Morphine Potentiates Dysbiotic Microbial and Metabolic Shifts in Acute SIV Infection
Gregory M Sindberg1, Shannon E Callen2, Santanu Banerjee3,4
1Department of Veterinary Biosciences, University of Minnesota, Saint Paul, MN, USA.
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.
Insights
Early simian immunodeficiency virus (SIV) infection combined with morphine causes significant gut microbiome and metabolic changes. These early alterations in gut microbes may drive inflammation and faster progression to AIDS.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Human Immunodeficiency Virus (HIV) pathogenesis is linked to microbial translocation, inflammation, and replication.
- Opioid use exacerbates HIV progression to Acquired Immunodeficiency Syndrome (AIDS).
- Early-stage interactions between HIV, opioids, and the gut microbiome remain understudied.
Purpose of the Study:
- To investigate the impact of early Simian Immunodeficiency Virus (SIV) infection and opioid use on the gut microbiome and metabolome.
- To identify early microbial and metabolic changes that may precede translocation events in HIV pathogenesis.
Main Methods:
- SIV-infected non-human primates were studied at ≤21 days post-infection, with and without morphine co-administration.
- Fecal samples underwent 16S rRNA gene sequencing for microbial community analysis.
- Metabolite profiling was performed using mass spectrometry.
Main Results:
- SIV infection alone showed minor changes within the studied timeframe.
- Co-administration of morphine and SIV led to significant alterations in microbial communities and metabolic profiles.
- These changes occurred independently of the duration of morphine exposure.
Conclusions:
- Early microbial dysbiosis occurs in SIV-infected primates treated with morphine.
- These early gut microbiome and metabolic shifts likely contribute to later translocation events in SIV/HIV pathogenesis.
- Metabolic profiles may serve as predictive biomarkers for therapeutic interventions to slow HIV progression.
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