The gut microbiome of individuals with human immunodeficiency virus (HIV) is a topic of growing scientific interest, as recent research has linked severe immunodeficiency in HIV infection with changes in both the bacterial and viral communities of the gut. At the last edition of B·DEBATE, which was held on Barcelona (Spain) on 30th June-1st July 2016 under the theme, “The Barcelona Debates on the Human Microbiome. From Microbes to Medicines”, Dr. Roger Paredes covered the latest on this topic.
Roger Paredes, PhD MD, is a member of the B·DEBATE Scientific Committee and the principal investigator at the Microbial Genomics research group from the IrsiCaixa AIDS Research Institute in Badalona (Spain). His research focuses on the role of gut microbiota in (HIV) infection in order to find novel approaches to avoid HIV-related chronic inflammation. At B·DEBATE, Paredes took the time to speak with GMFH editors.
Another scientist investigating the gut microbiome in HIV infection, Dr. Catherine Lozupone from the Department of Medicine at University of Colorado Anschutz Medical Campus in Aurora (USA), corresponded later with GMFH editors about the significance of the work from the Paredes lab.
GMFH: What is already known about HIV infection and the human gut microbiome?
RP: The main clinical problems of people living with HIV in industrialized countries are related to premature ageing, which involves precocious development of chronic diseases including type 2 diabetes, dislipidemia, cardiovascular diseases, osteoporosis, and frailty syndrome. Such diseases have been associated with chronic inflammation and immune senescence in HIV-infected subjects.
Current research is studying the role of the human gut microbiome in HIV pathogenesis and its ability to improve immune status of HIV-infected subjects. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. However, the HIV microbiome science is still [in] its early stages and little is known regarding whether [a consistent HIV-specific dysbiosis pattern exists] and which factors are relevant in shaping the microbiome in people living with HIV.
GMFH: What are the most relevant new findings in your research group regarding the effects of HIV on the gut microbiota?
RP: We have shown in two independent cohorts of HIV-1 infected subjects and HIV-1-negative controls in Europe -one cohort in Barcelona, Spain (n=156) and the other one in Stockholm, Sweden (n=84)- that men who have sex with men (MSM) often have a distinct composition of the faecal microbiota, with increased microbial richness and diversity and enrichment in [Prevotella compared to] non-MSM individuals. The increased abundance of Prevotella in MSM individuals remains to be fully understood, but could be related to local inflammation through unprotected anal intercourse or the exposure of the colo-rectal mucosa to hyperosmolar substances like semen or lubricants. There were no differences between heterosexual subjects (HTS) and people who acquired HIV-1 infection through intravenous drug use. This association was independent of HIV-1 status, and had only a limited contribution of diet effects. After accounting for sexual orientation, there was no solid evidence of [a gut bacterial signature specific to HIV]. However HIV-1 infection remains associated [with] reduced bacterial richness, more so in subjects with suboptimal CD4+ T-cell count recovery under antiretroviral therapy. These findings suggest that reductions in microbial richness rather than changes in Bacteroides or Prevotella enterotype are [the] hallmark changes of HIV infection.
GMFH: What is the role of sexual preference in findings about gut microbiota composition?
RP: Sexual behaviour may instead explain the differences in Bacteroides versus Prevotella predominance that had been previously associated with HIV infection. To our knowledge, this is the first evidence that, in addition to genetic and environmental factors, factors related [to] sexual practice might also affect the gut microbiota composition.
Although HIV infection is associated with low microbial gene counts and virus expansion, particularly in advanced disease and immune discordance, other factors like lifestyle, diet, exercise, antibiotics and possibly genetics may also reduce gene richness. Future studies should evaluate if interventions to increase gut bacterial richness could improve HIV-associated immune dysfunction.
Dr. Catherine Lozupone emphasizes the importance of the work from the Paredes lab in elucidating that MSM sexual behaviour can be a confounding factor when investigating microbiome differences in individuals with HIV. Her lab has found similar results using a population of high-risk MSM as a control cohort. A recent review, led by Lozupone, reported that enteric viruses may contribute to further gastrointestinal damage and HIV disease progression by direct infection of cells along the gastrointestinal tract. Therefore, researchers should take into account the potentially under-appreciated role of the enteric virome in HIV-associated gastroenteritis and disease pathogenesis.
Paredes says, from what we know so far about the gut microbiome, future therapeutic approaches for HIV-infected subjects may include: 1) full inhibition of HIV replication; 2) control of the viruses, such as adenovirus and cytomegalovirus, that expand with HIV infection; 3) recovery of the gut microbial ecosystem post-infection through microbiota-targeted interventions, including faecal microbiota transplantation, prebiotics, and probiotics; and 4) lifestyle interventions targeting microbiome changes.
Noguera-Julian M, Rocafort M, Guillén Y, et al. EBioMedicine. 2016; 5:135-46. doi:10.1016/j.ebiom.2016.01.032.
Palmer BE, Li SX, Lozupone CA. The HIV-associated enteric microbiome has gone viral. Cell Host Microbe. 2016; 19(3):270-2. doi:10.1016/j.chom.2016.02.014.