Characterizing microbiota-directed fiber snack food prototypes in gnotobiotic mice and humans

Malnutrition, encompassing the dual burden of undernutrition and obesity, is a global health challenge. Developing microbiota-directed foods (MDF) that reconfigure the gut community in ways that improve nutritional status is a formidable challenge given microbiota complexity, dynamism and interpersonal variations, and limited knowledge of how products of microbial biotransformation of food components influence host physiology. In the present study, gnotobiotic mice, colonized with intact microbiota from nine obese adults, were fed a diet high in saturated fats and low in fruits and vegetables (HiSF-LoFV). Fiber-discriminatory responses of bacterial taxa, carbohydrate active enzyme genes (CAZymes) and metabolic pathways were identified using feature reduction methods. Snack food prototypes containing one, two or four fibers were administered for 2-week periods in a study of overweight and obese adults consuming a controlled HiSF-LoFV diet. Applying feature reduction methods to datasets of serially sampled microbiomes, concurrent measurements of 1300 plasma proteins, and mass spectrometry of fecal glycans identified fiber-specific changes in the representation of CAZymes that correlated with alterations in the plasma proteome indicative of improved metabolic and immune status. These results provide an example of the translatability of results from gnotobiotic mice to humans and an approach for deciphering structure-function relationships connecting food, the microbiome and aspects of host physiology.