Vitamin D and Phenylbutyrate Supplementation Does Not Modulate Gut Derived Immune Activation in HIV-1

Nutrients. 2019 Jul 21;11(7):1675. doi: 10.3390/nu11071675.


Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals (n = 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks ( NCT01702974). Baseline and per-protocol plasma samples at week 16 were analysed for soluble CD14, the antimicrobial peptide LL-37, kynurenine/tryptophan-ratio, TMAO, choline, and betaine. Assessment of the gut microbiota involved 16S rRNA gene sequencing of colonic biopsies. Vitamin D + phenylbutyrate treatment significantly increased 25-hydroxyvitamin D levels (p < 0.001) but had no effects on sCD14, the kynurenine/tryptophan-ratio, TMAO, or choline levels. Subgroup-analyses of vitamin D insufficient subjects demonstrated a significant increase of LL-37 in the treatment group (p = 0.02), whereas treatment failed to significantly impact LL-37-levels in multiple regression analysis. Further, no effects on the microbiota was found in number of operational taxonomic units (p = 0.71), Shannon microbial diversity index (p = 0.82), or in principal component analyses (p = 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-naïve HIV-1 individuals with active viral replication.

Keywords: HIV-1; LL-37; TMAO; clinical trial; kynurenine/tryptophan ratio; microbiota; phenylbutyrate; vitamin D.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use*
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Gastrointestinal Microbiome
  • HIV Infections / therapy*
  • HIV-1*
  • Humans
  • Immunity, Innate
  • Male
  • Middle Aged
  • Phenylbutyrates / administration & dosage
  • Phenylbutyrates / pharmacology*
  • Vitamin D / administration & dosage
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D / pharmacology*
  • Young Adult


  • Anti-HIV Agents
  • Phenylbutyrates
  • Vitamin D
  • 25-hydroxyvitamin D

Associated data