The Effects of Smoking on Respiratory Microbiota Diversity and Composition: A Systematic Review with Exploratory Meta-Analysis.

Smoking is a major modifier of respiratory health, but its effects on the respiratory microbiota remain incompletely defined across airway niches and exposure types. We conducted a PRISMA-guided systematic review of PubMed, Web of Science, and Scopus, to identify human studies using culture-independent sequencing to examine associations between smoking and microbiota composition and diversity in anatomically defined upper and lower airway sites. Thirteen studies met the inclusion criteria. The exploratory meta-analysis of bronchoalveolar lavage inverse Simpson diversity from two studies did not provide a precise pooled estimate between smoking and diversity and was highly heterogeneous (SMD -1.63, 95% CI -5.07 to 1.81; I2 = 96%). Across studies, smoking was more often associated with reduced alpha diversity. In the oropharynx, smokers more consistently showed higher abundance of Streptococcus, Veillonella, Actinomyces, and Atopobium, with lower abundance of Neisseria and other oral commensals. In the lower airways, smoking was more often associated with reduced Prevotella and Veillonella. Nasal and nasopharyngeal findings were smaller and more variable. Overall, current evidence suggests site-specific smoking-associated respiratory microbiota remodeling. However, precise pooled estimates remain limited by substantial inter-study heterogeneity. Therefore, the meta-analysis should be interpreted as exploratory and hypothesis-generating.