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Open AccessArticle

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

1
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, 14152 Stockholm, Sweden
2
Clinical Microbiomics, 2200 Copenhagen, Denmark
3
Center for Infectious Medicine (CIM), F59, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, 14152 Stockholm, Sweden
4
Department of Internal Medicine, Faculty of Medicine, Black Lion University Hospital and Addis Ababa University, 1176 Addis Ababa, Ethiopia
5
Armauer Hansen Research Institute (AHRI), 1005 Addis Ababa, Ethiopia
6
Department of Medicine, Division of Infectious Diseases, Karolinska University Hospital Huddinge, 14152 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(7), 1675; https://doi.org/10.3390/nu11071675
Received: 20 June 2019 / Revised: 16 July 2019 / Accepted: 17 July 2019 / Published: 21 July 2019
(This article belongs to the Special Issue Targeted Nutrition in Chronic Disease)
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. View Full-Text
Keywords: HIV-1; vitamin D; phenylbutyrate; clinical trial; TMAO; microbiota; LL-37; kynurenine/tryptophan ratio HIV-1; vitamin D; phenylbutyrate; clinical trial; TMAO; microbiota; LL-37; kynurenine/tryptophan ratio
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Missailidis, C.; Sørensen, N.; Ashenafi, S.; Amogne, W.; Kassa, E.; Bekele, A.; Getachew, M.; Gebreselassie, N.; Aseffa, A.; Aderaye, G.; Andersson, J.; Brighenti, S.; Bergman, P. Vitamin D and Phenylbutyrate Supplementation Does Not Modulate Gut Derived Immune Activation in HIV-1. Nutrients 2019, 11, 1675.

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