ABSTRACT
Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, on Staphylococcal enterotoxin B (SEB)-mediated ARDS in female mice. Single-cell RNA sequencing data showed that the lung epithelial cells from AEA-treated mice showed increased levels of antimicrobial peptides (AMPs) and tight junction proteins. MiSeq sequencing data on 16S RNA and LEfSe analysis demonstrated that SEB caused significant alterations in the microbiota, with increases in pathogenic bacteria in both the lungs and the gut, while treatment with AEA reversed this effect and induced beneficial bacteria. AEA treatment suppressed inflammation both in the lungs as well as gut-associated mesenteric lymph nodes (MLNs). AEA triggered several bacterial species that produced increased levels of short-chain fatty acids (SCFAs), including butyrate. Furthermore, administration of butyrate alone could attenuate SEB-mediated ARDS. Taken together, our data indicate that AEA treatment attenuates SEB-mediated ARDS by suppressing inflammation and preventing dysbiosis, both in the lungs and the gut, through the induction of AMPs, tight junction proteins, and SCFAs that stabilize the gut-lung microbial axis driving immune homeostasis.
Subject(s)
Arachidonic Acids/therapeutic use , Endocannabinoids/therapeutic use , Gastrointestinal Microbiome , Gastrointestinal Tract/pathology , Lung/pathology , Polyunsaturated Alkamides/therapeutic use , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/microbiology , Animals , Antimicrobial Peptides/metabolism , Arachidonic Acids/pharmacology , Butyrates/metabolism , Cecum/pathology , Cell Separation , Colon/drug effects , Colon/pathology , Discriminant Analysis , Dysbiosis/complications , Dysbiosis/microbiology , Endocannabinoids/pharmacology , Enterotoxins , Female , Gastrointestinal Tract/drug effects , Lymph Nodes/drug effects , Lymph Nodes/pathology , Lymphocyte Activation/drug effects , Mice, Inbred C57BL , Pneumonia/drug therapy , Pneumonia/microbiology , Polyunsaturated Alkamides/pharmacology , Respiratory Distress Syndrome/complications , T-Lymphocytes/drug effectsABSTRACT
The current outbreak of COVID-19 (coronavirus) has been identified by World Health Organization (WHO) as a global pandemic. With the emergence of the COVID-19 virus and considering the lack of effective pharmaceutical treatment for it, there is an urgent need to identify safe and effective drugs or potential adjuvant therapy in this regard. Bioactive lipids with an array of known health-promoting properties can be suggested as effective agents in alleviating acute respiratory stress induced by virus. The bioactive lipid amide, oleoylethanolamide (OEA), due to several distinctive homeostatic properties, including anti-inflammatory activities, modulation of immune response, and anti-oxidant effects can be considered as a novel potential pharmacological alternative for the management of COVID-19.