Glycoside hydrolase-mediated glucomannan catabolism in Segatella copri, a target of microbiota-directed foods for malnourished children

Preclinical and clinical studies have identified candidate bioactive polysaccharides in a microbiota-directed food used to treat acutely malnourished Bangladeshi children during complementary feeding. Findings related to this microbiota-directed complementary food (MDCF-2) may enable the design of prebiotic formulations that mimic its effects and offer more flexibility for administration and precise dosing. Using glucomannan as an example, we present an approach for manipulating Segatella copri, a prominent bacterial MDCF-2 'target', using glycans from sustainable sources that combines comparative genomic analyses of its carbohydrate-active enzymes, their biochemical characterization, and their expression in vitro and in gnotobiotic mice containing human gut microbes. The results reveal a unique, multifunctional enzyme whose expression is induced by glucomannan and that catabolizes it plus other MDCF-2 polysaccharides.