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Merck

Chronic opioid use modulates human enteric microbiota and intestinal barrier integrity.

Gut microbes (2021-07-28)
Angélica Cruz-Lebrón, Ramona Johnson, Claire Mazahery, Zach Troyer, Samira Joussef-Piña, Miguel E Quiñones-Mateu, Christopher M Strauch, Stanley L Hazen, Alan D Levine
RESUMEN

Over the past three decades the United States has experienced a devastating opioid epidemic. One of the many debilitating side effects of chronic opioid use is opioid-induced bowel dysfunction. We investigated the impact of methadone maintenance treatment (MMT) on the gut microbiome, the gut bacterial metabolite profile, and intestinal barrier integrity. An imbalance in key bacterial communities required for production of short-chain fatty acids (SCFAs), mucus degradation, and maintenance of barrier integrity was identified. Consistent with dysbiosis, levels of fecal SCFAs were reduced in MMT. We demonstrated that metabolites synthesized by Akkermansia muciniphila modulate intestinal barrier integrity in vitro by strengthening the pore pathway and regulating tight junction protein expression. This study provides essential information about the therapeutic potential of A. muciniphila and warrants development of new clinical strategies that aim to normalize the gut microbiome in individuals affected by chronic opioid use.

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Sigma-Aldrich
Anticuerpo anti-gliceraldehído-3-fosfato deshidrogenasa, clon 6C5, clone 6C5, Chemicon®, from mouse
Sigma-Aldrich
Sodium propionate, ≥99.0%
Sigma-Aldrich
Sodium butyrate, ≥98.5% (GC)
Sigma-Aldrich
Naloxone hydrochloride dihydrate, ≥98% (TLC and titration), powder
Sigma-Aldrich
(±)-Methadone hydrochloride, powder, ≥98%
Sigma-Aldrich
Anti-Claudin-1 (C-terminal) antibody produced in rabbit, ~1.0 mg/mL, affinity isolated antibody