Exploring the Causal Relationship Between Saliva Microbiota Abundance and Chronic Obstructive Pulmonary Disease/Idiopathic Pulmonary Fibrosis: A Two-Sample Mendelian Randomization Study

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are progressive lung diseases with overlapping risk factors but distinct pathologies. This study employed bidirectional two-sample Mendelian randomization (MR) to explore potential causal relationships between saliva microbiota abundance and the risk of both diseases. Saliva microbiota abundance datasets were analyzed for forward and reverse causal associations with both diseases. Of 44 datasets, 43 met the inclusion criteria for instrumental variable selection. MR analyses were performed using inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods. Steiger filtering confirmed directionality. Sensitivity analyses included Cochran's Q, MR-Egger intercept, MR-PRESSO, and leave-one-out to assess heterogeneity, pleiotropy, and the influence of individual variants. In forward MR, higher abundance of species parvula was significantly associated with reduced COPD risk (IVW OR = 0.9546, 95% CI = 0.9224-0.9879, P = 0.0020; adjusted P = 0.019). Nominal inverse associations were observed for Bacilli, Porphyromonas, and Fusobacterium with IPF, though these did not remain significant after multiple testing correction. All key associations passed Steiger directionality tests, with no evidence of horizontal pleiotropy or heterogeneity. In reverse MR, COPD showed a nominal positive association with Periodonticum abundance. This exploratory study suggests potential directional associations between specific salivary microbiota and chronic respiratory diseases. Parvula abundance may be protective against COPD, while Bacilli, Porphyromonas, and Fusobacterium may influence IPF risk. These findings support the salivary microbiome as a potential contributor to respiratory disease pathogenesis and warrant further validation in mechanistic and longitudinal studies.