Imbalance in the oral bacterial flora as a risk factor for acute exacerbation in idiopathic pulmonary fibrosis

Introduction: Microbiome imbalance could be one of the risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). However, little is known about the role of the oral bacterial flora in AE-IPF. Aims: To investigate the significance of oral bacterial flora as a risk factor for AE-IPF. Methods: A total of 142 patients with IPF (77 German and 65 Japanese), 264 healthy subjects (164 German and 100 Japanese) and 31 Japanese patients with bacterial pneumonia were prospectively collected. Baseline serum levels of antibodies against 16 bacteria of the oral flora were measured by ELISA. The correlations between baseline serum levels of these antibodies and the incidence of AE-IPF were evaluated. Results: Baseline serum levels of Porphyromonas type III, IV, V, and Fusobacterium antibodies were significantly higher in the Japanese IPF patients compared with the other 4 groups (Japanese healthy, Japanese pneumonia, German healthy and German IPF). Baseline serum levels of several antibacterial antibodies (Porphyromonas type I, III, IV, V, Tannerella, and Campylobacter) were positively correlated with the occurrence of AE-IPF (AUC 0.554-0.608), whereas others (Aggregatibacter, Prevotella and Fusobcterium) were negatively correlated (AUC 0.400-0.441). Among them, the ratio of Tannerella to Aggregatibacter was significantly associated with the occurrence of AE-IPF (AUC 0.520-0.747, p=0.015). In the multivariate analysis, the ratio of Tannerella to Aggregatibacter > 0.72 and Japanese ethnicity were independent risk factors for AE-IPF (hazard ratio 2.23, p=0.03; 4.48, p=0.0002). Conclusions: An imbalance in the oral bacterial flora could be a risk factor for AE-IPF.