Chronic Opioid Administration is Associated with Prevotella-dominated Dysbiosis in SIVmac251 Infected, cART-treated Macaques

Johnson, Samuel D.; Fox, Howard S.; Buch, Shilpa; Byrareddy, Siddappa N.

doi:10.1007/s11481-021-09993-4

Cited by 9 publications

(12 citation statements)

References 43 publications

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“…Our findings morphine perturbs the diversity of the gut microbiota at the community level agrees with previous reports that show that morphine distorts the gut bacterial microbiome (Zhang et al, 2019;Johnson et al, 2021). Further, our findings agree with the previous reports that show that morphine exposure causes the depletion of SCFA-producing bacteria (Sindberg et al, 2019;Gicquelais et al, 2020;Johnson et al, 2021).…”

Section: Discussionsupporting

confidence: 93%

“…The influence of the fecal microbiome on brain functions, such as neurogenesis, was ascertained after fecal transplants obtained from old mice promoted hippocampal neurogenesis in germ-free mice ( Kundu et al, 2019 ). Our findings morphine perturbs the diversity of the gut microbiota at the community level agrees with previous reports that show that morphine distorts the gut bacterial microbiome ( Zhang et al, 2019 ; Johnson et al, 2021 ). Further, our findings agree with the previous reports that show that morphine exposure causes the depletion of SCFA-producing bacteria ( Sindberg et al, 2019 ; Gicquelais et al, 2020 ; Johnson et al, 2021 ).…”

Section: Discussionsupporting

confidence: 93%

“…Using 341F/805R primers, a 465 bp amplicon was generated by targeting the V3 and V4 regions of the 16S rRNA gene. Then, sequencing was performed on the Illumina MiSeq platform (according to the manufacturer’s specifications) at LC Sciences to yield 250 bp paired-end reads in either direction ( Johnson et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

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Systems biology analyses reveal enhanced chronic morphine distortion of gut-brain interrelationships in simian human immunodeficiency virus infected rhesus macaques

et al. 2022

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BackgroundCommonly used opioids, such as morphine have been implicated in augmented SIV/HIV persistence within the central nervous system (CNS). However, the extent of myeloid cell polarization and viral persistence in different brain regions remains unclear. Additionally, the additive effects of morphine on SIV/HIV dysregulation of gut-brain crosstalk remain underexplored. Therefore, studies focused on understanding how drugs of abuse such as morphine affect immune dynamics, viral persistence and gut-brain interrelationships are warranted.Materials and methodsFor a total of 9 weeks, rhesus macaques were ramped-up, and twice daily injections of either morphine (n = 4) or saline (n = 4) administered. This was later followed with infection with SHIVAD8EO variants. At necropsy, mononuclear cells were isolated from diverse brain [frontal lobe, cerebellum, medulla, putamen, hippocampus (HIP) and subventricular zone (SVZ)] and gut [lamina propria (LP) and muscularis (MUSC) of ascending colon, duodenum, and ileum] regions. Multiparametric flow cytometry was used to were profile for myeloid cell polarity/activation and results corroborated with indirect immunofluorescence assays. Simian human immunodeficiency virus (SHIV) DNA levels were measured with aid of the digital droplet polymerase chain reaction (PCR) assay. Luminex assays were then used to evaluate soluble plasma/CSF biomarker levels. Finally, changes in the fecal microbiome were evaluated using 16S rRNA on the Illumina NovaSeq platform.ResultsFlow Cytometry-based semi-supervised analysis revealed that morphine exposure led to exacerbated M1 (CD14/CD16)/M2 (CD163/CD206) polarization in activated microglia that spanned across diverse brain regions. This was accompanied by elevated SHIV DNA within the sites of neurogenesis–HIP and SVZ. HIP/SVZ CD16+ activated microglia positively correlated with SHIV DNA levels in the brain (r = 0.548, p = 0.042). Simultaneously, morphine dependence depleted butyrate-producing bacteria, including Ruminococcus (p = 0.05), Lachnospira (p = 0.068) genera and Roseburia_sp_831b (p = 0.068). Finally, morphine also altered the regulation of CNS inflammation by reducing the levels of IL1 Receptor antagonist (IL1Ra).ConclusionThese findings are suggestive that morphine promotes CNS inflammation by altering receptor modulation, increasing myeloid brain activation, distorting gut-brain crosstalk, and causing selective enhancement of SHIV persistence in sites of neurogenesis.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

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Systems biology analyses reveal enhanced chronic morphine distortion of gut-brain interrelationships in simian human immunodeficiency virus infected rhesus macaques

et al. 2022

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“…Reduced relative abundance of Roseburia has been reported in humans on opioid drugs ( 35 ). Firmicutes is reduced but Prevotella relative abundance was found to be increased in the above study testing effects of opioids on rhesus macaques ( 27 ). In a study with African American men, interrelationships were found between type 2 diabetes mellitus, metformin treatment, and opioid usage for Bifidobacterium and Prevotella genera ( 36 ).…”

Section: Discussionmentioning

confidence: 73%

“…Bacteroidetes relative abundance is also greater in simian immunodeficiency virus (SIV)-infected rhesus macaques treated with morphine ( 27 ). In mice, proliferation of Enterococcus faecalis correlates with gut dysbiosis due to morphine treatment ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Developmental Exposure to Oxycodone on Gut Microbiota and Relationship to Adult Behaviors and Metabolism

et al. 2022

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This is the first work to show in a rodent model that in utero exposure to an opioid drug can lead to longstanding effects on the gut microbiota when examined at adulthood. Further, such bacterial changes are associated with metabolic host responses. Given the similarities between rodent and human microbiomes, it raises cause for concern that similar effects may become evident in children born to mothers taking oxycodone and other opioid drugs.

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Opioid abuse and SIV infection in non-human primates

et al. 2023

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Chronic Opioid Administration is Associated with Prevotella-dominated Dysbiosis in SIVmac251 Infected, cART-treated Macaques

Cited by 9 publications

References 43 publications

Systems biology analyses reveal enhanced chronic morphine distortion of gut-brain interrelationships in simian human immunodeficiency virus infected rhesus macaques

Systems biology analyses reveal enhanced chronic morphine distortion of gut-brain interrelationships in simian human immunodeficiency virus infected rhesus macaques

Long-Term Effects of Developmental Exposure to Oxycodone on Gut Microbiota and Relationship to Adult Behaviors and Metabolism

Opioid abuse and SIV infection in non-human primates

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