The common causal relationship between intestinal flora and respiratory diseases based on the theory of "lung and large intestine being interior-exterior related"_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

CAO Zhenghua ¹ , HU Shaodan ² , SUN Feng ² , JIANG Guolu ¹ ,  SHI Li ²

1. Changchun University of Traditional Chinese Medicine, Changchun, 130117, P. R. China;
2. Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, P. R. China;

Corresponding?author：

SHI Li, Email: shili0648@163.com

Keywords：

Mendelian randomization; respiratory system diseases; causal relationship; chronic obstructive pulmonary disease

DOI：

10.7507/1007-4848.202408017

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To comprehensively evaluate the causal relationship between gut microbiota and 9 respiratory diseases, explore whether there are common mechanisms among these 9 respiratory diseases, and delves into the potential commonalities in the nascent stage of chronic obstructive pulmonary disease (pre-COPD) by focusing on COPD, emphysema, and chronic bronchitis. Methods Mendelian randomization was used to explore the causal relationship between gut microbiota and 9 respiratory diseases, sensitivity analysis was conducted, and robustness was verified. Single nucleotide polymorphisms of common gut microbiota were mapped to genes to explore their common mechanisms. Results Mendelian randomization studies found that 66 gut microbiota had a causal relationship with 9 respiratory diseases, and 15 gut microbiota might be potential common mechanisms for these 9 respiratory diseases, with a total of 85 potential genes. GO functional enrichment analysis found that these genes were mainly enriched in biological functions such as synaptic transmission, synaptic membrane, cytokine activity, and growth factor binding. KEGG enrichment analysis showed that these genes were mainly enriched in glutamatergic synapses, relaxin signaling pathway, calcium signaling pathway, Rap1 signaling pathway, and PI3K-Akt signaling pathway. Allisonella and Prevotellaceae might be protective factors for pre-COPD, while Howardella might be a risk factor. Ten protective genes and six risk genes for the pre-COPD were identified. Conclusion This study further confirms the correlation between the lung-gut axis and the lung-colon connection, explores the potential common mechanisms of 9 respiratory diseases, investigates the potential mechanisms of pre-COPD based on the common gut microbiota of COPD, chronic bronchitis, and emphysema, and provides some ideas for the early prevention and treatment of COPD, and diagnosis of pre-COPD from the perspective of gut microbiota.

1.	莫芳芳, 馬師雷, 李鴻濤, 等. 基于中醫古籍研究的“肺與大腸相表里”理論源流及其內涵探討. 環球中醫藥, 2015, 8(2): 165-168.Mo FF, Ma SL, Li HT, et al. Discussion on the origin and connotation of the "lung and large intestine being interior exteriorly related" based on TCM classics. Glob Tradit Chin Med, 2015, 8(2): 165-168.
2.	張蕓, 史鎖芳. “肺與大腸相表里”學說的現代研究進展. 中醫研究, 2015, 28(5): 73-75.Zhang Y, SHI SF. Modern research progress of the theory of "lung and large intestine are external and internal". Tradit Chin Med Res, 2015, 28(5): 73-75.
3.	李玉平, 翟海英, 楊長福. “肺與大腸相表里”理論的研究. 中國中醫基礎醫學雜志, 2024, 30(2): 336-341.Li YP, Zhai HY, Yang CF. Research on the theory of "lung and large intestine connecting externally and internally". J Basic Chin Med, 2024, 30(2): 336-341.
4.	劉聲, 楊國旺, 王笑民. 從胚胎上皮細胞基因表達譜變化分析肺與大腸相表里內涵. 中醫學報, 2016, 31(3): 390-393.Liu S, Yang GW, Wang XM. The connotation of lung and large intestine being interior-exteriorly related based on the gene expression of embryo epithelial cells. Acta Chin Med, 2016, 31(3): 390-393.
5.	Wang X, Hou L, Cui M, et al. The traditional Chinese medicine and non-small cell lung cancer: From a gut microbiome perspective. Front Cell Infect Microbiol, 2023, 13: 1151557.
6.	彭楊月, 常滿, 牛盼迪, 等. 發酵中藥改善腸道屏障和腸道菌群的研究進展. 中國現代應用藥學, 2023, 40(11): 1563-1570.Peng YY, Chang M, Niu PD, et al. Research progress of fermented traditional chinese medicine in improving intestinal barrier and intestinal flora. Chin J Mod Appl Pharm, 2023, 40(11): 1563-1570.
7.	段曉穎, 邢慧資, 桑鋒, 等. 中藥對腸黏膜屏障的作用機制研究進展. 中國現代應用藥學, 2019, 36(16): 2106-2111.Duan XY, Xing HZ, Sang F, et al. Research progress on mechanism of traditional Chinese medicine on intestinal mucosal barrier. Chin J Mod Appl Pharm, 2019, 36(16): 2106-2111.
8.	王晗笑, 欒哲宇, 封繼宏. 基于“肺與大腸相表里”探討中醫藥調控腸道菌群治療慢性阻塞性肺疾病的內涵. 中國實驗方劑學雜志, 2024, 30(3): 169-177.Wang HX, Luan ZY, Feng JH. Connotation of traditional Chinese medicine in treatment of chronic obstructive pulmonary disease by regulating gut microbiota based on "lung and large intestine being interior-exterior related". Chin J Exp Tradit Med Form, 2024, 30(3): 169-177.
9.	Zheng XL, Yang Y, Wang BJ, et al. Synchronous dynamic research on respiratory and intestinal microflora of chronic bronchitis rat model. Chin J Integr Med, 2017, 23(3): 196-200.
10.	Lee SH, Kim J, Kim NH, et al. Gut microbiota composition and metabolite profiling in smokers: A comparative study between emphysema and asymptomatic individuals with therapeutic implications. Thorax, 2023, 78(11): 1080-1089.
11.	徐文濤, 王雪峰, 楊建樹, 等. 宣白承氣湯對流感病毒和肺炎鏈球菌共感染致肺腸免疫損傷的影響. 中國中西醫結合雜志, 2023, 43(11): 1350-1358.Xu WT, Wang XF, Yang JS, et al. Effect of Xuanbai Chengqi decoction on pulmonary and intestinal immune injury induced by coinfection of influenza virus and streptococcus pneumoniae. Chin J Integr Tradit West Med, 2023, 43(11): 1350-1358.
12.	時艷杰, 張穎, 甘雨, 等. 基于基于“肺與大腸相表里”的理論探討射干止咳膠囊對耐甲氧西林金黃色葡萄球菌感染肺炎大鼠腸道菌群的影響. 中華中醫藥學刊, 2024.Epub ahead of print Shi YJ, Zhang Y, Gan Y, et al. Effect of Shegan Zhike capsule on intestinal flora of pneumonia rats infected with methicillin-resistant staphylococcus aureus based on the theory of 'lung and large intestine'. Chin Arch Tradit Chin Med, 2024. [Epub ahead of print].
13.	張明慧, 冀蒙, 高靜東, 等. 中藥多糖抗纖維化作用機制研究進展. 中草藥, 2024, 55(4): 1063-1074.Zhang MH, Ji M, Gao JD, et al. Research progress on anti-fibrotic effects of polysaccharides from traditional Chinese medicine. Chin Tradit Herb Drug, 2024, 55(4): 1063-1074.
14.	Liu JQ, Zhou HB, Bai WF, et al. Assessment of progression of pulmonary fibrosis based on metabonomics and analysis of intestinal microbiota. Artif Cells Nanomed Biotechnol, 2024, 52(1): 201-217.
15.	蘭春, 胡燕, 王孟清, 等. “培土生金”理法方藥用于支氣管哮喘的作用機制研究進展. 世界科學技術-中醫藥現代化, 2023, 25(10): 3328-3335.Lan C, Hu Y, Wang MQ, et al. Literature research on the mechanism of "tonifying the spleen to help the lung" in the treatment of bronchial asthma. Mod Tradit Chin Med Materia Medica-World Sci Tech, 2023, 25(10): 3328-3335.
16.	Wei X, Wang F, Tan P, et al. The interactions between traditional Chinese medicine and gut microbiota in cancers: Current status and future perspectives. Pharmacol Res, 2024, 203: 107148.
17.	Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA, 2017, 318(19): 1925-1926.
18.	Agustí A, Melén E, DeMeo DL, et al. Pathogenesis of chronic obstructive pulmonary disease: Understanding the contributions of gene-environment interactions across the lifespan. Lancet Respir Med, 2022, 10(5): 512-524.
19.	Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: The STROBE-MR statement. JAMA, 2021, 326(16): 1614-1621.
20.	Kurilshikov A, Medina-Gomez C, Bacigalupe R, et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat Genet, 2021, 53(2): 156-165.
21.	Burgess S, Scott RA, Timpson NJ, et al. Using published data in Mendelian randomization: A blueprint for efficient identification of causal risk factors. Eur J Epidemiol, 2015, 30(7): 543-552.
22.	He M, Xu C, Yang R, et al. Causal relationship between human blood metabolites and risk of ischemic stroke: A Mendelian randomization study. Front Genet, 2024, 15: 1333454.
23.	Yang J, Yan B, Zhao B, et al. Assessing the causal effects of human serum metabolites on 5 major psychiatric disorders. Schizophr Bull, 2020, 46(4): 804-813.
24.	Ran B, Qin J, Wu Y, et al. Causal role of immune cells in chronic obstructive pulmonary disease: Mendelian randomization study. Expert Rev Clin Immunol, 2024, 20(4): 413-421.
25.	Yuan J, Xiong X, Zhang B, et al. Genetically predicted C-reactive protein mediates the association between rheumatoid arthritis and atlantoaxial subluxation. Front Endocrinol (Lausanne), 2022, 13: 1054206.
26.	Choi KW, Chen CY, Stein MB, et al. Assessment of bidirectional relationships between physical activity and depression among adults: A 2-sample Mendelian randomization study. JAMA Psychiatry, 2019, 76(4): 399-408.
27.	Cheng ZX, Hua JL, Jie ZJ, et al. Genetic insights into the gut-lung axis: Mendelian randomization analysis on gut microbiota, lung function, and COPD. Int J Chron Obstruct Pulmon Dis, 2024, 19: 643-653.
28.	Pierce BL, Burgess S. Efficient design for Mendelian randomization studies: Subsample and 2-sample instrumental variable estimators. Am J Epidemiol, 2013, 178(7): 1177-1184.
29.	Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ, 2018, 362: k601.
30.	Sanderson E. Multivariable Mendelian randomization and mediation. Cold Spring Harb Perspect Med, 2021, 11(2): a038984.
31.	Burgess S, Thompson SG. Erratum to: Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol, 2017, 32(5): 391-392.
32.	Cai J, Li X, Wu S, et al. Assessing the causal association between human blood metabolites and the risk of epilepsy. J Transl Med, 2022, 20(1): 437.
33.	Shi Y, Feng S, Yan M, et al. Inflammatory bowel disease and celiac disease: A bidirectional Mendelian randomization study. Front Genet, 2022, 13: 928944.
34.	Soriano JB, Polverino F, Cosio BG. What is early COPD and why is it important? Eur Respir J, 2018, 52(6): 1801448.
35.	Balint D, Brito IL. Human-gut bacterial protein-protein interactions: Understudied but impactful to human health. Trends Microbiol, 2024, 32(4): 325-332.
36.	Muller E, Shiryan I, Borenstein E. Multi-omic integration of microbiome data for identifying disease-associated modules. Nat Commun, 2024, 15(1): 2621.
37.	Dai H, Han J, Wang T, et al. Recent advances in gut microbiota-associated natural products: Structures, bioactivities, and mechanisms. Nat Prod Rep, 2023, 40(6): 1078-1093.
38.	Gou H, Su H, Liu D, et al. Traditional medicine Pien Tze Huang suppresses colorectal tumorigenesis through restoring gut microbiota and metabolites. Gastroenterology, 2023, 165(6): 1404-1419.
39.	Zhong X, Yan J, Wei X, et al. Shenxiang Suhe pill improves cardiac function through modulating gut microbiota and serum metabolites in rats after acute myocardial infarction. Pharm Biol, 2024, 62(1): 1-12.
40.	Wang N, Chen S, Xie Y, et al. The Sanbi Decoction alleviates intervertebral disc degeneration in rats through intestinal flora and serum metabolic homeostasis modulation. Phytomedicine, 2024, 127: 155480.
41.	Wang T, Wang Y, Yao Y. Gut microbe guides alveolar macrophages to fight flu. Cell Host Microbe, 2024, 32(3): 296-298.
42.	Azzouz D, Omarbekova A, Heguy A, et al. Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Ann Rheum Dis, 2019, 78(7): 947-956.
43.	Henke MT, Kenny DJ, Cassilly CD, et al. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci U S A, 2019, 116(26): 12672-12677.
44.	Breban M, Tap J, Leboime A, et al. Faecal microbiota study reveals specific dysbiosis in spondyloarthritis. Ann Rheum Dis, 2017, 76(9): 1614-1622.
45.	Sun M, Zhang F, Lu F, et al. Integrating fecal metabolomics and intestinal microbiota to study the mechanism of cannabidiol in the treatment of idiopathic pulmonary fibrosis. Front Pharmacol, 2024, 15: 1358626.
46.	Chen H, Li S, Pan B, et al. Qing-Kai-Ling oral liquid alleviated pneumonia via regulation of intestinal flora and metabolites in rats. Front Microbiol, 2023, 14: 1194401.
47.	Messaoudene M, Pidgeon R, Richard C, et al. A natural polyphenol exerts antitumor activity and circumvents anti-PD-1 resistance through effects on the gut microbiota. Cancer Discov, 2022, 12(4): 1070-1087.
48.	Lu X, Xiong L, Zheng X, et al. Structure of gut microbiota and characteristics of fecal metabolites in patients with lung cancer. Front Cell Infect Microbiol, 2023, 13: 1170326.
49.	Liu P, Tan XY, Zhang HQ, et al. Optimal compatibility proportional screening of trichosanthis pericarpium-trichosanthis radix and its anti-inflammatory components effect on experimental zebrafish and coughing mice. J Ethnopharmacol, 2024, 319(Pt 1): 117096.
50.	Dou C, Hu L, Ding X, et al. Microbiota alterations in lung, ileum, and colon of guinea pigs with cough variant asthma. Int J Mol Sci, 2024, 25(4): 2449.
51.	Yang S, Guo J, Kong Z, et al. Causal effects of gut microbiota on sepsis and sepsis-related death: Insights from genome-wide Mendelian randomization, single-cell RNA, bulk RNA sequencing, and network pharmacology. J Transl Med, 2024, 22(1): 10.
52.	Tett A, Pasolli E, Masetti G, et al. Prevotella diversity, niches and interactions with the human host. Nat Rev Microbiol, 2021, 19(9): 585-599.
53.	Meldrum OW, Donaldson GC, Narayana JK, et al. Accelerated lung function decline and mucus-microbe evolution in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2024, 210(3): 298-310.
54.	Madapoosi SS, Cruickshank-Quinn C, Opron K, et al. Lung microbiota and metabolites collectively associate with clinical outcomes in milder stage chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2022, 206(4): 427-439.
55.	Horn KJ, Schopper MA, Drigot ZG, et al. Airway prevotella promote TLR2-dependent neutrophil activation and rapid clearance of streptococcus pneumoniae from the lung. Nat Commun, 2022, 13(1): 3321.
56.	Wu BG, Sulaiman I, Tsay JJ, et al. Episodic aspiration with oral commensals induces a MyD88-dependent, pulmonary T-helper cell type 17 response that mitigates susceptibility to streptococcus pneumoniae. Am J Respir Crit Care Med, 2021, 203(9): 1099-1111.
57.	Yang D, Chen X, Wang J, et al. Dysregulated lung commensal bacteria drive interleukin-17B production to promote pulmonary fibrosis through their outer membrane vesicles. Immunity, 2019, 50(3): 692-706.
58.	Zemanick ET, Wagner BD, Robertson CE, et al. Airway microbiota across age and disease spectrum in cystic fibrosis. Eur Respir J, 2017, 50(5): 1700832.
59.	Denner DR, Sangwan N, Becker JB, et al. Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways. J Allergy Clin Immunol, 2016, 137(5): 1398-1405.
60.	Qian X, Zhang HY, Li QL, et al. Integrated microbiome, metabolome, and proteome analysis identifies a novel interplay among commensal bacteria, metabolites and candidate targets in non-small cell lung cancer. Clin Transl Med, 2022, 12(6): e947.
61.	Jiang Q, Xu Q, Kenéz á, et al. Klebsiella pneumoniae infection is associated with alterations in the gut microbiome and lung metabolome. Microbiol Res, 2022, 263: 127139.
62.	Hu C, van Meel ER, Medina-Gomez C, et al. A population-based study on associations of stool microbiota with atopic diseases in school-age children. J Allergy Clin Immunol, 2021, 148(2): 612-620.
63.	Bernatchez E, Gold MJ, Langlois A, et al. Methanosphaera stadtmanae induces a typeⅣhypersensitivity response in a mouse model of airway inflammation. Physiol Rep, 2017, 5(7): e13163.
64.	Zhang X, Li PH, Wang D, et al. Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of "influenza-subacute thyroiditis-hypothyroidism". Front Microbiol, 2024, 15: 1354989.
65.	Zheng L, Liu C, Wang H, et al. Intact lung tissue and bronchoalveolar lavage fluid are both suitable for the evaluation of murine lung microbiome in acute lung injury. Microbiome, 2024, 12(1): 56.
66.	梁可克, 王志旺, 黃柯婷, 等. PI3K-AKT信號通路調控慢阻肺氣道重塑及中藥干預作用研究新進展. 中藥藥理與臨床, 2024, 40(5): 103-108.Liang KK, Wang ZW, Huang KT, et al. Traditional Chinese medicine regulates airway remodeling of chronic obstructive pulmonary disease via PI3K-AKT signaling pathway: A review. Pharm Clin Chin Materia Medica, 2024, 40(5): 103-108.
67.	王祁, 趙博, 高璐, 等. 基于PI3K/AKT/mTOR信號通路探討野黃芩苷聯合虎杖苷抗慢性支氣管炎的作用機制. 中國病理生理雜志, 2023, 39(10): 1780-1788.Wang Q, Zhao B, Gao L, et al. Effects of scutellarin combined with polydatin on chronic bronchitis via PI3K/AKT/mTOR signaling pathway. Chin J Pathophysiol, 2023, 39(10): 1780-1788.
68.	王艷梅, 梁彥昌, 甘德堃, 等. 青蒿素基于PI3K/Akt信號通路減輕卵清蛋白哮喘大鼠的氣道炎癥和氣道重塑的分析. 中國實驗方劑學雜志, 2024, 30(13): 114-119.Wang YM, Liang YC, Gan DK, et al. Attenuation of airway inflammation and airway remodeling in ovalbumin asthmatic rats by artemisinin through PI3K/Akt signaling pathway. Chin J Exp Tradit Med Form, 2024, 30(13): 114-119.
69.	尹香琳, 張婧瑤, 劉衛東, 等. 1-磷酸鞘氨醇受體2介導PI3K/AKT/eNOS通路抑制甲型流感病毒誘導的病毒性肺炎. 中國病理生理雜志, 2018, 34(11): 2062-2067.Yin XL, Zhang JY, Liu WD, et al. Sphingosine-1-phosphate receptor 2 attenuates influenza A virus-induced viral pneumonia through PI3K/AKT/eNOS pathway. Chin J Pathophysiol, 2018, 34(11): 2062-2067.
70.	周雯, 駱亞莉, 周世琴, 等. 基于網絡藥理學和動物實驗探究益氣養陰活血方治療肺纖維化的作用. 中成藥, 2023, 45(3): 973-978.Zhou W, Luo YL, Zhou SQ, et al. To explore the effect of Yiqi Yangyin Huoxue recipe on pulmonary fibrosis based on network pharmacology and animal experiments. Chin Tradit Patent Med, 2023, 45(3): 973-978.
71.	陳稀煩, 魏曉炎, 侯樂萍. 華蟾素對肺癌大鼠PI3K/AKT信號通路的抑制作用. 中國現代應用藥學, 2020, 37(4): 425-430.Chen XF, Wei XY, Hou LP. Inhibitory effect of cinobufotalin on lung cancer rats PI3K/AKT signaling pathway. Chin J Mod Appl Pharm, 2020, 37(4): 425-430.
72.	Casas M, den Dekker HT, Kruithof CJ, et al. The effect of early growth patterns and lung function on the development of childhood asthma: A population based study. Thorax, 2018, 73(12): 1137-1145.
73.	Bui DS, Lodge CJ, Burgess JA, et al. Childhood predictors of lung function trajectories and future COPD risk: A prospective cohort study from the first to the sixth decade of life. Lancet Respir Med, 2018, 6(7): 535-544.
74.	Belgrave DCM, Granell R, Turner SW, et al. Lung function trajectories from pre-school age to adulthood and their associations with early life factors: A retrospective analysis of three population-based birth cohort studies. Lancet Respir Med, 2018, 6(7): 526-534.
75.	Martinez FJ, Han MK, Allinson JP, et al. At the root: Defining and halting progression of early chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2018, 197(12): 1540-1551.

1. 莫芳芳, 馬師雷, 李鴻濤, 等. 基于中醫古籍研究的“肺與大腸相表里”理論源流及其內涵探討. 環球中醫藥, 2015, 8(2): 165-168.Mo FF, Ma SL, Li HT, et al. Discussion on the origin and connotation of the "lung and large intestine being interior exteriorly related" based on TCM classics. Glob Tradit Chin Med, 2015, 8(2): 165-168.
2. 張蕓, 史鎖芳. “肺與大腸相表里”學說的現代研究進展. 中醫研究, 2015, 28(5): 73-75.Zhang Y, SHI SF. Modern research progress of the theory of "lung and large intestine are external and internal". Tradit Chin Med Res, 2015, 28(5): 73-75.
3. 李玉平, 翟海英, 楊長福. “肺與大腸相表里”理論的研究. 中國中醫基礎醫學雜志, 2024, 30(2): 336-341.Li YP, Zhai HY, Yang CF. Research on the theory of "lung and large intestine connecting externally and internally". J Basic Chin Med, 2024, 30(2): 336-341.
4. 劉聲, 楊國旺, 王笑民. 從胚胎上皮細胞基因表達譜變化分析肺與大腸相表里內涵. 中醫學報, 2016, 31(3): 390-393.Liu S, Yang GW, Wang XM. The connotation of lung and large intestine being interior-exteriorly related based on the gene expression of embryo epithelial cells. Acta Chin Med, 2016, 31(3): 390-393.
5. Wang X, Hou L, Cui M, et al. The traditional Chinese medicine and non-small cell lung cancer: From a gut microbiome perspective. Front Cell Infect Microbiol, 2023, 13: 1151557.
6. 彭楊月, 常滿, 牛盼迪, 等. 發酵中藥改善腸道屏障和腸道菌群的研究進展. 中國現代應用藥學, 2023, 40(11): 1563-1570.Peng YY, Chang M, Niu PD, et al. Research progress of fermented traditional chinese medicine in improving intestinal barrier and intestinal flora. Chin J Mod Appl Pharm, 2023, 40(11): 1563-1570.
7. 段曉穎, 邢慧資, 桑鋒, 等. 中藥對腸黏膜屏障的作用機制研究進展. 中國現代應用藥學, 2019, 36(16): 2106-2111.Duan XY, Xing HZ, Sang F, et al. Research progress on mechanism of traditional Chinese medicine on intestinal mucosal barrier. Chin J Mod Appl Pharm, 2019, 36(16): 2106-2111.
8. 王晗笑, 欒哲宇, 封繼宏. 基于“肺與大腸相表里”探討中醫藥調控腸道菌群治療慢性阻塞性肺疾病的內涵. 中國實驗方劑學雜志, 2024, 30(3): 169-177.Wang HX, Luan ZY, Feng JH. Connotation of traditional Chinese medicine in treatment of chronic obstructive pulmonary disease by regulating gut microbiota based on "lung and large intestine being interior-exterior related". Chin J Exp Tradit Med Form, 2024, 30(3): 169-177.
9. Zheng XL, Yang Y, Wang BJ, et al. Synchronous dynamic research on respiratory and intestinal microflora of chronic bronchitis rat model. Chin J Integr Med, 2017, 23(3): 196-200.
10. Lee SH, Kim J, Kim NH, et al. Gut microbiota composition and metabolite profiling in smokers: A comparative study between emphysema and asymptomatic individuals with therapeutic implications. Thorax, 2023, 78(11): 1080-1089.
11. 徐文濤, 王雪峰, 楊建樹, 等. 宣白承氣湯對流感病毒和肺炎鏈球菌共感染致肺腸免疫損傷的影響. 中國中西醫結合雜志, 2023, 43(11): 1350-1358.Xu WT, Wang XF, Yang JS, et al. Effect of Xuanbai Chengqi decoction on pulmonary and intestinal immune injury induced by coinfection of influenza virus and streptococcus pneumoniae. Chin J Integr Tradit West Med, 2023, 43(11): 1350-1358.
12. 時艷杰, 張穎, 甘雨, 等. 基于基于“肺與大腸相表里”的理論探討射干止咳膠囊對耐甲氧西林金黃色葡萄球菌感染肺炎大鼠腸道菌群的影響. 中華中醫藥學刊, 2024.Epub ahead of print Shi YJ, Zhang Y, Gan Y, et al. Effect of Shegan Zhike capsule on intestinal flora of pneumonia rats infected with methicillin-resistant staphylococcus aureus based on the theory of 'lung and large intestine'. Chin Arch Tradit Chin Med, 2024. [Epub ahead of print].
13. 張明慧, 冀蒙, 高靜東, 等. 中藥多糖抗纖維化作用機制研究進展. 中草藥, 2024, 55(4): 1063-1074.Zhang MH, Ji M, Gao JD, et al. Research progress on anti-fibrotic effects of polysaccharides from traditional Chinese medicine. Chin Tradit Herb Drug, 2024, 55(4): 1063-1074.
14. Liu JQ, Zhou HB, Bai WF, et al. Assessment of progression of pulmonary fibrosis based on metabonomics and analysis of intestinal microbiota. Artif Cells Nanomed Biotechnol, 2024, 52(1): 201-217.
15. 蘭春, 胡燕, 王孟清, 等. “培土生金”理法方藥用于支氣管哮喘的作用機制研究進展. 世界科學技術-中醫藥現代化, 2023, 25(10): 3328-3335.Lan C, Hu Y, Wang MQ, et al. Literature research on the mechanism of "tonifying the spleen to help the lung" in the treatment of bronchial asthma. Mod Tradit Chin Med Materia Medica-World Sci Tech, 2023, 25(10): 3328-3335.
16. Wei X, Wang F, Tan P, et al. The interactions between traditional Chinese medicine and gut microbiota in cancers: Current status and future perspectives. Pharmacol Res, 2024, 203: 107148.
17. Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA, 2017, 318(19): 1925-1926.
18. Agustí A, Melén E, DeMeo DL, et al. Pathogenesis of chronic obstructive pulmonary disease: Understanding the contributions of gene-environment interactions across the lifespan. Lancet Respir Med, 2022, 10(5): 512-524.
19. Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: The STROBE-MR statement. JAMA, 2021, 326(16): 1614-1621.
20. Kurilshikov A, Medina-Gomez C, Bacigalupe R, et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat Genet, 2021, 53(2): 156-165.
21. Burgess S, Scott RA, Timpson NJ, et al. Using published data in Mendelian randomization: A blueprint for efficient identification of causal risk factors. Eur J Epidemiol, 2015, 30(7): 543-552.
22. He M, Xu C, Yang R, et al. Causal relationship between human blood metabolites and risk of ischemic stroke: A Mendelian randomization study. Front Genet, 2024, 15: 1333454.
23. Yang J, Yan B, Zhao B, et al. Assessing the causal effects of human serum metabolites on 5 major psychiatric disorders. Schizophr Bull, 2020, 46(4): 804-813.
24. Ran B, Qin J, Wu Y, et al. Causal role of immune cells in chronic obstructive pulmonary disease: Mendelian randomization study. Expert Rev Clin Immunol, 2024, 20(4): 413-421.
25. Yuan J, Xiong X, Zhang B, et al. Genetically predicted C-reactive protein mediates the association between rheumatoid arthritis and atlantoaxial subluxation. Front Endocrinol (Lausanne), 2022, 13: 1054206.
26. Choi KW, Chen CY, Stein MB, et al. Assessment of bidirectional relationships between physical activity and depression among adults: A 2-sample Mendelian randomization study. JAMA Psychiatry, 2019, 76(4): 399-408.
27. Cheng ZX, Hua JL, Jie ZJ, et al. Genetic insights into the gut-lung axis: Mendelian randomization analysis on gut microbiota, lung function, and COPD. Int J Chron Obstruct Pulmon Dis, 2024, 19: 643-653.
28. Pierce BL, Burgess S. Efficient design for Mendelian randomization studies: Subsample and 2-sample instrumental variable estimators. Am J Epidemiol, 2013, 178(7): 1177-1184.
29. Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ, 2018, 362: k601.
30. Sanderson E. Multivariable Mendelian randomization and mediation. Cold Spring Harb Perspect Med, 2021, 11(2): a038984.
31. Burgess S, Thompson SG. Erratum to: Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol, 2017, 32(5): 391-392.
32. Cai J, Li X, Wu S, et al. Assessing the causal association between human blood metabolites and the risk of epilepsy. J Transl Med, 2022, 20(1): 437.
33. Shi Y, Feng S, Yan M, et al. Inflammatory bowel disease and celiac disease: A bidirectional Mendelian randomization study. Front Genet, 2022, 13: 928944.
34. Soriano JB, Polverino F, Cosio BG. What is early COPD and why is it important? Eur Respir J, 2018, 52(6): 1801448.
35. Balint D, Brito IL. Human-gut bacterial protein-protein interactions: Understudied but impactful to human health. Trends Microbiol, 2024, 32(4): 325-332.
36. Muller E, Shiryan I, Borenstein E. Multi-omic integration of microbiome data for identifying disease-associated modules. Nat Commun, 2024, 15(1): 2621.
37. Dai H, Han J, Wang T, et al. Recent advances in gut microbiota-associated natural products: Structures, bioactivities, and mechanisms. Nat Prod Rep, 2023, 40(6): 1078-1093.
38. Gou H, Su H, Liu D, et al. Traditional medicine Pien Tze Huang suppresses colorectal tumorigenesis through restoring gut microbiota and metabolites. Gastroenterology, 2023, 165(6): 1404-1419.
39. Zhong X, Yan J, Wei X, et al. Shenxiang Suhe pill improves cardiac function through modulating gut microbiota and serum metabolites in rats after acute myocardial infarction. Pharm Biol, 2024, 62(1): 1-12.
40. Wang N, Chen S, Xie Y, et al. The Sanbi Decoction alleviates intervertebral disc degeneration in rats through intestinal flora and serum metabolic homeostasis modulation. Phytomedicine, 2024, 127: 155480.
41. Wang T, Wang Y, Yao Y. Gut microbe guides alveolar macrophages to fight flu. Cell Host Microbe, 2024, 32(3): 296-298.
42. Azzouz D, Omarbekova A, Heguy A, et al. Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Ann Rheum Dis, 2019, 78(7): 947-956.
43. Henke MT, Kenny DJ, Cassilly CD, et al. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci U S A, 2019, 116(26): 12672-12677.
44. Breban M, Tap J, Leboime A, et al. Faecal microbiota study reveals specific dysbiosis in spondyloarthritis. Ann Rheum Dis, 2017, 76(9): 1614-1622.
45. Sun M, Zhang F, Lu F, et al. Integrating fecal metabolomics and intestinal microbiota to study the mechanism of cannabidiol in the treatment of idiopathic pulmonary fibrosis. Front Pharmacol, 2024, 15: 1358626.
46. Chen H, Li S, Pan B, et al. Qing-Kai-Ling oral liquid alleviated pneumonia via regulation of intestinal flora and metabolites in rats. Front Microbiol, 2023, 14: 1194401.
47. Messaoudene M, Pidgeon R, Richard C, et al. A natural polyphenol exerts antitumor activity and circumvents anti-PD-1 resistance through effects on the gut microbiota. Cancer Discov, 2022, 12(4): 1070-1087.
48. Lu X, Xiong L, Zheng X, et al. Structure of gut microbiota and characteristics of fecal metabolites in patients with lung cancer. Front Cell Infect Microbiol, 2023, 13: 1170326.
49. Liu P, Tan XY, Zhang HQ, et al. Optimal compatibility proportional screening of trichosanthis pericarpium-trichosanthis radix and its anti-inflammatory components effect on experimental zebrafish and coughing mice. J Ethnopharmacol, 2024, 319(Pt 1): 117096.
50. Dou C, Hu L, Ding X, et al. Microbiota alterations in lung, ileum, and colon of guinea pigs with cough variant asthma. Int J Mol Sci, 2024, 25(4): 2449.
51. Yang S, Guo J, Kong Z, et al. Causal effects of gut microbiota on sepsis and sepsis-related death: Insights from genome-wide Mendelian randomization, single-cell RNA, bulk RNA sequencing, and network pharmacology. J Transl Med, 2024, 22(1): 10.
52. Tett A, Pasolli E, Masetti G, et al. Prevotella diversity, niches and interactions with the human host. Nat Rev Microbiol, 2021, 19(9): 585-599.
53. Meldrum OW, Donaldson GC, Narayana JK, et al. Accelerated lung function decline and mucus-microbe evolution in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2024, 210(3): 298-310.
54. Madapoosi SS, Cruickshank-Quinn C, Opron K, et al. Lung microbiota and metabolites collectively associate with clinical outcomes in milder stage chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2022, 206(4): 427-439.
55. Horn KJ, Schopper MA, Drigot ZG, et al. Airway prevotella promote TLR2-dependent neutrophil activation and rapid clearance of streptococcus pneumoniae from the lung. Nat Commun, 2022, 13(1): 3321.
56. Wu BG, Sulaiman I, Tsay JJ, et al. Episodic aspiration with oral commensals induces a MyD88-dependent, pulmonary T-helper cell type 17 response that mitigates susceptibility to streptococcus pneumoniae. Am J Respir Crit Care Med, 2021, 203(9): 1099-1111.
57. Yang D, Chen X, Wang J, et al. Dysregulated lung commensal bacteria drive interleukin-17B production to promote pulmonary fibrosis through their outer membrane vesicles. Immunity, 2019, 50(3): 692-706.
58. Zemanick ET, Wagner BD, Robertson CE, et al. Airway microbiota across age and disease spectrum in cystic fibrosis. Eur Respir J, 2017, 50(5): 1700832.
59. Denner DR, Sangwan N, Becker JB, et al. Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways. J Allergy Clin Immunol, 2016, 137(5): 1398-1405.
60. Qian X, Zhang HY, Li QL, et al. Integrated microbiome, metabolome, and proteome analysis identifies a novel interplay among commensal bacteria, metabolites and candidate targets in non-small cell lung cancer. Clin Transl Med, 2022, 12(6): e947.
61. Jiang Q, Xu Q, Kenéz á, et al. Klebsiella pneumoniae infection is associated with alterations in the gut microbiome and lung metabolome. Microbiol Res, 2022, 263: 127139.
62. Hu C, van Meel ER, Medina-Gomez C, et al. A population-based study on associations of stool microbiota with atopic diseases in school-age children. J Allergy Clin Immunol, 2021, 148(2): 612-620.
63. Bernatchez E, Gold MJ, Langlois A, et al. Methanosphaera stadtmanae induces a typeⅣhypersensitivity response in a mouse model of airway inflammation. Physiol Rep, 2017, 5(7): e13163.
64. Zhang X, Li PH, Wang D, et al. Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of "influenza-subacute thyroiditis-hypothyroidism". Front Microbiol, 2024, 15: 1354989.
65. Zheng L, Liu C, Wang H, et al. Intact lung tissue and bronchoalveolar lavage fluid are both suitable for the evaluation of murine lung microbiome in acute lung injury. Microbiome, 2024, 12(1): 56.
66. 梁可克, 王志旺, 黃柯婷, 等. PI3K-AKT信號通路調控慢阻肺氣道重塑及中藥干預作用研究新進展. 中藥藥理與臨床, 2024, 40(5): 103-108.Liang KK, Wang ZW, Huang KT, et al. Traditional Chinese medicine regulates airway remodeling of chronic obstructive pulmonary disease via PI3K-AKT signaling pathway: A review. Pharm Clin Chin Materia Medica, 2024, 40(5): 103-108.
67. 王祁, 趙博, 高璐, 等. 基于PI3K/AKT/mTOR信號通路探討野黃芩苷聯合虎杖苷抗慢性支氣管炎的作用機制. 中國病理生理雜志, 2023, 39(10): 1780-1788.Wang Q, Zhao B, Gao L, et al. Effects of scutellarin combined with polydatin on chronic bronchitis via PI3K/AKT/mTOR signaling pathway. Chin J Pathophysiol, 2023, 39(10): 1780-1788.
68. 王艷梅, 梁彥昌, 甘德堃, 等. 青蒿素基于PI3K/Akt信號通路減輕卵清蛋白哮喘大鼠的氣道炎癥和氣道重塑的分析. 中國實驗方劑學雜志, 2024, 30(13): 114-119.Wang YM, Liang YC, Gan DK, et al. Attenuation of airway inflammation and airway remodeling in ovalbumin asthmatic rats by artemisinin through PI3K/Akt signaling pathway. Chin J Exp Tradit Med Form, 2024, 30(13): 114-119.
69. 尹香琳, 張婧瑤, 劉衛東, 等. 1-磷酸鞘氨醇受體2介導PI3K/AKT/eNOS通路抑制甲型流感病毒誘導的病毒性肺炎. 中國病理生理雜志, 2018, 34(11): 2062-2067.Yin XL, Zhang JY, Liu WD, et al. Sphingosine-1-phosphate receptor 2 attenuates influenza A virus-induced viral pneumonia through PI3K/AKT/eNOS pathway. Chin J Pathophysiol, 2018, 34(11): 2062-2067.
70. 周雯, 駱亞莉, 周世琴, 等. 基于網絡藥理學和動物實驗探究益氣養陰活血方治療肺纖維化的作用. 中成藥, 2023, 45(3): 973-978.Zhou W, Luo YL, Zhou SQ, et al. To explore the effect of Yiqi Yangyin Huoxue recipe on pulmonary fibrosis based on network pharmacology and animal experiments. Chin Tradit Patent Med, 2023, 45(3): 973-978.
71. 陳稀煩, 魏曉炎, 侯樂萍. 華蟾素對肺癌大鼠PI3K/AKT信號通路的抑制作用. 中國現代應用藥學, 2020, 37(4): 425-430.Chen XF, Wei XY, Hou LP. Inhibitory effect of cinobufotalin on lung cancer rats PI3K/AKT signaling pathway. Chin J Mod Appl Pharm, 2020, 37(4): 425-430.
72. Casas M, den Dekker HT, Kruithof CJ, et al. The effect of early growth patterns and lung function on the development of childhood asthma: A population based study. Thorax, 2018, 73(12): 1137-1145.
73. Bui DS, Lodge CJ, Burgess JA, et al. Childhood predictors of lung function trajectories and future COPD risk: A prospective cohort study from the first to the sixth decade of life. Lancet Respir Med, 2018, 6(7): 535-544.
74. Belgrave DCM, Granell R, Turner SW, et al. Lung function trajectories from pre-school age to adulthood and their associations with early life factors: A retrospective analysis of three population-based birth cohort studies. Lancet Respir Med, 2018, 6(7): 526-534.
75. Martinez FJ, Han MK, Allinson JP, et al. At the root: Defining and halting progression of early chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2018, 197(12): 1540-1551.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesThe common causal relationship between intestinal flora and respiratory diseases based on the theory of "lung and large intestine being interior-exterior related"

Abstract Full text Figures/Tables Video References Cited by

Format

Content