Downregulation of ACE, AGTR1, and ACE2 genes mediating SARS-CoV-2 pathogenesis by gut microbiota members and their postbiotics on Caco-2 cells
Coronavirus disease-2019 (COVID-19) is a complex infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can cause also gastrointestinal symptoms. There are various factors that determine the host susceptibility and severity of infection, including the renin-angiote...
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| creator | Ahmadi Badi, Sara Malek, Amin Paolini, Alessandro Rouhollahi Masoumi, Mahya Seyedi, Seyed Amirhesam Amanzadeh, Amir Masotti, Andrea Khatami, Shohreh Siadat, Seyed Davar |
| description | Coronavirus disease-2019 (COVID-19) is a complex infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can cause also gastrointestinal symptoms. There are various factors that determine the host susceptibility and severity of infection, including the renin-angiotensin system, the immune response, and the gut microbiota. In this regard, we aimed to investigate the gene expression of ACE, AGTR1, ACE2, and TMPRSS2, which mediate SARS-CoV-2 pathogenesis by Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, and Bacteroides fragilis on Caco-2 cells. Also, the enrichment analysis considering the studied genes was analyzed on raw data from the microarray analysis of COVID-19 patients.
Caco-2 cells were treated with live, heat-inactivated form and cell free supernatants of A. muciniphila, F. prausnitzii, B. thetaiotaomicron and B. fragilis for overnight. After RNA extraction and cDNA synthesis, the expression of studied genes was assessed by RT-qPCR. DNA methylation of studied genes was analyzed by Partek® Genomics Suite® software on the GSE174818 dataset. We used GSE164805 and GSE166552 datasets from COVID-19 patients to perform enrichment analysis by considering the mentioned genes via GEO2R, DAVID. Finally, the related microRNAs to GO terms concerned on the studied genes were identified by miRPath.
The downregulation of ACE, AGTR1, and ACE2 genes by A. muciniphila, F. prausnitzii, B. thetaiotaomicron, and B. fragilis in live, heat-inactivated, and cell-free supernatants was reported for the first time. These genes had hypomethylated DNA status in COVID-19 patients' raw data. The highest fold enrichment in upregulated RAS pathways and immune responses belonged to ACE, AGTR1, and ACE2 by considering the protein-protein interaction network. The common miRNAs targeting the studied genes were reported as miR-124-3p and miR-26b-5p.
In combination with our experimental data and bioinformatic analysis, we showed the potential of A. muciniphila, F. prausnitzii, B. thetaiotaomicron, and B. fragilis and their postbiotics to reduce ACE, ATR1, and ACE2 expression, which are essential genes that drive upregulated biological processes in COVID-19 patients.
Accordingly, due to the potential of studied bacteria on the alteration of ACE, AGTR1, ACE2 genes expression, understanding their correlation with demonstrated miRNAs expression could be valuable. These findings suggest the importance of considering target |
| doi_str_mv | 10.1016/j.micpath.2022.105798 |
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Caco-2 cells were treated with live, heat-inactivated form and cell free supernatants of A. muciniphila, F. prausnitzii, B. thetaiotaomicron and B. fragilis for overnight. After RNA extraction and cDNA synthesis, the expression of studied genes was assessed by RT-qPCR. DNA methylation of studied genes was analyzed by Partek® Genomics Suite® software on the GSE174818 dataset. We used GSE164805 and GSE166552 datasets from COVID-19 patients to perform enrichment analysis by considering the mentioned genes via GEO2R, DAVID. Finally, the related microRNAs to GO terms concerned on the studied genes were identified by miRPath.
The downregulation of ACE, AGTR1, and ACE2 genes by A. muciniphila, F. prausnitzii, B. thetaiotaomicron, and B. fragilis in live, heat-inactivated, and cell-free supernatants was reported for the first time. These genes had hypomethylated DNA status in COVID-19 patients' raw data. The highest fold enrichment in upregulated RAS pathways and immune responses belonged to ACE, AGTR1, and ACE2 by considering the protein-protein interaction network. The common miRNAs targeting the studied genes were reported as miR-124-3p and miR-26b-5p.
In combination with our experimental data and bioinformatic analysis, we showed the potential of A. muciniphila, F. prausnitzii, B. thetaiotaomicron, and B. fragilis and their postbiotics to reduce ACE, ATR1, and ACE2 expression, which are essential genes that drive upregulated biological processes in COVID-19 patients.
Accordingly, due to the potential of studied bacteria on the alteration of ACE, AGTR1, ACE2 genes expression, understanding their correlation with demonstrated miRNAs expression could be valuable. These findings suggest the importance of considering targeted gut microbiota intervention when designing the possible therapeutic strategy for controlling the COVID-19.
•Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, and Bacteroides fragilis, important gut microbiota members, downregulated expression of ACE, AGTR1, and ACE2 genes mediating SARS-CoV-2 pathogenesis on Caco-2 cell line.•Postbiotic forms including, heat-inactivated and cell-free supernatants derived from A. muciniphila, F. prausnitzii, B. thetaiotaomicron, B. fragilis reduced genes expression of ACE, AGTR1, and ACE2 favored to reducing of COVID-19 infection in human intestinal epithelial cells, Caco-2 cells.•Hypomethylated status of ACE, AGTR1, and ACE2 were demonstrated by DNA methylation analysis on GSE174818 in COVID-19 patients and healthy control.•ACE, AGTR1, and ACE2 had highest fold enrichment in upregulated process especially, renin angiotensin system activity and immune response, in COVID-19 patients compared with healthy control based on the enrichment analysis of differentially expressed genes (DEGs) derived two microarray datasets, GSE164805 and GSE166552.•The most important microRNAs which target ACE, AGTR1, and ACE2 genes to control expression were identified, miR-124-3p and miR-26b-5p related to GO terms from enrichment analysis.</description><identifier>ISSN: 0882-4010</identifier><identifier>EISSN: 1096-1208</identifier><identifier>DOI: 10.1016/j.micpath.2022.105798</identifier><identifier>PMID: 36174833</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Angiotensin-Converting Enzyme 2 - genetics ; Caco-2 Cells ; COVID-19 ; COVID-19 - genetics ; Down-Regulation ; Gastrointestinal Microbiome - genetics ; Gut microbiota ; Humans ; MicroRNAs - genetics ; Peptidyl-Dipeptidase A - genetics ; Postbiotics ; Receptor, Angiotensin, Type 1 - genetics ; Renin angiotensin system ; SARS-CoV-2 ; SARS-CoV2</subject><ispartof>Microbial pathogenesis, 2022-12, Vol.173 (Pt A), p.105798-105798, Article 105798</ispartof><rights>2022 Elsevier Ltd</rights><rights>Copyright © 2022 Elsevier Ltd. All rights reserved.</rights><rights>2022 Published by Elsevier Ltd. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-ade033fe26cbe1499b16ee13868532c7dde2f9231dce08fc5eb97f715fdba3903</citedby><cites>FETCH-LOGICAL-c467t-ade033fe26cbe1499b16ee13868532c7dde2f9231dce08fc5eb97f715fdba3903</cites><orcidid>0000-0001-8679-1277</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.micpath.2022.105798$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36174833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ahmadi Badi, Sara</creatorcontrib><creatorcontrib>Malek, Amin</creatorcontrib><creatorcontrib>Paolini, Alessandro</creatorcontrib><creatorcontrib>Rouhollahi Masoumi, Mahya</creatorcontrib><creatorcontrib>Seyedi, Seyed Amirhesam</creatorcontrib><creatorcontrib>Amanzadeh, Amir</creatorcontrib><creatorcontrib>Masotti, Andrea</creatorcontrib><creatorcontrib>Khatami, Shohreh</creatorcontrib><creatorcontrib>Siadat, Seyed Davar</creatorcontrib><title>Downregulation of ACE, AGTR1, and ACE2 genes mediating SARS-CoV-2 pathogenesis by gut microbiota members and their postbiotics on Caco-2 cells</title><title>Microbial pathogenesis</title><addtitle>Microb Pathog</addtitle><description>Coronavirus disease-2019 (COVID-19) is a complex infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can cause also gastrointestinal symptoms. There are various factors that determine the host susceptibility and severity of infection, including the renin-angiotensin system, the immune response, and the gut microbiota. In this regard, we aimed to investigate the gene expression of ACE, AGTR1, ACE2, and TMPRSS2, which mediate SARS-CoV-2 pathogenesis by Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, and Bacteroides fragilis on Caco-2 cells. Also, the enrichment analysis considering the studied genes was analyzed on raw data from the microarray analysis of COVID-19 patients.
Caco-2 cells were treated with live, heat-inactivated form and cell free supernatants of A. muciniphila, F. prausnitzii, B. thetaiotaomicron and B. fragilis for overnight. After RNA extraction and cDNA synthesis, the expression of studied genes was assessed by RT-qPCR. DNA methylation of studied genes was analyzed by Partek® Genomics Suite® software on the GSE174818 dataset. We used GSE164805 and GSE166552 datasets from COVID-19 patients to perform enrichment analysis by considering the mentioned genes via GEO2R, DAVID. Finally, the related microRNAs to GO terms concerned on the studied genes were identified by miRPath.
The downregulation of ACE, AGTR1, and ACE2 genes by A. muciniphila, F. prausnitzii, B. thetaiotaomicron, and B. fragilis in live, heat-inactivated, and cell-free supernatants was reported for the first time. These genes had hypomethylated DNA status in COVID-19 patients' raw data. The highest fold enrichment in upregulated RAS pathways and immune responses belonged to ACE, AGTR1, and ACE2 by considering the protein-protein interaction network. The common miRNAs targeting the studied genes were reported as miR-124-3p and miR-26b-5p.
In combination with our experimental data and bioinformatic analysis, we showed the potential of A. muciniphila, F. prausnitzii, B. thetaiotaomicron, and B. fragilis and their postbiotics to reduce ACE, ATR1, and ACE2 expression, which are essential genes that drive upregulated biological processes in COVID-19 patients.
Accordingly, due to the potential of studied bacteria on the alteration of ACE, AGTR1, ACE2 genes expression, understanding their correlation with demonstrated miRNAs expression could be valuable. These findings suggest the importance of considering targeted gut microbiota intervention when designing the possible therapeutic strategy for controlling the COVID-19.
•Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, and Bacteroides fragilis, important gut microbiota members, downregulated expression of ACE, AGTR1, and ACE2 genes mediating SARS-CoV-2 pathogenesis on Caco-2 cell line.•Postbiotic forms including, heat-inactivated and cell-free supernatants derived from A. muciniphila, F. prausnitzii, B. thetaiotaomicron, B. fragilis reduced genes expression of ACE, AGTR1, and ACE2 favored to reducing of COVID-19 infection in human intestinal epithelial cells, Caco-2 cells.•Hypomethylated status of ACE, AGTR1, and ACE2 were demonstrated by DNA methylation analysis on GSE174818 in COVID-19 patients and healthy control.•ACE, AGTR1, and ACE2 had highest fold enrichment in upregulated process especially, renin angiotensin system activity and immune response, in COVID-19 patients compared with healthy control based on the enrichment analysis of differentially expressed genes (DEGs) derived two microarray datasets, GSE164805 and GSE166552.•The most important microRNAs which target ACE, AGTR1, and ACE2 genes to control expression were identified, miR-124-3p and miR-26b-5p related to GO terms from enrichment analysis.</description><subject>Angiotensin-Converting Enzyme 2 - genetics</subject><subject>Caco-2 Cells</subject><subject>COVID-19</subject><subject>COVID-19 - genetics</subject><subject>Down-Regulation</subject><subject>Gastrointestinal Microbiome - genetics</subject><subject>Gut microbiota</subject><subject>Humans</subject><subject>MicroRNAs - genetics</subject><subject>Peptidyl-Dipeptidase A - genetics</subject><subject>Postbiotics</subject><subject>Receptor, Angiotensin, Type 1 - genetics</subject><subject>Renin angiotensin system</subject><subject>SARS-CoV-2</subject><subject>SARS-CoV2</subject><issn>0882-4010</issn><issn>1096-1208</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1v1DAQtRCILoWfAPKRQ7P4Ix_2BbQKbUGqhNQWrpbjTLJeJfFiO0X9E_zmOt2lghMnazxv3nszD6G3lKwpoeWH3Xq0Zq_jds0IY-mvqKR4hlaUyDKjjIjnaEWEYFlOKDlBr0LYEUJkzuVLdMJLWuWC8xX6_dn9mjz086CjdRN2Hd7U52d4c3l7Tc-wntqlZriHCQIeobUJN_X4ZnN9k9XuR8bwYsI99m3AzT3u54iTN-8a66JOM2MDPjxSxS1Yj_cuxKVnTcBJstbGJRoDwxBeoxedHgK8Ob6n6PvF-W39Jbv6dvm13lxlJi-rmOkWCOcdsNI0QHMpG1oCUC5KUXBmqrYF1knGaWuAiM4U0Miqq2jRtY3mkvBT9PHAu5-btJSBKXo9qL23o_b3ymmr_u1Mdqt6d6dkQamQIhG8PxJ493OGENVow7KCnsDNQbGKkZwVVVkmaHGAppOE4KF7kqFELVmqnTpmqZYs1SHLNPfub49PU3_CS4BPBwCkS91Z8CoYC5NJIXkwUbXO_kfiAaT7s_w</recordid><startdate>20221201</startdate><enddate>20221201</enddate><creator>Ahmadi Badi, Sara</creator><creator>Malek, Amin</creator><creator>Paolini, Alessandro</creator><creator>Rouhollahi Masoumi, Mahya</creator><creator>Seyedi, Seyed Amirhesam</creator><creator>Amanzadeh, Amir</creator><creator>Masotti, Andrea</creator><creator>Khatami, Shohreh</creator><creator>Siadat, Seyed Davar</creator><general>Elsevier Ltd</general><general>Published by Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8679-1277</orcidid></search><sort><creationdate>20221201</creationdate><title>Downregulation of ACE, AGTR1, and ACE2 genes mediating SARS-CoV-2 pathogenesis by gut microbiota members and their postbiotics on Caco-2 cells</title><author>Ahmadi Badi, Sara ; Malek, Amin ; Paolini, Alessandro ; Rouhollahi Masoumi, Mahya ; Seyedi, Seyed Amirhesam ; Amanzadeh, Amir ; Masotti, Andrea ; Khatami, Shohreh ; Siadat, Seyed Davar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-ade033fe26cbe1499b16ee13868532c7dde2f9231dce08fc5eb97f715fdba3903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Angiotensin-Converting Enzyme 2 - genetics</topic><topic>Caco-2 Cells</topic><topic>COVID-19</topic><topic>COVID-19 - genetics</topic><topic>Down-Regulation</topic><topic>Gastrointestinal Microbiome - genetics</topic><topic>Gut microbiota</topic><topic>Humans</topic><topic>MicroRNAs - genetics</topic><topic>Peptidyl-Dipeptidase A - genetics</topic><topic>Postbiotics</topic><topic>Receptor, Angiotensin, Type 1 - genetics</topic><topic>Renin angiotensin system</topic><topic>SARS-CoV-2</topic><topic>SARS-CoV2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ahmadi Badi, Sara</creatorcontrib><creatorcontrib>Malek, Amin</creatorcontrib><creatorcontrib>Paolini, Alessandro</creatorcontrib><creatorcontrib>Rouhollahi Masoumi, Mahya</creatorcontrib><creatorcontrib>Seyedi, Seyed Amirhesam</creatorcontrib><creatorcontrib>Amanzadeh, Amir</creatorcontrib><creatorcontrib>Masotti, Andrea</creatorcontrib><creatorcontrib>Khatami, Shohreh</creatorcontrib><creatorcontrib>Siadat, Seyed Davar</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Microbial pathogenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ahmadi Badi, Sara</au><au>Malek, Amin</au><au>Paolini, Alessandro</au><au>Rouhollahi Masoumi, Mahya</au><au>Seyedi, Seyed Amirhesam</au><au>Amanzadeh, Amir</au><au>Masotti, Andrea</au><au>Khatami, Shohreh</au><au>Siadat, Seyed Davar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulation of ACE, AGTR1, and ACE2 genes mediating SARS-CoV-2 pathogenesis by gut microbiota members and their postbiotics on Caco-2 cells</atitle><jtitle>Microbial pathogenesis</jtitle><addtitle>Microb Pathog</addtitle><date>2022-12-01</date><risdate>2022</risdate><volume>173</volume><issue>Pt A</issue><spage>105798</spage><epage>105798</epage><pages>105798-105798</pages><artnum>105798</artnum><issn>0882-4010</issn><eissn>1096-1208</eissn><abstract>Coronavirus disease-2019 (COVID-19) is a complex infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can cause also gastrointestinal symptoms. There are various factors that determine the host susceptibility and severity of infection, including the renin-angiotensin system, the immune response, and the gut microbiota. In this regard, we aimed to investigate the gene expression of ACE, AGTR1, ACE2, and TMPRSS2, which mediate SARS-CoV-2 pathogenesis by Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, and Bacteroides fragilis on Caco-2 cells. Also, the enrichment analysis considering the studied genes was analyzed on raw data from the microarray analysis of COVID-19 patients.
Caco-2 cells were treated with live, heat-inactivated form and cell free supernatants of A. muciniphila, F. prausnitzii, B. thetaiotaomicron and B. fragilis for overnight. After RNA extraction and cDNA synthesis, the expression of studied genes was assessed by RT-qPCR. DNA methylation of studied genes was analyzed by Partek® Genomics Suite® software on the GSE174818 dataset. We used GSE164805 and GSE166552 datasets from COVID-19 patients to perform enrichment analysis by considering the mentioned genes via GEO2R, DAVID. Finally, the related microRNAs to GO terms concerned on the studied genes were identified by miRPath.
The downregulation of ACE, AGTR1, and ACE2 genes by A. muciniphila, F. prausnitzii, B. thetaiotaomicron, and B. fragilis in live, heat-inactivated, and cell-free supernatants was reported for the first time. These genes had hypomethylated DNA status in COVID-19 patients' raw data. The highest fold enrichment in upregulated RAS pathways and immune responses belonged to ACE, AGTR1, and ACE2 by considering the protein-protein interaction network. The common miRNAs targeting the studied genes were reported as miR-124-3p and miR-26b-5p.
In combination with our experimental data and bioinformatic analysis, we showed the potential of A. muciniphila, F. prausnitzii, B. thetaiotaomicron, and B. fragilis and their postbiotics to reduce ACE, ATR1, and ACE2 expression, which are essential genes that drive upregulated biological processes in COVID-19 patients.
Accordingly, due to the potential of studied bacteria on the alteration of ACE, AGTR1, ACE2 genes expression, understanding their correlation with demonstrated miRNAs expression could be valuable. These findings suggest the importance of considering targeted gut microbiota intervention when designing the possible therapeutic strategy for controlling the COVID-19.
•Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, and Bacteroides fragilis, important gut microbiota members, downregulated expression of ACE, AGTR1, and ACE2 genes mediating SARS-CoV-2 pathogenesis on Caco-2 cell line.•Postbiotic forms including, heat-inactivated and cell-free supernatants derived from A. muciniphila, F. prausnitzii, B. thetaiotaomicron, B. fragilis reduced genes expression of ACE, AGTR1, and ACE2 favored to reducing of COVID-19 infection in human intestinal epithelial cells, Caco-2 cells.•Hypomethylated status of ACE, AGTR1, and ACE2 were demonstrated by DNA methylation analysis on GSE174818 in COVID-19 patients and healthy control.•ACE, AGTR1, and ACE2 had highest fold enrichment in upregulated process especially, renin angiotensin system activity and immune response, in COVID-19 patients compared with healthy control based on the enrichment analysis of differentially expressed genes (DEGs) derived two microarray datasets, GSE164805 and GSE166552.•The most important microRNAs which target ACE, AGTR1, and ACE2 genes to control expression were identified, miR-124-3p and miR-26b-5p related to GO terms from enrichment analysis.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>36174833</pmid><doi>10.1016/j.micpath.2022.105798</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-8679-1277</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Microbial pathogenesis, 2022-12, Vol.173 (Pt A), p.105798-105798, Article 105798 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Angiotensin-Converting Enzyme 2 - genetics Caco-2 Cells COVID-19 COVID-19 - genetics Down-Regulation Gastrointestinal Microbiome - genetics Gut microbiota Humans MicroRNAs - genetics Peptidyl-Dipeptidase A - genetics Postbiotics Receptor, Angiotensin, Type 1 - genetics Renin angiotensin system SARS-CoV-2 SARS-CoV2 |
| title | Downregulation of ACE, AGTR1, and ACE2 genes mediating SARS-CoV-2 pathogenesis by gut microbiota members and their postbiotics on Caco-2 cells |
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