The respiratory tract microbiome and its relationship to lung cancer and environmental exposures found in rural China.

We previously reported that bacterial diversity in sputum samples from never smoking women in rural China varied by lung cancer status and household air pollution (HAP) exposure type. Here we expand upon our associations between environmental exposures and respiratory tract microbiota with an additional 90 never smoking women from Xuanwei, China. DNA from sputum samples of cases (n=45) and controls (n=45) was extracted using a multi-step enzymatic and physical lysis, followed by a standardized clean-up. V1-V2 regions of 16S rRNA genes were PCR-amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high-quality sequences were evaluated for diversity and taxonomic membership. In our population of nonsmokers, increased risk of lung cancer was associated with lower alpha-diversity compared to higher alpha diversity [(Shannon: ORhigh = 1.00 (reference), ORmedium = 3.84 (1.02-14.48), ORlow = 3.78 (1.03-13.82); Observed Species: ORhigh = 1.00 (reference), ORmedium = 2.37 (0.67-8.48), ORlow = 2.01 (0.58-6.97); PD Whole Tree: ORhigh = 1.00 (reference), ORmedium = 3.04 (0.85-10.92), ORlow = 2.53 (0.72-8.96)], as well as a decreased relative abundance of Fusobacteria [(ORhigh = 1.00 (reference), ORmedium = 1.24 (0.42-3.66), ORlow = 2.01 (0.63-6.44), ptrend = 0.03)]. Increasing alpha diversity was associated with smoky coal use compared to clean fuel use among all subjects (Observed Species p=0.001; PD Whole Tree p=0.006; Shannon p=0.0002), as well as cases (Observed Species p=0.02; PD Whole Tree p=0.03; Shannon p=0.03) and controls (Observed Species p=0.01; PD Whole Tree p=0.05; Shannon p=0.002). Increased diversity was also associated with presence of livestock (Observed Species p=0.02; PD Whole Tree p=0.02; Shannon p=0.03) in the home for cases. Our study is the first to report that decreased microbial diversity is associated with risk of lung cancer. Larger studies are necessary to elucidate the direct and indirect effects attributed to the disease-specific, HAP-specific, and animal-specific associations. This article is protected by copyright. All rights reserved.