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Published on: June 1, 2022
Exploring the Causal Relationship Between Saliva Microbiota Abundance and Chronic Obstructive Pulmonary
Haixia Wei1, Chunlan Han1, Yongna Song1
1Pulmonary and Critical Care Medicine, Zhengzhou Central Hospital, Zhengzhou, 450000, People's Republic of China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Higher parvula abundance may protect against chronic obstructive pulmonary disease (COPD). Specific salivary bacteria may also influence idiopathic pulmonary fibrosis (IPF) risk, suggesting a role for the oral microbiome in respiratory health.
Area of Science:
- Microbiome research
- Genetics
- Respiratory medicine
Background:
- Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are distinct progressive lung diseases.
- Both IPF and COPD share overlapping risk factors but have different underlying pathologies.
- The role of salivary microbiota in the pathogenesis of these respiratory diseases is not fully understood.
Purpose of the Study:
- To investigate potential causal relationships between salivary microbiota abundance and the risk of IPF and COPD.
- To explore bidirectional associations using Mendelian randomization.
- To identify specific salivary microbial species that may influence the development of these lung diseases.
Main Methods:
- Bidirectional two-sample Mendelian randomization (MR) analysis was performed.
- Forty-three saliva microbiota datasets were analyzed for genetic associations with IPF and COPD.
- Standard MR methods (IVW, MR-Egger, weighted median) and sensitivity analyses were employed to ensure robustness.
Main Results:
- Increased abundance of *parvula* was significantly associated with a reduced risk of COPD (OR = 0.9546, P = 0.0020).
- Nominal inverse associations were observed between IPF risk and the abundance of Bacilli, *Porphyromonas*, and *Fusobacterium*, though not statistically significant after corrections.
- No significant evidence of heterogeneity or horizontal pleiotropy was detected, and directionality was confirmed.
Conclusions:
- Specific salivary microbial profiles may have a causal impact on the risk of developing COPD and IPF.
- *Parvula* may offer a protective effect against COPD.
- These findings highlight the salivary microbiome as a potential factor in respiratory disease pathogenesis, meriting further investigation.

