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This bacterium forms biofilms and expresses adhesins that facilitate its adhesion to and invasion of gingival epithelial cells. These processes disrupt the epithelial barrier and trigger oral inflammation, and in some cases, systemic inflammation. Conventional antimicrobial strategies predominantly depend on the utilization of antibiotics. Nevertheless, this can result in the proliferation of drug-resistant strains and the disruption of the oral microbiome equilibrium. As the predominant human milk oligosaccharide, 2\u2032-Fucosyllactose (2\u2032-FL) demonstrates considerable promise in inhibiting pathogenic bacterial adhesion and fortifying epithelial barrier function, mediated by its characteristic structural and bioactive attributes. In this study, we showed that 2\u2032-FL attenuates the expression of virulence genes in F. nucleatum, reduces biofilm formation, and suppresses the bacterium\u2019s ability to adhere to human gingival epithelial cells (HGECs). Furthermore, at the transcriptional level, 2\u2032-FL suppressed F. nucleatum-induced inflammatory cytokine overexpression in both HGECs and RAW 264.7 macrophages, and upregulated barrier-related proteins (ZO-1, Occludin) and MUC-1 gene expression in HGECs. In vivo studies demonstrated the inhibitory effect of 2\u2032-FL on F. nucleatum-induced periodontal injury in Balb\/c mice. Furthermore, 16S rRNA sequencing analysis demonstrated that 2\u2032-FL modulated oral microbiota composition of healthy volunteers and significantly reduced the abundance of Fusobacterium.<\/jats:p>","DOI":"10.3390\/microorganisms14071603","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:01:28Z","timestamp":1784768488000},"page":"1603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["2\u2032-Fucosyllactose Attenuates Fusobacterium nucleatum Virulence and Modulates the Oral Microbiota"],"prefix":"10.3390","volume":"14","author":[{"given":"Xinyu","family":"Wu","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China"},{"name":"Key Laboratory of Molecular Microbiology and Technology, Nankai University, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Han","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China"},{"name":"Key Laboratory of Molecular Microbiology and Technology, Nankai University, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China"},{"name":"Key Laboratory of Molecular Microbiology and Technology, Nankai University, Tianjin 300457, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengang","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China"},{"name":"Key Laboratory of Molecular Microbiology and Technology, Nankai University, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Hao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China"},{"name":"Key Laboratory of Molecular Microbiology and Technology, Nankai University, Tianjin 300457, 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