Abstract
Aims: Children with HIV exhibit chronic inflammation and immune dysfunction despite antiretroviral therapy (ART). Strategies targeting persistent inflammation are needed to improve health in people living with HIV. The gut microbiota likely interacts with the immune system, but the clinical implications of modulating the dysbiosis by nutritional supplementation are unclear. Methods: Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected on ART were randomized to supplementation with a daily mixture of symbiotics, omega-3/6 fatty acids and amino acids, or placebo four weeks, in combination with ART. We analyzed inflammatory markers and T-cell activation changes and their correlations with shifts in fecal microbiota. Results: Twenty-four HIV-infected children were recruited and randomized to receive a symbiotic nutritional supplement or placebo. Mean age was 12 ± 3.9 years, 62.5% were female. All were on ART and had HIV RNA < 50/mL. We did not detect changes in inflammatory (IL-6, IL-7, IP-10), microbial translocation (sCD14), mucosal integrity markers (IFABP, zonulin) or the kynurenine to tryptophan ratio, or changes in markers of the adaptive immune response in relation to the intervention. However, we found correlations between several key bacteria and the assessed inflammatory and immunological parameters, supporting a role of the microbiota in immune modulation in children with HIV. Conclusions: In this exploratory study, a four-week nutritional supplementation had no significant effects in terms of decreasing inflammation, microbial translocation, or T-cell activation in HIV-infected children. However, the correlations found support the interaction between gut microbiota and the immune system.
Highlights
It is well known that HIV-infected children present persistent immune dysfunction despite early antiretroviral treatment (ART) [1–4]
All were on antiretroviral therapy (ART) and virologically suppressed
We considered the fold changes from baseline parameters and the microbiota
Summary
It is well known that HIV-infected children present persistent immune dysfunction despite early antiretroviral treatment (ART) [1–4]. Recent studies have pointed out the potential influence of the microbiome [5–8]. Several studies have underlined the potential role of subsequent microbial translocation and gut microbiota-immune system interactions in the persistent immune dysfunction associated with chronic HIV infection [5,11]. The persistence of thymic function in children may hypothetically play a role for gut-associated-lymphoid tissue (GALT) immune reconstitution despite HIV infection [17], leading to differences in terms of dysbiosis when compared to the infection acquired later in life. Recent evidence has raised the question of whether childhood might be the optimal window for intervention targeting microbial communities, potentially impacting the bacteria-immune system interplay, influencing different metabolic and inflammatory conditions. Few attempts targeting the microbiome have included children [19], and none to our knowledge has included symbiotics
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