Utilization efficiency of human milk oligosaccharides by human-associated Akkermansia is strain-dependent

Abstract Akkermansia muciniphila are mucin degrading bacteria found in the human gut and are often associated with positive human health. However, despite being detected as early as one month of age, little is known about the role of Akkermansia in the infant gut. Human milk oligosaccharides (HMOs) are abundant components of human milk and are structurally similar to the oligosaccharides that comprise mucin, the preferred growth substrate of human-associated Akkermansia . A limited subset of intestinal bacteria has been shown to grow well on HMOs and mucin. We therefore examined the ability of genomically diverse strains of Akkermansia to grow on HMOs. First, we screened 85 genomes representing the four known Akkermansia phylogroups to examine their metabolic potential to degrade HMOs. Furthermore, we examined the ability of representative isolates to grow on individual HMOs in a mucin background and analyzed the resulting metabolites. All Akkermansia genomes were equipped with an array of glycoside hydrolases associated with HMO-deconstruction. Representative strains were all able to grow on HMOs with varying efficiency and growth yield. Strain CSUN-19 belonging to the AmIV phylogroup, grew to the highest level in the presence of fucosylated and sialylated HMOs. This activity may be partially related to the increased copy numbers and/or the enzyme activities of the α-fucosidases, α-sialidases, and β-galactosidases. Utilization of HMOs by strains of Akkermansia suggests that ingestion of HMOs by an infant may enrich for these potentially beneficial bacteria. Further studies are required to realize this opportunity and deliver long-lasting metabolic benefits to the human host. Importance Human milk oligosaccharides (HMOs) are utilized by a limited subset of bacteria in the infant gut. Akkermansia are detected in infants as young as one month of age and are thought to contribute to the HMO deconstruction capacity of the infant. Here, using phylogenomics, we examined the genomic capacity of different Akkermansia phylogroups to potentially deconstruct HMOs. Furthermore, we experimentally showed that strains from all the currently known phylogroups of Akkermansia can deconstruct all the major types of HMOs, albeit with different utilization efficiencies. This study thus examines Akkermansia -HMO interactions that can potentially influence the gut microbial ecology during the first 1,000 days of life - a critical phase for the development of the gut microbiome and infant health. This study will be of interest to a wide range of scientists from microbiologists, glycochemists/glycobiologists, to functional food developers investigating Akkermansia as probiotics or functional foods containing milk oligosaccharides as prebiotics.