Glycoside hydrolase–mediated glucomannan catabolism in <i>Segatella copri</i> , a target of microbiota-directed foods for malnourished children

Evidence is emerging that perturbed postnatal gut microbiota development is causally related to childhood undernutrition. Clinical trials in undernourished Bangladeshi children found that a polysaccharide-rich, microbiota-directed complementary food (MDCF-2) designed to repair this perturbation produced superior ponderal and linear growth compared to a standard ready-to-use supplementary food. Subsequent analyses disclosed several candidate bioactive polysaccharides in the MDCF and their bacterial targets, notably strains of Segatella copri that possess carbohydrate-active enzymes (CAZymes) organized into polysaccharide utilization loci (PULs) targeting these glycans. A Bangladeshi S. copri isolate (BgF5_2) containing these PULs metabolized MDCF-2 glycans and promoted MDCF-dependent weight gain in a gnotobiotic mouse model emulating the clinical trials. Identifying prebiotic mixtures that mimic the effects of MDCF-2 would offer new options for…