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Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia

Author

Listed:
  • Lucie Bernard-Raichon

    (New York University Grossman School of Medicine)

  • Mericien Venzon

    (New York University Grossman School of Medicine
    New York University Grossman School of Medicine)

  • Jon Klein

    (Yale School of Medicine)

  • Jordan E. Axelrad

    (New York University Grossman School of Medicine)

  • Chenzhen Zhang

    (New York University Grossman School of Medicine)

  • Alexis P. Sullivan

    (New York University Grossman School of Medicine)

  • Grant A. Hussey

    (New York University Grossman School of Medicine)

  • Arnau Casanovas-Massana

    (Yale School of Public Health)

  • Maria G. Noval

    (New York University Grossman School of Medicine)

  • Ana M. Valero-Jimenez

    (New York University Grossman School of Medicine)

  • Juan Gago

    (New York University Grossman School of Medicine
    New York University Grossman School of Medicine)

  • Gregory Putzel

    (New York University Grossman School of Medicine
    New York University School of Medicine)

  • Alejandro Pironti

    (New York University Grossman School of Medicine
    New York University School of Medicine)

  • Evan Wilder

    (New York University Grossman School of Medicine)

  • Lorna E. Thorpe

    (New York University Grossman School of Medicine
    New York University School of Medicine)

  • Dan R. Littman

    (New York University Grossman School of Medicine
    Howard Hughes Medical Institute)

  • Meike Dittmann

    (New York University Grossman School of Medicine)

  • Kenneth A. Stapleford

    (New York University Grossman School of Medicine)

  • Bo Shopsin

    (New York University Grossman School of Medicine
    New York University School of Medicine
    New York University Grossman School of Medicine)

  • Victor J. Torres

    (New York University Grossman School of Medicine
    New York University School of Medicine)

  • Albert I. Ko

    (Yale School of Public Health)

  • Akiko Iwasaki

    (Yale School of Medicine
    Howard Hughes Medical Institute)

  • Ken Cadwell

    (New York University Grossman School of Medicine
    New York University Grossman School of Medicine
    New York University Grossman School of Medicine
    New York University School of Medicine)

  • Jonas Schluter

    (New York University Grossman School of Medicine
    New York University Grossman School of Medicine
    New York University School of Medicine)

Abstract

Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.

Suggested Citation

  • Lucie Bernard-Raichon & Mericien Venzon & Jon Klein & Jordan E. Axelrad & Chenzhen Zhang & Alexis P. Sullivan & Grant A. Hussey & Arnau Casanovas-Massana & Maria G. Noval & Ana M. Valero-Jimenez & Jua, 2022. "Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33395-6
    DOI: 10.1038/s41467-022-33395-6
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    References listed on IDEAS

    as
    1. Christian Gaebler & Zijun Wang & Julio C. C. Lorenzi & Frauke Muecksch & Shlomo Finkin & Minami Tokuyama & Alice Cho & Mila Jankovic & Dennis Schaefer-Babajew & Thiago Y. Oliveira & Melissa Cipolla & , 2021. "Evolution of antibody immunity to SARS-CoV-2," Nature, Nature, vol. 591(7851), pages 639-644, March.
    2. Jonas Schluter & Jonathan U. Peled & Bradford P. Taylor & Kate A. Markey & Melody Smith & Ying Taur & Rene Niehus & Anna Staffas & Anqi Dai & Emily Fontana & Luigi A. Amoretti & Roberta J. Wright & Se, 2020. "The gut microbiota is associated with immune cell dynamics in humans," Nature, Nature, vol. 588(7837), pages 303-307, December.
    3. Carolina Lucas & Patrick Wong & Jon Klein & Tiago B. R. Castro & Julio Silva & Maria Sundaram & Mallory K. Ellingson & Tianyang Mao & Ji Eun Oh & Benjamin Israelow & Takehiro Takahashi & Maria Tokuyam, 2020. "Longitudinal analyses reveal immunological misfiring in severe COVID-19," Nature, Nature, vol. 584(7821), pages 463-469, August.
    4. Ken Cadwell & John Y. Liu & Sarah L. Brown & Hiroyuki Miyoshi & Joy Loh & Jochen K. Lennerz & Chieko Kishi & Wumesh Kc & Javier A. Carrero & Steven Hunt & Christian D. Stone & Elizabeth M. Brunt & Ram, 2008. "A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells," Nature, Nature, vol. 456(7219), pages 259-263, November.
    5. Jian Zheng & Lok-Yin Roy Wong & Kun Li & Abhishek Kumar Verma & Miguel E. Ortiz & Christine Wohlford-Lenane & Mariah R. Leidinger & C. Michael Knudson & David K. Meyerholz & Paul B. McCray & Stanley P, 2021. "COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice," Nature, Nature, vol. 589(7843), pages 603-607, January.
    6. Linlin Bao & Wei Deng & Baoying Huang & Hong Gao & Jiangning Liu & Lili Ren & Qiang Wei & Pin Yu & Yanfeng Xu & Feifei Qi & Yajin Qu & Fengdi Li & Qi Lv & Wenling Wang & Jing Xue & Shuran Gong & Mingy, 2020. "The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice," Nature, Nature, vol. 583(7818), pages 830-833, July.
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