Lower respiratory microbiome in patients with stable bronchiectasis in North and South China

Lower respiratory microbiome in patients with stable bronchiectasis in North and South China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Lower respiratory microbiome in patients with stable bronchiectasis in North and South China Gao Bingrui, Feng Cong, Huang Shanshan, Chen Haiyan, Wang Manrui, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3907668/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: To compare microbiome in the lower respiratory tract of patients with stable bronchiectasis in North and South China. Methods: Demographic and Sequencing data were collected from patients who underwent bronchoalveolar lavage fluid macro-genomic sequencing testing between September 2021 to September 2022 at Hainan Hospital of the General Hospital of the People's Liberation Army (Sanya, Hainan, South) and the Eighth Medical Center of the General Hospital of the People's Liberation Army (Haidian, Beijing, North). The patients were grouped according to the clinical test results, and the sequencing data were analyzed twice to compare the microbiome differences among different groups. Results We enrolled 75 patients, 42 in the North and 33 in the South. The number of smokers in the Northern group was higher than that in the Southern group and the FEV1/FVC (%) value was lower than that in the Southern group; otherwise, the groups had no significant differences. The most abundance bacteria in the lower respiratory tract of the Northern group were Pseudomonas aeruginosa , Klebsiella pneumoniae , and Nocardia wilsonii , while the Southern group were H. influenzae , P. aeruginosa , and Prevotella intermedia . According to the severity of the patients with bronchiectasis (BSI), there was also a difference in the abundance of microbiome in the lower respiratory tract in patients with stable bronchiectasis from the North and South. Conclusion The lower respiratory tract microbiome of patients with stable bronchiectasis differed significantly between the North and South in China. The microbiome of the Southern group was more similar to that reported in the international literature, while the Northern group was significantly different from the results of other studies. P. aeruginosa and Klebsiella pneumoniae were most abundant in the Northern group, while H. influenzae and P. aeruginosa were most abundant in the Southern group, These findings can guide antibiotic treatment of exacerbations. Bronchiectasis Lower Respiratory Tract Microbiome Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Bronchiectasis is characterized by chronic airway inflammation.[ 1 ] The disease is highly heterogeneous, and many patients suffer from chronic exacerbation, which seriously affects the quality of life and causes economic burden. Studies showed that the global prevalence of bronchiectasis increased yearly up. Until 2017, the prevalence in China was about 174.45/100 000.[ 2 ] Repeated acute exacerbations of bronchiectasis can lead to aggravation of the patient’s condition and impair pulmonary function, resulting in poor outcomes prognosis and a gradual decline in quality of life. The lower respiratory tract microbiome is one of the factors that lead to the transition from stable to acute exacerbations of bronchiectasis. Our previous studies found that bacteria that were previously thought to rarely coexist with humans, such as non-tuberculous mycobacteria , Nocardia , and Pneumocystis japonicus [ 3 – 5 ], can also colonize the lower respiratory tract of patients with stable bronchiectasis. Currently, there is a lack of research on the mechanisms of microbiome in the lungs of patients with bronchiectasis, and there may be substantial differences among regions and populations. There are few studies comparing lower respiratory tract microbiome in patients with stable bronchiectasis in Northern and Southern China, or the correlation between the microbiome and the disease. This study compared the microbiome characteristics of the lower respiratory tract in patients with stable bronchiectasis in the Northern and Southern regions of China, and the correlation between the microbiome composition and the severity of bronchiectasis was investigated. It also provides a new potential therapeutic target for the treatment of bronchiectasis. Subject and Methods 1.Subjects We collected 75 patients with stable bronchiectasis in Hainan Hospital of PLA General Hospital (Sanya, Hainan) and the Eighth Medical Center of PLA General Hospital (Haidian, Beijing) from September 2021 to September 2022. We recorded gender, age, body mass index (BMI), whether the patients smoked or not, sputum, hemoptysis, and other characteristics. We measures pulmonary functions and gas exchange, and bronchoalveolar lavage fluid was taken from the patients for culture and Metagenomic sequencing. Inclusion criteria: (1) bronchiectasis diagnosed by lung computed tomography; (2) treatment without antibiotics for 3 months and without changes in general conditions such as worsening of cough or sputum index; (3) 18–90 years; (4) completed pulmonary function, bronchoscopy, and macro-genomic sequencing of bronchoalveolar lavage fluid. Exclusion criteria: (1) acute exacerbation of bronchiectasis; (2) use of antibiotics within 4 weeks; (3) severe cardiovascular or cerebrovascular diseases and a life expectancy of less than one year; (4) active infections; (5) inability to complete examinations. Based on these criteria, 75 patients were enrolled, including 40 males and 35 females, aged 26–81. This study was approved by The Ethics Committee of the General Hospital of the People's Liberation Army approved the study (number-309202109091530). Informed consent was obtained from all subjects and/or their legal guardians. 2. Methods 1). Baseline data: We recorded age, gender, height, weight, disease history, smoking history, and whether hemoptysis occurred. Lung computed tomography was used to determine the site of bronchiectasis; the same technician performed pulmonary function ventilation and gas exchange examinations at each hospital. After completing the examinations, the standard of care was delivered according to the relevant guidelines.[ 6 ] The alveolar lavage fluid was taken for Metagenomic sequencing. 2). Metagenomic sequencing 2).1) DNA extraction, library construction and on-line sequencing. Bronchoalveolar lavage fluid samples were placed in a dry ice environment and sent to genetic company for PACEseq metagenomic sequencing. DNA extraction was performed according to the manufacturer’s instructions. DNA library construction was performed using the QIAseq Ultralow Input Library Kit (Illumina) library construction kit (QIAGEN, Hiden, Germany) Quality assessment was performed using Qubit (Thermo Fisher, Waltham, USA) and Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, USA). The libraries with satisfactory quality were subjected to metagenomic sequencing on the Nextseq550 (Illumina, San Diego, USA) platform. 2).2) Data processing and analysis Non-compliant DNA sequences (low-quality, low-complexity or small fragments) were removed from the raw files after mNGS sequencing using fastp. Using BMA software, the sequencing data were compared to the human reference genome (hg38). Using Kraken software, the remaining unknowns were identified and compared to assess the species information of microorganisms. The number of sequences detected by the microorganism and the number of sequences per million sequences measured for that microorganism were calculated separately. Sequence data that support the findings of this study have been deposited in the China National Center for BioInformation ( https://www.cncb.ac.cn/ ), code CRA0144053. Pulmonary function tests Measurements were taken using a Yeager Spirometer (MasterScreen Pneumo) by the same technician performing pulmonary function for at least 3 years. Refer to the Pulmonary Function Guidelines for the procedure [ 7 ]. After environmental calibration, volumetric calibration, and calibration verification, 3–4 acceptable spirometry curves were obtained, with the difference between the two best spirometers not exceeding 5% or not exceeding 150 ml. The maximum value was selected for analysis. The metrics analyzed were absolute FEV1, FEV1 as a percentage of predicted value, and FEV1/FVC (%). 4. Bronchiectasis severity score The severity of bronchiectasis was assessed using the bronchiectasis severity index (BSI) score, the E-FACED score, and the Reiff score. The E-FACED score included age, FVE1 as a percentage of predicted value, whether there had been an exacerbation leading to hospitalization within the previous year, the mMRC score, the presence of Pseudomonas aeruginosa colonization, and the number of lobes affected on imaging. Scores of 0–3 were classified as mild, 4–6 was moderate, and 7–9 was severe. The BSI score was relatively comprehensive, with the addition of BMI, imaging of cumulative cystic bronchial expansion of 3 or more lobes, and other microbial colonization compared to the E-FACED score.BSI scores 0–4 were classified as mild, 5–8 as moderate, and ≥ 9 as severe. The Reiff score was used to assess the severity of bronchiectasis based on the imaging of patients with bronchial expansion. The Reiff score was used to assess the severity of bronchial extension based on imaging of patients with bronchial extension. 5. Statistical analysis SPSS26.0 software was used to test and analyze the metrics. The normality of distribution was tested, and the metrics between the two groups was compared using independent samples t-tests or non-parametric tests. The chi-square test was used to compare the count data of 2 or more groups. Difference where p-value < 0.05 were considered significant. Result 1. Patients information We considered 75 patients were included, including 42 in the Northern group and 33 in the Southern group. There were no significant differences between the groups regarding gender, age, body mass index, history of hemoptysis, BSI score, E-FACED assessment and FEV1%. There were significantly more smoking patients in the Northern group than in the Southern group, and the FEV1/FVC ratio of Southern group was more significantly than that of the Northern group (Table 1 ). Table 1 Baseline data of patients with bronchiectasis by gender Baseline information Northern group Southern group value P Number of examples 42 33 Sex (m/f) 23/19 17/16 χ 2 = 0.08 0.78 Age (years) 57 ± 11 55 ± 13 t = 0.47 0.64 BMI (kg/m2) 24.8 ± 10.9 21.2 ± 3.7 t = 1.77 0.08 Smoking history 23/19 9/24 χ 2 = 5.7 0.02 Hemoptysis 18/24 15/18 χ 2 = 0.05 0.82 FEV1% 73.4 ± 24.6 76.7 ± 16.9 t = 1.10 0.28 FEV1/FVC(%) 68.4 ± 14.0 77.8 ± 12.4 t = 2.56 0.02 BSI score 8.1 ± 3.7 6.9 ± 4.1 t = 1.37 0.18 E-Faced score 1.7 ± 1.2 1.3 ± 1.5 t = 1.15 0.08 FEV1: forced expiratory flow in one second; FVC: forced vital capacity 2. Lower respiratory tract microbiome in patients with stable bronchiectasis Analysis of the lower respiratory tract microbiome of the Southern and Northern groups revealed that the α-diversity of the groups was not statistically different at the genus or species taxonomic levels (P = 0.83 and P = 0.91, respectively). However, in the comparison of species abundance between the two groups, there were differences in specific flora between the Southern group and the Northern group (Fig. 1 a). At the genus level, the highest species abundance in the Northern group was found in Pseudomonas spp, Prevotella spp and Streptococcus spp , which were also more prevalent in the Southern group; however, Haemophilus spp had the highest abundance in the Southern group, which was significantly different from the Northern group. At the species level, the most abundant species in the Northern group were P. aeruginosa , Klebsiella pneumoniae and Nocardia gelsenkirchen , whereas the most abundant species in the Southern group were H. influenzae , P. aeruginosa and Prevotella intermedia (Fig. 1 b). 3. Differences in lower respiratory tract microbiome between patients with severe and mild-to-moderate bronchiectasis Based on the BSI score, patients were categorized into those with severe bronchiectasis (BSI ≥ 9 points) and mild-moderate dilatation (BSI < 9 points). In the Northern group, there were 22 severe and 18 mild-moderate patients, while in the Southern group, there were 13 severe and 21 mild-moderate disease. The α-diversity of lower respiratory tract microbiome in patients with severe versus mild-to- moderate bronchiectasis was not significantly different at the genus or species classification levels (P = 0.39 and P = 0.93, respectively) (Fig. 2 a). However, the two groups showed differences in species abundance. At the genus level, the microorganisms with the highest abundance in the lower respiratory tract of patients with severe bronchiectasis were Pseudomonas spp. , Proteus spp . and Streptococcus spp . In patients with mild-to-moderate severity, Haemophilus spp . and Klebsiella spp . were significantly more abundant than those in patients of the severe group, compared to the lower abundance of Pseudomonas spp . At the species level, the most abundant species in the lower respiratory tract of patients with severe bronchiectasis were P. aeruginosa , Clostridium nucleatum, and Stenotrophomonas maltophilia , whereas H. influenzae , Klebsiella pneumoniae , and Nocardi were the most abundant species in patients with mild to moderate disease (Fig. 2 b). 4. Differences in lower respiratory tract microbiome in patients with different severity of bronchiectasis between the North and the South. Significant differences at the genus and species levels existed in the Northern and Southern groups. At the species level, the Chao1 index of patients with severe bronchiectasis in the Northern group was significantly lower than that of patients with mild-to-moderate bronchiectasis, suggesting that the alpha diversity of the lower respiratory tract microbiome was lower in patients with severe bronchiectasis in the Northern group, whereas the Southern group showed the same trend but did not show significant differences; at the genus level, the Chao1 index of patients with severe bronchiectasis in the Southern group was significantly higher than that of the mild-to-moderate group, and the same trend could be observed in the Northern group, however, there was no significant difference in the Northern group (Fig. 3 ). At the species level, differentially represented species could be found in the severe and mild-moderate branched expansion patients in the Northern group (Fig. 4 a). In contrast, in the comparison of severe and mild-moderate in the Southern group, differentially represented species were identified only in mild-moderate patients (Fig. 4 b). Discussion Lower respiratory tract microbiome is an intense area of research. In the past, it was believed that the lower respiratory tract of healthy people was gnotobiology, however, with the development of molecular testing techniques, studies found that microorganisms colonize the lower respiratory tract of healthy people. These microorganisms are similar to the microorganisms of the upper respiratory tract [ 8 ] This finding suggests that the upper respiratory tract may be a source of lower respiratory tract microorganisms. Several studies showed that patients with bronchiectasis have a higher diversity of intestinal microorganisms than the healthy population. Aeromonas butyricola , Prevotella and Coccidioides faecalis abundances were significantly lower in patients with bronchiectasis [ 9 ]. Metabolomics studies have suggested significant changes in the metabolism of the microbiome in both groups, suggesting that the“gut-pulmonary” axis may play a role in the pathogenesis of bronchiectasis [ 10 , 11 ]. There are significant changes in the metabolism of the two flora, suggesting that the“gut-pulmonary” axis may play a role in the pathogenesis of bronchiectasis. The lungs of patients with structural lung diseases represented by bronchiectasis usually have long-term microbial colonization, and studies on stable bronchiectasis found that the top three genera of lower respiratory tract colonizers in patients with stable bronchiectasis are Pseudomonas, Haemophilus , and Streptococcus , respectively in Global [ 13 – 16 ]. However, the results of our study were inconsistent with those of the both groups. It was also observed that P. aeruginosa and H. influenzae in the Southern group were “mutually exclusive”, i.e., these two bacteria were the core of the colonization [ 17 ]. P. aeruginosa and H. influenzae in the Southern group were “mutually exclusive”, i.e., in the specimens with these two bacteria as the core taxa, their background organisms seldom existed in each other's strains, which aligns with previous reports. P. aeruginosa colonization was associated with lower pulmonary function, more severe disease and more severe hemoptysis.[ 18 ]. We performed interquartile spacing of the abundance of the strains, and classified the upper quartile as the core taxa and the lower as the satellite or background group, as described previously [ 13 ]. In the present study, there were differences in the core taxa between the North and the South, in which P. aeruginosa ranked first in abundance in the Northern group and third in the Southern group. Patients with P. aeruginosa as the core taxa had 19 groups of background genera and 30 species. In contrast, patients with H. influenzae as the core taxa had 24 groups of background genera and 40 species, which were all higher than P. aeruginosa. This result is consistent with the reports in the Global literature. In addition, based on the BSI score, we divided the patients with bronchiectasis into a severe group and a mild-moderate group for comparison, and the results showed that the proportion of patients with P. aeruginosa as a core taxa was higher in the severe group. In contrast, the proportion of patients with H. influenzae as a core taxa was higher in the mild-moderate group. In the North-South subgroup, we observed a higher proportion of hemoptysis in patients in the severe group in the South. Interestingly, among the background bacteria with H. influenzae as the core taxa, we found P. aeruginosa , which differs from the other studies. A study on the co-culture of P. aeruginosa and Staphylococcus aureus found that P. aeruginosa inhibited the growth of Staphylococcus aureus [ 19 ]. However, there are no co-culture studies of P. aeruginosa and H. influenzae , and there is a lack of studies on the mechanism of symbiosis between these bacteria and humans; therefore, we cannot determine whether there is a “mutually exclusive” relationship between the two bacteria. In the past, bacteria were thought not to be able to coexist with humans body, but now, such as non-tuberculous mycobacteria (NTM), Pneumocystis japonicus, and Nocardia, were detected in patients with stable bronchiectasis. In recent years, the isolation rate of NTM has increased in China, especially in hot and humid and coastal areas. The elderly people, those with underlying diseases, and immunocompromised people are more likely to suffer from the disease. Previously, it was believed that there was no human-to-human transmission of NTM; however, some studies found that there may be mutual transmission of NTM among patients with cystic fibrosis.[ 20 ] When NTM enters the body, it is phagocytosed by macrophages and multiplies within them. Alveolar macrophages are an essential component of the intrinsic immunity of the lungs. It remains unclear how NTM reaches a dynamic equilibrium with intrinsic lung immunity during the stabilization phase of bronchiectasis. Pneumocystis japonicus was previously thought to be unable to coexist with healthy individuals, however, this organism has been detected in patients with stable chronic obstructive pulmonary disease (COPD)[ 4 ]. With the development of molecular detection technology, our understanding of lower respiratory tract microbiome will deepen, and our understanding of the interplay between lower respiratory tract microbiome and the body's autoimmunity in patients with bronchiectasis will become more comprehensive, guiding patient treatment. In summary, we found that the colonization of the lower respiratory tract by P. aeruginosa differed between the North and South in patients with stable bronchiectasis, with P. aeruginosa having a higher isolation rate in different geographic regions. In contrast Acinetobacter baumannii colonization was more common in the Northern group. In patients with severe bronchiectasis, there was a higher proportion of P. aeruginosa and a higher proportion of hemoptysis, similar to previous studies. Compared to H. influenzae , P. aeruginosa had significantly lower numbers as background groups. There are some limitations to our study. First, this was not a multicenter study; the sample size was relatively small. Second, we did not stratify according to temperature, humidity or air pollution level. Therefore, we hope that more institutions and regions can be included in subsequent studies, and more detailed subgroup studies can be conducted for various causes of bronchiectasis, to explore more deeply the mechanisms of exacerbation in different patients with bronchiectasis and to provide targeted treatment. These studies will help improve patients’ quality of life with stable bronchiectasis, reduce the incidence of adverse events, and improve outcomes. Declarations Conflict of Interest: All authors indicated no conflicts of interest. Authors ’ Contributions: Gao Bingrui: study design, data collection, statistical analysis, and paper writing; Feng Cong: paper writing and proofreading; Huang Shanshan: data collection, study supervision; Chen Haiyan: cooperation with bronchoscopy and data collection; Wang Manrui: cooperation with pulmonary function tests and data collection; Guo Yinghua: study supervision, study design and paper revision; Xie Lixin: study supervision, providing guidance and financial support for study implementation. Consent for publication: NOT APPLICABLE. Ethical Approval : This study was approved by The Ethics Committee of the General Hospital of the People's Liberation Army approved the study and (number-309202109091530). Informed consent was obtained from all subjects and/or their legal guardians. Funding: The Eighth Medical Center of the General Hospital of PLA supported the project (MS202211005). Availability of data and materials : Sequence data that support the findings of this study have been deposited in the China National Center for BioInformation (https://www.cncb.ac.cn/), code CRA0144053. References Polverino E, Goeminne P C, McDonnell M J, et al. European Respiratory Society guidelines for the management of adult bronchiectasis [J]. Eur Respir J, 2017, 50(3).doi:10.1183/13993003.00629-2017 Feng J, Sun L, Sun X, et al. Increasing prevalence and burden of bronchiectasis in urban Chinese adults, 2013-2017: a nationwide population-based cohort study [J]. Respir Res, 2022, 23(1): 111.doi:10.1186/s12931-022-02023-8 Gopalaswamy R, Shanmugam S, Mondal R, et al. Of tuberculosis and non-tuberculous mycobacterial infections - a comparative analysis of epidemiology, diagnosis and treatment [J]. J Biomed Sci, 2020, 27(1): 74.doi:10.1186/s12929-020-00667-6 Vera C, Rueda Z V. Transmission and Colonization of Pneumocystis jirovecii [J]. J Fungi (Basel), 2021, 7(11).doi:10.3390/jof7110979 Lynch J P, 3rd, Reid G, Clark N M. Nocardia spp.: A Rare Cause of Pneumonia Globally [J]. Semin Respir Crit Care Med, 2020, 41(4): 538-54.doi:10.1055/s-0040-1708816 中华医学会呼吸病学分会呼吸危重症医学学组, 中国医师协会呼吸医师分会危重症医学工作委员会. ICU患者支气管肺泡灌洗液采集,送检,检测及结果解读规范[J]. 中华结核和呼吸杂志, 2020, 43(9):13. [J].doi:10.3760/cma.j.cn112147‑20200506‑00566 中华医学会. 常规肺功能检查基层指南(2018年)[J]. 中华全科医师杂志, 2019, 18(006):511-518. [J].doi:10.3760/cma.j.issn.1671⁃7368.2019.06.003 Wypych T P, Wickramasinghe L C, Marsland B J. The influence of the microbiome on respiratory health [J]. Nat Immunol, 2019, 20(10): 1279-90.doi:10.1038/s41590-019-0451-9 Wang W W, Mao B, Liu Y, et al. Altered fecal microbiome and metabolome in adult patients with non-cystic fibrosis bronchiectasis [J]. Respir Res, 2022, 23(1): 317.doi:10.1186/s12931-022-02229-w Bowerman K L, Rehman S F, Vaughan A, et al. Disease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease [J]. Nat Commun, 2020, 11(1): 5886.doi:10.1038/s41467-020-19701-0 Stokholm J, Blaser M J, Thorsen J, et al. Maturation of the gut microbiome and risk of asthma in childhood [J]. Nat Commun, 2018, 9(1): 141.doi:10.1038/s41467-017-02573-2 肖雄, 许毅娇, 陈志盛, et al. 慢性阻塞性肺疾病患者肺泡灌洗液宏基因组测序分析 %J 中国病原生物学杂志 [J]. 2022, 17(10): 1188-91.doi:10.13350/j.cjpb.221016 Cuthbertson L, Walker A W, Oliver A E, et al. Lung function and microbiota diversity in cystic fibrosis [J]. Microbiome, 2020, 8(1): 45.doi:10.1186/s40168-020-00810-3 Dicker A J, Lonergan M, Keir H R, et al. The sputum microbiome and clinical outcomes in patients with bronchiectasis: a prospective observational study [J]. Lancet Respir Med, 2021, 9(8): 885-96.doi:10.1016/S2213-2600(20)30557-9 Richardson H, Dicker A J, Barclay H, et al. The microbiome in bronchiectasis [J]. Eur Respir Rev, 2019, 28(153).doi:10.1183/16000617.0048-2019 Woo T E, Lim R, Heirali A A, et al. A longitudinal characterization of the Non-Cystic Fibrosis Bronchiectasis airway microbiome [J]. Sci Rep, 2019, 9(1): 6871.doi:10.1038/s41598-019-42862-y Mac Aogain M, Narayana J K, Tiew P Y, et al. Integrative microbiomics in bronchiectasis exacerbations [J]. Nat Med, 2021, 27(4): 688-99.doi:10.1038/s41591-021-01289-7 Rigauts C, Aizawa J, Taylor S L, et al. R othia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease [J]. Eur Respir J, 2022, 59(5).doi:10.1183/13993003.01293-2021 Tognon M, Kohler T, Luscher A, et al. Transcriptional profiling of Pseudomonas aeruginosa and Staphylococcus aureus during in vitro co-culture [J]. BMC Genomics, 2019, 20(1): 30.doi:10.1186/s12864-018-5398-y Daley C L, Iaccarino J M, Lange C, et al. Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline [J]. Clin Infect Dis, 2020, 71(4): 905-13.doi:10.1093/cid/ciaa1125 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3907668","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":270257018,"identity":"bffb4e38-771f-4c7c-ae0e-af9d46ff3928","order_by":0,"name":"Gao Bingrui","email":"","orcid":"","institution":"Chinese People’s Liberation Army (PLA) General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gao","middleName":"","lastName":"Bingrui","suffix":""},{"id":270257019,"identity":"ad5ba756-14d5-4592-83a9-30d5c3d08bab","order_by":1,"name":"Feng Cong","email":"","orcid":"","institution":"First Medical Center of Chinese PLA General 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wang","middleName":"","lastName":"Manrui","suffix":""},{"id":270257023,"identity":"e66b52f8-9bb2-4ffe-8d7d-e748357b99d0","order_by":5,"name":"Guo Yinghua","email":"","orcid":"","institution":"Chinese People’s Liberation Army (PLA) General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Guo","middleName":"","lastName":"Yinghua","suffix":""},{"id":270257024,"identity":"fafdb62f-0bd6-4107-a4cd-84b9652af30f","order_by":6,"name":"Xie Lixin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIie3PsQrCMBCA4QsHmQ7qmIIPcSAUh4AP4hIQsvkGHQoFXQRXfZuUgB37ChVfIG4dLW4Okrg55Jvv5+4AsuwfIQgHk6ICsRtTE3DipJflUe44eZEDaTUPVC2SxrlH54k8rTxUALXeRpOylaa7rD1VHuwIN7tvYkmBxC7QO+lZND6eSCyCM3I+rBUHlZTMW8AFaYkRZVoy/8Ld9aRJeYlsUn7hwd8fNKlNcR6eY6h1PPlkfhvPsizLvnkBfwk6d3zK0XIAAAAASUVORK5CYII=","orcid":"","institution":"Chinese People’s Liberation Army (PLA) General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xie","middleName":"","lastName":"Lixin","suffix":""}],"badges":[],"createdAt":"2024-01-29 03:00:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3907668/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3907668/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50565911,"identity":"30e99e76-9a93-4976-b61c-71c223132e86","added_by":"auto","created_at":"2024-02-02 15:10:53","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":743424,"visible":true,"origin":"","legend":"\u003cp\u003eAnalysis of lower respiratory tract microbiome in patients with North and South bronchiectasis\u003c/p\u003e","description":"","filename":"floatimage1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3907668/v1/788582aa8b06b94ce94c3d27.jpg"},{"id":50565914,"identity":"8cc9c87e-a1a8-4d9e-85e0-cddb97524148","added_by":"auto","created_at":"2024-02-02 15:10:53","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":784378,"visible":true,"origin":"","legend":"\u003cp\u003eLower respiratory tract microbiome in patients with severe versus mild-to-moderate bronchiectasis\u003c/p\u003e","description":"","filename":"floatimage2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3907668/v1/0a4ae5a2a9acddeff1345ff4.jpg"},{"id":50565912,"identity":"335dff85-16c0-4d93-addf-3024b7259811","added_by":"auto","created_at":"2024-02-02 15:10:53","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":83360,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of α-diversity of lower respiratory tract microbiome in patients with different severity of bronchiectasis in the Northern and Southern groups\u003c/p\u003e","description":"","filename":"floatimage3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3907668/v1/712dd0bc5e0f08e9ff97768a.jpg"},{"id":50565913,"identity":"14727b41-bb38-4546-80ee-2d10a6354f32","added_by":"auto","created_at":"2024-02-02 15:10:53","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":858173,"visible":true,"origin":"","legend":"\u003cp\u003eDifferences in lower respiratory tract microbiome in patients with different severity of bronchiectasis in the Northern and Southern groups\u003c/p\u003e","description":"","filename":"floatimage4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3907668/v1/744879465f2189841a83eb02.jpg"},{"id":85369269,"identity":"2c598a78-91a1-4075-bd2f-80278bebc00f","added_by":"auto","created_at":"2025-06-25 07:17:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2936144,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3907668/v1/987e1eb2-d776-4a3e-ba37-033aaac3894b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Lower respiratory microbiome in patients with stable bronchiectasis in North and South China","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBronchiectasis is characterized by chronic airway inflammation.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] The disease is highly heterogeneous, and many patients suffer from chronic exacerbation, which seriously affects the quality of life and causes economic burden. Studies showed that the global prevalence of bronchiectasis increased yearly up. Until 2017, the prevalence in China was about 174.45/100 000.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Repeated acute exacerbations of bronchiectasis can lead to aggravation of the patient\u0026rsquo;s condition and impair pulmonary function, resulting in poor outcomes prognosis and a gradual decline in quality of life.\u003c/p\u003e \u003cp\u003eThe lower respiratory tract microbiome is one of the factors that lead to the transition from stable to acute exacerbations of bronchiectasis. Our previous studies found that bacteria that were previously thought to rarely coexist with humans, such as \u003cem\u003enon-tuberculous mycobacteria\u003c/em\u003e, \u003cem\u003eNocardia\u003c/em\u003e, and \u003cem\u003ePneumocystis japonicus\u003c/em\u003e [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], can also colonize the lower respiratory tract of patients with stable bronchiectasis. Currently, there is a lack of research on the mechanisms of microbiome in the lungs of patients with bronchiectasis, and there may be substantial differences among regions and populations. There are few studies comparing lower respiratory tract microbiome in patients with stable bronchiectasis in Northern and Southern China, or the correlation between the microbiome and the disease. This study compared the microbiome characteristics of the lower respiratory tract in patients with stable bronchiectasis in the Northern and Southern regions of China, and the correlation between the microbiome composition and the severity of bronchiectasis was investigated. It also provides a new potential therapeutic target for the treatment of bronchiectasis.\u003c/p\u003e"},{"header":"Subject and Methods","content":"\u003cp\u003e1.Subjects\u003c/p\u003e \u003cp\u003eWe collected 75 patients with stable bronchiectasis in Hainan Hospital of PLA General Hospital (Sanya, Hainan) and the Eighth Medical Center of PLA General Hospital (Haidian, Beijing) from September 2021 to September 2022. We recorded gender, age, body mass index (BMI), whether the patients smoked or not, sputum, hemoptysis, and other characteristics. We measures pulmonary functions and gas exchange, and bronchoalveolar lavage fluid was taken from the patients for culture and Metagenomic sequencing. Inclusion criteria: (1) bronchiectasis diagnosed by lung computed tomography; (2) treatment without antibiotics for 3 months and without changes in general conditions such as worsening of cough or sputum index; (3) 18–90 years; (4) completed pulmonary function, bronchoscopy, and macro-genomic sequencing of bronchoalveolar lavage fluid. Exclusion criteria: (1) acute exacerbation of bronchiectasis; (2) use of antibiotics within 4 weeks; (3) severe cardiovascular or cerebrovascular diseases and a life expectancy of less than one year; (4) active infections; (5) inability to complete examinations.\u003c/p\u003e \u003cp\u003eBased on these criteria, 75 patients were enrolled, including 40 males and 35 females, aged 26–81. This study was approved by The Ethics Committee of the General Hospital of the People's Liberation Army approved the study (number-309202109091530). Informed consent was obtained from all subjects and/or their legal guardians.\u003c/p\u003e \u003cp\u003e2. Methods\u003c/p\u003e \u003cp\u003e1). Baseline data: We recorded age, gender, height, weight, disease history, smoking history, and whether hemoptysis occurred. Lung computed tomography was used to determine the site of bronchiectasis; the same technician performed pulmonary function ventilation and gas exchange examinations at each hospital. After completing the examinations, the standard of care was delivered according to the relevant guidelines.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] The alveolar lavage fluid was taken for Metagenomic sequencing.\u003c/p\u003e \u003cp\u003e2). Metagenomic sequencing\u003c/p\u003e \u003cp\u003e2).1) DNA extraction, library construction and on-line sequencing.\u003c/p\u003e \u003cp\u003eBronchoalveolar lavage fluid samples were placed in a dry ice environment and sent to genetic company for PACEseq metagenomic sequencing. DNA extraction was performed according to the manufacturer’s instructions. DNA library construction was performed using the QIAseq Ultralow Input Library Kit (Illumina) library construction kit (QIAGEN, Hiden, Germany) Quality assessment was performed using Qubit (Thermo Fisher, Waltham, USA) and Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, USA). The libraries with satisfactory quality were subjected to metagenomic sequencing on the Nextseq550 (Illumina, San Diego, USA) platform.\u003c/p\u003e \u003cp\u003e2).2) Data processing and analysis\u003c/p\u003e \u003cp\u003eNon-compliant DNA sequences (low-quality, low-complexity or small fragments) were removed from the raw files after mNGS sequencing using fastp. Using BMA software, the sequencing data were compared to the human reference genome (hg38). Using Kraken software, the remaining unknowns were identified and compared to assess the species information of microorganisms. The number of sequences detected by the microorganism and the number of sequences per million sequences measured for that microorganism were calculated separately. Sequence data that support the findings of this study have been deposited in the China National Center for BioInformation (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cncb.ac.cn/\u003c/span\u003e\u003cspan address=\"https://www.cncb.ac.cn/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), code CRA0144053.\u003c/p\u003e \u003cp\u003ePulmonary function tests\u003c/p\u003e \u003cp\u003eMeasurements were taken using a Yeager Spirometer (MasterScreen Pneumo) by the same technician performing pulmonary function for at least 3 years. Refer to the Pulmonary Function Guidelines for the procedure [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. After environmental calibration, volumetric calibration, and calibration verification, 3–4 acceptable spirometry curves were obtained, with the difference between the two best spirometers not exceeding 5% or not exceeding 150 ml. The maximum value was selected for analysis. The metrics analyzed were absolute FEV1, FEV1 as a percentage of predicted value, and FEV1/FVC (%).\u003c/p\u003e \u003cp\u003e4. Bronchiectasis severity score\u003c/p\u003e \u003cp\u003eThe severity of bronchiectasis was assessed using the bronchiectasis severity index (BSI) score, the E-FACED score, and the Reiff score. The E-FACED score included age, FVE1 as a percentage of predicted value, whether there had been an exacerbation leading to hospitalization within the previous year, the mMRC score, the presence of \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e colonization, and the number of lobes affected on imaging. Scores of 0–3 were classified as mild, 4–6 was moderate, and 7–9 was severe. The BSI score was relatively comprehensive, with the addition of BMI, imaging of cumulative cystic bronchial expansion of 3 or more lobes, and other microbial colonization compared to the E-FACED score.BSI scores 0–4 were classified as mild, 5–8 as moderate, and ≥ 9 as severe. The Reiff score was used to assess the severity of bronchiectasis based on the imaging of patients with bronchial expansion. The Reiff score was used to assess the severity of bronchial extension based on imaging of patients with bronchial extension.\u003c/p\u003e \u003cp\u003e5. Statistical analysis\u003c/p\u003e \u003cp\u003eSPSS26.0 software was used to test and analyze the metrics. The normality of distribution was tested, and the metrics between the two groups was compared using independent samples t-tests or non-parametric tests. The chi-square test was used to compare the count data of 2 or more groups. Difference where p-value \u0026lt; 0.05 were considered significant.\u003c/p\u003e"},{"header":"Result","content":"\u003cp\u003e1. Patients information\u003c/p\u003e\u003cp\u003eWe considered 75 patients were included, including 42 in the Northern group and 33 in the Southern group. There were no significant differences between the groups regarding gender, age, body mass index, history of hemoptysis, BSI score, E-FACED assessment and FEV1%. There were significantly more smoking patients in the Northern group than in the Southern group, and the FEV1/FVC ratio of Southern group was more significantly than that of the Northern group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline data of patients with bronchiectasis by gender\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003cp\u003einformation\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNorthern group\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSouthern group\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003evalue\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of\u003c/p\u003e \u003cp\u003eexamples\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (m/f)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23/19\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17/16\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e = 0.08\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 ± 11\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 ± 13\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003et = 0.47\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.8 ± 10.9\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.2 ± 3.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003et = 1.77\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23/19\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9/24\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e = 5.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoptysis\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18/24\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15/18\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e = 0.05\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFEV1%\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73.4 ± 24.6\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.7 ± 16.9\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003et = 1.10\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFEV1/FVC(%)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.4 ± 14.0\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.8 ± 12.4\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003et = 2.56\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBSI score\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.1 ± 3.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.9 ± 4.1\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003et = 1.37\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE-Faced score\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.7 ± 1.2\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3 ± 1.5\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003et = 1.15\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eFEV1: forced expiratory flow in one second; FVC: forced vital capacity\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e2. Lower respiratory tract microbiome in patients with stable bronchiectasis\u003c/p\u003e\u003cp\u003eAnalysis of the lower respiratory tract microbiome of the Southern and Northern groups revealed that the α-diversity of the groups was not statistically different at the genus or species taxonomic levels (P = 0.83 and P = 0.91, respectively). However, in the comparison of species abundance between the two groups, there were differences in specific flora between the Southern group and the Northern group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). At the genus level, the highest species abundance in the Northern group was found in \u003cem\u003ePseudomonas spp, Prevotella spp\u003c/em\u003e and \u003cem\u003eStreptococcus spp\u003c/em\u003e, which were also more prevalent in the Southern group; however, \u003cem\u003eHaemophilus spp\u003c/em\u003e had the highest abundance in the Southern group, which was significantly different from the Northern group. At the species level, the most abundant species in the Northern group were \u003cem\u003eP. aeruginosa\u003c/em\u003e, \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e and \u003cem\u003eNocardia gelsenkirchen\u003c/em\u003e, whereas the most abundant species in the Southern group were \u003cem\u003eH. influenzae\u003c/em\u003e, \u003cem\u003eP. aeruginosa\u003c/em\u003e and \u003cem\u003ePrevotella intermedia\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eb).\u003c/p\u003e\u003cp\u003e \u003c/p\u003e\u003cp\u003e3. Differences in lower respiratory tract microbiome between patients with severe and mild-to-moderate bronchiectasis\u003c/p\u003e\u003cp\u003eBased on the BSI score, patients were categorized into those with severe bronchiectasis (BSI ≥ 9 points) and mild-moderate dilatation (BSI \u0026lt; 9 points). In the Northern group, there were 22 severe and 18 mild-moderate patients, while in the Southern group, there were 13 severe and 21 mild-moderate disease. The α-diversity of lower respiratory tract microbiome in patients with severe versus mild-to- moderate bronchiectasis was not significantly different at the genus or species classification levels (P = 0.39 and P = 0.93, respectively) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). However, the two groups showed differences in species abundance. At the genus level, the microorganisms with the highest abundance in the lower respiratory tract of patients with severe bronchiectasis were \u003cem\u003ePseudomonas spp.\u003c/em\u003e, \u003cem\u003eProteus spp\u003c/em\u003e. and \u003cem\u003eStreptococcus spp\u003c/em\u003e. In patients with mild-to-moderate severity, \u003cem\u003eHaemophilus spp\u003c/em\u003e. and \u003cem\u003eKlebsiella spp\u003c/em\u003e. were significantly more abundant than those in patients of the severe group, compared to the lower abundance of \u003cem\u003ePseudomonas spp\u003c/em\u003e. At the species level, the most abundant species in the lower respiratory tract of patients with severe bronchiectasis were \u003cem\u003eP. aeruginosa\u003c/em\u003e, Clostridium nucleatum, and \u003cem\u003eStenotrophomonas maltophilia\u003c/em\u003e, whereas \u003cem\u003eH. influenzae\u003c/em\u003e, \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e, and \u003cem\u003eNocardi\u003c/em\u003e were the most abundant species in patients with mild to moderate disease (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003eb).\u003c/p\u003e\u003cp\u003e4. Differences in lower respiratory tract microbiome in patients with different severity of bronchiectasis between the North and the South.\u003c/p\u003e\u003cp\u003eSignificant differences at the genus and species levels existed in the Northern and Southern groups. At the species level, the Chao1 index of patients with severe bronchiectasis in the Northern group was significantly lower than that of patients with mild-to-moderate bronchiectasis, suggesting that the alpha diversity of the lower respiratory tract microbiome was lower in patients with severe bronchiectasis in the Northern group, whereas the Southern group showed the same trend but did not show significant differences; at the genus level, the Chao1 index of patients with severe bronchiectasis in the Southern group was significantly higher than that of the mild-to-moderate group, and the same trend could be observed in the Northern group, however, there was no significant difference in the Northern group (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e3\u003c/span\u003e). At the species level, differentially represented species could be found in the severe and mild-moderate branched expansion patients in the Northern group (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003ea). In contrast, in the comparison of severe and mild-moderate in the Southern group, differentially represented species were identified only in mild-moderate patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003eb).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eLower respiratory tract microbiome is an intense area of research. In the past, it was believed that the lower respiratory tract of healthy people was gnotobiology, however, with the development of molecular testing techniques, studies found that microorganisms colonize the lower respiratory tract of healthy people. These microorganisms are similar to the microorganisms of the upper respiratory tract [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] This finding suggests that the upper respiratory tract may be a source of lower respiratory tract microorganisms. Several studies showed that patients with bronchiectasis have a higher diversity of intestinal microorganisms than the healthy population. \u003cem\u003eAeromonas butyricola\u003c/em\u003e, \u003cem\u003ePrevotella\u003c/em\u003e and \u003cem\u003eCoccidioides faecalis\u003c/em\u003e abundances were significantly lower in patients with bronchiectasis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Metabolomics studies have suggested significant changes in the metabolism of the microbiome in both groups, suggesting that the\u0026ldquo;gut-pulmonary\u0026rdquo; axis may play a role in the pathogenesis of bronchiectasis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. There are significant changes in the metabolism of the two flora, suggesting that the\u0026ldquo;gut-pulmonary\u0026rdquo; axis may play a role in the pathogenesis of bronchiectasis.\u003c/p\u003e \u003cp\u003eThe lungs of patients with structural lung diseases represented by bronchiectasis usually have long-term microbial colonization, and studies on stable bronchiectasis found that the top three genera of lower respiratory tract colonizers in patients with stable bronchiectasis are \u003cem\u003ePseudomonas, Haemophilus\u003c/em\u003e, and \u003cem\u003eStreptococcus\u003c/em\u003e, respectively in Global [\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, the results of our study were inconsistent with those of the both groups.\u003c/p\u003e \u003cp\u003eIt was also observed that \u003cem\u003eP. aeruginosa\u003c/em\u003e and \u003cem\u003eH. influenzae\u003c/em\u003e in the Southern group were \u0026ldquo;mutually exclusive\u0026rdquo;, i.e., these two bacteria were the core of the colonization [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. \u003cem\u003eP. aeruginosa\u003c/em\u003e and \u003cem\u003eH. influenzae\u003c/em\u003e in the Southern group were \u0026ldquo;mutually exclusive\u0026rdquo;, i.e., in the specimens with these two bacteria as the core taxa, their background organisms seldom existed in each other's strains, which aligns with previous reports. \u003cem\u003eP. aeruginosa\u003c/em\u003e colonization was associated with lower pulmonary function, more severe disease and more severe hemoptysis.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe performed interquartile spacing of the abundance of the strains, and classified the upper quartile as the core taxa and the lower as the satellite or background group, as described previously [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In the present study, there were differences in the core taxa between the North and the South, in which \u003cem\u003eP. aeruginosa\u003c/em\u003e ranked first in abundance in the Northern group and third in the Southern group. Patients with \u003cem\u003eP. aeruginosa\u003c/em\u003e as the core taxa had 19 groups of background genera and 30 species. In contrast, patients with \u003cem\u003eH. influenzae\u003c/em\u003e as the core taxa had 24 groups of background genera and 40 species, which were all higher than \u003cem\u003eP. aeruginosa.\u003c/em\u003e This result is consistent with the reports in the Global literature.\u003c/p\u003e \u003cp\u003eIn addition, based on the BSI score, we divided the patients with bronchiectasis into a severe group and a mild-moderate group for comparison, and the results showed that the proportion of patients with \u003cem\u003eP. aeruginosa\u003c/em\u003e as a core taxa was higher in the severe group. In contrast, the proportion of patients with \u003cem\u003eH. influenzae\u003c/em\u003e as a core taxa was higher in the mild-moderate group. In the North-South subgroup, we observed a higher proportion of hemoptysis in patients in the severe group in the South.\u003c/p\u003e \u003cp\u003eInterestingly, among the background bacteria with \u003cem\u003eH. influenzae\u003c/em\u003e as the core taxa, we found \u003cem\u003eP. aeruginosa\u003c/em\u003e, which differs from the other studies. A study on the co-culture of \u003cem\u003eP. aeruginosa\u003c/em\u003e and \u003cem\u003eStaphylococcus aureus\u003c/em\u003e found that \u003cem\u003eP. aeruginosa\u003c/em\u003e inhibited the growth of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, there are no co-culture studies of \u003cem\u003eP. aeruginosa\u003c/em\u003e and \u003cem\u003eH. influenzae\u003c/em\u003e, and there is a lack of studies on the mechanism of symbiosis between these bacteria and humans; therefore, we cannot determine whether there is a \u0026ldquo;mutually exclusive\u0026rdquo; relationship between the two bacteria. In the past, bacteria were thought not to be able to coexist with humans body, but now, such as non-tuberculous mycobacteria (NTM), Pneumocystis japonicus, and Nocardia, were detected in patients with stable bronchiectasis. In recent years, the isolation rate of NTM has increased in China, especially in hot and humid and coastal areas. The elderly people, those with underlying diseases, and immunocompromised people are more likely to suffer from the disease. Previously, it was believed that there was no human-to-human transmission of NTM; however, some studies found that there may be mutual transmission of NTM among patients with cystic fibrosis.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] When NTM enters the body, it is phagocytosed by macrophages and multiplies within them. Alveolar macrophages are an essential component of the intrinsic immunity of the lungs. It remains unclear how NTM reaches a dynamic equilibrium with intrinsic lung immunity during the stabilization phase of bronchiectasis. \u003cem\u003ePneumocystis japonicus\u003c/em\u003e was previously thought to be unable to coexist with healthy individuals, however, this organism has been detected in patients with stable chronic obstructive pulmonary disease (COPD)[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. With the development of molecular detection technology, our understanding of lower respiratory tract microbiome will deepen, and our understanding of the interplay between lower respiratory tract microbiome and the body's autoimmunity in patients with bronchiectasis will become more comprehensive, guiding patient treatment.\u003c/p\u003e \u003cp\u003eIn summary, we found that the colonization of the lower respiratory tract by \u003cem\u003eP. aeruginosa\u003c/em\u003e differed between the North and South in patients with stable bronchiectasis, with \u003cem\u003eP. aeruginosa\u003c/em\u003e having a higher isolation rate in different geographic regions. In contrast \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e colonization was more common in the Northern group. In patients with severe bronchiectasis, there was a higher proportion of \u003cem\u003eP. aeruginosa\u003c/em\u003e and a higher proportion of hemoptysis, similar to previous studies. Compared to \u003cem\u003eH. influenzae\u003c/em\u003e, \u003cem\u003eP. aeruginosa\u003c/em\u003e had significantly lower numbers as background groups.\u003c/p\u003e \u003cp\u003eThere are some limitations to our study. First, this was not a multicenter study; the sample size was relatively small. Second, we did not stratify according to temperature, humidity or air pollution level.\u003c/p\u003e \u003cp\u003eTherefore, we hope that more institutions and regions can be included in subsequent studies, and more detailed subgroup studies can be conducted for various causes of bronchiectasis, to explore more deeply the mechanisms of exacerbation in different patients with bronchiectasis and to provide targeted treatment. These studies will help improve patients\u0026rsquo; quality of life with stable bronchiectasis, reduce the incidence of adverse events, and improve outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u0026nbsp;\u003c/strong\u003eAll\u0026nbsp;authors\u0026nbsp;indicated\u0026nbsp;no\u0026nbsp;conflicts\u0026nbsp;of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e\u0026rsquo;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Contributions:\u0026nbsp;\u003c/strong\u003eGao Bingrui: study design, data collection, statistical analysis, and paper writing; Feng Cong: paper writing and proofreading; Huang Shanshan: data collection, study supervision; Chen Haiyan: cooperation with bronchoscopy and data collection; Wang Manrui: cooperation with pulmonary function tests and data collection; Guo Yinghua: study supervision, study design and paper revision; Xie Lixin: study supervision, providing guidance and financial support for study implementation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent for publication: NOT APPLICABLE.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e:\u0026nbsp;This\u0026nbsp;study\u0026nbsp;was\u0026nbsp;approved\u0026nbsp;by\u0026nbsp;The\u0026nbsp;Ethics\u0026nbsp;Committee\u0026nbsp;of\u0026nbsp;the\u0026nbsp;General Hospital of the People\u0026apos;s Liberation Army approved the study and (number-309202109091530).\u0026nbsp;Informed consent\u0026nbsp;was obtained from all subjects and/or their legal guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThe\u0026nbsp;Eighth\u0026nbsp;Medical\u0026nbsp;Center\u0026nbsp;of\u0026nbsp;the\u0026nbsp;General\u0026nbsp;Hospital\u0026nbsp;of PLA supported the project (MS202211005).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e:\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eSequence data that support the findings of this study have been deposited in the China National Center for BioInformation (https://www.cncb.ac.cn/), code CRA0144053.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePolverino E, Goeminne P C, McDonnell M J, et al. European Respiratory Society guidelines for the management of adult bronchiectasis [J]. Eur Respir J, 2017, 50(3).doi:10.1183/13993003.00629-2017\u003c/li\u003e\n\u003cli\u003eFeng J, Sun L, Sun X, et al. Increasing prevalence and burden of bronchiectasis in urban Chinese adults, 2013-2017: a nationwide population-based cohort study [J]. Respir Res, 2022, 23(1): 111.doi:10.1186/s12931-022-02023-8\u003c/li\u003e\n\u003cli\u003eGopalaswamy R, Shanmugam S, Mondal R, et al. Of tuberculosis and non-tuberculous mycobacterial infections - a comparative analysis of epidemiology, diagnosis and treatment [J]. J Biomed Sci, 2020, 27(1): 74.doi:10.1186/s12929-020-00667-6\u003c/li\u003e\n\u003cli\u003eVera C, Rueda Z V. Transmission and Colonization of Pneumocystis jirovecii [J]. J Fungi (Basel), 2021, 7(11).doi:10.3390/jof7110979\u003c/li\u003e\n\u003cli\u003eLynch J P, 3rd, Reid G, Clark N M. Nocardia spp.: A Rare Cause of Pneumonia Globally [J]. Semin Respir Crit Care Med, 2020, 41(4): 538-54.doi:10.1055/s-0040-1708816\u003c/li\u003e\n\u003cli\u003e中华医学会呼吸病学分会呼吸危重症医学学组, 中国医师协会呼吸医师分会危重症医学工作委员会. ICU患者支气管肺泡灌洗液采集,送检,检测及结果解读规范[J]. 中华结核和呼吸杂志, 2020, 43(9):13. [J].doi:10.3760/cma.j.cn112147‑20200506‑00566\u003c/li\u003e\n\u003cli\u003e中华医学会. 常规肺功能检查基层指南(2018年)[J]. 中华全科医师杂志, 2019, 18(006):511-518. [J].doi:10.3760/cma.j.issn.1671⁃7368.2019.06.003\u003c/li\u003e\n\u003cli\u003eWypych T P, Wickramasinghe L C, Marsland B J. The influence of the microbiome on respiratory health [J]. Nat Immunol, 2019, 20(10): 1279-90.doi:10.1038/s41590-019-0451-9\u003c/li\u003e\n\u003cli\u003eWang W W, Mao B, Liu Y, et al. Altered fecal microbiome and metabolome in adult patients with non-cystic fibrosis bronchiectasis [J]. Respir Res, 2022, 23(1): 317.doi:10.1186/s12931-022-02229-w\u003c/li\u003e\n\u003cli\u003eBowerman K L, Rehman S F, Vaughan A, et al. Disease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease [J]. Nat Commun, 2020, 11(1): 5886.doi:10.1038/s41467-020-19701-0\u003c/li\u003e\n\u003cli\u003eStokholm J, Blaser M J, Thorsen J, et al. Maturation of the gut microbiome and risk of asthma in childhood [J]. Nat Commun, 2018, 9(1): 141.doi:10.1038/s41467-017-02573-2\u003c/li\u003e\n\u003cli\u003e肖雄, 许毅娇, 陈志盛, et al. 慢性阻塞性肺疾病患者肺泡灌洗液宏基因组测序分析 %J 中国病原生物学杂志 [J]. 2022, 17(10): 1188-91.doi:10.13350/j.cjpb.221016\u003c/li\u003e\n\u003cli\u003eCuthbertson L, Walker A W, Oliver A E, et al. Lung function and microbiota diversity in cystic fibrosis [J]. Microbiome, 2020, 8(1): 45.doi:10.1186/s40168-020-00810-3\u003c/li\u003e\n\u003cli\u003eDicker A J, Lonergan M, Keir H R, et al. The sputum microbiome and clinical outcomes in patients with bronchiectasis: a prospective observational study [J]. Lancet Respir Med, 2021, 9(8): 885-96.doi:10.1016/S2213-2600(20)30557-9\u003c/li\u003e\n\u003cli\u003eRichardson H, Dicker A J, Barclay H, et al. The microbiome in bronchiectasis [J]. Eur Respir Rev, 2019, 28(153).doi:10.1183/16000617.0048-2019\u003c/li\u003e\n\u003cli\u003eWoo T E, Lim R, Heirali A A, et al. A longitudinal characterization of the Non-Cystic Fibrosis Bronchiectasis airway microbiome [J]. Sci Rep, 2019, 9(1): 6871.doi:10.1038/s41598-019-42862-y\u003c/li\u003e\n\u003cli\u003eMac Aogain M, Narayana J K, Tiew P Y, et al. Integrative microbiomics in bronchiectasis exacerbations [J]. Nat Med, 2021, 27(4): 688-99.doi:10.1038/s41591-021-01289-7\u003c/li\u003e\n\u003cli\u003eRigauts C, Aizawa J, Taylor S L, et al. R othia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease [J]. Eur Respir J, 2022, 59(5).doi:10.1183/13993003.01293-2021\u003c/li\u003e\n\u003cli\u003eTognon M, Kohler T, Luscher A, et al. Transcriptional profiling of Pseudomonas aeruginosa and Staphylococcus aureus during in vitro co-culture [J]. BMC Genomics, 2019, 20(1): 30.doi:10.1186/s12864-018-5398-y\u003c/li\u003e\n\u003cli\u003eDaley C L, Iaccarino J M, Lange C, et al. Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline [J]. Clin Infect Dis, 2020, 71(4): 905-13.doi:10.1093/cid/ciaa1125\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bronchiectasis, Lower Respiratory Tract, Microbiome","lastPublishedDoi":"10.21203/rs.3.rs-3907668/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3907668/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eTo\u003cstrong\u003e \u003c/strong\u003ecompare microbiome in the lower respiratory tract of patients with stable bronchiectasis in North and South China.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eDemographic and Sequencing data were collected from patients who underwent bronchoalveolar lavage fluid macro-genomic sequencing testing between September 2021 to September 2022 at Hainan Hospital of the General Hospital of the People's Liberation Army (Sanya, Hainan, South) and the Eighth Medical Center of the General Hospital of the People's Liberation Army (Haidian, Beijing, North). The patients were grouped according to the clinical test results, and the sequencing data were analyzed twice to compare the microbiome differences among different groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eWe enrolled 75 patients, 42 in the North and 33 in the South. The number of smokers in the Northern group was higher than that in the Southern group and the FEV1/FVC (%) value was lower than that in the Southern group; otherwise, the groups had no significant differences. The most abundance bacteria in the lower respiratory tract of the Northern group were \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e, and \u003cem\u003eNocardia wilsonii\u003c/em\u003e, while the Southern group were \u003cem\u003eH. influenzae\u003c/em\u003e, \u003cem\u003eP. aeruginosa\u003c/em\u003e, and \u003cem\u003ePrevotella intermedia\u003c/em\u003e. According to the severity of the patients with bronchiectasis (BSI), there was also a difference in the abundance of microbiome in the lower respiratory tract in patients with stable bronchiectasis from the North and South.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion \u003c/strong\u003eThe\u003cstrong\u003e \u003c/strong\u003elower respiratory tract microbiome of patients with stable bronchiectasis differed significantly between the North and South in China. The microbiome of the Southern group was more similar to that reported in the international literature, while the Northern group was significantly different from the results of other studies. \u003cem\u003eP. aeruginosa \u003c/em\u003eand \u003cem\u003eKlebsiella pneumoniae \u003c/em\u003ewere most abundant in the Northern group, while \u003cem\u003eH. influenzae\u003c/em\u003e and \u003cem\u003eP. aeruginosa\u003c/em\u003e were most abundant in the Southern group, These findings can guide antibiotic treatment of exacerbations.\u003c/p\u003e","manuscriptTitle":"Lower respiratory microbiome in patients with stable bronchiectasis in North and South China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-02 15:10:49","doi":"10.21203/rs.3.rs-3907668/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dac237d4-5673-4f44-8aaf-3b29f79388ea","owner":[],"postedDate":"February 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-25T07:09:04+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-02 15:10:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3907668","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3907668","identity":"rs-3907668","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}