(P06-017-25) Non-targeted Metabolite Profiling of Dried Blood Spots After Treatment With Rice Bran Included in Ready-to-Use Therapeutic Food (RUTF) for Malnourished Indonesian Children

Objectives: Standard therapeutic feeding for children with uncomplicated acute malnutrition (AM) is RUTF, a lipid-based paste combining milk powder, electrolytes, and micronutrients. Adding rice bran, a nutrient-dense food rich in prebiotics, enhances the quality of RUTF. This study aimed to investigate the metabolite profile, focusing on lipids of children treated with RUTF compared to RUTF supplemented with 5% rice bran.

Methods: A double-blinded, randomized controlled trial was conducted in Jember, Indonesia (NCT05319717). Eligible children were randomly assigned to 2 treatment groups, RUTF (control, n=105) and RUTF+5% rice bran (intervention, n=95), and stratified into 6-23 and 24-59 months age groups. Dried blood spots (DBS) were collected at baseline, week 8 (treatment period) and week 16 (follow-up). Non-targeted metabolomics was performed using UPLC-MS/MS by Metabolon®. Biochemical classification and median scale relative abundances were applied to statistical and metabolic pathway-bioinformatics analysis using p-value < 0.05 and q-value < 0.1 for significance. Correlations were conducted between metabolites and growth outcomes.

Results: There were 463 DBS collected from 158 children across 3 time points. The dataset comprises 883 chemicals, of which 744 are annotated. Lipids were the most abundant metabolites detected (356). Partial least squares-discriminant analysis revealed weak separation (PC1 10.67%, PC2 9.95%) between age groups (Q²=0.41, P < 0.05). A total of 2 lipids had >3 fold change in abundance during treatment in RB group and 1 for control from week 0-8. Sphingomyelins were significantly associated with weight-for-age (r=0.28) and height-for-age (r=0.26) Z scores, as mid-upper arm circumference (r=0.38). In comparison, weight (r=0.43) and height (r=0.46) are significantly related to glycholithocholate sulfate.

Conclusions: DBS metabolomics revealed the importance of lipid metabolism, especially secondary bile acid metabolism and sphingomyelin sub-pathways, to children's growth during malnutrition treatment. These findings have important implications for understanding metabolic outcomes following treatment of children with AM in Indonesia who are at increased risk for chronic metabolic diseases into adolescence and adulthood.

Funding Sources: NIH R21HD113211 (Ryan).