Childhood severe acute malnutrition is associated with metabolomic changes in adulthood
Debbie S. Thompson, Celine Bourdon, Paraskevi Massara, Michael S. Boyne, Terrence E. Forrester, Gerard Bryan Gonzales, Robert H. J. Bandsma
Debbie S. Thompson, Celine Bourdon, Paraskevi Massara, Michael S. Boyne, Terrence E. Forrester, Gerard Bryan Gonzales, Robert H. J. Bandsma
View: Text | PDF
Clinical Medicine Clinical Research and Public Health Metabolism

Childhood severe acute malnutrition is associated with metabolomic changes in adulthood

Abstract

BACKGROUND Severe acute malnutrition (SAM) is a major contributor to global mortality in children under 5 years. Mortality has decreased; however, the long-term cardiometabolic consequences of SAM and its subtypes, severe wasting (SW) and edematous malnutrition (EM), are not well understood. We evaluated the metabolic profiles of adult SAM survivors using targeted metabolomic analyses.METHODS This cohort study of 122 adult SAM survivors (SW = 69, EM = 53) and 90 age-, sex-, and BMI-matched community participants (CPs) quantified serum metabolites using direct flow injection mass spectrometry combined with reverse-phase liquid chromatography. Univariate and sparse partial least square discriminant analyses (sPLS-DAs) assessed differences in metabolic profiles and identified the most discriminative metabolites.RESULTS Seventy-seven metabolite variables were significant in distinguishing between SAM survivors (28.4 ± 8.8 years, 24.0 ± 6.1 kg/m2) and CPs (28.4 ± 8.9 years, 23.3 ± 4.4 kg/m2) (mean ± SDs) in univariate and sPLS-DA models. Compared with CPs, SAM survivors had less liver fat; higher branched-chain amino acids (BCAAs), urea cycle metabolites, and kynurenine/tryptophan (KT) ratio (P < 0.001); and lower β-hydroxybutyric acid and acylcarnitine/free carnitine ratio (P < 0.001), which were both associated with hepatic steatosis (P < 0.001). SW and EM survivors had similar metabolic profiles as did stunted and nonstunted SAM survivors.CONCLUSION Adult SAM survivors have distinct metabolic profiles that suggest reduced β-oxidation and greater risk of type 2 diabetes (BCAAs, KT ratio, urea cycle metabolites) compared with CPs. This indicates that early childhood SAM exposure has long-term metabolic consequences that may worsen with age and require targeted clinical management.FUNDING Health Research Council of New Zealand, Caribbean Public Health Agency, Centre for Global Child Health at the Hospital for Sick Children. DST is an Academic Fellow and a Restracomp Fellow at the Centre for Global Child Health. GBG is a postdoctoral fellow of the Research Foundation Flanders.

Authors

Debbie S. Thompson, Celine Bourdon, Paraskevi Massara, Michael S. Boyne, Terrence E. Forrester, Gerard Bryan Gonzales, Robert H. J. Bandsma

×

Figure 6

Participant pairwise similarity.

Options: View larger image (or click on image) Download as PowerPoint
Participant pairwise similarity. Participant pairwise similarity (n = 15...
Participant pairwise similarity (n = 155) presented by heatmaps (left) and networks (right) generated from (A) clinical characteristics, (B) body composition, (C) metabolite variables, and (D) all data types integrated by SNF to form 2 or 4 (K = 2 vs. K = 4) clusters of participants based on the spectral clustering of similarity matrices. The alluvial plot illustrates the redistribution of participants classified into either 2 or 4 clusters where each flow line, colored as per legend, represents the redistribution of a participant between groups. Heatmap colors indicate similarity between participants (dark blue, low similarity; progression toward yellow, increasing similarity). Colors in top horizontal border code for participant attributes: SAM survivors (blue) versus community participants (red) and men (dark) versus women (pale). In network plots, nodes (circles) represent participants colored in gray scale by cluster assignment as per vertical border legend on right of heatmaps. Network edges (lines) represent participants’ pairwise similarities: as per legend, colors indicate contributing data type(s), and both edge thickness and length reflect similarity between participant pairs (i.e., long edges connect participants with low similarity, and short edges connect those with high similarity). Normalized Mutual Information (NMI) metrics assess clustering quality by indicating whether cluster assignment reflects known group labels (e.g., sex or SAM exposure); NMI values are between 0 and 1, with 1 indicating perfect cluster alignment with group labels and 0 having no mutual information (i.e., groups are completely split across clusters). CP, community participant; SNF, similarity network fusion.