Morphine use induces gastric microbial dysbiosis driving gastric inflammation through TLR2 signalling which is attenuated by proton pump inhibition
Background and Purpose Opioids are the standard drug for pain management; however, their effects on gastric dysfunction are relatively understudied. Opioid users have a higher incidence of gastric pathology leading to increased hospitalization. Herein, we investigated the consequences of morphine us...
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creator | Ghosh, Nillu Kesh, Kousik Singh, Praveen Kumar Sharma, Umakant Chupikova, Irina Ramakrishnan, Sundaram Roy, Sabita |
description | Background and Purpose
Opioids are the standard drug for pain management; however, their effects on gastric dysfunction are relatively understudied. Opioid users have a higher incidence of gastric pathology leading to increased hospitalization. Herein, we investigated the consequences of morphine use on gastric pathology and the underlying mechanisms. We further investigated the therapeutic benefit of proton pump inhibition to overcome morphine‐mediated gastric inflammation.
Experimental Approach
Mice were implanted with 25 mg slow‐release morphine and placebo pellets. Gastric microbiome analyses were performed. Gastric damage was assayed. Gastric pH was measured. Germ‐free and TLR2KO mice were used to investigate the mechanisms. Gastroprotective studies were performed with the proton pump inhibitor (PPI) omeprazole.
Key Results
Chronic morphine treatment alters gastric microbial composition and induces preferential expansion of pathogenic bacterial communities such as Streptococcus and Pseudomonas. Morphine causes disruption of the gastric mucosal layer, increases apoptosis, and elevates inflammatory cytokines. Moreover, morphine‐mediated gastric pathology was significantly attenuated in germ‐free mice, and reconstitution of morphine gastric microbiome in germ‐free mice resulted gastric inflammation. In addition, morphine‐mediated gastric inflammation was attenuated in TLR2KO mice. Morphine causes a decrease in gastric pH, which contributes to gastric dysbiosis leads to gastric inflammation. Omeprazole treatment inhibits gastric acidity, rescuing morphine‐induced gastric dysbiosis and preventing inflammation.
Conclusion and Implications
This study attributes morphine‐induced gastric acidity as a driver of gastric dysbiosis and pathology and proposes the therapeutic use of PPI as an inexpensive approach for the clinical management of morphine‐associated pathophysiology.
Morphine treatment increases gastric acid secretion which causes dysbiosis of gastric microbiome. The dysbiotic gastric microbiome induces gastric inflammation through TLR2‐mediated signaling. Omeprazole prevents morphine‐induced gastric damage by regulating gastric acid secretion and restoring normal gastric microbiota. |
doi_str_mv | 10.1111/bph.16025 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2759962584</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2811113727</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3535-646feb38bb113de1d711afb0d9bb4f553f5965a33e155f3d7c86622d7b7f20873</originalsourceid><addsrcrecordid>eNp1kbtOHDEUhi0UFBaSgheILNFAMWCP15ctAUGItFEQIvXIHts7B80t9hi0z5EXjidLKJByGhfn-z_Z_hE6puSc5rkwY3NOBSn5HlrQpRQFZ4p-QAtCiCwoVeoAHcb4REheSv4RHTDBFWdCLtDv70MYG-gdTtFh6G2qXcQbHacANe6gDoMB3WK7jQaGCBHbAM_Qb94Y6H2ru05PMPR4asKQNg1-XD-UOMKm1207wy8N1A3OaT1Nrk96chabLR7DMOXUmLoxexowMFs-oX2v2-g-v55H6OftzeP1XbH-8fXb9eW6qBlnvBBL4Z1hyhhKmXXUSkq1N8SujFl6zpnnK8E1Y45y7pmVtRKiLK000pdESXaETnfefI1fycWp6iDWrm1174YUq1Ly1UqUXC0zevIOfRpSyK_LlJo7YLKchWc7Kv9ajMH5agzQ6bCtKKlmqspNVX-byuyXV2MynbNv5L9qMnCxA16gddv_m6qr-7ud8g9d95-2</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2811113727</pqid></control><display><type>article</type><title>Morphine use induces gastric microbial dysbiosis driving gastric inflammation through TLR2 signalling which is attenuated by proton pump inhibition</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library (Open Access Collection)</source><source>Alma/SFX Local Collection</source><creator>Ghosh, Nillu ; Kesh, Kousik ; Singh, Praveen Kumar ; Sharma, Umakant ; Chupikova, Irina ; Ramakrishnan, Sundaram ; Roy, Sabita</creator><creatorcontrib>Ghosh, Nillu ; Kesh, Kousik ; Singh, Praveen Kumar ; Sharma, Umakant ; Chupikova, Irina ; Ramakrishnan, Sundaram ; Roy, Sabita</creatorcontrib><description>Background and Purpose
Opioids are the standard drug for pain management; however, their effects on gastric dysfunction are relatively understudied. Opioid users have a higher incidence of gastric pathology leading to increased hospitalization. Herein, we investigated the consequences of morphine use on gastric pathology and the underlying mechanisms. We further investigated the therapeutic benefit of proton pump inhibition to overcome morphine‐mediated gastric inflammation.
Experimental Approach
Mice were implanted with 25 mg slow‐release morphine and placebo pellets. Gastric microbiome analyses were performed. Gastric damage was assayed. Gastric pH was measured. Germ‐free and TLR2KO mice were used to investigate the mechanisms. Gastroprotective studies were performed with the proton pump inhibitor (PPI) omeprazole.
Key Results
Chronic morphine treatment alters gastric microbial composition and induces preferential expansion of pathogenic bacterial communities such as Streptococcus and Pseudomonas. Morphine causes disruption of the gastric mucosal layer, increases apoptosis, and elevates inflammatory cytokines. Moreover, morphine‐mediated gastric pathology was significantly attenuated in germ‐free mice, and reconstitution of morphine gastric microbiome in germ‐free mice resulted gastric inflammation. In addition, morphine‐mediated gastric inflammation was attenuated in TLR2KO mice. Morphine causes a decrease in gastric pH, which contributes to gastric dysbiosis leads to gastric inflammation. Omeprazole treatment inhibits gastric acidity, rescuing morphine‐induced gastric dysbiosis and preventing inflammation.
Conclusion and Implications
This study attributes morphine‐induced gastric acidity as a driver of gastric dysbiosis and pathology and proposes the therapeutic use of PPI as an inexpensive approach for the clinical management of morphine‐associated pathophysiology.
Morphine treatment increases gastric acid secretion which causes dysbiosis of gastric microbiome. The dysbiotic gastric microbiome induces gastric inflammation through TLR2‐mediated signaling. Omeprazole prevents morphine‐induced gastric damage by regulating gastric acid secretion and restoring normal gastric microbiota.</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/bph.16025</identifier><identifier>PMID: 36585367</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Acidity ; Analgesics, Opioid - pharmacology ; Animals ; Apoptosis ; Dysbacteriosis ; Dysbiosis - chemically induced ; gastric inflammation ; Gastric juice ; gastric microbiome ; Gastric mucosa ; germ‐free mice ; Inflammation ; Inflammation - drug therapy ; Mice ; Microbiomes ; Morphine ; Morphine - pharmacology ; Omeprazole ; Omeprazole - pharmacology ; opioid ; Opioids ; Pathology ; proton pump inhibition ; Proton pump inhibitors ; Proton Pump Inhibitors - adverse effects ; TLR2 protein ; Toll-Like Receptor 2 ; Toll-like receptors</subject><ispartof>British journal of pharmacology, 2023-06, Vol.180 (12), p.1582-1596</ispartof><rights>2022 British Pharmacological Society.</rights><rights>2023 The British Pharmacological Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3535-646feb38bb113de1d711afb0d9bb4f553f5965a33e155f3d7c86622d7b7f20873</citedby><cites>FETCH-LOGICAL-c3535-646feb38bb113de1d711afb0d9bb4f553f5965a33e155f3d7c86622d7b7f20873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbph.16025$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbph.16025$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36585367$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ghosh, Nillu</creatorcontrib><creatorcontrib>Kesh, Kousik</creatorcontrib><creatorcontrib>Singh, Praveen Kumar</creatorcontrib><creatorcontrib>Sharma, Umakant</creatorcontrib><creatorcontrib>Chupikova, Irina</creatorcontrib><creatorcontrib>Ramakrishnan, Sundaram</creatorcontrib><creatorcontrib>Roy, Sabita</creatorcontrib><title>Morphine use induces gastric microbial dysbiosis driving gastric inflammation through TLR2 signalling which is attenuated by proton pump inhibition</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Background and Purpose
Opioids are the standard drug for pain management; however, their effects on gastric dysfunction are relatively understudied. Opioid users have a higher incidence of gastric pathology leading to increased hospitalization. Herein, we investigated the consequences of morphine use on gastric pathology and the underlying mechanisms. We further investigated the therapeutic benefit of proton pump inhibition to overcome morphine‐mediated gastric inflammation.
Experimental Approach
Mice were implanted with 25 mg slow‐release morphine and placebo pellets. Gastric microbiome analyses were performed. Gastric damage was assayed. Gastric pH was measured. Germ‐free and TLR2KO mice were used to investigate the mechanisms. Gastroprotective studies were performed with the proton pump inhibitor (PPI) omeprazole.
Key Results
Chronic morphine treatment alters gastric microbial composition and induces preferential expansion of pathogenic bacterial communities such as Streptococcus and Pseudomonas. Morphine causes disruption of the gastric mucosal layer, increases apoptosis, and elevates inflammatory cytokines. Moreover, morphine‐mediated gastric pathology was significantly attenuated in germ‐free mice, and reconstitution of morphine gastric microbiome in germ‐free mice resulted gastric inflammation. In addition, morphine‐mediated gastric inflammation was attenuated in TLR2KO mice. Morphine causes a decrease in gastric pH, which contributes to gastric dysbiosis leads to gastric inflammation. Omeprazole treatment inhibits gastric acidity, rescuing morphine‐induced gastric dysbiosis and preventing inflammation.
Conclusion and Implications
This study attributes morphine‐induced gastric acidity as a driver of gastric dysbiosis and pathology and proposes the therapeutic use of PPI as an inexpensive approach for the clinical management of morphine‐associated pathophysiology.
Morphine treatment increases gastric acid secretion which causes dysbiosis of gastric microbiome. The dysbiotic gastric microbiome induces gastric inflammation through TLR2‐mediated signaling. Omeprazole prevents morphine‐induced gastric damage by regulating gastric acid secretion and restoring normal gastric microbiota.</description><subject>Acidity</subject><subject>Analgesics, Opioid - pharmacology</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Dysbacteriosis</subject><subject>Dysbiosis - chemically induced</subject><subject>gastric inflammation</subject><subject>Gastric juice</subject><subject>gastric microbiome</subject><subject>Gastric mucosa</subject><subject>germ‐free mice</subject><subject>Inflammation</subject><subject>Inflammation - drug therapy</subject><subject>Mice</subject><subject>Microbiomes</subject><subject>Morphine</subject><subject>Morphine - pharmacology</subject><subject>Omeprazole</subject><subject>Omeprazole - pharmacology</subject><subject>opioid</subject><subject>Opioids</subject><subject>Pathology</subject><subject>proton pump inhibition</subject><subject>Proton pump inhibitors</subject><subject>Proton Pump Inhibitors - adverse effects</subject><subject>TLR2 protein</subject><subject>Toll-Like Receptor 2</subject><subject>Toll-like receptors</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kbtOHDEUhi0UFBaSgheILNFAMWCP15ctAUGItFEQIvXIHts7B80t9hi0z5EXjidLKJByGhfn-z_Z_hE6puSc5rkwY3NOBSn5HlrQpRQFZ4p-QAtCiCwoVeoAHcb4REheSv4RHTDBFWdCLtDv70MYG-gdTtFh6G2qXcQbHacANe6gDoMB3WK7jQaGCBHbAM_Qb94Y6H2ru05PMPR4asKQNg1-XD-UOMKm1207wy8N1A3OaT1Nrk96chabLR7DMOXUmLoxexowMFs-oX2v2-g-v55H6OftzeP1XbH-8fXb9eW6qBlnvBBL4Z1hyhhKmXXUSkq1N8SujFl6zpnnK8E1Y45y7pmVtRKiLK000pdESXaETnfefI1fycWp6iDWrm1174YUq1Ly1UqUXC0zevIOfRpSyK_LlJo7YLKchWc7Kv9ajMH5agzQ6bCtKKlmqspNVX-byuyXV2MynbNv5L9qMnCxA16gddv_m6qr-7ud8g9d95-2</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Ghosh, Nillu</creator><creator>Kesh, Kousik</creator><creator>Singh, Praveen Kumar</creator><creator>Sharma, Umakant</creator><creator>Chupikova, Irina</creator><creator>Ramakrishnan, Sundaram</creator><creator>Roy, Sabita</creator><general>Blackwell Publishing 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>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>202306</creationdate><title>Morphine use induces gastric microbial dysbiosis driving gastric inflammation through TLR2 signalling which is attenuated by proton pump inhibition</title><author>Ghosh, Nillu ; Kesh, Kousik ; Singh, Praveen Kumar ; Sharma, Umakant ; Chupikova, Irina ; Ramakrishnan, Sundaram ; Roy, Sabita</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3535-646feb38bb113de1d711afb0d9bb4f553f5965a33e155f3d7c86622d7b7f20873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acidity</topic><topic>Analgesics, Opioid - pharmacology</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Dysbacteriosis</topic><topic>Dysbiosis - chemically induced</topic><topic>gastric inflammation</topic><topic>Gastric juice</topic><topic>gastric microbiome</topic><topic>Gastric mucosa</topic><topic>germ‐free mice</topic><topic>Inflammation</topic><topic>Inflammation - drug therapy</topic><topic>Mice</topic><topic>Microbiomes</topic><topic>Morphine</topic><topic>Morphine - pharmacology</topic><topic>Omeprazole</topic><topic>Omeprazole - pharmacology</topic><topic>opioid</topic><topic>Opioids</topic><topic>Pathology</topic><topic>proton pump inhibition</topic><topic>Proton pump inhibitors</topic><topic>Proton Pump Inhibitors - adverse effects</topic><topic>TLR2 protein</topic><topic>Toll-Like Receptor 2</topic><topic>Toll-like receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ghosh, Nillu</creatorcontrib><creatorcontrib>Kesh, Kousik</creatorcontrib><creatorcontrib>Singh, Praveen Kumar</creatorcontrib><creatorcontrib>Sharma, Umakant</creatorcontrib><creatorcontrib>Chupikova, Irina</creatorcontrib><creatorcontrib>Ramakrishnan, Sundaram</creatorcontrib><creatorcontrib>Roy, Sabita</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ghosh, Nillu</au><au>Kesh, Kousik</au><au>Singh, Praveen Kumar</au><au>Sharma, Umakant</au><au>Chupikova, Irina</au><au>Ramakrishnan, Sundaram</au><au>Roy, Sabita</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Morphine use induces gastric microbial dysbiosis driving gastric inflammation through TLR2 signalling which is attenuated by proton pump inhibition</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2023-06</date><risdate>2023</risdate><volume>180</volume><issue>12</issue><spage>1582</spage><epage>1596</epage><pages>1582-1596</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><abstract>Background and Purpose
Opioids are the standard drug for pain management; however, their effects on gastric dysfunction are relatively understudied. Opioid users have a higher incidence of gastric pathology leading to increased hospitalization. Herein, we investigated the consequences of morphine use on gastric pathology and the underlying mechanisms. We further investigated the therapeutic benefit of proton pump inhibition to overcome morphine‐mediated gastric inflammation.
Experimental Approach
Mice were implanted with 25 mg slow‐release morphine and placebo pellets. Gastric microbiome analyses were performed. Gastric damage was assayed. Gastric pH was measured. Germ‐free and TLR2KO mice were used to investigate the mechanisms. Gastroprotective studies were performed with the proton pump inhibitor (PPI) omeprazole.
Key Results
Chronic morphine treatment alters gastric microbial composition and induces preferential expansion of pathogenic bacterial communities such as Streptococcus and Pseudomonas. Morphine causes disruption of the gastric mucosal layer, increases apoptosis, and elevates inflammatory cytokines. Moreover, morphine‐mediated gastric pathology was significantly attenuated in germ‐free mice, and reconstitution of morphine gastric microbiome in germ‐free mice resulted gastric inflammation. In addition, morphine‐mediated gastric inflammation was attenuated in TLR2KO mice. Morphine causes a decrease in gastric pH, which contributes to gastric dysbiosis leads to gastric inflammation. Omeprazole treatment inhibits gastric acidity, rescuing morphine‐induced gastric dysbiosis and preventing inflammation.
Conclusion and Implications
This study attributes morphine‐induced gastric acidity as a driver of gastric dysbiosis and pathology and proposes the therapeutic use of PPI as an inexpensive approach for the clinical management of morphine‐associated pathophysiology.
Morphine treatment increases gastric acid secretion which causes dysbiosis of gastric microbiome. The dysbiotic gastric microbiome induces gastric inflammation through TLR2‐mediated signaling. Omeprazole prevents morphine‐induced gastric damage by regulating gastric acid secretion and restoring normal gastric microbiota.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>36585367</pmid><doi>10.1111/bph.16025</doi><tpages>15</tpages></addata></record> |
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subjects | Acidity Analgesics, Opioid - pharmacology Animals Apoptosis Dysbacteriosis Dysbiosis - chemically induced gastric inflammation Gastric juice gastric microbiome Gastric mucosa germ‐free mice Inflammation Inflammation - drug therapy Mice Microbiomes Morphine Morphine - pharmacology Omeprazole Omeprazole - pharmacology opioid Opioids Pathology proton pump inhibition Proton pump inhibitors Proton Pump Inhibitors - adverse effects TLR2 protein Toll-Like Receptor 2 Toll-like receptors |
title | Morphine use induces gastric microbial dysbiosis driving gastric inflammation through TLR2 signalling which is attenuated by proton pump inhibition |
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