Shelf-Stable MDCF-2 for Children With Undernutrition

Background: Children with acute malnutrition have immature gut microbial communities compared to age-matched children with healthy growth that can not be repaired by existing therapeutic foods (Subramanian et al., Nature. 2014). Hence, investigators' recent work in Bangladesh has focused on developing Microbiota-Directed Complementary Foods (MDCF) containing locally-available food ingredients, that repair the gut microbiota of children with acute malnutrition to a configuration that resembles that of healthy children living in the same urban community (Raman et al., Science 2019; Gherig et al., Science 2019). The investigators recently completed a randomized, controlled proof-of-concept (POC) study of current lead microbiota-directed complementary food, MDCF-2 compared to a standard ready-to-use supplementary food (RUSF), in Bangladeshi children with moderate acute malnutrition (MAM)(Chen et al., N Engl J Med 2021). Children who received MDCF-2 for 3 months exhibited significantly greater repair of their gut microbial communities and faster rates of ponderal growth compared to those treated with RUSF (a formulation that was not designed based on knowledge of its effects on the gut microbiota). The superior effect of MDCF-2 on gut microbiota repair and weight gain was even more notable as the RUSF was significantly more energy dense than MDCF-2. In the aforementioned POC study, MDCF-2 was prepared fresh daily in icddr,b field kitchens prior to distribution and supervised administration to study participants. The lack of a shelf-stable, bio-equivalent formulation of MDCF-2 limits the ability to perform larger studies in Bangladesh as well as in other geographic settings. This pre-POC study in Bangladeshi children with MAM will assess the bioequivalence of MDCF prototypes that the investigators have developed with the potential for improved storage stability compared to current MDCF-2, using the degree of microbiota repair after 4-weeks of treatment as the primary ou