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

• Main Authors: Catharina Missailidis, Nikolaj Sørensen, Senait Ashenafi, Wondwossen Amogne, Endale Kassa, Amsalu Bekele, Meron Getachew, Nebiat Gebreselassie, Abraham Aseffa, Getachew Aderaye, Jan Andersson, Susanna Brighenti, Peter Bergman
• Format: Article
• Language: English
• Published: MDPI AG 2019-07-01
• Series: Nutrients
• Subjects: HIV-1; vitamin D; phenylbutyrate; clinical trial; TMAO; microbiota; LL-37; kynurenine/tryptophan ratio
• Online Access: https://www.mdpi.com/2072-6643/11/7/1675

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&#239;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&#239;ve HIV-1 individuals with active viral replication.