Study on the Intestinal Microecological Characteristics of Different Airflow Obstruction Phenotypes in Asthma Patients_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LI Haoxuan ¹ , CHEN Yaoxin ¹ , CHEN Xinming ¹ , CHEN Xinyao ¹ , XU Junhao ¹ ,  XU Yinji ^1,2

1. Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China;
2. Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China;

Corresponding author：

XU Yinji, Email: xuyinji@163.com

Keywords：

Asthma phenotype; Fixed airflow obstruction; Gut microbiota; 16S rDNA sequencing

DOI：

10.7507/1671-6205.202402012

Video：

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Objective To explore the composition of intestinal microbiota between patients with fixed airflow obstruction asthma, reversible airflow obstruction asthma, and healthy control, and analyze the correlation between key differential bacterial distribution and clinical characteristics. Methods Fifteen patients with fixed airflow obstruction asthma (FAO) and 13 patients with reversible airflow obstruction asthma (RAO) were included, along with 11 matched healthy control subjects. Clinical data were collected, and lung function tests and induced sputum examination were performed. Blood and stool samples were tested to compare the gut microbiota status among the groups, and analyze the relationship between gut microbiota abundance and patients' blood routine, IgE levels, lung function, and induced sputum. Results The dominant bacterial compositions were similar in the three groups, but there were differences in the abundance of some species. Compared to the RAO group, the FAO group showed a significant increase in the genera of Bacteroides and Escherichia coli, while Pseudomonas was significantly decreased. The phylum Firmicutes was negatively correlated with the course of asthma, while the phylum Bacteroidetes and genus Bacteroides were positively correlated with the asthma course. Bacteroidetes was negatively correlated with Pre-BD FEV1/FVC, Pseudomonas was positively correlated with Pre-BD FEV1, Escherichia coli was negatively correlated with Post-BD FEV1/FVC, and Bacteroides was negatively correlated with Post-BD MMEF. The class Actinobacteria and the order Actinomycetales were negatively correlated with peripheral blood EOS%, while the order Enterobacteriales and the family Enterobacteriaceae were positively correlated with peripheral blood IgE levels. Furthermore, Actinobacteria and Actinomycetales were negatively correlated with induced sputum EOS%. Conclusions There are differences in the gut microbiota among patients with fixed airflow obstruction asthma, reversible airflow obstruction asthma, and healthy individuals. Bacteroides and Escherichia coli are enriched in the fixed airflow obstruction asthma group, while the Firmicutes are increased in the reversible airflow obstruction asthma group. These three microbiota may act together on Th2 cell-mediated inflammatory responses, influencing the process of airway remodeling, and thereby interfering with the occurrence of fixed airflow obstruction in asthma.

Citation： LI Haoxuan, CHEN Yaoxin, CHEN Xinming, CHEN Xinyao, XU Junhao, XU Yinji. Study on the Intestinal Microecological Characteristics of Different Airflow Obstruction Phenotypes in Asthma Patients. Chinese Journal of Respiratory and Critical Care Medicine, 2024, 23(4): 256-263. doi: 10.7507/1671-6205.202402012 Copy

1.	Lin J, Wang W, Chen P, et al. Prevalence and risk factors of asthma in mainland China: The CARE study. Respir Med, 2018, 137: 48-54.
2.	Hanania NA, Fortis S, Haselkorn T, et al. Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA. J Allergy Clin Immunol Pract, 2022, 10(1): 222-228.
3.	Rutting S, Tonga K O, King G G. Toward explaining fixed airflow obstruction in asthma. J Allergy Clin Immunol, 2022, 149(3): 890-892.
4.	李思念, 史菲. 固定气流受限性哮喘的研究进展. 内科, 2021, 16(1): 55-57.
5.	Zhou A, Lei Y, Tang L, et al. Gut Microbiota: the Emerging Link to Lung Homeostasis and Disease. J Bacteriol, 2021, 203(4): 1-12.
6.	Chiu C Y, Cheng M L, Chiang M H, et al. Gut microbial-derived butyrate is inversely associated with IgE responses to allergens in childhood asthma. Pediatr Allergy Immunol, 2019, 30(7): 689-697.
7.	Wang Z, Lai Z, Zhang X, et al. Altered gut microbiome compositions are associated with the severity of asthma. J Thorac Dis, 2021, 13(7): 4322-4338.
8.	中华医学会呼吸病学分会哮喘学组. 支气管哮喘防治指南(2020年版). 中华结核和呼吸杂志, 2020, 43(12): 1023-1048.
9.	Bennett G H, Carpenter L, Hao W, et al. Risk factors and clinical outcomes associated with fixed airflow obstruction in older adults with asthma. Ann Allergy Asthma Immunol, 2018, 120(2): 164-168.
10.	Graham B L, Steenbruggen I, Miller M R, et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med, 2019, 200(8): e70-e88.
11.	陈华萍, 王子, 李瑾, 等. 诱导痰细胞分类检查技术及应用. 中华肺部疾病杂志(电子版), 2020, 13(3): 399-402.
12.	Buendia E, Zakzuk J, San-Juan-Vergara H, et al. Gut microbiota components are associated with fixed airway obstruction in asthmatic patients living in the tropics. Sci Rep, 2018(1), 8: 9582.
13.	Mogensen I, Jacinto T, Alving K, et al. Inflammatory patterns in fixed airflow obstruction are dependent on the presence of asthma. PLoS One, 2020, 15(12): e243109.
14.	Smith B M, Zhao N, Olivenstein R, et al. Asthma and fixed airflow obstruction: Long-term trajectories suggest distinct endotypes. Clin Exp Allergy, 2021, 51(1): 39-48.
15.	Kim JH, Chang HS, Shin SW, et al. Lung Function Trajectory Types in Never-Smoking Adults With Asthma: Clinical Features and Inflammatory Patterns. Allergy Asthma Immunol Res, 2018, 10(6): 614-627.
16.	Shimizu K, Tanabe N, Oguma A, et al. Parenchymal destruction in asthma: Fixed airflow obstruction and lung function trajectory. J Allergy Clin Immunol, 2022, 149(3): 934-942.
17.	Lin W W, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest, 2007, 117(5): 1175-1183.
18.	Agrawal S, Agrawal A, Doughty B, et al. Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol, 2003, 171(10): 4984-4989.
19.	Netea MG, Kullberg BJ, de Jong DJ, et al. NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn's disease. Eur J Immunol, 2004, 34(7): 2052-2059.
20.	Vael C, Nelen V, Verhulst SL, et al. Early intestinal Bacteroides fragilis colonisation and development of asthma. BMC Pulm Med, 2008, 8: 19.
21.	Rutting S, Thamrin C, Cross T J, et al. Fixed Airflow Obstruction in Asthma: A Problem of the Whole Lung Not of Just the Airways. Front Physiol, 2022, 13: 898208.
22.	Duan H, Wang L, Huangfu M, et al. The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: Mechanisms and therapeutic potentials. Biomed Pharmacother, 2023, 165: 115276.
23.	Wang Q, Li F, Liang B, et al. A metagenome-wide association study of gut microbiota in asthma in UK adults. BMC Microbiol, 2018, 18(1): 114.
24.	Kieler IN, Shamzir KS, Vitger AD, et al. Gut microbiota composition may relate to weight loss rate in obese pet dogs. Vet Med Sci, 2017, 3(4): 252-262.
25.	Theiler A, Barnthaler T, Platzer W, et al. Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival. J Allergy Clin Immunol, 2019, 144(3): 764-776.
26.	Yip W, Hughes MR, Li Y, et al. Butyrate Shapes Immune Cell Fate and Function in Allergic Asthma. Front Immunol, 2021, 12: 628453.
27.	Sohn KH, Baek MG, Choi SM, et al. Alteration of Lung and Gut Microbiota in IL-13-Transgenic Mice Simulating Chronic Asthma. J Microbiol Biotechnol, 2020, 30(12): 1819-1826.

1. Lin J, Wang W, Chen P, et al. Prevalence and risk factors of asthma in mainland China: The CARE study. Respir Med, 2018, 137: 48-54.
2. Hanania NA, Fortis S, Haselkorn T, et al. Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA. J Allergy Clin Immunol Pract, 2022, 10(1): 222-228.
3. Rutting S, Tonga K O, King G G. Toward explaining fixed airflow obstruction in asthma. J Allergy Clin Immunol, 2022, 149(3): 890-892.
4. 李思念, 史菲. 固定气流受限性哮喘的研究进展. 内科, 2021, 16(1): 55-57.
5. Zhou A, Lei Y, Tang L, et al. Gut Microbiota: the Emerging Link to Lung Homeostasis and Disease. J Bacteriol, 2021, 203(4): 1-12.
6. Chiu C Y, Cheng M L, Chiang M H, et al. Gut microbial-derived butyrate is inversely associated with IgE responses to allergens in childhood asthma. Pediatr Allergy Immunol, 2019, 30(7): 689-697.
7. Wang Z, Lai Z, Zhang X, et al. Altered gut microbiome compositions are associated with the severity of asthma. J Thorac Dis, 2021, 13(7): 4322-4338.
8. 中华医学会呼吸病学分会哮喘学组. 支气管哮喘防治指南(2020年版). 中华结核和呼吸杂志, 2020, 43(12): 1023-1048.
9. Bennett G H, Carpenter L, Hao W, et al. Risk factors and clinical outcomes associated with fixed airflow obstruction in older adults with asthma. Ann Allergy Asthma Immunol, 2018, 120(2): 164-168.
10. Graham B L, Steenbruggen I, Miller M R, et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med, 2019, 200(8): e70-e88.
11. 陈华萍, 王子, 李瑾, 等. 诱导痰细胞分类检查技术及应用. 中华肺部疾病杂志(电子版), 2020, 13(3): 399-402.
12. Buendia E, Zakzuk J, San-Juan-Vergara H, et al. Gut microbiota components are associated with fixed airway obstruction in asthmatic patients living in the tropics. Sci Rep, 2018(1), 8: 9582.
13. Mogensen I, Jacinto T, Alving K, et al. Inflammatory patterns in fixed airflow obstruction are dependent on the presence of asthma. PLoS One, 2020, 15(12): e243109.
14. Smith B M, Zhao N, Olivenstein R, et al. Asthma and fixed airflow obstruction: Long-term trajectories suggest distinct endotypes. Clin Exp Allergy, 2021, 51(1): 39-48.
15. Kim JH, Chang HS, Shin SW, et al. Lung Function Trajectory Types in Never-Smoking Adults With Asthma: Clinical Features and Inflammatory Patterns. Allergy Asthma Immunol Res, 2018, 10(6): 614-627.
16. Shimizu K, Tanabe N, Oguma A, et al. Parenchymal destruction in asthma: Fixed airflow obstruction and lung function trajectory. J Allergy Clin Immunol, 2022, 149(3): 934-942.
17. Lin W W, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest, 2007, 117(5): 1175-1183.
18. Agrawal S, Agrawal A, Doughty B, et al. Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol, 2003, 171(10): 4984-4989.
19. Netea MG, Kullberg BJ, de Jong DJ, et al. NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn's disease. Eur J Immunol, 2004, 34(7): 2052-2059.
20. Vael C, Nelen V, Verhulst SL, et al. Early intestinal Bacteroides fragilis colonisation and development of asthma. BMC Pulm Med, 2008, 8: 19.
21. Rutting S, Thamrin C, Cross T J, et al. Fixed Airflow Obstruction in Asthma: A Problem of the Whole Lung Not of Just the Airways. Front Physiol, 2022, 13: 898208.
22. Duan H, Wang L, Huangfu M, et al. The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: Mechanisms and therapeutic potentials. Biomed Pharmacother, 2023, 165: 115276.
23. Wang Q, Li F, Liang B, et al. A metagenome-wide association study of gut microbiota in asthma in UK adults. BMC Microbiol, 2018, 18(1): 114.
24. Kieler IN, Shamzir KS, Vitger AD, et al. Gut microbiota composition may relate to weight loss rate in obese pet dogs. Vet Med Sci, 2017, 3(4): 252-262.
25. Theiler A, Barnthaler T, Platzer W, et al. Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival. J Allergy Clin Immunol, 2019, 144(3): 764-776.
26. Yip W, Hughes MR, Li Y, et al. Butyrate Shapes Immune Cell Fate and Function in Allergic Asthma. Front Immunol, 2021, 12: 628453.
27. Sohn KH, Baek MG, Choi SM, et al. Alteration of Lung and Gut Microbiota in IL-13-Transgenic Mice Simulating Chronic Asthma. J Microbiol Biotechnol, 2020, 30(12): 1819-1826.

Chinese Journal of Respiratory and Critical Care Medicine

Study on the Intestinal Microecological Characteristics of Different Airflow Obstruction Phenotypes in Asthma Patients

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