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.

Abstract

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 55mg 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 124g/L, P = 0.003; HIV-ve: 120 to 124g/L, P = 0.003), plasma ferritin (HIV+ : 15 to 34µg/L, P < 0.001; HIV-ve: 18 to 37µg/L, P < 0.001), and soluble transferrin receptor (HIV+ : 7.1 to 5.9mg/L, P < 0.001; HIV-ve: 6.6 to 5.7mg/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.