 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 02, 2022 |
| Title |
Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection [16S rRNA] |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
The gut microbiome is intricately coupled with immune regulation and metabolism, but its role in Coronavirus Disease 2019 (COVID-19) is not fully understood. Severe and fatal COVID-19 is characterized by poor anti-viral immunity and hypercoagulation, particularly in males. Via 16S sequencing of antibiotic-treated mice, we found that Clostridia species protect mammalian hosts from SARS-CoV-2 intranasal infection, both locally and systemically, via production of short-chain fatty acids (SCFAs). SCFAs reduced viral burdens in the airways and intestines by downregulating the SARS-CoV-2 entry receptor, angiotensin-converting enzyme 2 (ACE2), and enhancing adaptive immunity in male animals. In order to identify other mechanisms by which SCFAs influence the outcome of SARS-CoV-2 infection, we performed RNA-seq on lungs from male GF mice given control or SCFA water for two weeks. We identified a novel role for the gut microbiome in regulating systemic coagulation response by limiting megakaryocyte proliferation and platelet turnover via the Sh2b3-Mpl axis. Taken together, our findings have unraveled novel functions of SCFAs and fiber-fermenting gut bacteria that might be leveraged as pan-coronavirus therapeutics to dampen viral entry and hypercoagulation and promote adaptive anti-viral immunity.
|
| |
|
| Overall design |
8-week-old male C57BL/6 mice were given normal drinking water (n=2) or drinking water containing antibiotics (gentamicin or vancomycin; n=5 each) for two weeks. DNA was extracted from fecal pellets and the V4 region of the 16S rRNA gene was amplified using universal primers and sequenced on an Illumina MiSeq sequencer.
|
| |
|
| Contributor(s) |
Brown JA, Sanidad KZ, Lucotti S, Ananthanarayanan A, Basu S, Chen J, Shan M, Amir M, Schmidt F, Weisblum Y, Cioffi M, Li T, Rowdo FM, Martin ML, Guo C, Lyssiotis C, Layden BT, Dannenberg AJ, Bieniasz PD, Lee B, Inohara N, Matei I, Zeng MY |
| Citation(s) |
35915556 |
| Submission date |
Nov 29, 2021 |
| Last update date |
Aug 12, 2022 |
| Contact name |
Julia Brown |
| E-mail(s) |
jub4008@med.cornell.edu
|
| Organization name |
Weill Cornell Medicine
|
| Street address |
413 E 69th Street, 1252A
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (1) |
|
| Samples (12)
|
|
| This SubSeries is part of SuperSeries: |
| GSE189794 |
Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection |
|
| Relations |
| BioProject |
PRJNA784544 |
| SRA |
SRP348420 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE189791_16S_processed.xlsx |
85.0 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...