室内PAHs暴露相关因素与非吸烟女性肺癌特征肠道微生物的关联研究
Association between source of indoor PAHs exposure and gut microbiota of lung cancer in non-smoking women
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摘要:目的 探索室内多环芳烃(polycyclic aromatic hydrocarbons, PAHs)暴露相关因素与非吸烟女性肺癌特征肠道微生物的关联, 为进一步研究非吸烟女性肺癌病因提供依据。方法 通过问卷调查评估217例调查对象(非吸烟女性肺癌组109例, 对照组108例)室内PAHs相关因素的终生暴露量。使用线性判别分析效应量(linear discriminant analysis effect size, LEfSe)分析非吸烟女性肺癌患者的肠道微生物特征, 使用冗余分析(redundancy analysis, RDA)分析室内PAHs暴露对肠道微生物组的影响, 使用Spearman秩相关分析室内PAHs暴露与非吸烟女性肺癌特征肠道微生物的相关性。结果 病例组烹饪时间和室内燃香时间分别为42.0(36.0, 50.0)和15.0(6.0, 25.0)a, 对照组分别为41.5(33.0, 51.0)和12.5(5.0, 28.0)a, 病例组高于对照组(P < 0.001)。经LEfSe分析获得34个显著区分非吸烟女性肺癌与对照的特征肠道微生物菌属, 其中病例组富集24个, 对照组富集10个。RDA分析显示烹饪时间(r2=0.062, P=0.003)和燃香时间(r2=0.141, P=0.001)对肠道微生物组成的影响有统计学意义。norank_o_RF39菌属(rs=0.142, P=0.037)和活泼瘤胃球菌属(Ruminococcus gnavus group, rs=0.142, P=0.037)与烹饪时间的相关性有统计学意义; 塞利单胞菌属(Sellimonas, rs=0.142, P=0.037), Schaalia菌属(rs=0.142, P=0.037)和解黄酮菌属(Flavonifractor, rs=0.142, P=0.037)与燃香时间的相关性有统计学意义。结论 室内PAHs暴露相关因素与某些肠道微生物的显著相关表明PAHs可能与肠道微生物组变化相关, 进而可能在肺癌发生中发挥作用; 病例组烹饪时间的高暴露及其与非吸烟女性肺癌特征肠道微生物的相关表明烹饪来源的PAHs可能是引起非吸烟女性肺癌的重要因素。Abstract:Objective To explore the gut microbiota associated with indoor polycyclic aromatic hydrocarbons (PAHs) exposure in non-smoking female lung cancer patients, to provide a support for further study on the etiology of lung cancer in non-smoking women.Methods The lifetime indoor PAHs exposure of 217 subjects (109 non-smoking women with lung cancer and 108 controls) were assessed through questionnaires. Linear discriminant analysis effect size (LEfSe) analysis was used to identify gut microbiota biomarkers of lung cancer in non-smoking women. Redundancy analysis (RDA) was used to analyze the impact of indoor PAHs exposure on the gut microbiome, and Spearman correlation analysis was conducted to examine the relationship between indoor PAHs exposure and the selected gut microbiota biomarkers.Results The case group had cooking durations and indoor incense burning durations of 42.0 (36.0, 50.0) years and 15.0 (6.0, 25.0) years, respectively, while the control group had durations of 41.5 (33.0, 51.0) years and 12.5 (5.0, 28.0) years, respectively. The case group showed significantly higher values than the control group (P < 0.001). Additionally, LEfSe analysis identified 34 gut genera that distinguished non-smoking women with lung cancer from controls, with 24 genera enriched in the case group and 10 in the control group. RDA analysis demonstrated that cooking duration (r2=0.062, P=0.003) and incense burning duration (r2=0.141, P=0.001) had statistically effects on the composition of gut microbiota. The norank_o_RF39 (rs=0.142, P=0.037) and Ruminococcus gnavus group (rs=0.142, P=0.037) showed significant correlations with cooking duration. Sellimonas (rs=0.142, P=0.037), Schaalia (rs=0.142, P=0.037), and Flavonifractor (rs=0.142, P=0.037) exhibited significant correlations with incense burning duration.Conclusion The significant correlation between indoor PAHs exposure and gut microbiota suggests that PAHs may be associated with changes in the gut microbiome, which may play a role in the development of lung cancer. The higher cooking duration exposure in the case group and its correlation with gut microbiota biomarkers of lung cancer in non-smoking women indicate that PAHs from cooking fumes may be an important factor in the development of non-smoking female lung cancer.
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