Opioid Use, Gut Dysbiosis, Inflammation, and the Nervous System

Jalodia, Richa; Abu, Yaa; Oppenheimer, Mark; Herlihy, Bridget; Meng, Jingjing; Chupikova, Irina; Tao, Junyi; Ghosh, Nillu; Dutta, Rajib; Kolli, Udhghatri; Yan, Yan; Valdes, Eridania; Sharma, Madhulika; Sharma, Umakant; Moidunny, Shamsudheen; Roy, Sabita

doi:10.1007/s11481-021-10046-z

Cited by 18 publications

(16 citation statements)

References 203 publications

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“…Although studies presented here show the profound role of opioids and CPT‐11 on the gut microbiome, it still must be acknowledged that differences in the microbiome between humans and rodents may limit direct translation of these studies. However, major trends reflected in these data such as morphine‐induced microbial dysbiosis (Jalodia et al, 2022) and gut microbiota‐mediated accumulation of SN‐38 in intestines following CPT‐11 administration (Sparreboom et al, 1998) have been shown in humans, although differences in bacterial taxa with morphine or CPT‐11 administration may change depending on human or rodent models utilized. Additionally, further investigations are warranted to determine whether opioid treatment interferes with the metabolism of other anti‐cancer agents inactivated by UDP‐glycosyltransferases (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Although studies presented here show the profound role of opioids and CPT-11 on the gut microbiome, it still must be acknowledged that differences in the microbiome between humans and rodents may limit direct translation of these studies. However, major trends reflected in these data such as morphine-induced microbial dysbiosis (Jalodia et al, 2022) and gut microbiota-mediated accumulation of SN-38 in intestines following CPT-11 administration (Sparreboom et al, 1998) in this study (Allain et al, 2020;Ervin et al, 2020). Of interest, in parallel with CPT-11, it has been shown that reactivation of the inactive regorafenib-glucuronide to regorafenib by gut microbial β-glucuronidase enzymes in the GI tract contributes to the chemotherapeutic agent regorafenib's GI toxicity, which is inhibited with β-glucuronidase inhibition (Ervin et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

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Opioid‐induced microbial dysbiosis disrupts irinotecan (CPT‐11) metabolism and increases gastrointestinal toxicity in a murine model

Meng

Abu

Zhang

et al. 2023

British J Pharmacology

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Background and Purpose Opioids are commonly used for the management of cancer‐associated pain and chemotherapy‐induced diarrhoea. The chemotherapeutic irinotecan (CPT‐11) causes severe gastrointestinal (GI) toxicity due to deconjugation of inactive metabolite SN‐38 glucuronide (SN‐38G) by bacterial β‐glucuronidases to the active 7‐ethyl‐10‐hydroxycamptothecin (SN‐38). Opioids are known to cause gut microbial dysbiosis, this study evaluated whether CPT‐11 anti‐tumour efficacy and GI toxicity are exacerbated by opioid co‐administration. Experimental Approach Eight‐week‐old C57BL/6 male mice were co‐administration with CPT‐11 ± opioid. 16S rRNA sequencing was used for gut microbiome analysis. LC–MS analyses of plasma and intestinal extracts were performed to investigate the pharmacokinetic profile of CPT‐11. Histological analysis and quantitative real‐time polymerase chain reaction were used to determine the severity of intestinal tissue damage. Human liver microsome In vitro assay was performed to confirm the effects of opioids on CPT‐11 metabolism. Key Results Gut microbiome analysis showed that morphine treatment induced enrichment of β‐glucuronidase‐producing bacteria in the intestines of CPT‐11‐treated mice, resulting in SN‐38 accumulation and exacerbation of GI toxicity in the small intestine. Oral administration of both antibiotics and glucuronidase inhibitor protected mice against GI toxicity induced with CPT‐11 and morphine co‐administration, implicating a microbiome‐dependent mechanism. Additionally, morphine and loperamide decreased the plasma concentration of SN‐38 and compromised CPT‐11 anti‐tumour efficacy, this seemed to be microbiome independent. Conclusion and Implications Gut microbiota play a significant role in opioid and chemotherapeutic agent drug–drug interactions. Inhibition of gut microbial glucuronidase may also prevent adverse GI effects of CPT‐11 in patients on opioids.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Opioid‐induced microbial dysbiosis disrupts irinotecan (CPT‐11) metabolism and increases gastrointestinal toxicity in a murine model

Meng

Abu

Zhang

et al. 2023

British J Pharmacology

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“…For example, in animal models of addiction, increased colonization of Firmicutes was reported in samples of morphine-exposed mice31; however, in other studies, decreased colonization was observed in hydromorphone-exposed mice32 and oxycodone-exposed rats 33. Suggested mechanisms of gut dysbiosis in adult models include alterations in bacterial metabolites, including short-chain fatty acids, bile acids, and bacterial diversity 28,29…”

Section: The Early Gut Microbiomementioning

confidence: 99%

A Scoping Review of Neonatal Opioid Withdrawal and the Infant Gut Microbiome

McGlothen-Bell¹,

Groër²,

Brownell³

et al. 2023

Advances in Neonatal Care

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Background: While a growing body of literature has established the role of human milk as a mechanism of protection in the formation of the infant gut microbiome, it remains unclear the extent to which this association exists for infants with neonatal opioid withdrawal syndrome. Purpose: The purpose of this scoping review was to describe the current state of the literature regarding the influence of human milk on infant gut microbiota in infants with neonatal opioid withdrawal syndrome. Data Sources: CINAHL, PubMed, and Scopus databases were searched for original studies published from January 2009 through February 2022. Additionally, unpublished studies across relevant trial registries, conference proceedings, websites, and organizations were reviewed for possible inclusion. A total of 1610 articles met selection criteria through database and register searches and 20 through manual reference searches. Study Selection: Inclusion criteria were primary research studies, written in English, published between 2009 and 2022, including a sample of infants with neonatal opioid withdrawal syndrome/neonatal abstinence syndrome, and focusing on the relationship between the receipt of human milk and the infant gut microbiome. Data Extraction: Two authors independently conducted title/abstract and full-text review until there was consensus of study selection. Results: No studies satisfied the inclusion criteria, which resulted in an empty review. Implications for Practice and Research: Findings from this study document the paucity of data exploring the associations between human milk, the infant gut microbiome, and subsequent neonatal opioid withdrawal syndrome. Further, these results highlight the timely importance of prioritizing this area of scientific inquiry.

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“…The involvement of the gut-brain axis seems to be of increasing importance in inducing antinociceptive tolerance. Dysbiosis and associated immune dysregulation point towards the progression of neurological problems and OUDs [ 83 , 84 ], whereby reduced GI motility and OIC appear to worsen these effects.…”

Section: Future Directions and Conclusionmentioning

confidence: 99%

Pain and Opioid-Induced Gut Microbial Dysbiosis

Thomas

Watt

et al. 2022

Biomedicines

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Opioid-induced dysbiosis (OID) is a specific condition describing the consequences of opioid use on the bacterial composition of the gut. Opioids have been shown to affect the epithelial barrier in the gut and modulate inflammatory pathways, possibly mediating opioid tolerance or opioid-induced hyperalgesia; in combination, these allow the invasion and proliferation of non-native bacterial colonies. There is also evidence that the gut-brain axis is linked to the emotional and cognitive aspects of the brain with intestinal function, which can be a factor that affects mental health. For example, Mycobacterium, Escherichia coli and Clostridium difficile are linked to Irritable Bowel Disease; Lactobacillaceae and Enterococcacae have associations with Parkinson’s disease, and Alistipes has increased prevalence in depression. However, changes to the gut microbiome can be therapeutically influenced with treatments such as faecal microbiota transplantation, targeted antibiotic therapy and probiotics. There is also evidence of emerging therapies to combat OID. This review has collated evidence that shows that there are correlations between OID and depression, Parkinson’s Disease, infection, and more. Specifically, in pain management, targeting OID deserves specific investigations.

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Opioid Use, Gut Dysbiosis, Inflammation, and the Nervous System

Cited by 18 publications

References 203 publications

Opioid‐induced microbial dysbiosis disrupts irinotecan (CPT‐11) metabolism and increases gastrointestinal toxicity in a murine model

Opioid‐induced microbial dysbiosis disrupts irinotecan (CPT‐11) metabolism and increases gastrointestinal toxicity in a murine model

A Scoping Review of Neonatal Opioid Withdrawal and the Infant Gut Microbiome

Pain and Opioid-Induced Gut Microbial Dysbiosis

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