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Randomized Controlled Trial
. 2019 Jul 21;11(7):1675.
doi: 10.3390/nu11071675.

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

Catharina Missailidis  1 , Nikolaj Sørensen  2 , Senait Ashenafi  3 , Wondwossen Amogne  4 , Endale Kassa  4 , Amsalu Bekele  4 , Meron Getachew  4 , Nebiat Gebreselassie  5 , Abraham Aseffa  5 , Getachew Aderaye  4 , Jan Andersson  3   6 , Susanna Brighenti  3 , Peter Bergman  7
Affiliations
Randomized Controlled Trial

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

Catharina Missailidis et al. Nutrients. .

Abstract

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 (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 (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.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Vitamin D status assessed at baseline and at weeks 16 after daily supplementation with 5000 IU vitamin D and 500 mg phenylbutyrate (n = 81), or placebo (n = 86). P values are generated by Wilcoxon signed-rank and Mann-Whitney U test.
Figure 2
Figure 2
No significant treatment effects on microbiota was found in colonic biopsies from baseline and week 16 (treatment n = 7, placebo n = 16) in analyzes of number of operational taxonomic units (OTUs) (a), Shannon microbial diversity index (b).
Figure 3
Figure 3
No significant treatment effects on microbiota was found in colonic biopsies (treatment n = 7, placebo n = 16) in principal component analyses at baseline (a) and week 16 (b).
See this image and copyright information in PMC

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