Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis
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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/12/3305 |
| _version_ | 1797505996098109440 |
|---|---|
| author | Muthanna Sultan Kiesha Wilson Osama A. Abdulla Philip Brandon Busbee Alina Hall Taylor Carter Narendra Singh Saurabh Chatterjee Prakash Nagarkatti Mitzi Nagarkatti |
| author_facet | Muthanna Sultan Kiesha Wilson Osama A. Abdulla Philip Brandon Busbee Alina Hall Taylor Carter Narendra Singh Saurabh Chatterjee Prakash Nagarkatti Mitzi Nagarkatti |
| author_sort | Muthanna Sultan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T04:26:18Z |
| format | Article |
| id | doaj.art-e97990a5673844a6b7c2e09639c3e2f6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:26:18Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e97990a5673844a6b7c2e09639c3e2f62023-11-23T07:35:57ZengMDPI AGCells2073-44092021-11-011012330510.3390/cells10123305Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung AxisMuthanna Sultan0Kiesha Wilson1Osama A. Abdulla2Philip Brandon Busbee3Alina Hall4Taylor Carter5Narendra Singh6Saurabh Chatterjee7Prakash Nagarkatti8Mitzi Nagarkatti9Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC 29209, USAEnvironmental Health and Disease Laboratory, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USADepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC 29209, USADepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina School of Medicine, Columbia, SC 29209, USAAcute 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.https://www.mdpi.com/2073-4409/10/12/3305acute respiratory distress syndrome (ARDS)Staphylococcus enterotoxin B (SEB)anandamide (AEA)COVID-19microbiomeMiSeq sequencing |
| spellingShingle | Muthanna Sultan Kiesha Wilson Osama A. Abdulla Philip Brandon Busbee Alina Hall Taylor Carter Narendra Singh Saurabh Chatterjee Prakash Nagarkatti Mitzi Nagarkatti Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis Cells acute respiratory distress syndrome (ARDS) Staphylococcus enterotoxin B (SEB) anandamide (AEA) COVID-19 microbiome MiSeq sequencing |
| title | Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis |
| title_full | Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis |
| title_fullStr | Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis |
| title_full_unstemmed | Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis |
| title_short | Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis |
| title_sort | endocannabinoid anandamide attenuates acute respiratory distress syndrome through modulation of microbiome in the gut lung axis |
| topic | acute respiratory distress syndrome (ARDS) Staphylococcus enterotoxin B (SEB) anandamide (AEA) COVID-19 microbiome MiSeq sequencing |
| url | https://www.mdpi.com/2073-4409/10/12/3305 |
| work_keys_str_mv | AT muthannasultan endocannabinoidanandamideattenuatesacuterespiratorydistresssyndromethroughmodulationofmicrobiomeinthegutlungaxis AT kieshawilson endocannabinoidanandamideattenuatesacuterespiratorydistresssyndromethroughmodulationofmicrobiomeinthegutlungaxis AT osamaaabdulla endocannabinoidanandamideattenuatesacuterespiratorydistresssyndromethroughmodulationofmicrobiomeinthegutlungaxis AT philipbrandonbusbee endocannabinoidanandamideattenuatesacuterespiratorydistresssyndromethroughmodulationofmicrobiomeinthegutlungaxis AT alinahall endocannabinoidanandamideattenuatesacuterespiratorydistresssyndromethroughmodulationofmicrobiomeinthegutlungaxis AT taylorcarter endocannabinoidanandamideattenuatesacuterespiratorydistresssyndromethroughmodulationofmicrobiomeinthegutlungaxis AT narendrasingh endocannabinoidanandamideattenuatesacuterespiratorydistresssyndromethroughmodulationofmicrobiomeinthegutlungaxis AT saurabhchatterjee endocannabinoidanandamideattenuatesacuterespiratorydistresssyndromethroughmodulationofmicrobiomeinthegutlungaxis AT prakashnagarkatti endocannabinoidanandamideattenuatesacuterespiratorydistresssyndromethroughmodulationofmicrobiomeinthegutlungaxis AT mitzinagarkatti endocannabinoidanandamideattenuatesacuterespiratorydistresssyndromethroughmodulationofmicrobiomeinthegutlungaxis |