Kranzer, K. | bioRxiv Science

bioRxiv2025

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

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.

microbiology↗

bioRxiv2021

Tuberculostearic acid (TSA)-containing phosphatidylinositols as reliable marker to determine Mycobacterium tuberculosis bacterial burden

It is estimated that approximately one-fourth of the world's population is infected with strains of the Mycobacterium tuberculosis complex (MTBC), the causative agents of tuberculosis (TB). In this study, we present rationally developed molecular markers for bacterial burden, which are derived from mycobacterial phospholipids. Using lipidomic approaches, we show that tuberculostearic acid (TSA)-containing phosphatidylinositols (PI) are present in all clinically relevant MTBC lineages investigated. For the major abundant lipid PI 16:0_19:0 (TSA), a detection limit equivalent to 102 colony forming units (CFU) was determined for bacterial cultures and approximately 103 for cell culture systems. We further developed a mass spectrometry based targeted lipid assay, which - in contrast to bacterial quantification on solid medium - can be performed within several hours including sample preparation. Translation of this indirect and culture-free detection approach allowed the determination of pathogen loads in infected murine macrophages, human neutrophils and murine lung tissue. We show that marker lipids inferred from the mycobacterial PIs are increased in peripheral blood mononuclear cells (PBMCs) of TB patients beyond the lipid metabolic background in comparison to healthy controls. In a small cohort of drug-susceptible TB patients elevated levels of these marker molecules were detected at therapy start and declined following successful anti-tuberculosis treatment. The concentration of TSA-containing PIs can be used as correlate for reliable and rapid quantification of Mycobacterium tuberculosis (Mtb) burden in experimental in vitro model systems and may also provide a clinically relevant tool for monitoring TB therapy. One Sentence SummaryTuberculostearic acid containing phosphatidylinositols represent a novel, fast to measure, reliable correlate of Mycobacterium tuberculosis bacterial burden in experimental model systems, which makes a future clinical application conceivable.

biochemistry↗