Correlates of Gut Function in Children Hospitalized for Severe Acute Malnutrition, a Cross-sectional Study in Uganda

Objective: Children with severe acute malnutrition (SAM) may have impaired intestinal function, which can result in malabsorption, diarrhoea, and poor growth. This study evaluated the gut function of children with SAM using fecal and blood biomarkers and assessed their correlates. Methods: A cross-sectional study, nested in a randomized trial (, ISRCTN 16454889), was conducted at Mulago hospital, Uganda among subgroups of 400 children with complicated SAM and 30 community controls. Gut function was evaluated by 5 biomarkers: plasma citrulline, fecal myeloperoxidase and fecal neopterin, bacterially derived 16S rRNA gene and internal transcribed Spacer region (ITS) specific for Candida spp. in blood. Results: Compared with controls, children with SAM had lower median plasma citrulline (5.14 vs 27.4 mu mol/L, P < 0.001), higher median fecal myeloperoxidase (18083 vs 7482 ng/mL, P = 0.001), and fecal neopterin (541 vs 210 nmol/L, P < 0.001). A higher blood concentration of 16S rRNA gene copy numbers was observed among children with SAM (95 vs 28 copies/mu l, P = 0.05), whereas there was no difference in the blood concentration of Candida-specific ITS fragment. Among those with SAM, plasma citrulline was lower in children with edema, diarrhoea, dermatosis, and plasma C-reactive protein (CRP) >10 mg/L. Fecal neopterin was positively correlated with symptoms of fever and cough whereas it was negatively correlated with mid-upper arm circumference (MUAC), weight-for-height z score (WHZ), edema, and dermatosis. Conclusions: Children with complicated SAM seem to have impaired gut function characterized by reduced enterocyte mass, intestinal inflammation, and increased bacterial translocation.