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

## TL;DR

A human oral bacterium, Haemophilus parainfluenzae, changes gut microbes in mice without colonizing the gut, suggesting potential for postbiotic therapies.

## Contribution

Shows H. parainfluenzae alters gut microbiota and immune cells in mice without colonizing the gut.

## Key findings

- H. parainfluenzae enriched Bacteroides acidifaciens in gut microbiota.
- Reduced splenic dendritic cells, indicating systemic immunomodulation.
- Non-viable microbes may drive gut changes without colonization.

## Abstract

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.

To study the modulatory effect of oral H. parainfluenzae inoculation on the gut microbiota.

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.

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.

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.

The beneficial human oral commensal Haemophilus parainfluenzae drives a distinct post-antibiotic reconstitution trajectory of the gut microbiota in female NOD mice.

The treatment enriched Bacteroides acidifaciens, a gut commensal with multifaceted benefits, while a decrease in splenic CD11c+CD11b− cells (representative of dendritic cells) suggests systemic immunomodulation.

H. parainfluenzae inoculation did not establish ectopic gut colonization, and sustained oral colonization was not required for these effects, indicating that non-viable microbes may be sufficient to direct these responses, supporting future investigation of H. parainfluenzae as a postbiotic.