Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis

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.

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

“…4.7.3. The Relationship between Gut Microbiota, AEA, and Acute Respiratory Distress Syndrome AEA was found to attenuate acute respiratory distress syndrome through modulating the gut microbiota [420]. In this study, the researchers investigated the effect of AEA on staphylococcal enterotoxin B (SEB)-mediated acute respiratory distress syndrome.…”

“…In this study, the researchers investigated the effect of AEA on staphylococcal enterotoxin B (SEB)-mediated acute respiratory distress syndrome. SEB caused an increase in pathogenic bacteria in both the lungs and the gut [420]. AEAtreated mice showed increased level of anti-microbial peptides in the lung epithelial cells and prevented the increase in pathogenic bacteria induced by SEB [420].…”

“…SEB caused an increase in pathogenic bacteria in both the lungs and the gut [420]. AEAtreated mice showed increased level of anti-microbial peptides in the lung epithelial cells and prevented the increase in pathogenic bacteria induced by SEB [420]. AEA increased the level of several bacterial species (e.g., Lachnospiraceae and Clostridia) that produce elevated levels of SCFAs, such as butyrate and valerate, important for stabilizing the gut-lung microbial axis and suppressing inflammation [420].…”

“…AEA increased the level of several bacterial species (e.g., Lachnospiraceae and Clostridia) that produce elevated levels of SCFAs, such as butyrate and valerate, important for stabilizing the gut-lung microbial axis and suppressing inflammation [420]. In addition, AEA treatment increased the abundance of Muribaculaceae and reduced the abundance of Pseudomonas and Enterobacteriaceae [420].…”

The treatment of Qibai Pingfei Capsule on chronic obstructive pulmonary disease may be mediated by Th17 / Treg balance and gut-lung axis microbiota

“…The results suggested that the imbalance of COPD microbiota is related to the increase of harmful bacteria and affect the production of SCFAs. The correlations between the intestinal and pulmonary microbiota add pieces of evidence to the GLA [53,[64][65].…”