Severe anaemia in sub-Saharan African children: the roles of nutrition, metabolism and the gut microbiota in recovery

Abstract

Severe anaemia (Hb<5.0g/dl) affects almost 1 in 20 children in sub-Saharan Africa, and up to 1 in 4 child hospital admissions in this region (Muhe et al., 2000; Kiggundu et al., 2013). Micronutrient deficiency, malaria, infections and genetic factors contribute to its development. Severe childhood anaemia is associated with a high risk of mortality (19% within 6 months) (Phiri et al., 2008) and survivors experience long term health effects. Bacterial co-infection from gut-derived pathogenic bacteria is a frequent cause of death (Church and Maitland, 2014). Diet, altered metabolism, and the gut microbiota are thus implicated in severe anaemia, however interactions between these factors are poorly understood. The Transfusion and treatment of severe anaemia in African children study (TRACT) which assessed optimum transfusion dose, micronutrient supplementation, and prophylactic antibiotic treatment provided an opportunity to address these factors. The aim of this study was to characterise the diet of children in Eastern Uganda, and assess the impact on recovery from anaemia. It also aimed to assess whether interactions between diet and host metabolism or the gut microbiota were significantly altered in severely anaemic children, and whether changes in these were associated with recovery. A pilot study (n=19) was conducted to validate a 24-hour dietary recall method, which showed that the method had low inter-assessor variability, and high validity when compared to weighed food records. A subset (n=339) of children from the TRACT study in eastern Uganda were recruited to undergo dietary assessment and provide urine, plasma and faecal samples at admission, day 28 and day 180. A majority of children had diets which lacked diversity, reliant on a single carbohydrate-rich but micronutrient-poor food source. Food intake on admission was restricted in energy and micronutrients and was inadequate for a majority of children, but quantity and diversity increased as children recovered. Urine and plasma metabolic profiles reflected acute inadequate energy intake on admission (ketosis) and metabolic stress associated with critical illness (glycosuria and lipoprotein dysregulation), in addition to condition-specific effects including malaria-associated hyperphenylalaninaemia. These metabolic derangements resolved with treatment as children recovered. The gut microbiota of children in this study on admission lacked diversity and was dominated by potentially pathogenic Enterobacteriaceae and Enterococcus faecium. High levels of antibiotic use, in addition to low dietary diversity and dietary fibre intake contributed to reduced diversity and richness in species observed. Alterations in diet, metabolism and the gut microbiota were identified in this study in severely anaemic children, reflecting the causes and severity of this condition. Potential routes to reduce the impacts of these derangements were identified for future research.Open Acces