Distinct trajectory of gut microbiota driven by a human oral commensal: insights from a murine study

<h4>Background</h4>Oral microbes modulate the gut microbiota. <i>Haemophilus parainfluenzae</i>, 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.<h4>Objective</h4>To study the modulatory effect of oral <i>H. parainfluenzae</i> inoculation on the gut microbiota.<h4>Design</h4>Female NOD mice were orally inoculated with <i>H. parainfluenzae</i> 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.<h4>Results</h4>Despite prominent convergence of diversity and beta dissimilarity within each group, <i>H. parainfluenzae</i> led to distinct core microbiota and overall microbial community. While reducing the Firmicutes-to-Bacteroidetes ratio, <i>H. parainfluenzae</i> enriched Bacteroidaceae and its genus <i>Bacteroides</i>. <i>Bacteroides acidifaciens</i>, a beneficial gut commensal, was enriched in ASV-level analyses. The splenic dendritic cells were reduced. Notably, neither did <i>H. parainfluenzae</i> establish ectopic gut colonization, nor was sustained oral colonization required, indicating that non-viable microbes may be sufficient to direct these responses.<h4>Conclusions</h4><i>H. parainfluenzae</i> drives a distinct gut microbiota reconstitution trajectory, characterized by <i>B. acidifaciens</i> enrichment without establishing notable colonizations, supporting its role in the oral-gut axis and warranting future postbiotic research.