Objective Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. Design Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. Results FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. Conclusion The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically. Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. Shotgun metagenomics sequencing data for the microbiome of mice have been deposited in the NCBI BioProject database () under accession number PRJNA740117 () and may be re-used with appropriate acknowledgement. Raw data not included there can be obtained with the consent of the corresponding author.

中文翻译：

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粪便微生物转移和复合碳水化合物介导预防慢性阻塞性肺病

目的 慢性阻塞性肺疾病 (COPD) 是全球疾病和死亡的主要原因，最常见是由香烟烟雾引起的。发病机制仍知之甚少，限制了有效疗法的开发。胃肠道微生物群通过肠肺轴与慢性肺部疾病有关，但其作用尚不清楚。设计利用香烟烟雾（CS）诱导的慢性阻塞性肺病和粪便微生物转移（FMT）的体内小鼠模型，我们利用宏基因组学、蛋白质组学和代谢组学对粪便微生物群进行了表征。研究结果与气道和全身炎症、肺和肠道组织病理学以及肺功能相关。使用高抗性淀粉饮食的小鼠以及使用菊粉补充剂的随机、双盲、安慰剂对照试点研究对 16 名慢性阻塞性肺病患者的复合碳水化合物进行了评估。结果 FMT 缓解了 COPD 的标志性特征（炎症、肺泡破坏、肺功能受损）、胃肠道病理和全身免疫变化。戒烟具有额外的保护作用，并且在抗生素诱导的微生物组耗竭后，CS相关微生物群的转移足以增加肺部炎症，同时在没有接触CS的情况下抑制结肠免疫。疾病特征与 Muribaculaceae、Desulfovibrionaceae 和 Lachnospiraceae 科成员的相对丰度相关。蛋白质组学和代谢组学发现 CS 相关微生物群中葡萄糖和淀粉代谢的下调，并且给小鼠或人类患者补充复杂碳水化合物可改善疾病结果。结论 肠道微生物群与 COPD 发病机制有关，并且可以进行靶向治疗。数据可根据合理要求提供。与研究相关的所有数据都包含在文章中或作为补充信息上传。可根据合理要求提供数据。与研究相关的所有数据都包含在文章中或作为在线补充信息上传。小鼠微生物组的鸟枪法宏基因组测序数据已存入 NCBI BioProject 数据库（），登录号为 PRJNA740117（）并且可以在适当的确认下重新使用。未包含的原始数据可在通讯作者同意的情况下获得。