A single nutrient strategy for the rapid and efficient intervention of undernutrition in non-human primate

To date, the underlying mechanisms of undernutrition remain poorly understood primarily due to the inadequacy of animal models; reflecting in the high mortality and relapse associated with the current treatment protocols. Though non-human primates (NHPs) are phylogenetically closest to humans and could serve as an excellent tool for exploring human diseases including undernutrition, no defined criteria for determining undernutrition in NHPs are currently available. However, an initial evaluation of over 10,000 NHPs revealed about 6-8% exhibited signs of undernutrition. Here, by analyzing 1,636 Macaca fascicularis NHPs, we established a weight-for-age z-score (WAZ) based on body condition score (BCS < 2) as identifying NHPs exhibiting the typical human undernutrition symptoms. Furthermore, multi-organ analysis of liver, kidney, muscle, spleen and pancreas revealed the liver as the preferential organ in the pathogenesis of undernutrition. By comprehensive analysis of the undernourished NHP liver, we uncovered severe hepatic steatosis due to impaired lipid catabolism marked by increased MUFA and decreased PUFA levels, consistent with human occurrence. Thus, the major human undernutrition hallmarks were present in undernourished NHPs. Consequently, based on these characteristics, we developed a novel soybean-derived single-nutrient ready-to-use-therapeutic-supplement (RUTS) which rapidly reversed the undernutrition phenotype via modulating hepatic lipid catabolism mediated by enhanced bile acid homeostasis. Our findings have the potential to revolutionize the current understanding and management of undernutrition by rapidly bridging existing knowledge gaps, simplifying treatment protocols, and enhancing treatment effectiveness.