Interactions between fecal gut microbiome, enteric pathogens, and energy regulating hormones among acutely malnourished rural Gambian children.

BACKGROUND: The specific roles that gut microbiota, known pathogens, and host energy-regulating hormones play in the pathogenesis of non-edematous severe acute malnutrition (marasmus SAM) and moderate acute malnutrition (MAM) during outpatient nutritional rehabilitation are yet to be explored. METHODS: We applied an ensemble of sample-specific (intra- and inter-modality) association networks to gain deeper insights into the pathogenesis of acute malnutrition and its severity among children under 5 years of age in rural Gambia, where marasmus SAM is most prevalent. FINDINGS: Children with marasmus SAM have distinct microbiome characteristics and biologically-relevant multimodal biomarkers not observed among children with moderate acute malnutrition. Marasmus SAM was characterized by lower microbial richness and biomass, significant enrichments in Enterobacteriaceae, altered interactions between specific Enterobacteriaceae and key energy regulating hormones and their receptors. INTERPRETATION: Our findings suggest that marasmus SAM is characterized by the collapse of a complex system with nested interactions and key associations between the gut microbiome, enteric pathogens, and energy regulating hormones.  Further exploration of these systems will help inform innovative preventive and therapeutic interventions. FUNDING: The work was supported by the UK Medical Research Council (MRC; MC-A760-5QX00) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement; Bill and Melinda Gates Foundation (OPP 1066932) and the National Institute of Medical Research (NIMR), UK. This network analysis was supported by NIH U54GH009824 [CLD] and NSF OCE-1558453 [CLD].

Hormonal Correlates and Predictors of Nutritional Recovery in Malnourished African Children.

Background: Malnourished children show variable growth responses to nutritional rehabilitation. We aimed to investigate whether these differences could be explained by variations in growth and energy-regulating hormones. Methods: Quasi-experimental study: Children aged 6-24 months in rural Gambia were recruited to controls if weight-for-height z-score (WHZ) > -2 (n = 22), moderate acute malnutrition if WHZ < -2 and > -3 (n = 18) or severe acute malnutrition if WHZ < -3 (n = 20). Plasma hormone and salivary CRP levels were determined by ELISA. Results: In univariable analyses, increases in weight-for-age z-score (WAZ) in malnourished children were positively correlated with insulin (F-ratio 7.8, p = 0.006), C-peptide (F-ratio 12.2, p < 0.001) and cortisol (F-ratio 5.0, p = 0.03). In multivariable analysis, only baseline C-peptide (F-ratio 7.6, p = 0.009) predicted the changes in WAZ over 28 days of interventions. Conclusion: In rural Gambian, malnourished children, although it cannot be used in isolation, baseline C-peptide was a predictor of future response to rehabilitation.