate the effects of MET exposure, under a composite antibiotic background, on microbial community dynamics and resistome profiles in AGS systems and interpreted these effects from the perspectives of energy metabolism and community competition. Our findings demonstrate that MET exposure significantly enriched HBPs and multidrug resistance-related ARGs. Co-occurrence network analysis further identified that, among all sludge samples, 27 high-risk HBPs were strongly correlated with ARGs, virulence factor genes, and mobile genetic elements. Additionally, MET was also found to enhance ATP production in specific HBPs, conferring a competitive edge that facilitates ARG accumulation. Furthermore, the natural transformation and conjugation experiments further demonstrated the key role of MET in promoting horizontal gene transfer. In summary, this study underscores the role of MET in exacerbating the ecological risk of antibiotic resistance in AGS systems by concurrently enriching pathogenic bacteria and facilitating the horizontal transfer of ARGs, thereby highlighting the potential environmental impacts of MET as a pervasive contaminant on the propagation of resistance within wastewater treatment ecosystems. [Display omitted] • MET reshapes microbial community structure and functions in AGS systems. • MET amplifies the antibiotic resistome in AGS systems. • MET-driven energy-metabolic coupling promotes high-risk HBPs proliferation. • MET promotes ARGs transfer through improved transformation and conjugation efficiency. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Hazardous Materials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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Header DbId: egs
DbLabel: Engineering Source
An: 190885282
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
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Items – Name: Title
  Label: Title
  Group: Ti
  Data: Metformin drives the antibiotic resistome in activated sludge by reshaping microbial communities and promoting horizontal gene transfer.
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  Data: <searchLink fieldCode="AR" term="%22Yi%2C+Jiaming%22">Yi, Jiaming</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Zhengtao%22">Li, Zhengtao</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Han%2C+Xuezhu%22">Han, Xuezhu</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Jingpeng%22">Li, Jingpeng</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Haotian%22">Liu, Haotian</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhu%2C+Lin%22">Zhu, Lin</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> lzhu@zjgsu.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Wang%2C+Meizhen%22">Wang, Meizhen</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> wmz@zjgsu.edu.cn</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Hazardous+Materials%22">Journal of Hazardous Materials</searchLink>. Jan2026, Vol. 501, pN.PAG-N.PAG. 1p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Metformin%22">Metformin</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+resistance+in+bacteria%22">Drug resistance in bacteria</searchLink><br /><searchLink fieldCode="DE" term="%22Wastewater+treatment%22">Wastewater treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Activated+sludge+process%22">Activated sludge process</searchLink><br /><searchLink fieldCode="DE" term="%22Horizontal+gene+transfer%22">Horizontal gene transfer</searchLink><br /><searchLink fieldCode="DE" term="%22Pathogenic+bacteria%22">Pathogenic bacteria</searchLink><br /><searchLink fieldCode="DE" term="%22Metagenomics%22">Metagenomics</searchLink><br /><searchLink fieldCode="DE" term="%22Microbial+communities%22">Microbial communities</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Aerobic granular sludge (AGS) serves as a major reservoir and dissemination hotspot for human bacterial pathogens (HBPs) and antibiotic resistance genes (ARGs). Metformin (MET) as an emerging contaminant, which exacerbates antibiotic resistance and poses a problem for the stable operation of the activated sludge process in wastewater treatment plants. However, the specific mechanisms underlying the effects of MET stress on microbial communities and ARGs propagation in activated sludge remain poorly understood. In this study, we employed metagenomic analysis to investigate the effects of MET exposure, under a composite antibiotic background, on microbial community dynamics and resistome profiles in AGS systems and interpreted these effects from the perspectives of energy metabolism and community competition. Our findings demonstrate that MET exposure significantly enriched HBPs and multidrug resistance-related ARGs. Co-occurrence network analysis further identified that, among all sludge samples, 27 high-risk HBPs were strongly correlated with ARGs, virulence factor genes, and mobile genetic elements. Additionally, MET was also found to enhance ATP production in specific HBPs, conferring a competitive edge that facilitates ARG accumulation. Furthermore, the natural transformation and conjugation experiments further demonstrated the key role of MET in promoting horizontal gene transfer. In summary, this study underscores the role of MET in exacerbating the ecological risk of antibiotic resistance in AGS systems by concurrently enriching pathogenic bacteria and facilitating the horizontal transfer of ARGs, thereby highlighting the potential environmental impacts of MET as a pervasive contaminant on the propagation of resistance within wastewater treatment ecosystems. [Display omitted] • MET reshapes microbial community structure and functions in AGS systems. • MET amplifies the antibiotic resistome in AGS systems. • MET-driven energy-metabolic coupling promotes high-risk HBPs proliferation. • MET promotes ARGs transfer through improved transformation and conjugation efficiency. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Hazardous Materials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/j.jhazmat.2025.140887
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 1
        StartPage: N.PAG
    Subjects:
      – SubjectFull: Metformin
        Type: general
      – SubjectFull: Drug resistance in bacteria
        Type: general
      – SubjectFull: Wastewater treatment
        Type: general
      – SubjectFull: Activated sludge process
        Type: general
      – SubjectFull: Horizontal gene transfer
        Type: general
      – SubjectFull: Pathogenic bacteria
        Type: general
      – SubjectFull: Metagenomics
        Type: general
      – SubjectFull: Microbial communities
        Type: general
    Titles:
      – TitleFull: Metformin drives the antibiotic resistome in activated sludge by reshaping microbial communities and promoting horizontal gene transfer.
        Type: main
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          Name:
            NameFull: Yi, Jiaming
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            NameFull: Li, Zhengtao
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            NameFull: Han, Xuezhu
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            NameFull: Li, Jingpeng
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            NameFull: Liu, Haotian
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            NameFull: Zhu, Lin
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            NameFull: Wang, Meizhen
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          Dates:
            – D: 01
              M: 01
              Text: Jan2026
              Type: published
              Y: 2026
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            – Type: issn-print
              Value: 03043894
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              Value: 501
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            – TitleFull: Journal of Hazardous Materials
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