Exploring gut-lung axis crosstalk in SARS-CoV-2 infection : Insights from a hACE2 mouse model
© 2024 Wiley Periodicals LLC..
Based on the forefront of clinical research, there is a growing recognition that the gut microbiota, which plays a pivotal role in shaping both the innate and adaptive immune systems, may significantly contribute to the pathogenesis of coronavirus disease 2019 (COVID-19). Although an association between altered gut microbiota and COVID-19 pathogenesis has been established, the causative mechanisms remain incompletely understood. Additionally, the validation of the precise functional alterations within the gut microbiota relevant to COVID-19 pathogenesis has been limited by a scarcity of suitable animal experimental models. In the present investigation, we employed a newly developed humanized ACE2 knock-in (hACE2-KI) mouse model, capable of recapitulating critical aspects of pulmonary and intestinal infection, to explore the modifications in the gut microbiota following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Examination of fecal samples using 16S rRNA gene profiling unveiled a notable reduction in species richness and conspicuous alterations in microbiota composition at 6 days postinfection (dpi). These alterations were primarily characterized by a decline in beneficial bacterial species and an escalation in certain opportunistic pathogens. Moreover, our analysis entailed a correlation study between the gut microbiota and plasma cytokine concentrations, revealing the potential involvement of the Lachnospiraceae_NK4A136_group and unclassified_f_Lachnospiraceae genera in attenuating hyperinflammatory responses triggered by the infection. Furthermore, integration of gut microbiota data with RNA-seq analysis results suggested that the increased presence of Staphylococcus in fecal samples may signify the potential for bacterial coinfection in lung tissues via gut translocation. In summary, our hACE2-KI mouse model effectively recapitulated the observed alterations in the gut microbiota during SARS-CoV-2 infection. This model presents a valuable tool for elucidating gut microbiota-targeted strategies aimed at mitigating COVID-19.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:96 |
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| Enthalten in: |
Journal of medical virology - 96(2024), 1 vom: 14. Jan., Seite e29336 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Yu [VerfasserIn] |
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| Links: |
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| Themen: |
COVID-19 |
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| Anmerkungen: |
Date Completed 10.01.2024 Date Revised 14.02.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/jmv.29336 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Based on the forefront of clinical research, there is a growing recognition that the gut microbiota, which plays a pivotal role in shaping both the innate and adaptive immune systems, may significantly contribute to the pathogenesis of coronavirus disease 2019 (COVID-19). Although an association between altered gut microbiota and COVID-19 pathogenesis has been established, the causative mechanisms remain incompletely understood. Additionally, the validation of the precise functional alterations within the gut microbiota relevant to COVID-19 pathogenesis has been limited by a scarcity of suitable animal experimental models. In the present investigation, we employed a newly developed humanized ACE2 knock-in (hACE2-KI) mouse model, capable of recapitulating critical aspects of pulmonary and intestinal infection, to explore the modifications in the gut microbiota following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Examination of fecal samples using 16S rRNA gene profiling unveiled a notable reduction in species richness and conspicuous alterations in microbiota composition at 6 days postinfection (dpi). These alterations were primarily characterized by a decline in beneficial bacterial species and an escalation in certain opportunistic pathogens. Moreover, our analysis entailed a correlation study between the gut microbiota and plasma cytokine concentrations, revealing the potential involvement of the Lachnospiraceae_NK4A136_group and unclassified_f_Lachnospiraceae genera in attenuating hyperinflammatory responses triggered by the infection. Furthermore, integration of gut microbiota data with RNA-seq analysis results suggested that the increased presence of Staphylococcus in fecal samples may signify the potential for bacterial coinfection in lung tissues via gut translocation. In summary, our hACE2-KI mouse model effectively recapitulated the observed alterations in the gut microbiota during SARS-CoV-2 infection. This model presents a valuable tool for elucidating gut microbiota-targeted strategies aimed at mitigating COVID-19 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a gut dysbiosis | |
| 650 | 4 | |a gut microbiota | |
| 650 | 4 | |a hACE2 mouse model | |
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| 700 | 1 | |a Ma, Yifang |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Weiyang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xiaoyang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ruixuan |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yuwei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jintao |e verfasserin |4 aut | |
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