Rice bran in ready-to-use therapeutic foods for microbiota-targeted treatment of childhood malnutrition

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PROJECT SUMMARY Severe acute malnutrition (SAM) is the cause for nearly half of all child deaths under the age five. In Indonesia, SAM affects more than 2 million children and ~1% receive adequate treatment due to lack of access and coverage. Typical SAM treatment includes ready-to-use therapeutic foods (RUTF) which have shown immediate benefit and reduction in mortality rates, however, recovered children have persistent dysbiotic gut microbiota, leaving them susceptible to infection and malnutrition relapse as well as risk for chronic metabolic disease later in life. A growing focus has been placed on prebiotic foods in treatment of gut dysfunction, with little known regarding efficacy of prebiotic rich foods during SAM treatment and recovery. Rice bran contains prebiotics of growing significance to supporting favorable changes to commensal microbiota and microbiota metabolism. Rice Bran contains unique bioactive phytochemicals, lipids, and amino acids when compared to bran from other cereals. Compelling published and preliminary evidence from animals and humans support that rice bran positively influences the gut microbiome and metabolome for protection against diarrheal disease and supports healthy growth. Directed attention to improving SAM treatment of children with an innovative RUTF formulation containing rice bran is the basis for an ongoing double-blinded, randomized control trial (NCT05319717). This RCT is the first examination of rice bran during SAM treatment. The objective of this proposal is to examine whether the addition of rice bran to RUTFs results in changes to the recovering child’s microbiota and metabolism that provide enhanced protection against enteric infections, prevention of malnutrition relapse and promotion of blood metabolic profiles indicative of enhanced nutrient absorption. The hypothesis is that the RUTF + rice bran treatment will increase stool microbial diversity and favorably modulate the dried blood spot metabolome in SAM children when compared to a control RUTF. Dietary rice bran inclusion is expected to modulate both amino acid and lipid metabolism via gut microbiota in children recovered from SAM. Two proposed specific aims to explore this hypothesis are 1) Determine the effect of RUTF + rice bran on gut microbiota composition in the treatment of SAM compared to control RUTF in SAM in children ages 6-59 months and 2) Examine and establish EED marker and metabolite profiles associated with RUTF + rice bran in the treatment of SAM compared to control RUTF. Rice bran inclusion to RUTFs is anticipated to become a local, affordable solution that can enhance protection against microbial dysbiosis that is associated with malnutrition relapse, and results from stool and blood analysis will significantly advance our global knowledge of how to improve gut-directed SAM treatments.