TY - JOUR
T1 - Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia
AU - Yale IMPACT Research Team
AU - Bernard-Raichon, Lucie
AU - Venzon, Mericien
AU - Klein, Jon
AU - Axelrad, Jordan E.
AU - Zhang, Chenzhen
AU - Sullivan, Alexis P.
AU - Hussey, Grant A.
AU - Casanovas-Massana, Arnau
AU - Noval, Maria G.
AU - Valero-Jimenez, Ana M.
AU - Gago, Juan
AU - Putzel, Gregory
AU - Pironti, Alejandro
AU - Wilder, Evan
AU - Obaid, Abeer
AU - Lu-Culligan, Alice
AU - Nelson, Allison
AU - Brito, Anderson
AU - Nunez, Angela
AU - Martin, Anjelica
AU - Watkins, Annie
AU - Geng, Bertie
AU - Kalinich, Chaney
AU - Harden, Christina
AU - Todeasa, Codruta
AU - Jensen, Cole
AU - Kim, Daniel
AU - McDonald, David
AU - Shepard, Denise
AU - Courchaine, Edward
AU - White, Elizabeth B.
AU - Song, Eric
AU - Silva, Erin
AU - Kudo, Eriko
AU - DeIuliis, Giuseppe
AU - Rahming, Harold
AU - Park, Hong Jai
AU - Matos, Irene
AU - Nouws, Jessica
AU - Valdez, Jordan
AU - Fauver, Joseph
AU - Lim, Joseph
AU - Rose, Kadi Ann
AU - Anastasio, Kelly
AU - Brower, Kristina
AU - Glick, Laura
AU - Sharma, Lokesh
AU - Sewanan, Lorenzo
AU - Knaggs, Lynda
AU - Thorpe, Lorna E.
N1 - Funding Information:
We thank René Niehus for helpful discussions on the implementation of the various Bayesian analyses. We thank the NYU Langone’s Genome Technology Center, the NYU Langone’s Experimental Pathology Research Laboratory and the NYU Langone’s Microscopy Laboratory supported in part by NYU Langone Health’s Laura and Isaac Perlmutter Cancer Center Support (grant P30CA016087) from the National Cancer Institute Langone and by the NIH S10 OD021747 grant for use of their instruments and technical assistance. We also thank the Office of Science & Research High-Containment Laboratories at NYU Grossman School of Medicine for their support in the completion of this research. This work was in part funded by NYU Grossman School of Medicine startup research funds and NIH/NIAID DP2 award (DP2AI164318) to J.S., NIH/NCI R01CA269617 to Catherine Diefenbach and J.S., and the Yale School of Public Health and the Beatrice Kleinberg Neuwirth Fund, as well as NIH grants to K.C. (DK093668, AI121244, HL123340, AI130945, AI140754, DK124336), a Faculty Scholar grant from the Howard Hughes Medical Institute (K.C.), Crohn’s & Colitis Foundation (K.C.), Kenneth Rainin Foundation (K.C.), Judith & Stewart Colton Center of Autoimmunity (K.C.). Further funding was provided by grants from the NIH/NIAID to M.D. (R01AI143639 and R21AI139374), from the NIH to M.V. (5T32AI100853), by Jan Vilcek/David Goldfarb Fellowship Endowment Funds to A.M.V.J., by The G. Harold and Leila Y. Mathers Charitable Foundation to M.D., and by NYU Grossman School of Medicine Startup funds to M.D. and K.A.S., and the NYU Grossman School of Medicine COVID-19 seed research funds to V.J.T., and funds from the NYU Langone Health Antimicrobial-Resistant Pathogens Program to B.S., A.P., and V.J.T. K.C. and V.J.T. also receive support from NIH grant OT2HL161847. M.N. was supported by the American Heart Association Postdoctoral Fellowship 19-A0-00-1003686. IMPACT received support from the Yale COVID-19 Research Resource Fund. AI and DRL are Investigators of the Howard Hughes Medical Institute. A.I.K. received support from the Beatrice Kleinberg Neuwirth Fund, Bristol Meyers Squibb Foundation, and COVID-19 research funds from the Yale Schools of Public Health and Medicine.
Funding Information:
We thank René Niehus for helpful discussions on the implementation of the various Bayesian analyses. We thank the NYU Langone’s Genome Technology Center, the NYU Langone’s Experimental Pathology Research Laboratory and the NYU Langone’s Microscopy Laboratory supported in part by NYU Langone Health’s Laura and Isaac Perlmutter Cancer Center Support (grant P30CA016087) from the National Cancer Institute Langone and by the NIH S10 OD021747 grant for use of their instruments and technical assistance. We also thank the Office of Science & Research High-Containment Laboratories at NYU Grossman School of Medicine for their support in the completion of this research. This work was in part funded by NYU Grossman School of Medicine startup research funds and NIH/NIAID DP2 award (DP2AI164318) to J.S., NIH/NCI R01CA269617 to Catherine Diefenbach and J.S., and the Yale School of Public Health and the Beatrice Kleinberg Neuwirth Fund, as well as NIH grants to K.C. (DK093668, AI121244, HL123340, AI130945, AI140754, DK124336), a Faculty Scholar grant from the Howard Hughes Medical Institute (K.C.), Crohn’s & Colitis Foundation (K.C.), Kenneth Rainin Foundation (K.C.), Judith & Stewart Colton Center of Autoimmunity (K.C.). Further funding was provided by grants from the NIH/NIAID to M.D. (R01AI143639 and R21AI139374), from the NIH to M.V. (5T32AI100853), by Jan Vilcek/David Goldfarb Fellowship Endowment Funds to A.M.V.J., by The G. Harold and Leila Y. Mathers Charitable Foundation to M.D., and by NYU Grossman School of Medicine Startup funds to M.D. and K.A.S., and the NYU Grossman School of Medicine COVID-19 seed research funds to V.J.T., and funds from the NYU Langone Health Antimicrobial-Resistant Pathogens Program to B.S., A.P., and V.J.T. K.C. and V.J.T. also receive support from NIH grant OT2HL161847. M.N. was supported by the American Heart Association Postdoctoral Fellowship 19-A0-00-1003686. IMPACT received support from the Yale COVID-19 Research Resource Fund. AI and DRL are Investigators of the Howard Hughes Medical Institute. A.I.K. received support from the Beatrice Kleinberg Neuwirth Fund, Bristol Meyers Squibb Foundation, and COVID-19 research funds from the Yale Schools of Public Health and Medicine.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-33395-6
DO - 10.1038/s41467-022-33395-6
M3 - Article
C2 - 36319618
AN - SCOPUS:85141216627
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 5926
ER -