Randomized pilot trial of a synbiotic dietary supplement in chronic HIV-1 infection

Marco Schunter,Hiutung Chu,Delandy Mcconnell,Jennifer Brown,Sean S Crawford,J William Critchfield,Timothy L Hayes,Paul A Luciw,Barbara L Shacklett,Charles L Bevins,Stig Bengmark,David M Asmuth

doi:10.1186/1472-6882-12-84

Abstract

BackgroundInfection with HIV-1 results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function. While the development of highly active antiretroviral therapy (HAART) has been a major advancement in the treatment of HIV-1 infection, the need for novel complementary interventions to help restore intestinal structural and functional integrity remains unmet. Known properties of pre-, pro-, and synbiotics suggest that they may be useful tools in achieving this goal.MethodsThis was a 4-week parallel, placebo-controlled, randomized pilot trial in HIV-infected women on antiretroviral therapy. A synbiotic formulation (Synbiotic 2000®) containing 4 strains of probiotic bacteria (1010 each) plus 4 nondigestible, fermentable dietary fibers (2.5 g each) was provided each day, versus a fiber-only placebo formulation. The primary outcome was bacterial translocation. Secondary outcomes included the levels of supplemented bacteria in stool, the activation phenotype of peripheral T-cells and monocytes, and plasma levels of C-reactive protein and soluble CD14.ResultsMicrobial translocation, as measured by plasma bacterial 16S ribosomal DNA concentration, was not altered by synbiotic treatment. In contrast, the synbiotic formulation resulted in significantly elevated levels of supplemented probiotic bacterial strains in stool, including L. plantarum and P. pentosaceus, with the colonization of these two species being positively correlated with each other. T-cell activation phenotype of peripheral blood lymphocytes showed modest changes in response to synbiotic exposure, with HLA-DR expression slightly elevated on a minor population of CD4+ T-cells which lack expression of HLA-DR or PD-1. In addition, CD38 expression on CD8+ T-cells was slightly lower in the fiber-only group. Plasma levels of soluble CD14 and C-reactive protein were unaffected by synbiotic treatment in this study.ConclusionsSynbiotic treatment for 4 weeks can successfully augment the levels of probiotic species in the gut during chronic HIV-1 infection. Associated changes in microbial translocation appear to be absent, and markers of systemic immune activation appear largely unchanged. These findings may help inform future studies aimed at testing pre- and probiotic approaches to improve gut function and mucosal immunity in chronic HIV-1 infection.Trial registrationClinical Trials.gov: NCT00688311

Highlights

Infection with human immunodeficiency virus-1 (HIV-1) results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function
HIV-1 and simian immunodeficiency virus (SIV) cause direct damage to intestinal epithelial cells [7,8], and gene expression studies of the GI mucosa have revealed HIV-associated upregulation of genes involved in inflammatory and apoptosis pathways [9]
N=16 Allocated to Synbiotic 2000 Received intervention (n=16) Did not receive intervention (n=0)

Summary

Introduction

Infection with HIV-1 results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function. In terms of the intestinal microbiota, HIV infection has been associated with depressed levels of beneficial bifidobacteria and lactobacilli, and elevated levels of opportunistic pathogens including Pseudomonas aeruginosa and Candida albicans [10]. In light of this broad set of impacts on the intestinal mucosa, it is not surprising that basic functional tasks of the gut, such as efficient nutrient absorption and the maintenance of intestinal barrier function, are significantly compromised [11,12,13,14]

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Results

Conclusion