Utilization Efficiency of Human Milk Oligosaccharides by Human-Associated <i>Akkermansia</i> Is Strain Dependent.

Abstract

Akkermansia muciniphila is a mucin-degrading bacterium found in the human gut and is often associated with positive human health. However, despite being detected by as early as 1 month of age, little is known about the role of <i>Akkermansia</i> 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 <i>Akkermansia</i>. 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 <i>Akkermansia</i> to grow on HMOs. First, we screened 85 genomes representing the four known <i>Akkermansia</i> 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 <i>Akkermansia</i> genomes were equipped with an array of glycoside hydrolases associated with HMO deconstruction. Representative strains were all able to grow on HMOs with various efficiencies and growth yields. 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 study examines the utilization of individual purified HMOs by <i>Akkermansia</i> strains representing all known phylogroups. Further studies are required to examine how HMO ingestion influences gut microbial ecology in infants harboring different <i>Akkermansia</i> phylogroups. <b>IMPORTANCE</b> Human milk oligosaccharides (HMOs) are the third most abundant component of breast milk and provide several benefits to developing infants, including the recruitment of beneficial bacteria to the human gut. <i>Akkermansia</i> strains are largely considered beneficial bacteria and have been detected in colostrum, breast milk, and young infants. A. muciniphila Muc^T, belonging to the AmI phylogroup, contributes to the HMO deconstruction capacity of the infant. Here, using phylogenomics, we examined the genomic capacities of four <i>Akkermansia</i> phylogroups to deconstruct HMOs. Indeed, each phylogroup contained differences in their genomic capacities to deconstruct HMOs, and representative strains of each phylogroup were able to grow using HMOs. These <i>Akkermansia</i>-HMO interactions potentially influence gut microbial ecology in early life, a critical time for the development of the gut microbiome and infant health.