Lin, Wei-TingWei-TingLinLee, Shiao-PiengShiao-PiengLeeLi, ChinChinLiChang, Chia-BinChia-BinChangChien, Hsiu-ChuanHsiu-ChuanChienJANN-TAY WANGWu, Shu-FenShu-FenWuSONG-CHOU HSIEHTseng, Yu-ChaoYu-ChaoTseng2025-12-092025-12-092025https://scholars.lib.ntu.edu.tw/handle/123456789/734466Background: Oral microbes modulate the gut microbiota. Haemophilus parainfluenzae, a core human oral commensal with immunomodulatory properties, is reduced in autoimmune diseases, while mitigating Sjögren's syndrome-like disease with improved oral microbiota in female NOD mice. However, whether it modulates the gut microbiota remains unknown. Objective: To study the modulatory effect of oral H. parainfluenzae inoculation on the gut microbiota. Design: Female NOD mice were orally inoculated with H. parainfluenzae following antibiotic treatment. Fecal samples were collected pre- and post-inoculation for 16S rRNA gene sequencing. Splenic antigen-presenting cells were analyzed for systemic immunomodulation. Results: Despite prominent convergence of diversity and beta dissimilarity within each group, H. parainfluenzae led to distinct core microbiota and overall microbial community. While reducing the Firmicutes-to-Bacteroidetes ratio, H. parainfluenzae enriched Bacteroidaceae and its genus Bacteroides. Bacteroides acidifaciens, a beneficial gut commensal, was enriched in ASV-level analyses. The splenic dendritic cells were reduced. Notably, neither did H. parainfluenzae establish ectopic gut colonization, nor was sustained oral colonization required, indicating that non-viable microbes may be sufficient to direct these responses. Conclusions: H. parainfluenzae drives a distinct gut microbiota reconstitution trajectory, characterized by B. acidifaciens enrichment without establishing notable colonizations, supporting its role in the oral-gut axis and warranting future postbiotic research.enBacteroides acidifaciensHaemophilus parainfluenzaeNOD miceOral-gut axisectopic colonizationimmunomodulationpost-antibiotic reconstitutionpostbiotic[SDGs]SDG2[SDGs]SDG3journal article10.1080/20002297.2025.256952441158439