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

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. This examines the utilization of individual purified HMOs by Akkermansia strains representing all known phylogroups. Further studies are required to examine how HMO ingestion influences gut microbial ecology in infants harboring different Akkermansia phylogroups. Importance Human milk oligosaccharides (HMOs) are the third most abundant component of breast milk and provide several benefits to developing infants including recruitment of beneficial bacteria to the human gut. Akkermansia are largely considered beneficial bacteria and have been detected in colostrum, breast milk, and young infants. A. muciniphila MucT belonging to the AmI phylogroup contribute to the HMO deconstruction capacity of the infant. Here, using phylogenomics, we examined the genomic capacity of four Akkermansia phylogroups to deconstruct HMOs. Indeed, each phylogroup contained differences in the genomic capacity to deconstruct HMOs and representative strains of each phylogroup were able to grow using HMOs. These Akkermansia-HMO interactions potentially influence gut microbial ecology in early life - a critical time for the development of the gut microbiome and infant health.