阻塞性气道疾病中的痰短链脂肪酸、微生物组、炎症和粘液堵塞
2025/03/03
摘要
背景：短链脂肪酸（SCFAs）是由厌氧菌在肠道内发酵产生的，可能抑制嗜酸性炎症，同时可能促进中性炎症。然而，局部SCFA在2型主要阻塞性气道疾病的气道微生物群、炎症和粘液堵塞中的作用仍不清楚。
目的：研究阻塞性气道疾病患者痰液SCFA与痰液中厌氧菌相对丰度、中性粒细胞和嗜酸性粒细胞计数以及计算机断层扫描（CT）粘液栓评分之间的关联。
方法：前瞻性收集患有固定气流受限的哮喘、慢性阻塞性肺疾病（COPD）和哮喘-COPD重叠（ACO）的稳定患者的痰液样本和胸部CT。对痰液样本进行了SCFA浓度分析，包括正丁酸、乙酸和丙酸，使用16S rRNA测序分析了微生物组组成，并分析了炎性细胞的差异。
结果：在46名患者中，富含2型标志物的ACO患者，较高的SCFA水平与较高的拟杆菌门相对丰度和较低的变形菌门相对丰度相关。分层聚类分析发现了一个严重的嗜酸性粒细胞主导的炎症簇，其特征是较低的SCFA水平和较高的粘液栓评分。在两个中性粒细胞簇中，一个以较高的SCFA水平为特征，另一个以较低的SCFA水平为特征，较低的丁酸水平与较高的粘液栓评分显著相关。
结论：局部SCFA浓度可能与气道微生物群密切相关，并影响ACO富集人群的粘液堵塞。了解这些相互作用可以为针对SCFA或微生物群的治疗策略提供信息，以管理2型显性阻塞性气道疾病。
背景：短链脂肪酸（SCFAs）是由厌氧菌在肠道内发酵产生的，可能抑制嗜酸性炎症，同时可能促进中性炎症。然而，局部SCFA在2型主要阻塞性气道疾病的气道微生物群、炎症和粘液堵塞中的作用仍不清楚。
目的：研究阻塞性气道疾病患者痰液SCFA与痰液中厌氧菌相对丰度、中性粒细胞和嗜酸性粒细胞计数以及计算机断层扫描（CT）粘液栓评分之间的关联。
方法：前瞻性收集患有固定气流受限的哮喘、慢性阻塞性肺疾病（COPD）和哮喘-COPD重叠（ACO）的稳定患者的痰液样本和胸部CT。对痰液样本进行了SCFA浓度分析，包括正丁酸、乙酸和丙酸，使用16S rRNA测序分析了微生物组组成，并分析了炎性细胞的差异。
结果：在46名患者中，富含2型标志物的ACO患者，较高的SCFA水平与较高的拟杆菌门相对丰度和较低的变形菌门相对丰度相关。分层聚类分析发现了一个严重的嗜酸性粒细胞主导的炎症簇，其特征是较低的SCFA水平和较高的粘液栓评分。在两个中性粒细胞簇中，一个以较高的SCFA水平为特征，另一个以较低的SCFA水平为特征，较低的丁酸水平与较高的粘液栓评分显著相关。
结论：局部SCFA浓度可能与气道微生物群密切相关，并影响ACO富集人群的粘液堵塞。了解这些相互作用可以为针对SCFA或微生物群的治疗策略提供信息，以管理2型显性阻塞性气道疾病。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（J Allergy Clin Immunol. 2025 Feb 4:S0091-6749(25)00120-4. doi: 10.1016/j.jaci.2025.01.031.）
Sputum short-chain fatty acids, microbiome, inflammation, and mucus plugging in obstructive airway disease
Naoya Tanabe, Hisako Matsumoto, Chie Morimoto, Toyohiro Hirai
Abstract
Background: Short-chain fatty acids (SCFAs), produced by anaerobic bacteria through fermentation in the gut, may suppress eosinophilic inflammation while potentially promoting neutrophilic inflammation. However, the role of local SCFAs in airway microbiome, inflammation, and mucus plugging in type 2 dominant obstructive airway diseases remains unclear.
Objective: To investigate associations between sputum SCFAs and the relative abundance of anaerobic bacteria, neutrophil and eosinophil counts in sputum, and mucus plug scores on computed tomography (CT) in patients with obstructive airway diseases.
Methods: Sputum samples and chest CT were prospectively collected in stable patients with asthma with fixed airflow limitation, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO). Sputum samples were analyzed for SCFAs concentrations, including n-butyrate, acetate, and propionate, microbiome composition using 16S rRNA sequencing, and inflammatory cell differentials.
Results: In 46 patients, enriched for ACO with relatively high type 2 markers, higher SCFA levels were associated with higher relative abundance of phylum Bacteroidetes and lower relative abundance of phylum Proteobacteria. Hierarchical clustering identified a severe eosinophil-dominant inflammation cluster characterized by lower SCFAs levels and higher mucus plug scores. In the two neutrophilic clusters, one characterized by higher SCFAs levels and the other by lower SCFAs levels, lower butyrate levels were significantly associated with higher mucus plug scores.
Conclusion: Local SCFA concentrations may be closely associated with the airway microbiome and influence mucus plugging in ACO-enriched populations. Understanding these interactions could inform therapeutic strategies targeting SCFAs or the microbiome to manage type 2 dominant obstructive airway diseases.
Naoya Tanabe, Hisako Matsumoto, Chie Morimoto, Toyohiro Hirai
Abstract
Background: Short-chain fatty acids (SCFAs), produced by anaerobic bacteria through fermentation in the gut, may suppress eosinophilic inflammation while potentially promoting neutrophilic inflammation. However, the role of local SCFAs in airway microbiome, inflammation, and mucus plugging in type 2 dominant obstructive airway diseases remains unclear.
Objective: To investigate associations between sputum SCFAs and the relative abundance of anaerobic bacteria, neutrophil and eosinophil counts in sputum, and mucus plug scores on computed tomography (CT) in patients with obstructive airway diseases.
Methods: Sputum samples and chest CT were prospectively collected in stable patients with asthma with fixed airflow limitation, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO). Sputum samples were analyzed for SCFAs concentrations, including n-butyrate, acetate, and propionate, microbiome composition using 16S rRNA sequencing, and inflammatory cell differentials.
Results: In 46 patients, enriched for ACO with relatively high type 2 markers, higher SCFA levels were associated with higher relative abundance of phylum Bacteroidetes and lower relative abundance of phylum Proteobacteria. Hierarchical clustering identified a severe eosinophil-dominant inflammation cluster characterized by lower SCFAs levels and higher mucus plug scores. In the two neutrophilic clusters, one characterized by higher SCFAs levels and the other by lower SCFAs levels, lower butyrate levels were significantly associated with higher mucus plug scores.
Conclusion: Local SCFA concentrations may be closely associated with the airway microbiome and influence mucus plugging in ACO-enriched populations. Understanding these interactions could inform therapeutic strategies targeting SCFAs or the microbiome to manage type 2 dominant obstructive airway diseases.
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