Protective effects of Δ9-Tetrahydrocannabinol (THC) results from alteration in lung dysbiosis mediated by SEB-induced acute lung injury
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Abstract<p>Inhalation of Staphylococcal Enterotoxin B (SEB) is known to induce acute lung injury (ALI) and studies from our laboratory have shown that THC, a psychoactive ingredient found in Cannabis sativa, can attenuate the ALI. In the current study, we investigated the role played by lung microbiota in ALI with or without THC treatment. A dual-dose of SEB was given to C3H/HeJ mice, which were then treated either with vehicle or THC. SEB-administration caused ALI and 100% mortality while all THC-treated mice survived and suppressed the inflammation in the lungs. Furthermore, lung microbiota was collected and 16S rRNA sequencing was performed. The data were analyzed to determine the alpha and beta diversity. The major phylum was Proteobacteria, class Alphaproteobacteria and orders were Caulobacterles and Rhodobacteralesin in the lungs of vehicle-treated SEB group. Moreover, THC treatment led to elevated Firmicutes phylum due to significant increase in the beneficial genus, Lactobacillus. Lipopolysaccharide (LPS), gram negative bacterial endotoxin was found at significantly higher concentration in the BALF of vehicle-treated group in comparison with THC-treated mice. Beneficial metabolome levels were significantly higher in the colonic flush of THC-treated mice when compared to vehicle-treated SEB group, specifically butyric, propionic and acetic acids. Together, our data suggest that THC attenuates SEB-induced mortality and ALI by altering the microbiota in the lungs (Supported by NIH grants P01AT003961, R01AT006888, R01ES019313, R01MH094755, P20GM103641, R01AI129788 to PN and MN and MoHESR fellowship for AKM).</p>
