March 25, 2013
Over the years, a number of small studies have been published suggesting that there might be benefits associated with probiotic and/or prebiotic supplementation in people with HIV infection. Probiotics typically comprise live microbes that play a key role in maintaining gut health -- commonly known as "good bacteria" -- while prebiotics are food ingredients intended to stimulate the expansion and activity of these bacteria. The past decade has seen a renewed interest in gut health in HIV infection due to evidence that the virus severely depletes CD4 T cells in the GI tract, leading to diminished immune surveillance, compromised gut-wall integrity, and microbial translocation (the leakage of gut bacteria into the systemic circulation). Additionally, suppression of HIV replication by antiretroviral therapy (ART) does not necessarily restore gut CD4 T-cell numbers, and markers of microbial translocation have been associated with poor immune reconstitution despite ART.
To try to address the question of whether a combination of probiotics and prebiotics (referred to as synbiotic treatment) might serve as a useful adjunct to ART, Nichole Klatt and colleagues conducted a study in the animal model of SIV-infected pigtailed macaques. The results are published in the February issue of the Journal of Clinical Investigation. The researchers report that, compared to ART alone, adjunctive synbiotic treatment (the specific products used were VSL#3 and Culturelle) had positive effects on gut CD4 T cells and antigen-presenting cells, and also reduced fibrosis in local lymph tissue. The results appear encouraging, and were discussed in further detail at the recent CROI by senior author Jason Brenchley (the third talk in the symposium entitled Is Something Bugging You?).
Something that isn't mentioned in the JCI paper, or addressed directly in Brenchley's talk, is that previous work from this research group has shown that gut integrity in pigtailed macaques is unusually compromised even in uninfected animals; in a separate new paper published in the March 15 issue of the Journal of Immunology, they show that this correlates with the faster progression to AIDS that occurs in this monkey species. On the one hand, this may make pigtailed macaques a useful worst-case scenario in terms of modeling the contribution of microbial translocation to HIV pathogenesis and studying interventions like probiotics, but, on the other hand, the extent to which findings from this extreme situation can be extrapolated to humans is as yet unclear.
Available published data on synbiotic treatment in people with HIV appear limited, either involving individuals not on ART or on very short-term follow-up. As far as I can discern from a PubMed search, no trials have used the specific combination of VSL#3 and Culturelle. Currently, clinicaltrials.gov lists one open clinical trial of the probiotic Biola that is enrolling individuals both on and off ART; study sites are limited to Oslo, Norway, and Stockholm, Sweden. According to U.S.-based researchers, there are plans afoot to conduct a randomized, controlled clinical trial to assess whether the promising results from the Brenchley laboratory can be translated to humans with HIV infection.
Richard Jefferys is the coordinator of the Michael Palm HIV Basic Science, Vaccines & Prevention Project Weblog at the Treatment Action Group (TAG). The original blog post may be viewed here.