P0745 - Metagenomic analysis of the gut microbiome of term infants in the United States reveals widespread dysbiosis

Purpose: The neonatal period represents a unique stage of life when critical foundations of lifelong health are established. Throughout this period, the gut microbiome provides protection against infections and is crucial for the proper development of the immune system. Deviations from optimal microbiome compositions during the postnatal stage, conceptually referred to as dysbiosis, are associated with the absence of key infant-associated Bifidobacterium known to facilitate the utilization of human milk oligosaccharides (HMOs), increased enteric inflammation, and an increase in potentially pathogenic taxa. Although previous studies have revealed a marked dysbiosis in preterm infants born in the United States, evidence remains limited in term infants. To address this gap, we performed a nation-wide metagenomic survey to profile the current status of the US term infant microbiome. We assessed dysbiosis by measuring the abundance of beneficial and potentially pathogenic bacteria, the levels of antibiotic resistance genes, and the microbiome metabolic capacity to metabolize HMOs from breast milk.

Methods: Fecal samples from 227 infants (0-6 months of age) collected across five US states were examined using metagenomics sequencing. Sequences were analyzed to characterize the taxonomic and functional composition following the latest profiling of the Human Microbiome Project.

Results: Bifidobacterium are less abundant among term infants than generally assumed (20% on average). In contrast, potentially pathogenic species were identified to be the highest abundant species overall, including E. coli (12.6% mean abundance), Klebsiella pneumoniae (7%), Klebsiella oxytoca (2.5%), Enterobacter cloaceae (2.7%), and Streptococcus agalactiae (Group B Strep; 0.01%). These species are associated with increased risk of NEC, sepsis, gut inflammation and dysbiosis and were widespread distributed amongst US infants, independently of location, age, and diet. Analysis of the antibiotic resistance gene (ARG) load in the infant microbiomes across the US confirmed a high abundance of ARGs in all five states with signatures of unique ARG composition by state. Furthermore, the gut microbiome of US infants was limited in human milk oligosaccharide utilization capacity. In fact, only 3% of infants had the entire collection of known HMO genes necessary to fully capture, transport and metabolize HMOs from breast milk.

Conclusions: When considering the role of the gut microbiome in early life in shaping the immune system, protecting against pathogen colonization and maximizing nutrition from selective prebiotic fibers (e.g. HMOs), we found that 97% of infants in this survey had microbiomes which failed to provide these services and could be classified as dysbiotic. As direct links between early life gut microbiome composition and acute and long-term health have been extensively described, specifically with respect to immune system development and autoimmune disease risk, interventions to correct infant gut dysbiosis in early life will need to address current widespread deficiencies to restore full ecosystem services in term infants.