Abstract Background Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder driven by genetic, environmental, and immune factors.1 Its main forms, Crohn’s disease (CD) and ulcerative colitis (UC), share overlapping inflammatory pathways.2 Beyond traditional biomarkers, emerging molecular and microbial markers may improve disease monitoring and prediction of therapeutic response,3 supporting a personalized IBD management. Given the growing evidence linking oral and intestinal inflammation,4 this study characterized the salivary microbiota in IBD and its relationship with treatment and oral health. Methods Saliva samples were collected from controls (CT) and IBD patients and stored at -80 °C until processing. The V4 region of the 16S rRNA gene sequenced on an Illumina MiSeq platform. Sequences were processed in QIIME2 using Deblur for denoising, eHOMD database for taxonomic assignment, and dedicated plugins for α and β-diversity. Downstream analyses were performed in R. Differential abundance was assessed with ANCOM-BC2. Results 173 participants were included (46 CT, 83 CD, 44 UC). The salivary microbiota composition differed between CT and IBD weighted UniFrac (wU) P = 0.001, but not between UC and CD. α-diversity was higher in IBD than in CT (Shannon P = 0.000) (Figs. 1A-B). 5-ASA therapy was associated with compositional shifts in the oral microbiota (Fig. 2A, wU P = 0.037). After accounting for covariates (disease, periodontal health, BMI, smoking, other drugs), 5-ASA was linked to depletion of IBD-associated pathobionts, including Veillonella sp. (Fig. 2C), despite the increase of the periodontitis-derived Prevotella aurantiaca5. After adjusting for the effect of 5-ASA, the microbial signature still differentiated IBD from CT: IBD exhibited higher abundance of Treponema spp., Veillonella sp., Porphyromonas gingivalis, Propionibacterium acidifaciens, whereas Neisseria bacilliformis and other Treponema members were depleted (Fig. 1C). An interaction between IBD and periodontal status significantly influenced the composition of the salivary microbiota (Bray Curtis P = 0.031). In IBD, but not in CT, periodontal inflammation was associated with reduced α-diversity (Shannon P = 0.007), including a reduction in Fusobacterium pseudoperiodonticum and a Neisseriaceae member (Fig. 2D-F). Conclusion IBD was associated with distinct oral dysbiosis, characterized by higher diversity and expansion of inflammation-associated taxa. 5-ASA may exert a modulatory effect on the oral microbiota by reducing IBD-associated pathobionts, such as Veillonella spp., consistent with its anti-inflammatory action. The periodontal inflammation further amplified dysbiosis and reduced diversity specifically in IBD patients. Gomes, R. and Miranda, R. share first authorship. References: 1. Chhibba T, Gros B, King JA, et al. Environmental risk factors of inflammatory bowel disease: toward a strategy of preventative health. J Crohns Colitis. 2025;19(4). doi:10.1093/ECCO-JCC/JJAF042 2. Ruiz Castro PA, Yepiskoposyan H, Gubian S, et al. Systems biology approach highlights mechanistic differences between Crohn’s disease and ulcerative colitis. Scientific Reports 2021 11:1. 2021;11(1):1-14. doi:10.1038/s41598-021-91124-3 3. Casado-Bedmar M, Viennois E. MicroRNA and Gut Microbiota: Tiny but Mighty—Novel Insights into Their Cross-talk in Inflammatory Bowel Disease Pathogenesis and Therapeutics. J Crohns Colitis. 2022;16(6):992-1005. doi:10.1093/ECCO-JCC/JJAB223 4. Wang A, Zhai Z, Ding Y, Wei J, Wei Z, Cao H. The oral-gut microbiome axis in inflammatory bowel disease: from inside to insight. Front Immunol. 2024;15:1430001. doi:10.3389/FIMMU.2024.1430001/FULL 5. Sakamoto M, Suzuki N, Okamoto M. Prevotella aurantiaca sp. nov., isolated from the human oral cavity. Int J Syst Evol Microbiol. 2010 Mar;60(Pt 3):500-503. doi: 10.1099/ijs.0.012831-0. Epub 2009 Aug 4. PMID: 19654360. Conflict of interest: Gomes, Rute: I declare that I have no conflicts of interest. Miranda, Rita: I declare that I have no conflicts of interest. Gomes, Ana: I declare no conflicts of interest. Rodrigues, Cláudio: I declare no conflicts of interest. Soares, Caroline: No conflicts Couto, Joana: I declare that I have no conflicts of interest related to this research. Mendes, Karina: I declare that I have no conflicts of interest. Pereira, Pedro: I declare that I have no conflicts of interest. Silva, Gonçalo: I declare that I have no conflicts of interest. Duarte, Mariana: Nothing to declare. Lopes, Pedro: None. Sousa, Paula Cristina: Receipt of honoraria or consultation fees: Celltrion Participation in a company sponsored speaker’s bureau: Johnson & Johnson Support for attending meetings: Johnson & Johnson Dr. Falk Norgine Pfizer Abbvie. Martins, Diana: Nothing to declare. Cancela, Eugénia Maria: I haveńt conflits of interest Santiago, Mafalda: No conflicts of interest Dias, Sandra: I declare that I have no conflicts of interest Carneiro, António: Nothing to declare. Correia, Maria: Nothing to declare. Veiga, Nelio: Nothing to declare. Rosa, Nuno: Nothing to declare. Magro, Fernando: Fernando Magro served as speaker and received honoraria from Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, Vifor. Ministro, Paula: I declare that I have served as a speaker and received honoraria from Ferring, Falk, MSD, Johnson and Johnson, AbbVie, Lilly, Celltrion, Takeda and Tillotts.
Gomes et al. (Thu,) studied this question.