The effect of vitamin D and calcium supplementation on gut microbiota composition in adolescents living with HIV in Southern Africa

Abstract

Adolescents living with HIV are at risk of delayed growth and of increased susceptibility to infections, potentially linked to vitamin D insufficiency, which is common in people living with HIV. We analyzed rectal swab microbiota compositions before and after 48 weeks supplementation with high-dose vitamin D and calcium, or placebo, embedded in a randomized controlled trial conducted in Zambia and Zimbabwe (Pan African Clinical Trials Registry PACTR20200989766029). In a sub-cohort of 244 participants, we first assessed baseline associations of the rectal swab microbiota with vitamin D metabolites, parathyroid hormone (PTH), and bone mineral density (BMD). We then analyzed longitudinal changes in rectal swab microbiota and intestinal barrier integrity during supplementation and examined whether the baseline microbiota influenced the treatment response. At baseline, anaerobic taxa within the class Clostridia were positively associated with PTH, 1,25(OH)2D, and BMD, and negatively associated with 24,25(OH)2D. After supplementation, Shannon diversity was decreased ({beta}Std=-0.495, CI [-0.802, -0.188], p=0.0018), median Bray-Curtis dissimilarity from baseline samples was increased ({beta}Std=0.399, CI [0.086, 0.712], p=0.013), and abundance of Clostridia_vadinBB60_group was decreased (log2fc=-1.715, CI [-2.596, -0.835], q=0.043) in the intervention arm. The intervention did not affect the intestinal barrier integrity, measured by intestinal fatty acid binding protein (iFABP) concentration in blood plasma. On average, PTH concentrations decreased and BMD increased during supplementation. However, higher baseline abundance of Clostridia-member UCG-009 predicted a smaller reduction in PTH concentrations during supplementation (log2fcstd=1.200 CI [0.656, 1.744], q=0.012), while higher baseline abundances of Enterococcus (log2fcstd=-1.220 CI [-1.807, -0.632], q=0.022) and Fournierella (log2fcstd=-1.122 CI [-1.694, -0.551], q=0.025) predicted a smaller increase in BMD. In conclusion, there was a reduction of an anaerobic taxon of the class Clostridia following vitamin D supplementation. Further, the microbiota appeared to moderate the effect of the intervention on PTH and bone density.