Both HIV and oral iron interventions may alter gut microbiota composition and increase gut inflammation. We determined the effect of oral iron supplementation on gut microbiota composition, gut inflammation, and iron status in iron-depleted South Africa school-aged children living with HIV (HIV+) but virally suppressed on antiretroviral therapy and children without HIV (HIV-ve).
In this before-after intervention study with case–control comparisons, we provided 55 mg elemental iron from ferrous sulphate, once daily for 3 months, to 33 virally suppressed (< 50 HIV RNA copies/mL) HIV+ and 31 HIV-ve children. At baseline and endpoint, we assessed microbial composition of faecal samples (16S rRNA sequencing), and markers of gut inflammation (faecal calprotectin), anaemia (haemoglobin) and iron status (plasma ferritin, soluble transferrin receptor). This study was nested within a larger trial registered at clinicaltrials.gov as NCT03572010.
HIV+ (11.3y SD ± 1.8, 46% male) and HIV−ve (11.1y SD ± 1.7, 52% male) groups did not significantly differ in age or sex ratio. Following iron supplementation, improvements were observed in haemoglobin (HIV+ : 118 to 124 g/L, P = 0.003; HIV−ve: 120 to 124 g/L, P = 0.003), plasma ferritin (HIV+ : 15 to 34 µg/L, P < 0.001; HIV−ve: 18 to 37 µg/L, P < 0.001), and soluble transferrin receptor (HIV+ : 7.1 to 5.9 mg/L, P < 0.001; HIV−ve: 6.6 to 5.7 mg/L, P < 0.001), with no significant change in the relative abundance of any genera, alpha diversity of the gut microbiota (HIV+ : P = 0.37; HIV−ve: P = 0.77), or faecal calprotectin (HIV+ : P = 0.42; HIV−ve: P = 0.80).
Our findings suggest that oral iron supplementation can significantly improve haemoglobin and iron status without increasing pathogenic gut microbial taxa or gut inflammation in iron-depleted virally suppressed HIV+ and HIV−ve school-age children.
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The data presented in this study are available on request from the corresponding author.
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We thank the study participants and their caregivers; the clinical, laboratory and support staff from the Family Centre for Research with Ubuntu, the Division of Human Nutrition at Stellenbosch University, and the Infectious Diseases Clinic at Tygerberg Hospital; C Brand (Stellenbosch University, South Africa), C Verspecht, L Rymenans and L De Commer (VIB and KU Leuven, Belgium), N Mikulic (ETH Zurich, Switzerland) and J Erhardt (Willstaett, Germany) for supporting sample processing and laboratory analyses; and R Laubscher (SAMRC Biostatistics Unit) for the nutrient conversions.
This research study was nested within a series of iron studies funded by the Thrasher Research Fund, USA (14199). The Raes lab is supported by KU Leuven, VIB and the Rega institute. RYT is funded by a post-doctoral fellowship from the Research Foundation Flanders (FWO-Vlaanderen, Grant Number 1234321 N). CG is supported by the L’Oréal-UNESCO for Women in Science sub-Saharan Africa Fellowship Programme, the Harry Crossley Foundation, and the Ernst and Ethel Eriksen Trust. The work reported herein was also made possible through funding by the South African Medical Research Council (SAMRC) through its Division of Research Capacity Development under the SAMRC Bongani Mayosi National Health Scholars Programme from funding received from the South African National Treasury. The content hereof is the sole responsibility of the authors and does not necessarily represent the official views of the SAMRC or the funders.
Conflict of interest
The authors declare no conflicts of interest.
The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the health research ethics committees of ETH Zurich (EK 2018-N-40, 28 June 2018) and Stellenbosch University (M18/05/017, 17 July 2018, and S18/06/136, 27 August 2018).
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Written informed assent to participate in the study was obtained from all participants (children) involved in the study. Written informed consent was obtained from caregivers (parent or legal guardian).
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Written informed assent for the publication of study results was obtained from all participants involved in the study. Written informed consent was obtained from caregivers.
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Goosen, C., Proost, S., Tito, R.Y. et al. The effect of oral iron supplementation on the gut microbiota, gut inflammation, and iron status in iron-depleted South African school-age children with virally suppressed HIV and without HIV. Eur J Nutr 61, 2067–2078 (2022). https://doi.org/10.1007/s00394-021-02793-9