Fecal metabolome alterations in infants at risk of developing allergies during the first year of life

Introduction: Disturbances in the infant gut microbiome (GM) may increase the risk of developing allergies. This critical developmental period is characterized by rapid microbial colonization, which is influenced by factors like delivery mode and infant feeding practices. Objectives: The present study investigated changes in key GM taxa and fecal metabolites in relation to allergy development, delivery mode, age, and infant feeding practices during the first year of life. Methods: Seventy-two infants at risk of allergies, exclusively breastfed for at least 16 weeks, were followed in their first year. During this period, allergy manifestations were recorded and fecal samples collected at three time points. The samples were subjected to metabolic profiling covering host and microbial metabolites and fluorescent in situ hybridization to quantify Bifidobacterium spp. and the Eubacterium rectale/Clostridium coccoides group. Results: Strong age-associated metabolic shifts were observed, particularly in aromatic amino acid metabolites, bile acids, B vitamins, and short and long-chain fatty acids. Feeding practices, specifically the introduction of complementary feeding and the cessation of breastfeeding were significantly associated with changes to the fecal metabolome. Delivery mode had a pronounced impact on the metabolome, with differences between vaginal and Cesarean deliveries persisting until 6 months of age. Infants who developed an allergy during this period had lower Bifidobacterium spp. and significantly higher polyunsaturated fatty acid levels before the age of 16 weeks. Conclusion: This study offers valuable insights into the longitudinal development of the fecal metabolome and factors influencing it during infancy, a critical period for immune system development. Clinical trial registration: Clinicaltrials.gov identifier: NCT03067714, registered: 01/02/2017.