Opioid Use and Gut Dysbiosis in Cancer Pain Patients
Abstract
:1. Introduction
2. Gut Microbiota: Definitions, Basic Concepts, and Methodologies
3. The Effects of Opioid Use on the Gut Microbiota
3.1. Preclinical Evidence
3.2. Clinical Evidence
4. The Gut Microbiota–Brain Axis
5. Gut Dysbiosis and Neuroinflammation
6. Consequences of Gut-Microbiota Alterations on Reward and Addiction Processes
7. Opioid-Induced Gut Dysbiosis in Cancer Patients
8. Gut Microbiota: A New Target of Treatment
8.1. Probiotics and Prebiotics
8.2. Fecal Microbiota Transplantation
9. Conclusions
Funding
Conflicts of Interest
References
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Study | Opioid RoA Dosage | Treatment Duration | Findings on Dysbiosis | Findings on Analgesia |
---|---|---|---|---|
Lee et al. 2018 [29] | i.p. morphine 10, 20, 30, 40 mg/kg BID vs. s.c. morphine (implanted pellet) 25 mg | 4 days | Both intermittent or sustained morphine led to gut bacterial changes. Intermittent morphine increased relative abundance of Ruminococcus spp. and decreased Lactobacillus spp. Sustained morphine increased relative abundances in Clostridium spp. and the family Rikenellaceae. | Both intermittent and sustained morphine treatment regimens resulted in morphine tolerance. Intermittent, but not sustained, morphine altered microglial morphology, and hyperalgesia. |
Banerjee et al. 2016 [31] | s.c. morphine (implanted pellets) 25 mg | 24–48 h | Morphine induced significant gut microbial dysbiosis: expansion of gram-positive Firmicutes phylum and reduction of phylum Bacteroidetes (reduced Bacteroidetes/Firmicutes ratio). Elevated levels of IL17 were observed after morphine treatment. Gut dysbiosis was reversed by fecal transplantation. Morphine disrupted cholesterol/bile acid metabolism. | N.A. |
Kang et al. 2017 [30] | i.p. morphine 10 mg/kg (acute) vs. s.c. morphine (implanted pellets) 75 mg (chronic) | 5 days (after 5 days of ABX pretreatment) | Chronic, but not acute, administration of morphine, altered gut permeability, enhanced bacterial translocation, and increased IL-1beta. All these effects were prevented by ABX treatment. | Chronic morphine exposure resulted in antinociceptive tolerance (in tail immersion and acetic acid stretch assay). ABX reduced gut bacteria and prevented antinociceptive tolerance. |
Wang et al. 2018 [39] | s.c. morphine 25 mg vs. s.c. naltrexone 30 mg vs. s.c. morphine and naltrexone (implanted pellets) | 1–6 days +6 days post-treatment | At day 1, the microbiome from the morphine-treated group clustered distinctly from all other groups; bacterial translocation into the MLN was observed; this trend was maintained as long as day 6. Naltrexone antagonized these effects. At day 3, naltrexone-treated animals clustered distinctly from placebo (possible role for endogenous opioids in the basal host microbial profile). | Infection with E. faecalis augmented morphine induced analgesic tolerance (in tail flick test). |
Abu et al. 2022 [40] | i.p. hydromorphone 10 mg/kg OD | 3 days G11–G13 -beginning of GI development in the growing fetus -(G0 gestation day 0) | Brief hydromorphone exposure during pregnancy induced changes in both maternal and neonatal microbioma. In dams, Gram-negative bacteria increased and Gram-positive bacteria decreased. This trend was inverted in POE neonates. | N.A. |
Abu et al. 2023 [41] | s.c. hydromorphone 0.5–3.5 mg/kg BID (0.75 mg/kg dose increments every 3 days) Followed by i.p. methadone 10 mg/kg BID | 14 days pre-mating, then rotated to methadone | Methadone-exposed dams showed enriched aerobic, biofilm forming bacteria, and Gram-negative bacteria relative to control, and decreased relative abundance of Gram-positive bacteria. Dysbiosis of dams correlated with dysbiosis in POE neonates. | POE (methadone) increased sensitivity to thermal and mechanical pain. Supplementation with probiotics in dams altered neonatal gut microbiome and rescued hypersensitivity to thermal and mechanical pain. |
Zhang et al. 2019 [34] | s.c. morphine 5–40 mg/kg BID Escalating doses | 8 days | Chronic morphine induced gut dysbiosis: reduction in Actinobacteria and Firmicutes, Bifidobacteriaceae and Lactobacillaceae families, and Bifidobacterium and Lactobacillus gena; significant bacterial translocation was observed. Morphine initiated local gut inflammation through TLR2 and TLR4 activation (reversed in ABX mice): increased levels of proinflammatory cytokines IL6, IL1 beta, and TNF alfa. | Probiotic pretreatment attenuated morphine tolerance and prevented morphine-induced gut microbiota alterations. |
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Coluzzi, F.; Scerpa, M.S.; Loffredo, C.; Borro, M.; Pergolizzi, J.V.; LeQuang, J.A.; Alessandri, E.; Simmaco, M.; Rocco, M. Opioid Use and Gut Dysbiosis in Cancer Pain Patients. Int. J. Mol. Sci. 2024, 25, 7999. https://doi.org/10.3390/ijms25147999
Coluzzi F, Scerpa MS, Loffredo C, Borro M, Pergolizzi JV, LeQuang JA, Alessandri E, Simmaco M, Rocco M. Opioid Use and Gut Dysbiosis in Cancer Pain Patients. International Journal of Molecular Sciences. 2024; 25(14):7999. https://doi.org/10.3390/ijms25147999
Chicago/Turabian StyleColuzzi, Flaminia, Maria Sole Scerpa, Chiara Loffredo, Marina Borro, Joseph V. Pergolizzi, Jo Ann LeQuang, Elisa Alessandri, Maurizio Simmaco, and Monica Rocco. 2024. "Opioid Use and Gut Dysbiosis in Cancer Pain Patients" International Journal of Molecular Sciences 25, no. 14: 7999. https://doi.org/10.3390/ijms25147999