Progressive Changes in the Plasma Metabolome during Malnutrition in Juvenile Pigs

Severe acute malnutrition (SAM) is one of the leading nutrition-related causes of death in children under five years of age. The clinical features of SAM are well documented, but a comprehensive understanding of the development from a normal physiological state to SAM is lacking. Characterizing the temporal metabolomic change may help to understand the disease progression and to define nutritional rehabilitation strategies. Using a piglet model we hypothesized that a progressing degree of malnutrition induces marked plasma metabolite changes. Four-week-old weaned pigs were fed a nutrient-deficient maize diet (MAL) or nutritionally optimized reference diet (REF) for 7 weeks. Plasma collected weekly was subjected to LC-MS for a nontargeted profiling of metabolites with abundance differentiation. The MAL pigs showed markedly reduced body-weight gain and lean-mass proportion relative to the REF pigs. Levels of eight essential and four nonessential amino acids showed a time-dependent deviation in the MAL pigs from that in the REF. Choline metabolites and gut microbiomic metabolites generally showed higher abundance in the MAL pigs. The results demonstrated that young malnourished pigs had a profoundly perturbed metabolism, and this provides basic knowledge about metabolic changes during malnourishment, which may be of help in designing targeted therapeutic foods for refeeding malnourished children.