Probiotic/prebiotic supplement combination shows benefits in SIV-infected pigtailed macaques

Richard Jefferys, TAG

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 and 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 and reported 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 at the recent CROI by senior author Jason Brenchley. [1] The results were also published in the February 1st issue of the Journal of Clinical Investigation. [2]

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; [3] in a separate new paper published in the March 15th issue of the Journal of Immunology, they show that this correlates with the faster progression to AIDS that occurs in this monkey species. [4]

On the one hand, this may make pigtailed macaques a useful worst-case scenario in terms of modelling 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 appears limited, either involving individuals not on ART or very short-term follow-up. 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. [5]

According to US-based researchers, there are plans afoot to conduct a randomised controlled clinical trial to assess whether the promising results from the Brenchley laboratory can be translated to humans with HIV infection.

References:

Unless stated otherwise, references are to the Programme and Abstracts for the 20th Conference on Retroviruses and Opportunistic Infections (CROI), 3-6 March 2013, Atlanta.

http://www.retroconference.org

Klatt N et al. Treating microbial translocation in progressive HIV/SIV infections. 20th CROI, 2013. Oral abstract 53. Webcast third in session.
http://www.retroconference.org/2013b/Abstracts/48129.htm
http://webcasts.retroconference.org/console/player/19418?mediaType=audio
Klatt N et al. Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques. J Clin Invest. 2013;123(2):903–907. (1 February 2013). doi:10.1172/JCI66227.
http://www.jci.org/articles/view/66227
Klatt N et al. PCompromised gastrointestinal integrity in pigtail macaques is associated with increased microbial translocation, immune activation and IL-17 production in the absence of SIV infection. Mucosal Immunol. 2010 July; 3(4): 387–398.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891168/
Canary LA et al. Rate of AIDS Progression Is Associated with Gastrointestinal Dysfunction in Simian Immunodeficiency Virus–Infected Pigtail Macaques. Journal of Immunology, March 15, 2013, vol. 190 no. 6 2959-2965.
http://www.jimmunol.org/content/190/6/2959.abstract
Jefferys R. Probiotic/Prebiotic Supplement Combination Shows Benefits in SIV-Infected Pigtailed Macaques. TAG basic science blog. (15 March 2013).
http://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2013/03/probioticprebiotic-supplement-combination-shows-benefits-in-siv-infected-pigtailed-macaques.html