Lv Longxian, Peng Ling, Shi Ding, Shao Li, Jiang Huiyong, Yan Ren
State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
Department of Respiratory Disease, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People's Republic of China.
J Inflamm Res. 2022 Feb 15;15:987-1004. doi: 10.2147/JIR.S348047. eCollection 2022.
() is the most common cause of bacterial pneumonia, especially for people with immature or compromised immune systems. In addition to vaccination and antibiotics, immune regulation through microbial intervention has emerged in recent anti- infection research. This study investigated the therapeutic effect of a combination of live , and (CBLEB), a widely used probiotic drug, on infection in rats.
An immunocompromised -infection rat model was established by intraperitoneal injection of cyclophosphamide and nasal administration of strain ATCC49619. Samples from -infected, -infected and CBLEB-treated, and healthy rats were collected to determine blood indicators, serum cytokines, gut microbiota, faecal and serum metabolomes, lung- and colon-gene transcriptions, and histopathological features.
CBLEB treatment alleviated weight loss, inflammation, organ damage, increase in basophil percentage, red cell distribution width, and RANTES levels and decrease in total protein and albumin levels of immunocompromised -infection rats. Furthermore, CBLEB treatment alleviated dysbiosis in gut microbiota, including altered microbial composition and the aberrant abundance of opportunistic pathogenic bacterial taxa such as , and disorders in gut and serum metabolism, including altered metabolomic profiles and differentially enriched metabolites such as 2,4-di-tert-butylphenol in faeces and L-tyrosine in serum. The transcriptome analysis results indicated that the underlying mechanism by which CBLEB fights infection is mainly attributed to its regulation of immune-related pathways such as TLR and NLR signalling in the lungs and infection-, inflammation- or metabolism-related pathways such as TCR signalling in the colon.
The present study shows a potential value of CBLEB in the treatment of infection.
()是细菌性肺炎最常见的病因,尤其在免疫系统未成熟或受损的人群中。除了疫苗接种和抗生素治疗外,通过微生物干预进行免疫调节在最近的抗感染研究中已崭露头角。本研究调查了广泛使用的益生菌药物——活的()和()的组合(CBLEB)对大鼠()感染的治疗效果。
通过腹腔注射环磷酰胺和经鼻给予()菌株ATCC49619建立免疫受损的()感染大鼠模型。收集来自()感染、()感染和CBLEB治疗组以及健康大鼠的样本,以测定血液指标、血清细胞因子、肠道微生物群、粪便和血清代谢组、肺和结肠基因转录以及组织病理学特征。
CBLEB治疗减轻了免疫受损的()感染大鼠的体重减轻、炎症、器官损伤、嗜碱性粒细胞百分比增加、红细胞分布宽度增加、RANTES水平升高以及总蛋白和白蛋白水平降低。此外,CBLEB治疗减轻了肠道微生物群的失调,包括微生物组成改变和机会性致病细菌类群(如())的异常丰度,以及肠道和血清代谢紊乱,包括代谢组学谱改变和粪便中2,4-二叔丁基苯酚以及血清中L-酪氨酸等差异富集代谢物。转录组分析结果表明,CBLEB对抗()感染的潜在机制主要归因于其对肺部TLR和NLR信号等免疫相关途径以及结肠中TCR信号等感染、炎症或代谢相关途径的调节。
本研究显示了CBLEB在治疗()感染方面的潜在价值。