Evidence map›Paper›PMID 36585367›Full record

ArticleBritish journal of pharmacology2023

Morphine use induces gastric microbial dysbiosis driving gastric inflammation through TLR2 signalling which is attenuated by proton pump inhibition.

Nillu Ghosh, Kousik Kesh, Praveen Kumar Singh, Umakant Sharma, Irina Chupikova, Sundaram Ramakrishnan, Sabita Roy

Open access · greenAbstract read
In one paragraph

Article in British journal of pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
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  5. Efficacy and tolerability ofHealth science reports · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Nillu GhoshDepartment of Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Kousik KeshDepartment of Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Praveen Kumar SinghDepartment of Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Umakant SharmaDepartment of Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Irina ChupikovaDepartment of Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Sundaram RamakrishnanDepartment of Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Sabita RoyDepartment of Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.
University of Miami · USSylvester Comprehensive Cancer Center · US

Funding

Role of Microbial dysbiosis and altered metabolomics in the context of Opioid abuse and ART in HIV disease progressionR01DA043252 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ROY, SABITA · 2017 to 2021
$3.0M
Gut microbiota disruption by Morphine and in the context of HIV infection contributes to sustained immune activationR01DA037843 · NIDA · UNIVERSITY OF MINNESOTA · PI JOHNSON, TIMOTHY J, ROY, SABITA · 2014 to 2018
$2.8M
Microbial Dysbiosis and TLR2 Activation Contribute to Immune Activation, Inflammation and HIV Persistence in the Context of Opioid Abuse Despite ART TherapyR01DA044582 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ROY, SABITA · 2017 to 2021
$2.6M
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV R01DA050542 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ROY, SABITA · 2019 to 2023
$2.5M
Role of Gut Microbiome in HIV/Opioid Induced Peripheral NeuropathyR01DA047089 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HAO, SHUANGLIN, RAMAKRISHNAN, SUNDARAM · 2018 to 2022
$2.3M
The Role of Microbiome Modulation in Morphine-Induced Exacerbation of PancreatitisR01DK117576 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ROY, SABITA · 2018 to 2021
$2.0M
Mechanism underlying Morphine modulation of gut barrier function in the Context oR01DA034582 · NIDA · UNIVERSITY OF MINNESOTA · PI ROY, SABITA · 2013 to 2017
$1.6M
Multidisciplinary Training in Substance Abuse ResearchT32DA045734 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ROY, SABITA · 2019 to 2023
$1.0M
NIDA NIH HHS R01 DA034582NIDA NIH HHS R01 DA037843NIDA NIH HHS R01 DA043252NIDA NIH HHS R01 DA044582NIDA NIH HHS R01 DA047089NIDA NIH HHS R01 DA050542NIDA NIH HHS T32 DA045734NIDDK NIH HHS R01 DK117576
6 · The paper itself

Abstract

background and purposeOpioids 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

resultsChronic 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.

Indexed as

DysbiosisToll-Like Receptor 2Analgesics, OpioidAnimalsInflammationMiceMorphineOmeprazoleProton Pump InhibitorsAnalgesics, OpioidMorphineOmeprazoleProton Pump InhibitorsTlr2 protein, mouseToll-Like Receptor 2gastric inflammationgastric microbiomegerm-free miceopioidproton pump inhibition

Identifiers

PMID36585367
PMCPMC10175111
OpenAlexW4313339487

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.