Abstract
Human Immunodeficiency Virus (HIV) pathogenesis has been closely linked with microbial translocation, which is believed to drive inflammation and HIV replication. Opioid drugs have been shown to worsen this symptom, leading to a faster progression of HIV infection to Acquired Immunodeficiency Syndrome (AIDS). The interaction of HIV and opioid drugs has not been studied at early stages of HIV, particularly in the gut microbiome where changes may precede translocation events. This study modeled early HIV infection by examining Simian Immunodeficiency Virus (SIV)-infected primates at 21 days or less both independently and in the context of opioid use. Fecal samples were analyzed both for 16S analysis of microbial populations as well as metabolite profiles via mass spectrometry. Our results indicate that changes are minor in SIV treated animals in the time points examined, however animals treated with morphine and SIV had significant changes in their microbial communities and metabolic profiles. This occurred in a time-independent fashion with morphine regardless of how long the animal had morphine in its system. Globally, the observed changes support that microbial dysbiosis is occurring in these animals at an early time, which likely contributes to the translocation events observed later in SIV/HIV pathogenesis. Additionally, metabolic changes were predictive of specific treatment groups, which could be further developed as a diagnostic tool or future intervention target to overcome and slow the progression of HIV infection to AIDS.
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Funding
Funding for the study was provided by the following grants from the National Institute on Drug Abuse (NIDA) division of the National Institute of Health (https://www.drugabuse.gov/): R01 DA043252 (SR), R01 DA037843 (SR), K05 DA033881 (SR), R01 DA031202 (SR), R01 DA035203 (ShB), R01 DA043138 (ShB), R01 DA040397 (ShB), R01 DA044586 (ShB). GS was supported under NIDA training grant T32 DA007097. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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GS, ShB, and SR conceived the idea for the project. GS and VH analyzed and arranged figures from the bioinformatics data. SC, RH, and PC cared for the animals, delivered treatments, and handled sample collection. GS, SB, JM processed samples for 16S sequencing and metabolic analysis. FV performed histology staining and analysis. GS wrote the initial draft of the paper. GS, SC, ShB, and SR were the primary editors and reworked the manuscript. All authors have read and approved the final manuscript.
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H&E staining of ileum at necropsy shows immune infiltration. Histological data from each group show infiltration of immune cells into the lamina propria, however no significant difference was observed between the SIV and the morphine or morphine+ HIV groups. (PNG 1343 kb)
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Sindberg, G.M., Callen, S.E., Banerjee, S. et al. Morphine Potentiates Dysbiotic Microbial and Metabolic Shifts in Acute SIV Infection. J Neuroimmune Pharmacol 14, 200–214 (2019). https://doi.org/10.1007/s11481-018-9805-6
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DOI: https://doi.org/10.1007/s11481-018-9805-6