HUMAN MILK IS WIDELY CONSIDERED TO BE THE OPTIMAL FOOD FOR INFANTS. IN ADDITION TO BIOAVAILABLE NUTRIENTS, HUMAN MILK CONTAINS HOST-INDIGESTIBLE HUMAN MILK OLIGOSACCHARIDES (HMOS). WHILE INDIGESTIBLE BY THE INFANT HOST, HMOS ARE READILY USED BY BENEFICIAL MICROBES IN THE INFANT GUT. 2'-FUCOSYLACTOSE (2'FL) IS THE MOST ABUNDANT FUCOSYLATED HMO AND ACCOUNTS FOR UP TO 30% OF TOTAL HMOS. RECENTLY, 2'FL HAS BEEN GRANTED GENERALLY RECOGNIZED AS SAFE (GRAS) STATUS AND IS FREQUENTLY ADDED TO COMMERCIAL INFANT FORMULA TO MORE CLOSELY MIMIC THE COMPOSITION OF HUMAN MILK. 2'FL-SUPPLEMENTED FORMULA HAS BEEN SHOWN TO IMPROVE DIGESTIVE HEALTH IN FORMULA-FED INFANTS OVER CONVENTIONAL FORMULA. DESPITE KNOWLEDGE OF THE BENEFICIAL EFFECTS OF FUCOSYLATED HMOS AND OBSERVATION OF RAPID UTILIZATION OF FUCOSYLATED HMOS BY BIFIDOBACTERIUM INFANTIS - A DOMINANT MEMBER OF THE INFANT GUT, IT IS NOT WELL UNDERSTOOD HOW B. INFANTIS METABOLIZES THE FUCOSE COMPONENT FROM FUCOSYLATED HMOS. OUR PRELIMINARY STUDIES HAVE ESTABLISHED THAT B. INFANTIS CAN METABOLIZE FUCOSE TO PRODUCE 1,2-PROPANEDIOL (1,2PD). THIS PRODUCTION OF 1,2PD COULD SUPPORT CROSS-FEEDING BETWEEN B. INFANTIS AND OTHER BENEFICIAL GUT MICROBES THAT ARE CAPABLE OF PRODUCING PROPIONATE FROM 1,2PD. PROPIONATE PLAYS AN IMPORTANT ROLE IN CRITICAL REGULATORY PROCESSES.WE WILL INVESTIGATE B. INFANTIS METABOLISM OF 2'FL AND ITS EFFECTS ON THE RELATIONSHIP OF B. INFANTIS AND OTHER MEMBERS OF THE INFANT GUT MICROBIOME. TO UNDERSTAND B. INFANTIS METABOLISM OF 2'FL, WE WILL PROFILE METABOLITE PRODUCTION AND GENE EXPRESSION DURING B. INFANTIS GROWTH ON 2'FL. USING THIS UNDERSTANDING, WE WILL THEN EXPLORE THE EFFECTS OF B. INFANTIS METABOLISM ON THE INFANT GUT MICROBIAL COMMUNITY USING A SYSTEM THAT CLOSELY MIMICS THE INFANT GUT ENVIRONMENT. TRACKING METABOLIC PRODUCTION, GENERAL MICROBIAL COMMUNITY COMPOSITION, AND CHANGES IN THE RELATIVE FRACTIONS OF SPECIFIC MICROBES THROUGHOUT THE GROWTH PROCESS WILL GIVE INSIGHTINTO HOW B. INFANTIS METABOLISM OF 2'FL EFFECTS THE INFANT GUT. THIS WILL ADVANCE OUR UNDERSTANDING OF BIFIDOBACTERIAL HMO METABOLISM AND THE INTERACTIONS BETWEEN SPECIFIC BENEFICIAL MICROBES. FURTHER, THE PROPOSED WORK EXPLORES THE IMPLICATIONS OF BIFIDOBACTERIAL 2'FL METABOLISM IN A MODEL SYSTEM THAT SEEKS TO REPLICATE THE COMPETITIVE ENVIRONMENT OF THE INFANT GUT MICROBIOME. THIS TWO-FOLD APPROACH WILL ALLOW AN UNDERSTANDING OF THE USE OF BIFIDOBACTERIAL METABOLITES BY COMMENSAL INFANT GUT MICROBES AS WELL AS HOW COMPETITION AFFECTS BIFIDOBACTERIAL FUCOSE METABOLISM. OUR FINDINGS WILL PROVIDE INSIGHT INTO DYNAMIC MICROBIAL INTERACTION WITHIN THE INFANT GUT MICROBIOME AND WILL ENABLE FUTURE RESEARCH ON THE IMPACTS OF FUCOSYLATED HMO METABOLISM. THIS KNOWLEDGE WILL SERVE AS A FOUNDATION TO DEVELOP EFFECTIVE INTERVENTION STRATEGIES TO MODULATE INFANT GUT MICROBIAL COMPOSITION AND FUNCTION TO IMPROVE INFANT HEALTH AND DEVELOPMENT.
$113,928FY2020National Institute of Food and AgricultureUSDA
University Of Massachusetts, Amherst MA