痰短链脂肪酸与阻塞性气道疾病气道微生物组、炎症和黏液栓密切相关
2025/06/16
摘要
背景：短链脂肪酸（SCFAs）由厌氧菌在肠道内发酵产生，可抑制嗜酸性粒细胞炎症，同时可能促进中性粒细胞炎症。然而，局部 SCFAs在2型阻塞性气道疾病的气道微生物组、炎症和黏液堵塞中的作用仍不清楚。
目的：探讨阻塞性气道疾病患者痰SCFAs 与厌氧菌相对丰度、痰中性粒细胞和嗜酸性粒细胞计数以及CT图像上黏液栓评分之间的关系。
方法：前瞻性地收集伴有持续气流受限的稳定期哮喘、慢性阻塞性肺病和哮喘-慢性阻塞性肺病重叠（ACO）患者的痰液样本和胸部CT影像。对痰样本进行了分析，以检测SCFAs（包括正丁酸盐、乙酸盐和丙酸盐）的浓度，使用16S rRNA 测序法检测微生物组的组成以及炎症细胞的差异。
结果：在46例患者中，ACO患者2型标志物水平较高；且较高的SCFAs 水平与2型标记物水平升高、拟杆菌门细菌相对丰度增加和变形菌门细菌相对丰度降低有关。分层聚类确定了一个以嗜酸性粒细胞为主的集群，其特点是SCFAs水平较低和黏液栓评分较高。而在另两个中性粒细胞集群中，一个SCFAs水平较高，另一个SCFAs水平较低。较低的丁酸盐水平与较高的黏液栓评分显著相关。
结论：局部SCFA浓度可能与气道微生物组密切相关，并影响ACO患者的黏液堵塞。理解这些相互作用可为2型炎症为主的阻塞性气道疾病针对SCFAs或微生物组的治疗策略提供依据。
关键词： 短链脂肪酸；气道炎症；微生物组；哮喘；慢性阻塞性肺病；哮喘-慢性阻塞性肺病重叠；黏液；计算机断层扫描；影像学
文献来源：（Tanabe N, Matsumoto H, Morimoto C, et al. Sputum short-chain fatty acids, microbiome, inflammation, and mucus plugging in obstructive airway disease[J]. J Allergy Clin Immunol , 2025: S0091674925001204. DOI: 10.1016/j.jaci.2025.01.031.）
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 the airway microbiome, inflammation, and mucus plugging in type 2–dominant obstructive airway diseases remains unclear.
Objective：Our aim was 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 images in patients with obstructive airway diseases.
Methods：Sputum samples and chest computed tomography images were prospectively collected in stable patients with asthma with fixed airflow limitation, chronic obstructive pulmonary disease, and asthma–chronic obstructive pulmonary disease overlap (ACO). Sputum samples were analyzed for concentrations of SCFA, 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 levels of type 2 markers, higher SCFA levels were associated with higher relative abundance of bacteria of the phylum Bacteroidetes and lower relative abundance of bacteria of the phylum Proteobacteria. Hierarchic clustering identified a severe eosinophil-dominant inflammation cluster characterized by lower SCFAs levels and higher mucus plug scores. In the 2 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.
Key words：Short-chain fatty acid；airway inflammation；microbiome；asthma；COPD；asthma-COPD overlap；mucus；computed tomography；imaging
背景：短链脂肪酸（SCFAs）由厌氧菌在肠道内发酵产生，可抑制嗜酸性粒细胞炎症，同时可能促进中性粒细胞炎症。然而，局部 SCFAs在2型阻塞性气道疾病的气道微生物组、炎症和黏液堵塞中的作用仍不清楚。
目的：探讨阻塞性气道疾病患者痰SCFAs 与厌氧菌相对丰度、痰中性粒细胞和嗜酸性粒细胞计数以及CT图像上黏液栓评分之间的关系。
方法：前瞻性地收集伴有持续气流受限的稳定期哮喘、慢性阻塞性肺病和哮喘-慢性阻塞性肺病重叠（ACO）患者的痰液样本和胸部CT影像。对痰样本进行了分析，以检测SCFAs（包括正丁酸盐、乙酸盐和丙酸盐）的浓度，使用16S rRNA 测序法检测微生物组的组成以及炎症细胞的差异。
结果：在46例患者中，ACO患者2型标志物水平较高；且较高的SCFAs 水平与2型标记物水平升高、拟杆菌门细菌相对丰度增加和变形菌门细菌相对丰度降低有关。分层聚类确定了一个以嗜酸性粒细胞为主的集群，其特点是SCFAs水平较低和黏液栓评分较高。而在另两个中性粒细胞集群中，一个SCFAs水平较高，另一个SCFAs水平较低。较低的丁酸盐水平与较高的黏液栓评分显著相关。
结论：局部SCFA浓度可能与气道微生物组密切相关，并影响ACO患者的黏液堵塞。理解这些相互作用可为2型炎症为主的阻塞性气道疾病针对SCFAs或微生物组的治疗策略提供依据。
关键词： 短链脂肪酸；气道炎症；微生物组；哮喘；慢性阻塞性肺病；哮喘-慢性阻塞性肺病重叠；黏液；计算机断层扫描；影像学
文献来源：（Tanabe N, Matsumoto H, Morimoto C, et al. Sputum short-chain fatty acids, microbiome, inflammation, and mucus plugging in obstructive airway disease[J]. J Allergy Clin Immunol , 2025: S0091674925001204. DOI: 10.1016/j.jaci.2025.01.031.）
（南方医科大学南方医院 黄海伦 龚钊乾 赵海金）
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 the airway microbiome, inflammation, and mucus plugging in type 2–dominant obstructive airway diseases remains unclear.
Objective：Our aim was 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 images in patients with obstructive airway diseases.
Methods：Sputum samples and chest computed tomography images were prospectively collected in stable patients with asthma with fixed airflow limitation, chronic obstructive pulmonary disease, and asthma–chronic obstructive pulmonary disease overlap (ACO). Sputum samples were analyzed for concentrations of SCFA, 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 levels of type 2 markers, higher SCFA levels were associated with higher relative abundance of bacteria of the phylum Bacteroidetes and lower relative abundance of bacteria of the phylum Proteobacteria. Hierarchic clustering identified a severe eosinophil-dominant inflammation cluster characterized by lower SCFAs levels and higher mucus plug scores. In the 2 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.
Key words：Short-chain fatty acid；airway inflammation；microbiome；asthma；COPD；asthma-COPD overlap；mucus；computed tomography；imaging
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