Morphine Potentiates Dysbiotic Microbial and Metabolic Shifts in Acute SIV Infection

Sindberg, Gregory M.; Callen, Shannon; Banerjee, Santanu; Meng, Jingjing; Hale, Vanessa L.; Hegde, R. K.; Cheney, Paul D.; Villinger, François; Roy, Sabita; Buch, Shilpa

doi:10.1007/s11481-018-9805-6

Cited by 32 publications

(19 citation statements)

References 83 publications

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“…These effects were antagonized by naltrexone (Wang et al 2018a). Additional studies have also demonstrated that morphine treatment results in a decrease in primary and secondary bile acids (Banerjee et al 2016;Sindberg et al 2018). These findings are especially important, because bile acids can prevent the overgrowth and translocation of gut bacteria.…”

Section: Bile Acids Andmentioning

confidence: 98%

“…Dysbiosis in response to opioid treatment can occur rapidly; within 1 day of morphine pellet implantation there is a dramatic shift in the gut microbiome of mice compared to placebo-treated animals (Wang et al 2018a). Nonhuman primate studies suggest that the resultant dysbiosis is maintained with long-term morphine treatment, despite the development of increasing tolerance to the drug (Sindberg et al 2018). At the phylum level, morphine treatment results in a relative reduction of Gramnegative Bacteroidetes and a relative expansion of Gram-positive Firmicutes, particularly potentially pathogenic bacterial families such as Enterococcaceae and Staphylococcaceae (Meng et al 2013(Meng et al , 2015aBanerjee et al 2016;Kang et al 2017;Wang et al 2018a).…”

Section: Opioidsmentioning

confidence: 99%

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A potential role for the gut microbiome in substance use disorders

2019

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Pathological substance use disorders represent a major public health crisis with limited effective treatment options. While much work has been done to understand the neuronal signaling networks and intracellular signaling cascades associated with prolonged drug use, these studies have yielded few successful treatment options for substance use disorders. In recent years, there has been a growing interest to explore interactions between the peripheral immune system, the gut microbiome and the CNS. In this review we will present a summary of existing evidence, suggesting a potential role for gut dysbiosis in the pathogenesis of substance use disorders. Clinical evidence of gut dysbiosis in human subjects with substance use disorder as well as preclinical evidence of gut dysbiosis in animal models of drug addiction are discussed in detail. Additionally, we examine how changes in the gut microbiome and its metabolites may not only be a consequence of substance use disorders but may in fact play a role in mediating behavioral response to drugs of abuse. While much work still needs to be done, understanding the interplay of gut microbiome in substance use disorders may offers a promising avenue for future therapeutic development.

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Section: Bile Acids Andmentioning

confidence: 98%

Section: Opioidsmentioning

confidence: 99%

A potential role for the gut microbiome in substance use disorders

2019

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“…However, in some experiments, other opioid agents were used, such as loperamide [136,137] or hydromorphone [138], and there are some common patterns in the microbial composition of animals irrespective of the type of opioid used, allowing to draw some general conclusions on the effect of opioids on microbiota. Moreover, some of these changes have also been observed in non-human primates [139], as well as in opioid user cirrhotic patients compared to those not on opioids [140], or in heroin addicts [141], further supporting the complexity and translational relevance of the results.…”

Section: The Role Of Mors In the Gut Microbiota: Dysbiosis Opioid Tolerancementioning

confidence: 69%

“…The bidirectional interaction between motility and microbiota is well-known [136,153], and as mentioned above, loperamide-induced dysbiosis resembles in some aspects that caused by morphine [136,137]. In addition, changes in bile acid metabolism due to opioids may also contribute to the consequence of dysbiosis [134,139].…”

Section: The Role Of Mors In the Gut Microbiota: Dysbiosis Opioid Tolerancementioning

confidence: 93%

On the Role of Peripheral Sensory and Gut Mu Opioid Receptors: Peripheral Analgesia and Tolerance

et al. 2020

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There is growing evidence on the role of peripheral µ-opioid receptors (MORs) in analgesia and analgesic tolerance. Opioid analgesics are the mainstay in the management of moderate to severe pain, and their efficacy in the alleviation of pain is well recognized. Unfortunately, chronic treatment with opioid analgesics induces central analgesic tolerance, thus limiting their clinical usefulness. Numerous molecular mechanisms, including receptor desensitization, G-protein decoupling, β-arrestin recruitment, and alterations in the expression of peripheral MORs and microbiota have been postulated to contribute to the development of opioid analgesic tolerance. However, these studies are largely focused on central opioid analgesia and tolerance. Accumulated literature supports that peripheral MORs mediate analgesia, but controversial results on the development of peripheral opioid receptors-mediated analgesic tolerance are reported. In this review, we offer evidence on the consequence of the activation of peripheral MORs in analgesia and analgesic tolerance, as well as approaches that enhance analgesic efficacy and decrease the development of tolerance to opioids at the peripheral sites. We have also addressed the advantages and drawbacks of the activation of peripheral MORs on the sensory neurons and gut (leading to dysbiosis) on the development of central and peripheral analgesic tolerance.

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“…Another important area of opioid-induced dysbiosis is bile acid formation. Chronic opioid treatment leads to reductions in both primary and secondary bile acid transformation (Banerjee et al, 2016;Wang et al, 2018;Sindberg et al, 2019). Bile acids are not only important for nutrient absorption and metabolism but also inhibit the expansion and translocation of certain pathogenic bacteria (Yoon et al, 2017).…”

Section: Nociceptin Neurocircuitry and Motivationmentioning

confidence: 99%

Pain, Motivation, Migraine, and the Microbiome: New Frontiers for Opioid Systems and Disease

et al. 2020

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For decades the broad role of opioids in addiction, neuropsychiatric disorders, and pain states has been somewhat well established. However, in recent years, with the rise of technological advances, not only is the existing dogma being challenged, but we are identifying new disease areas in which opioids play a critical role. This review highlights four new areas of exploration in the opioid field. The most recent addition to the opioid family, the nociceptin receptor system, shows promise as the missing link in understanding the neurocircuitry of motivation. It is well known that activation of the kappa opioid receptor system modulates negative affect and dysphoria, but recent studies now implicate the kappa opioid system in the modulation of negative affect associated with pain. Opioids are critical in pain management; however, the often-forgotten delta opioid receptor system has been identified as a novel therapeutic target for headache disorders and migraine. Lastly, changes to the gut microbiome have been shown to directly contribute to many of the symptoms of chronic opioid use and opioid related behaviors. This review summarizes the findings from each of these areas with an emphasis on identifying new therapeutic targets. SIGNIFICANCE STATEMENT The focus of this minireview is to highlight new disease areas or new aspects of disease in which opioids have been implicated; this includes pain, motivation, migraine, and the microbiome. In some cases, this has resulted in the pursuit of a novel therapeutic target and resultant clinical trial. We believe this is very timely and will be a refreshing take on reading about opioids and disease.

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Morphine Potentiates Dysbiotic Microbial and Metabolic Shifts in Acute SIV Infection

Cited by 32 publications

References 83 publications

A potential role for the gut microbiome in substance use disorders

A potential role for the gut microbiome in substance use disorders

On the Role of Peripheral Sensory and Gut Mu Opioid Receptors: Peripheral Analgesia and Tolerance

Pain, Motivation, Migraine, and the Microbiome: New Frontiers for Opioid Systems and Disease

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