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Disruption of gut homeostasis by opioids accelerates HIV disease progression.

Meng J, Sindberg GM, Roy S - Front Microbiol (2015)

Bottom Line: Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Infection, Inflammation, and Vascular Biology, Medical School, University of Minnesota, Minneapolis, MN USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Both human immunodeficiency virus (HIV) infection and opioid abuse induce disruption of gut homeostasis. (A) Opioids and HIV infection can induce intestinal barrier disruption and subsequent microbial translocation. (B) Opioids and HIV infection can induce an abnormal inflammatory response in the gut. (C) Opioids and HIV infection has been shown to induce dysbiosis in the gut microbiome.
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Figure 5: Both human immunodeficiency virus (HIV) infection and opioid abuse induce disruption of gut homeostasis. (A) Opioids and HIV infection can induce intestinal barrier disruption and subsequent microbial translocation. (B) Opioids and HIV infection can induce an abnormal inflammatory response in the gut. (C) Opioids and HIV infection has been shown to induce dysbiosis in the gut microbiome.

Mentions: However, the effects of opioid abuse on GI homeostasis during HIV infection are not well studied although both opioids and HIV have been shown to disrupt the intestinal homeostasis through the similar pathways (Figure 5). As previously described, both HIV/SIV infection and morphine treatment can induce the intestinal epithelial barrier damage. Indeed, humans infected with HIV who use heroin have been shown to have greater amounts of LPS in their serum compared with non-users (Ancuta et al., 2008), implying that disruption of barrier function within the gut is more severe in drug using HIV patients. An investigation of gut biopsy from HIV-infected patients displays microtubule depolymerization, which is expected to be associated with intestinal tight junction disorganization and as a result of MLCK activation (Clayton et al., 2001; Turner, 2006). Interestingly, our study also shows that morphine treatment alone induces intestinal tight junction disruption and bacterial translocation by activating MLCK (Meng et al., 2013). Therefore, it is conceivable that opioids and HIV infection either synergistically or additively modulate MLCK activation explaining the more sever gut barrier dysfunction observed in drug abusing HIV infected patients. This was recently validated by our studies where it was demonstrated that opioids exacerbated HIV induced gut barrier disruption, increased bacterial translocation from the gut lumen, and sustained systemic inflammation with an increase in both IL-6 and TNF-α using a rodents model of HIV (Sindberg et al., 2014).


Disruption of gut homeostasis by opioids accelerates HIV disease progression.

Meng J, Sindberg GM, Roy S - Front Microbiol (2015)

Both human immunodeficiency virus (HIV) infection and opioid abuse induce disruption of gut homeostasis. (A) Opioids and HIV infection can induce intestinal barrier disruption and subsequent microbial translocation. (B) Opioids and HIV infection can induce an abnormal inflammatory response in the gut. (C) Opioids and HIV infection has been shown to induce dysbiosis in the gut microbiome.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4481162&req=5

Figure 5: Both human immunodeficiency virus (HIV) infection and opioid abuse induce disruption of gut homeostasis. (A) Opioids and HIV infection can induce intestinal barrier disruption and subsequent microbial translocation. (B) Opioids and HIV infection can induce an abnormal inflammatory response in the gut. (C) Opioids and HIV infection has been shown to induce dysbiosis in the gut microbiome.
Mentions: However, the effects of opioid abuse on GI homeostasis during HIV infection are not well studied although both opioids and HIV have been shown to disrupt the intestinal homeostasis through the similar pathways (Figure 5). As previously described, both HIV/SIV infection and morphine treatment can induce the intestinal epithelial barrier damage. Indeed, humans infected with HIV who use heroin have been shown to have greater amounts of LPS in their serum compared with non-users (Ancuta et al., 2008), implying that disruption of barrier function within the gut is more severe in drug using HIV patients. An investigation of gut biopsy from HIV-infected patients displays microtubule depolymerization, which is expected to be associated with intestinal tight junction disorganization and as a result of MLCK activation (Clayton et al., 2001; Turner, 2006). Interestingly, our study also shows that morphine treatment alone induces intestinal tight junction disruption and bacterial translocation by activating MLCK (Meng et al., 2013). Therefore, it is conceivable that opioids and HIV infection either synergistically or additively modulate MLCK activation explaining the more sever gut barrier dysfunction observed in drug abusing HIV infected patients. This was recently validated by our studies where it was demonstrated that opioids exacerbated HIV induced gut barrier disruption, increased bacterial translocation from the gut lumen, and sustained systemic inflammation with an increase in both IL-6 and TNF-α using a rodents model of HIV (Sindberg et al., 2014).

Bottom Line: Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Infection, Inflammation, and Vascular Biology, Medical School, University of Minnesota, Minneapolis, MN USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus