Resveratrol-mediated attenuation of superantigen-driven acute respiratory distress syndrome is mediated by microbiota in the lungs and gut.
Pharmacol Res
; 167: 105548, 2021 05.
Article
in English
| MEDLINE | ID: covidwho-1135540
ABSTRACT
Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of agents, including Staphylococcal Enterotoxin B (SEB). Interestingly, a significant proportion of patients with COVID-19, also develop ARDS. In the absence of effective treatments, ARDS results in almost 40% mortality. Previous studies from our laboratory demonstrated that resveratrol (RES), a stilbenoid, with potent anti-inflammatory properties can attenuate SEB-induced ARDS. In the current study, we investigated the role of RES-induced alterations in the gut and lung microbiota in the regulation of ARDS. Our studies revealed that SEB administration induced inflammatory cytokines, ARDS, and 100% mortality in C3H/HeJ mice. Additionally, SEB caused a significant increase in pathogenic Proteobacteria phylum and Propionibacterium acnes species in the lungs. In contrast, RES treatment attenuated SEB-mediated ARDS and mortality in mice, and significantly increased probiotic Actinobacteria phylum, Tenericutes phylum, and Lactobacillus reuteri species in both the colon and lungs. Colonic Microbiota Transplantation (CMT) from SEB-injected mice that were treated with RES as well as the transfer of L. reuteri into recipient mice inhibited the production of SEB-mediated induction of pro-inflammatory cytokines such as IFN-γ and IL-17 but increased that of anti-inflammatory IL-10. Additionally, such CMT and L. reuteri recipient mice exposed to SEB, showed a decrease in lung-infiltrating mononuclear cells, cytotoxic CD8+ T cells, NKT cells, Th1 cells, and Th17 cells, but an increase in the population of regulatory T cells (Tregs) and Th3 cells, and increase in the survival of mice from SEB-mediated ARDS. Together, the current study demonstrates that ARDS induced by SEB triggers dysbiosis in the lungs and gut and that attenuation of ARDS by RES may be mediated, at least in part, by alterations in microbiota in the lungs and the gut, especially through the induction of beneficial bacteria such as L. reuteri.
Keywords
ARDS; Cytokine storm; DiOC(6)(3) (3,3'-Dihexyloxacarbocyanine iodide, PubChem CID: 9894321); Microbiota; Resveratrol; SEB; Superantigen; butyric acid (PubChem CID: 264); carboxymethylcellulose (PubCID: 24748); interleukin 1beta (PubChem CID: 159483); iso butyric acid (PubChem CID: 6590) and acetic acid (PubChem CID: 176); lipopolysaccharide (LPS, PubChem CID: 451715); metronidazole (Bioxtra, PubChem CID: 24896667); propionic acid (PubChem CID: 1032); resveratrol (PubChem CID: 445154)
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Respiratory Distress Syndrome
/
Superantigens
/
Colon
/
Enterotoxins
/
Fecal Microbiota Transplantation
/
Gastrointestinal Microbiome
/
Resveratrol
/
Lung
/
Anti-Inflammatory Agents
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Pharmacol Res
Journal subject:
Pharmacology
Year:
2021
Document Type:
Article
Affiliation country:
J.phrs.2021.105548
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