{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:44:43Z","timestamp":1785422683011,"version":"3.56.0"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI177613"],"award-info":[{"award-number":["AI177613"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["002569F221"],"award-info":[{"award-number":["002569F221"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2026,2,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Fusobacterium nucleatum<\/jats:italic>\n                      is a common member of the oral microbiota frequently associated with extra-oral infections and diverse polymicrobial environments, including chronic airway diseases and colorectal tumors. Yet, its interactions with co-colonizing microbiota remain poorly defined. Here, we investigate cross-feeding interspecies dynamics between\n                      <jats:italic toggle=\"yes\">F. nucleatum<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Segatella oris,<\/jats:italic>\n                      a glycan-foraging anaerobe enriched in the airways, oral cavity, and gastrointestinal tumors. Using broth cultures, cell-free supernatants, and co-culture on primary human airway epithelial cells, we identify microbe-microbe and microbe-host interactions that shape nutrient acquisition, biofilm formation, gene expression, and host responses. While mucin or\n                      <jats:italic toggle=\"yes\">S. oris<\/jats:italic>\n                      supernatants modestly enhanced\n                      <jats:italic toggle=\"yes\">F. nucleatum<\/jats:italic>\n                      growth, both conditions triggered transcriptional remodeling, including induction of the\n                      <jats:italic toggle=\"yes\">nan<\/jats:italic>\n                      operon for sialic acid catabolism, suggesting reliance on glycan degradation by\n                      <jats:italic toggle=\"yes\">S. oris<\/jats:italic>\n                      . Conversely,\n                      <jats:italic toggle=\"yes\">S. oris<\/jats:italic>\n                      exhibited differential expression of multiple polysaccharide utilization loci (PULs) when exposed to\n                      <jats:italic toggle=\"yes\">F. nucleatum<\/jats:italic>\n                      or its metabolites. Biofilm formation by\n                      <jats:italic toggle=\"yes\">F. nucleatum<\/jats:italic>\n                      was strongly inhibited by\n                      <jats:italic toggle=\"yes\">S. oris<\/jats:italic>\n                      and its supernatants\n                      <jats:italic toggle=\"yes\">,<\/jats:italic>\n                      indicative of metabolic regulation. Dual and triple RNA-seq revealed that epithelial responses were predominately shaped by\n                      <jats:italic toggle=\"yes\">F. nucleatum,<\/jats:italic>\n                      with enrichment of inflammatory and cancer-associated pathways; however, co-colonization with\n                      <jats:italic toggle=\"yes\">S. oris<\/jats:italic>\n                      modulated the expression of genes linked to the unfolded protein response and apoptosis, among others. These findings demonstrate that glycan-mediated cross-feeding and microbial interactions shape the physiology and pathogenic potential of\n                      <jats:italic toggle=\"yes\">F. nucleatum<\/jats:italic>\n                      in mucosal environments. This work underscores the importance of modeling polymicrobial communities under host-relevant conditions to better understand pathobiont behavior at the epithelial interface.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Fusobacterium nucleatum<\/jats:italic>\n                        is increasingly recognized as a pathobiont in mucosal diseases, including colorectal cancers and chronic airway infections, yet its functional interactions with co-colonizing microbiota remain poorly understood. Here, we demonstrate that\n                        <jats:italic toggle=\"yes\">F. nucleatum<\/jats:italic>\n                        engages in bidirectional interactions with\n                        <jats:italic toggle=\"yes\">Segatella oris,<\/jats:italic>\n                        a glycan-foraging anaerobe also enriched in mucin-rich environments. Through nutrient cross-feeding and transcriptional modulation, these interactions shape bacterial behavior and the host epithelial response. Notably, glycan degradation by\n                        <jats:italic toggle=\"yes\">S. oris<\/jats:italic>\n                        enables\n                        <jats:italic toggle=\"yes\">F. nucleatum<\/jats:italic>\n                        access to sialic acids, while\n                        <jats:italic toggle=\"yes\">F. nucleatum<\/jats:italic>\n                        suppresses the expression of multiple polysaccharide utilization loci in\n                        <jats:italic toggle=\"yes\">S. oris,<\/jats:italic>\n                        revealing a reciprocal ecological influence. Co-colonization of the airway epithelial surface also modulates gene expression linked to inflammation and cancer. These findings advance our understanding of polymicrobial dynamics at mucosal interfaces and highlight the importance of incorporating microbe-microbe-host interactions into reductionist models of infection and disease.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.00922-25","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T14:00:17Z","timestamp":1769004017000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Cross-feeding interactions between\n                    <i>Fusobacterium nucleatum<\/i>\n                    and the glycan forager\n                    <i>Segatella oris<\/i>"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0723-3195","authenticated-orcid":true,"given":"Joshua R.","family":"Fletcher","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04b6b6f76","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine","place":["Raleigh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Areej","family":"Malik","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04b6b6f76","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine","place":["Raleigh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Driggers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04b6b6f76","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine","place":["Raleigh, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-1676","authenticated-orcid":true,"given":"Ryan C.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2012-13-6-r42"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12167"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.126573.111"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/07357907.2024.2359980"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.03.021"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2197836"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2017.08.007"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2021.03.022"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00153-21"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01813-19"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-73950-3"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1507090"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-96746-5"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2019.10.39"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/mbo3.204"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.11.008"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2012.08.008"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-019-0679-5"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.007302-0"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-48862-3"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053653"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302x.1990.tb00418.x"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2002.tb11392.x"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/anae.1997.0140"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-302x.2003.00069.x"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302x.1991.tb00486.x"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302x.1995.tb00130.x"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000788"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu716"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1022"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00177-08"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005846"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc01b01s00"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36735-z"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00471.2016"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-016-0956-2"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.7563.2"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06503.x"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01338-24"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.4c00279"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.009910"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1139\/o75-169"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.56.380"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24152803"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.819144"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111329"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.01.010"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.07.006"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202152891"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2011.04.003"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1045"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad328"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00481-20"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.psib-0009-2018"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-022-2172-x"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/all.14715"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-007-0298-7"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.034"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/fty082"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-025-00717-7"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.11.034"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00081-24"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000031120"}],"container-title":["mSystems"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msystems.00922-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msystems.00922-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:02:05Z","timestamp":1771336925000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/msystems.00922-25"}},"subtitle":[],"editor":[{"given":"Sarah M.","family":"Allard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,17]]},"references-count":65,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2,17]]}},"alternative-id":["10.1128\/msystems.00922-25"],"URL":"https:\/\/doi.org\/10.1128\/msystems.00922-25","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.06.18.660387","asserted-by":"object"}]},"ISSN":["2379-5077"],"issn-type":[{"value":"2379-5077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,17]]},"assertion":[{"value":"2025-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00922-25"}}