Excessive inflammatory and metabolic responses to acute SARS-CoV-2 infection are associated with a distinct gut microbiota composition
Abstract Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. In order to understand potential mechanisms and interactions that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalised COVID-19 patients and compared those with the most severe outcome (i.e. death) to those with severe non-fatal disease, or mild/moderate disease, that recovered. A distinct subset of 8 cytokines and 140 metabolites in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the faecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts. In contrast, less severe clinical outcomes associated with clusters of anti-inflammatory microbes such asBifidobacteriumorRuminococcus, short chain fatty acids (SCFAs) and IL-17A. Our study uncovered distinct mechanistic modules that link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2 and other infectious agents..
Medienart: |
Preprint |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
bioRxiv.org - (2023) vom: 11. Nov. Zur Gesamtaufnahme - year:2023 |
---|
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Albrich, Werner C. [VerfasserIn] |
---|
Links: |
Volltext [kostenfrei] |
---|
Themen: |
---|
doi: |
10.1101/2021.10.26.465865 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
XBI032901496 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | XBI032901496 | ||
003 | DE-627 | ||
005 | 20231205150301.0 | ||
007 | cr uuu---uuuuu | ||
008 | 211029s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1101/2021.10.26.465865 |2 doi | |
035 | |a (DE-627)XBI032901496 | ||
035 | |a (biorXiv)10.1101/2021.10.26.465865 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Albrich, Werner C. |e verfasserin |4 aut | |
245 | 1 | 0 | |a Excessive inflammatory and metabolic responses to acute SARS-CoV-2 infection are associated with a distinct gut microbiota composition |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
520 | |a Abstract Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. In order to understand potential mechanisms and interactions that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalised COVID-19 patients and compared those with the most severe outcome (i.e. death) to those with severe non-fatal disease, or mild/moderate disease, that recovered. A distinct subset of 8 cytokines and 140 metabolites in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the faecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts. In contrast, less severe clinical outcomes associated with clusters of anti-inflammatory microbes such asBifidobacteriumorRuminococcus, short chain fatty acids (SCFAs) and IL-17A. Our study uncovered distinct mechanistic modules that link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2 and other infectious agents. | ||
650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
700 | 1 | |a Ghosh, Tarini Shankar |4 aut | |
700 | 1 | |a Ahearn-Ford, Sinead |4 aut | |
700 | 1 | |a Mikaeloff, Flora |4 aut | |
700 | 1 | |a Lunjani, Nonhlanhla |4 aut | |
700 | 1 | |a Forde, Brian |4 aut | |
700 | 1 | |a Suh, Noémie |4 aut | |
700 | 1 | |a Kleger, Gian-Reto |4 aut | |
700 | 1 | |a Pietsch, Urs |4 aut | |
700 | 1 | |a Frischknecht, Manuel |4 aut | |
700 | 1 | |a Garzoni, Christian |4 aut | |
700 | 1 | |a Forlenza, Rossella |4 aut | |
700 | 1 | |a Horgan, Mary |4 aut | |
700 | 1 | |a Sadlier, Corinna |4 aut | |
700 | 1 | |a Negro, Tommaso Rochat |4 aut | |
700 | 1 | |a Pugin, Jérôme |4 aut | |
700 | 1 | |a Wozniak, Hannah |4 aut | |
700 | 1 | |a Cerny, Andreas |4 aut | |
700 | 1 | |a Neogi, Ujjwal |0 (orcid)0000-0002-0844-3338 |4 aut | |
700 | 1 | |a O’Toole, Paul W. |4 aut | |
700 | 1 | |a O’Mahony, Liam |0 (orcid)0000-0003-4705-3583 |4 aut | |
773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2023) vom: 11. Nov. |
773 | 1 | 8 | |g year:2023 |g day:11 |g month:11 |
856 | 4 | 0 | |u http://dx.doi.org/10.1101/2021.10.26.465865 |z kostenfrei |3 Volltext |
912 | |a GBV_XBI | ||
951 | |a AR | ||
952 | |j 2023 |b 11 |c 11 |