A study in HIV‑positive people gave them high‑dose vitamin D and phenylbutyrate for 16 weeks. While vitamin D levels went up, the combo did not change most gut‑related inflammation markers or the gut microbiome. Only a small subgroup with low vitamin D showed a modest rise in the antimicrobial peptide LL‑37, and this effect disappeared after adjusting for other factors.

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-na&#xef;ve HIV-1-infected individuals (<i>n</i> = 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 (Clinicaltrials.gov 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 (<i>p</i> &lt; 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 (<i>p</i> = 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 (<i>p</i> = 0.71), Shannon microbial diversity index (<i>p</i> = 0.82), or in principal component analyses (<i>p</i> = 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-na&#xef;ve HIV-1 individuals with active viral replication.