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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

European Journal of Nutrition volume 61, pages 2067–2078 (2022)Cite this article

Abstract

Purpose

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).

Methods

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.

Results

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).

Conclusion

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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Availability of data and material

The data presented in this study are available on request from the corresponding author.

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Acknowledgements

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.

Funding

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.

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Author notes

  1. Charlene Goosen and Sebastian Proost contributed equally.

Authors and Affiliations

  1. Division of Human Nutrition, Department of Global Health, Stellenbosch University, Cape Town, South Africa

    Charlene Goosen & Renée Blaauw

  2. Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium

    Sebastian Proost, Raul Y. Tito & Jeroen Raes

  3. Center for Microbiology, VIB, Leuven, Belgium

    Sebastian Proost, Raul Y. Tito & Jeroen Raes

  4. Laboratory of Human Nutrition, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland

    Jeannine Baumgartner & Michael B. Zimmermann

  5. Family Centre for Research With Ubuntu, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa

    Shaun L. Barnabas & Mark F. Cotton

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  1. Charlene Goosen
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Contributions

CG designed the nested study, conducted the research, analysed the data (other than the microbiota data), and wrote the original draft of the paper. SP performed the microbiota analysis and visualisation. RYT processed 16S sequencing data. JB supervised the data analysis (other than the microbiota data). SLB, MFC, MBZ and JR provided study resources. RB supervised the research study and provided study resources. All authors reviewed the paper and read and approved the final manuscript.

Corresponding authors

Correspondence to Charlene Goosen or Jeroen Raes.

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Conflict of interest

The authors declare no conflicts of interest.

Ethics approval

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).

Consent to participate

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).

Consent for publication

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

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