{"doi":"10.1101/2021.07.26.453919","title":"Utilization efficiency of human milk oligosaccharides by human-associated\n                  <i>Akkermansia</i>\n                  is strain-dependent","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  <jats:italic>Akkermansia muciniphila</jats:italic>\n                  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\n                  <jats:italic>Akkermansia</jats:italic>\n                  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\n                  <jats:italic>Akkermansia</jats:italic>\n                  . 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\n                  <jats:italic>Akkermansia</jats:italic>\n                  to grow on HMOs. First, we screened 85 genomes representing the four known\n                  <jats:italic>Akkermansia</jats:italic>\n                  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\n                  <jats:italic>Akkermansia</jats:italic>\n                  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\n                  <jats:italic>Akkermansia</jats:italic>\n                  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.\n                </jats:p>\n                <jats:sec>\n                  <jats:title>Importance</jats:title>\n                  <jats:p>\n                    Human milk oligosaccharides (HMOs) are utilized by a limited subset of bacteria in the infant gut.\n                    <jats:italic>Akkermansia</jats:italic>\n                    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\n                    <jats:italic>Akkermansia</jats:italic>\n                    phylogroups to potentially deconstruct HMOs. Furthermore, we experimentally showed that strains from all the currently known phylogroups of\n                    <jats:italic>Akkermansia</jats:italic>\n                    can deconstruct all the major types of HMOs, albeit with different utilization efficiencies. This study thus examines\n                    <jats:italic>Akkermansia</jats:italic>\n                    -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.\n                  </jats:p>\n                  <jats:p>\n                    This study will be of interest to a wide range of scientists from microbiologists, glycochemists/glycobiologists, to functional food developers investigating\n                    <jats:italic>Akkermansia</jats:italic>\n                    as probiotics or functional foods containing milk oligosaccharides as prebiotics.\n                  </jats:p>\n                </jats:sec>","journal":null,"year":null,"id":595475,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1521574,"name":"Shanthi G. Parkar","orcid":"0000-0002-5737-7867","position":1,"is_corresponding":false},{"id":1521575,"name":"Nina Kirmiz","orcid":null,"position":2,"is_corresponding":false},{"id":1521576,"name":"Stephanie Hartel","orcid":null,"position":3,"is_corresponding":false},{"id":1116947,"name":"Erik Hearn","orcid":null,"position":4,"is_corresponding":false},{"id":1521577,"name":"Marziiah Hossine","orcid":null,"position":5,"is_corresponding":false},{"id":882953,"name":"Arinnae Kurdian","orcid":null,"position":6,"is_corresponding":false},{"id":1521578,"name":"Claudia Mendoza","orcid":null,"position":7,"is_corresponding":false},{"id":1267965,"name":"Katherine Orr","orcid":null,"position":8,"is_corresponding":false},{"id":1178226,"name":"Loren Padilla","orcid":null,"position":9,"is_corresponding":false},{"id":1521579,"name":"Katherine Ramirez","orcid":null,"position":10,"is_corresponding":false},{"id":1521580,"name":"Priscilla Salcedo","orcid":null,"position":11,"is_corresponding":false},{"id":971314,"name":"Erik Serrano","orcid":"0000-0003-4188-9080","position":12,"is_corresponding":false},{"id":279898,"name":"Biswa Choudhury","orcid":null,"position":13,"is_corresponding":false},{"id":1059148,"name":"Mousumi Paulchakrabarti","orcid":null,"position":14,"is_corresponding":false},{"id":382864,"name":"Craig T. Parker","orcid":"0000-0002-7719-8882","position":15,"is_corresponding":false},{"id":382859,"name":"Steven Huynh","orcid":"0000-0002-5940-606X","position":16,"is_corresponding":false},{"id":1150950,"name":"Kerry Cooper","orcid":null,"position":17,"is_corresponding":false},{"id":80286,"name":"Gilberto E. Flores","orcid":"0000-0002-3338-611X","position":18,"is_corresponding":false},{"id":1178227,"name":"Estefani Luna","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Utilization efficiency of human milk oligosaccharides by human-associated <i>Akkermansia</i> is strain-dependent","abstract":"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.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21097893","pmcid":null,"openalex_id":"https://openalex.org/W3186383081","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"5TL4GM118977-05","title":"BUILD@CSUN"},{"funder_name":"National Institutes of Health","grant_id":"5SC2GM122620-02","title":"Integrated studies into the genomic, metabolic, and cultivable diversity of the human gut symbiont Akkermansia muciniphila"},{"funder_name":"National Institutes of Health","grant_id":"5SC1GM136546-02","title":"Mechanisms and consequences of human milk oligosaccharide growth and bile stress across diverse strains of the potential therapeutic bacterium, Akkermansia muciniphila."},{"funder_name":"National Institutes of Health","grant_id":"5UL1GM118976-09","title":"BUILD PODER II"},{"funder_name":"National Institutes of Health","grant_id":"2RL5GM118975-06","title":"BUILD PODER II"}],"total_grants":5,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/07/28/2021.07.26.453919.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/07/28/2021.07.26.453919.full.pdf","host_type":"repository"},{"url":"https://doi.org/10.1101/2021.07.26.453919","host_type":"repository"},{"url":"https://doi.org/10.1128/aem.01487-21","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/34669436","host_type":""},{"url":"http://dx.doi.org/10.1128/AEM.01487-21","host_type":""},{"url":"https://dx.doi.org/10.1101/2021.07.26.453919","host_type":""},{"url":"https://dx.doi.org/10.1128/aem.01487-21","host_type":""}],"fields_of_study":["Infant Nutrition and Health","Digestive system and related health","Probiotics and Fermented Foods","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Akkermansia muciniphila","Akkermansia","Biology","Mucin","Bacteria","Microbiology","Gut flora","Verrucomicrobia","Biochemistry","Genetics","Bacteroides","Milk, Human","Infant","Oligosaccharides","Microbial Ecology","Gastrointestinal Microbiome","Humans","Female"],"sdg_mappings":[{"sdg_number":2,"sdg_label":"2. Zero hunger"},{"sdg_number":3,"sdg_label":"3. Good health"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T17:30:53.463453Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}