DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa.
Division of Pulmonary, Critical Care, and Sleep Medicine, New York University School of Medicine, New York, NY, United States.
EBioMedicine. 2021 May;67:103374. doi: 10.1016/j.ebiom.2021.103374. Epub 2021 May 8.
The relationship between tuberculosis (TB), one of the leading infectious causes of death worldwide, and the microbiome, which is critical for health, is poorly understood.
To identify potential microbiome-host interactions, profiling of the oral, sputum and stool microbiota [n = 58 cases, n = 47 culture-negative symptomatic controls (SCs)] and whole blood transcriptome were done in pre-treatment presumptive pulmonary TB patients. This was a cross-sectional study. Microbiota were also characterised in close contacts of cases (CCCs, n = 73) and close contacts of SCs (CCSCs, n = 82) without active TB.
Cases and SCs each had similar α- and β-diversities in oral washes and sputum, however, β-diversity differed in stool (PERMANOVA p = 0•035). Cases were enriched with anaerobes in oral washes, sputum (Paludibacter, Lautropia in both) and stool (Erysipelotrichaceae, Blautia, Anaerostipes) and their stools enriched in microbial genes annotated as amino acid and carbohydrate metabolic pathways. In pairwise comparisons with their CCCs, cases had Megasphaera-enriched oral and sputum microbiota and Bifidobacterium-, Roseburia-, and Dorea-depleted stools. Compared to their CCSCs, SCs had reduced α-diversities and many differential taxa per specimen type. Cases differed transcriptionally from SCs in peripheral blood (PERMANOVA p = 0•001). A co-occurrence network analysis showed stool taxa, Erysipelotrichaceae and Blautia, to negatively co-correlate with enriched "death receptor" and "EIF2 signalling" pathways whereas Anaerostipes positively correlated with enriched "interferon signalling", "Nur77 signalling" and "inflammasome" pathways; all of which are host pathways associated with disease severity. In contrast, none of the taxa enriched in SCs correlated with host pathways.
TB-specific microbial relationships were identified in oral washes, induced sputum, and stool from cases before the confounding effects of antibiotics. Specific anaerobes in cases' stool predict upregulation of pro-inflammatory immunological pathways, supporting the gut microbiota's role in TB.
European & Developing Countries Clinical Trials Partnership, South African-Medical Research Council, National Institute of Allergy and Infectious Diseases.
结核病（TB）是全球主要传染病死因之一，而微生物组对健康至关重要，但人们对两者之间的关系知之甚少。
为了确定潜在的微生物组-宿主相互作用，我们对治疗前疑似肺结核患者的口腔、痰和粪便微生物组（n=58 例，n=47 例培养阴性的症状对照者[SCs]）和全血转录组进行了分析。这是一项横断面研究。我们还对病例的密切接触者（CCCs，n=73）和 SCs 的密切接触者（CCSCs，n=82）的微生物组进行了研究，这些人没有活动性 TB。
病例和 SCs 的口腔冲洗液和痰液中的 α-和 β-多样性相似，但粪便中的 β-多样性不同（PERMANOVA p=0.035）。病例的口腔冲洗液、痰液（Paludibacter、Lautropia 均存在）和粪便（Erysipelotrichaceae、Blautia、Anaerostipes）中富含厌氧菌，其粪便中富含微生物基因注释为氨基酸和碳水化合物代谢途径。与 CCCs 相比，病例的口腔和痰液中 Megasphaera 富集，粪便中双歧杆菌、Roseburia 和 Dorea 减少。与 CCSCs 相比，SCs 的每种标本类型的 α-多样性和许多差异分类群都减少了。与 SCs 相比，病例的外周血转录组有差异（PERMANOVA p=0.001）。共现网络分析显示，粪便分类群 Erysipelotrichaceae 和 Blautia 与富集的“死亡受体”和“EIF2 信号”途径呈负相关，而 Anaerostipes 与富集的“干扰素信号”、“Nur77 信号”和“炎症小体”途径呈正相关；所有这些途径都是与疾病严重程度相关的宿主途径。相比之下，SCs 中富集的任何分类群都与宿主途径无关。
在抗生素的混杂作用之前，我们从病例的口腔冲洗液、诱导痰和粪便中鉴定出了 TB 特异的微生物关系。病例粪便中的特定厌氧菌预测促炎免疫途径的上调，支持了肠道微生物群在 TB 中的作用。
欧洲和发展中国家临床试验伙伴关系、南非医学研究理事会、美国国立过敏和传染病研究所。
