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

Authors: LUNA, ESTEFANI - California State University; PARKAR, SHANTHI - California State University; KIRMIZ, NINA - California State University; HARTEL, STEPHANIE - California State University; HEARN, ERIK - California State University; HOSSINE, MARZIIAH - California State University; KURDIAN, ARINNAE - California State University; MENDOZA, CLAUDIA - California State University; ORR, KATHERINE - California State University; PADILLA, LOREN - California State University; RAMIREZ, KATHERINE - California State University; SALCEDO, P - California State University; SERRANO, P - California State University; CHOUDHURY, BISWA - University Of California, San Diego; PAULCHAKRABARTI, MOUSUMI - University Of California, San Diego; Parker, Craig; Huynh, Steven; COOPER, KERRY - University Of Arizona; FLORES, GILBERTO - California State University

Submitted to: Applied and Environmental Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/11/2021
Publication Date: 10/20/2021
Citation: Luna, E., Parkar, S., Kirmiz, N., Hartel, S., Hearn, E., Hossine, M., Kurdian, A., Mendoza, C., Orr, K., Padilla, L., Ramirez, K., Salcedo, P., Serrano, P., Choudhury, B., Paulchakrabarti, M., Parker, C.T., Huynh, S., Cooper, K.K., Flores, G.E. 2021. Utilization efficiency of human milk oligosaccharides by human-associated Akkermansia is strain-dependent. Applied and Environmental Microbiology. 88(1). Article e01487-21. https://doi.org/10.1128/AEM.01487-21.
DOI: https://doi.org/10.1128/AEM.01487-21

Interpretive Summary: Akkermansia muciniphila are human gut bacteria that play a role in mucosal homeostasis and are often associated with positive human health. A. muciniphila degrade mucin and paradoxically, promote mucus production by enhancing the differentiation of gut epithelial cells, thereby. In adults, a decreased abundance of Akkermansia is associated with metabolic impairments, ulcerative colitis, and inflammatory bowel disease. In infants, a decrease in mucosal residents such as Akkermansia is associated with a compromised immune system and the development of atopic dermatitis. 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 a diverse collection of Akkermansia strains to grow on HMOs. First, we screened 85 genomes representing the four known Akkermansia phylogroups to determine 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 '-fucosidases, '-sialidases, and ß-galactosidases. Utilization of HMOs by strains of Akkermansia suggests that ingestion of HMOs by an infant in early in life 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.

Technical 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 '-fucosidases, '-sialidases, and ß-galactosidases. Utilization of HMOs by strains of Akkermansia suggests that ingestion of HMOs by an infant in early in life 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.