biostudies-literatureFletcher JRNational Institute of Allergy and Infectious DiseasesCystic Fibrosis Foundatione0092225https://www.ebi.ac.uk/biostudies/studies/S-EPMC12911393biostudies-literatureUnknown11(2)<i>Fusobacterium nucleatum</i> 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 <i>F. nucleatum</i> and <i>Segatella oris,</i> 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 <i>S. oris</i> supernatants modestlmSystemsCross-feeding interactions between &lt;i&gt;Fusobacterium nucleatum&lt;/i&gt; and the glycan forager &lt;i&gt;Segatella oris&lt;/i&gt;.PMC12911393002569F221AI177613Fletcher JRMalik ADriggers JHunter RCfalseCross-feeding interactions between &lt;i&gt;Fusobacterium nucleatum&lt;/i&gt; and the glycan forager &lt;i&gt;Segatella oris&lt;/i&gt;.<i>Fusobacterium nucleatum</i> 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 <i>F. nucleatum</i> and <i>Segatella oris,</i> 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 <i>S. oris</i> supernatants modestl2026-01-01T00:00:00Z2026 Feb2026-07-16T05:06:52.195Z2026-07-10T03:08:30.139ZS-EPMC129113934156262410.1128/msystems.00922-25