# Hepatocyte Growth Factor Differentially Modulates Oral Microbiota in Early vs. Late Experimental Periodontitis

## TL;DR

HGF changes oral bacteria in early and late stages of gum disease, which may explain why it helps early but worsens late-stage disease.

## Contribution

HGF's stage-dependent modulation of the periodontal microbiome is newly characterized.

## Key findings

- HGF significantly altered bacterial diversity and composition during periodontitis.
- Lactobacillus showed opposite trends in early and late stages in HGF-Tg mice.
- Certain bacteria correlated with inflammation and bone metabolism markers.

## Abstract

Periodontitis is a chronic disease caused by an imbalance in oral bacteria. We previously found that hepatocyte growth factor (HGF) can protect against early-stage disease but worsen it later. In this study, we examined how HGF affects bacteria attached to ligatures placed around teeth in mice with periodontitis. We compared normal mice and mice with high HGF levels, analyzing bacterial composition, inflammatory markers, and bone metabolism indicators at different disease stages. HGF significantly changed bacterial diversity and composition over time. Some bacteria, like Lactobacillus, showed opposite patterns in early and late stages, matching the different effects of HGF. Certain bacteria were linked to inflammation and bone loss, and predicted inflammatory pathways varied with disease stage. These findings suggest HGF shapes bacterial communities in ways that may explain its stage-dependent impact on periodontitis.

Background: Periodontitis is a chronic disease triggered by disturbed oral microbiota. We have previously reported that hepatocyte growth factor (HGF) could mitigate early-stage experimental periodontitis but exacerbate the condition in its late stage. Here, we investigated the impact of HGF on the periodontal microbiome during periodontitis progression. Methods: We established ligation-induced periodontitis in wild-type (WT) mice and HGF high-expression transgenic (HGF-Tg) mice. We quantified the levels of IL-6 and TNF-α in periodontal tissues, as well as the serum concentrations of CTXI and PINP. Ligatures were collected on days 0, 7, and 28 after ligation for 16S rRNA sequencing and microbial analysis. Results: HGF significantly altered the diversity of ligatures during periodontitis. Interestingly, specific microbial genera, such as Lactobacillus, exhibited opposing trends between the two disease stages of HGF-Tg mice, aligning with the different effects of HGF on periodontitis progression. We also identified some taxa, such as Sphingomonas, associated with IL-6, TNF-α, CTXI, and PINP. The predicted inflammatory pathways (e.g., IL-17 signaling pathways) were enriched in HGF-Tg mice on day 28 but decreased on day 7. Conclusions: HGF exerted different influences on the microbiota of ligatures during early and late stages of periodontitis, which may account for the divergent effects of HGF on periodontitis progression.