Disruption of gut homeostasis by opioids accelerates HIV disease progression

Cumulative studies during the past 30 years have established the correlation between opioid abuse and human immunodeficiency virus (HIV) infection. Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients. Recently, it was revealed that disruption of gut homeostasis and subsequent microbial translocation play important roles in pathological activation of the immune system during HIV infection and contributes to accelerated disease progression. Similarly, opioids have been shown to modulate gut immunity and induce gut bacterial translocation. This review will explore the mechanisms by which opioids accelerate HIV disease progression by disrupting gut homeostasis. Better understanding of these mechanisms will facilitate the search for new therapeutic interventions to treat HIV infection especially in opioid abusing population

16S Intestinal Microbiome Sequences of Rhesus Macaques Treated with Chronic Morphine for 92 Days, SIV for 21 Days, or in Combination (Morphine for 70 Days then SIV+Morphine for 21 Days)

Rhesus Macaque fecal matter was sequenced at different intervals after receiving Morphine I.V., SIV infection, or in sequence. The intervals are as follows: Morphine for 92 days, SIV for 21 days, or a sequence of morphine for 70 days then SIV+Morphine for 21 days. This was used to look for microbial and metabolic changes due to the treatments

16S Intestinal Microbiome Sequences of Rhesus Macaques Treated with Chronic Morphine for 92 Days, SIV for 21 Days, or in Combination (Morphine for 70 Days then SIV+Morphine for 21 Days)

The dataset contains 78 FASTQ files which are 16S V4 region sequences from with the file names indicating the following information: Mo104 indicates the experiment number as was defined by our collaborators at University of Nebraska - Omaha; ##### (i.e. 39909) indicates the Rhesus Macaque animal number that was assigned; 09112013 indicates MonthDayYear that each sample was collected; S## (i.e. S70) is an internal number assigned by the UMGC sequencing core to each sequence; L0001 = an internal number assigned by UMGC; R1 = Read 1, as assigned by the UMGC sequencing core; 001 = an internal number assigned by UMGC. This information is also contained in the metadata txt file.Rhesus Macaque fecal matter was sequenced at different intervals after receiving Morphine I.V., SIV infection, or in sequence. The intervals are as follows: Morphine for 92 days, SIV for 21 days, or a sequence of morphine for 70 days then SIV+Morphine for 21 days. This was used to look for microbial and metabolic changes due to the treatments.NIDA (NIH

Disruption of gut homeostasis by opioids accelerates HIV disease progression

Cumulative studies during the past 30 years have established the correlation between opioid abuse and human immunodeficiency virus (HIV) infection. Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients. Recently, it was revealed that disruption of gut homeostasis and subsequent microbial translocation play important roles in pathological activation of the immune system during HIV infection and contributes to accelerated disease progression. Similarly, opioids have been shown to modulate gut immunity and induce gut bacterial translocation. This review will explore the mechanisms by which opioids accelerate HIV disease progression by disrupting gut homeostasis. Better understanding of these mechanisms will facilitate the search for new therapeutic interventions to treat HIV infection especially in opioid abusing population

Opioid Exacerbation of Gram-positive sepsis, induced by Gut Microbial Modulation, is Rescued by IL-17A Neutralization

Sepsis is the predominant cause of mortality in ICUs, and opioids are the preferred analgesic in this setting. However, the role of opioids in sepsis progression has not been well characterized. The present study demonstrated that morphine alone altered the gut microbiome and selectively induced the translocation of Gram-positive gut bacteria in mice. Using a murine model of poly-microbial sepsis, we further demonstrated that morphine treatment led to predominantly Gram-positive bacterial dissemination. Activation of TLR2 by disseminated Gram-positive bacteria induced sustained up-regulation of IL-17A and IL-6. We subsequently showed that overexpression of IL-17A compromised intestinal epithelial barrier function, sustained bacterial dissemination and elevated systemic inflammation. IL-17A neutralization protected barrier integrity and improved survival in morphine-treated animals. We further demonstrated that TLR2 expressed on both dendritic cells and T cells play essential roles in IL-17A production. Additionally, intestinal sections from sepsis patients on opioids exhibit similar disruption in gut epithelial integrity, thus establishing the clinical relevance of this study. This is the first study to provide a mechanistic insight into the opioid exacerbation of sepsis and show that neutralization of IL-17A might be an effective therapeutic strategy to manage Gram-positive sepsis in patients on an opioid regimen

An infectious murine model for studying the systemic effects of opioids on early HIV pathogenesis in the gut

Opioids are known to exacerbate HIV pathogenesis, however current studies have been limited by models of HIV infection. Given that HIV causes many systemic effects via direct infection of host cells as well as indirect bystander effects, it is important to establish a systemic infection model in a small animal so that genetic tools can be utilized to elucidate the mechanisms of action. In this study, we describe the systemic effects of EcoHIV infection, a modified HIV which can infect mouse cells, in conjunction with morphine. We observed that EcoHIV infection with opioid treatment induces bacterial translocation from the lumen of the gut into systemic compartments such as liver, which is similar to observations in human patients with LPS. Bacterial translocation corresponds with alterations in gut morphology, disorganization of the tight junction protein occludin, and a concurrent increase in systemic inflammation in both IL-6 and TNFα. Long term infection also had increased expression of inflammatory cytokines in the CNS when co-treated with morphine. Overall, we conclude that EcoHIV is an appropriate model to study the effects of opioids on HIV pathogenesis, including the HIV-induced pathology at early stages of pathogenesis in the gut

Morphine Potentiates Dysbiotic Microbial and Metabolic Shifts in Acute SIV Infection

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

Humidity as a non-pharmaceutical intervention for influenza A.

Influenza is a global problem infecting 5-10% of adults and 20-30% of children annually. Non-pharmaceutical interventions (NPIs) are attractive approaches to complement vaccination in the prevention and reduction of influenza. Strong cyclical reduction of absolute humidity has been associated with influenza outbreaks in temperate climates. This study tested the hypothesis that raising absolute humidity above seasonal lows would impact influenza virus survival and transmission in a key source of influenza virus distribution, a community school. Air samples and objects handled by students (e.g. blocks and markers) were collected from preschool classrooms. All samples were processed and PCR used to determine the presence of influenza virus and its amount. Additionally samples were tested for their ability to infect cells in cultures. We observed a significant reduction (p < 0.05) in the total number of influenza A virus positive samples (air and fomite) and viral genome copies upon humidification as compared to control rooms. This suggests the future potential of artificial humidification as a possible strategy to control influenza outbreaks in temperate climates. There were 2.3 times as many ILI cases in the control rooms compared to the humidified rooms, and whether there is a causal relationship, and its direction between the number of cases and levels of influenza virus in the rooms is not known. Additional research is required, but this is the first prospective study suggesting that exogenous humidification could serve as a scalable NPI for influenza or other viral outbreaks