Causal influence of gut microbiota on small cell lung cancer: a Mendelian randomization study

IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Clinical Respiratory Journal Pub Date : 2024-04-29 DOI:10.1111/crj.13764
Wenjing Yang, Xinxia Fan, Wangshu Li, Yan Chen
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Abstract

Background

Previous studies have hinted at a significant link between lung cancer and the gut microbiome, yet their causal relationship remains to be elucidated.

Methods

GWAS data for small cell lung cancer (SCLC) was extracted from the FinnGen consortium, comprising 179 cases and 218 613 controls. Genetic variation data for 211 gut microbiota were obtained as instrumental variables from MiBioGen. Mendelian randomization (MR) was employed to determine the causal relationship between the two, with inverse variance weighting (IVW) being the primary method for causal analysis. The MR results were validated through several sensitivity analyses.

Results

The study identified a protective effect against SCLC for the genus Eubacterium ruminantium group (OR = 0.413, 95% CI: 0.223–0.767, p = 0.00513), genus Barnesiella (OR = 0.208, 95% CI: 0.0640–0.678, p = 0.00919), family Lachnospiraceae (OR = 0.319, 95% CI: 0.107–0.948, p = 0.03979), and genus Butyricimonas (OR = 0.376, 95% CI: 0.144–0.984, p = 0.04634). Conversely, genus Intestinibacter (OR = 3.214, 95% CI: 1.303–7.926, p = 0.01125), genus Eubacterium oxidoreducens group (OR = 3.391, 95% CI: 1.215–9.467, p = 0.01973), genus Bilophila (OR = 3.547, 95% CI: 1.106–11.371, p = 0.03315), and order Bacillales (OR = 1.860, 95% CI: 1.034–3.347, p = 0.03842) were found to potentially promote the onset of SCLC.

Conclusion

We identified potential causal relationships between certain gut microbiota and SCLC, offering new insights into microbiome-mediated mechanisms of SCLC pathogenesis, resistance, mutations, and more.

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肠道微生物群对小细胞肺癌的因果影响:孟德尔随机研究
背景 以前的研究暗示肺癌与肠道微生物组之间存在重要联系,但它们之间的因果关系仍有待阐明。 方法 从芬兰基因联盟(FinnGen consortium)中提取了小细胞肺癌(SCLC)的 GWAS 数据,其中包括 179 例病例和 218 613 例对照。211 个肠道微生物群的遗传变异数据作为工具变量从 MiBioGen 获得。孟德尔随机化(MR)被用来确定两者之间的因果关系,反方差加权(IVW)是因果分析的主要方法。通过多项敏感性分析验证了孟德尔随机分析的结果。 结果 研究发现,反刍优杆菌属组(OR = 0.413,95% CI:0.223-0.767,p = 0.00513)、巴氏杆菌属(OR = 0.208,95% CI:0.0640-0.678,P = 0.00919)、Lachnospiraceae 科(OR = 0.319,95% CI:0.107-0.948,P = 0.03979)和 Butyricimonas 属(OR = 0.376,95% CI:0.144-0.984,P = 0.04634)。相反,肠杆菌属(OR = 3.214,95% CI:1.303-7.926,p = 0.01125)、Eubacterium oxidoreducens 组属(OR = 3.391,95% CI:1.215-9.467,p = 0.01973)、Bilophila 属(OR = 3.547,95% CI:1.106-11.371,p = 0.03315)和 Bacillales 目(OR = 1.860,95% CI:1.034-3.347,p = 0.03842)被发现可能会促进 SCLC 的发病。 结论 我们确定了某些肠道微生物群与 SCLC 之间的潜在因果关系,为了解微生物介导的 SCLC 发病机制、抵抗力、突变等提供了新的视角。
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来源期刊
Clinical Respiratory Journal
Clinical Respiratory Journal 医学-呼吸系统
CiteScore
3.70
自引率
0.00%
发文量
104
审稿时长
>12 weeks
期刊介绍: Overview Effective with the 2016 volume, this journal will be published in an online-only format. Aims and Scope The Clinical Respiratory Journal (CRJ) provides a forum for clinical research in all areas of respiratory medicine from clinical lung disease to basic research relevant to the clinic. We publish original research, review articles, case studies, editorials and book reviews in all areas of clinical lung disease including: Asthma Allergy COPD Non-invasive ventilation Sleep related breathing disorders Interstitial lung diseases Lung cancer Clinical genetics Rhinitis Airway and lung infection Epidemiology Pediatrics CRJ provides a fast-track service for selected Phase II and Phase III trial studies. Keywords Clinical Respiratory Journal, respiratory, pulmonary, medicine, clinical, lung disease, Abstracting and Indexing Information Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Embase (Elsevier) Health & Medical Collection (ProQuest) Health Research Premium Collection (ProQuest) HEED: Health Economic Evaluations Database (Wiley-Blackwell) Hospital Premium Collection (ProQuest) Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) ProQuest Central (ProQuest) Science Citation Index Expanded (Clarivate Analytics) SCOPUS (Elsevier)
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