More than Mycobacterium tuberculosis: site-of-disease microbial communities, and their functional and clinical profiles in tuberculous lymphadenitis.

More than Mycobacterium tuberculosis: site-of-disease microbial communities, and their functional and clinical profiles in tuberculous lymphadenitis.
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DOI:
10.1136/thorax-2022-219103
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发表时间:
2023-03
期刊:
影响因子:
10
通讯作者:
Theron G
Theron G
中科院分区:
医学1区
文献类型:
--
作者:
Nyawo GR;Naidoo CC;Wu B;Sulaiman I;Clemente JC;Li Y;Minnies S;Reeve BWP;Moodley S;Rautenbach C;Wright C;Singh S;Whitelaw A;Schubert P;Warren R;Segal L;Theron G

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淋巴结炎是肺外结核最常见的临床表现。微生物组对人类健康很重要,但在EPTB中未进行研究。我们分析了结核性淋巴结炎(TBL)的疾病部位淋巴结微生物组。从南非开普敦的158例预处理推定TBL患者中收集细针穿刺活检。进行16 S Illumina MiSeq rRNA基因测序。我们分析了89个明确的TBL(dTBL)和61个非TBL(nTBL),它们具有相似的α-但不同的β-二聚体(p=0.001)。在结核病状态分层之前,聚类确定了五种淋巴类型:分枝杆菌属显性、普雷沃菌属显性和链球菌属显性淋巴类型在dTBL中更常见,而棒状杆菌属显性淋巴类型和第五种淋巴类型(无显性分类)在nTBL中更常见。当仅限于dTBL时,聚类鉴定出具有低α多样性的分枝杆菌主导淋巴型和非分枝杆菌主导淋巴型(称为Prevotella-Corynebacterium,Prevotella-Streptococcus)。分枝杆菌dTBL淋巴型与HIV阳性和严重淋巴结炎的特征(如较大的淋巴结)相关。dTBL微生物群落富含潜在促炎微生物短链脂肪酸代谢途径(丙酸、丁酸)与nTBL。11%(7/61)的nTBL具有BLAST确认为结核分枝杆菌复合体的分枝杆菌读数。疾病部位的TBL在微生物上不是均一的。不同的微生物群落集群存在,在我们的环境中,与不同的临床特征和免疫调节潜力。非分枝杆菌为主的dTBL淋巴类型,其中包含结核病治疗的潜在目标分类群,与轻度,潜在的早期疾病有关。这些研究为研究微生物组在淋巴结核中的作用奠定了基础。这些淋巴类型的长期临床意义需要前瞻性验证。
Lymphadenitis is the most common extrapulmonary tuberculosis (EPTB) manifestation. The microbiome is important to human health but uninvestigated in EPTB. We profiled the site-of-disease lymph node microbiome in tuberculosis lymphadenitis (TBL). Fine-needle aspiration biopsies were collected from 158 pretreatment presumptive TBL patients in Cape Town, South Africa. 16S Illumina MiSeq rRNA gene sequencing was done. We analysed 89 definite TBLs (dTBLs) and 61 non-TBLs (nTBLs), which had similar α- but different β-diversities (p=0.001). Clustering identified five lymphotypes prior to TB status stratification: Mycobacterium-dominant, Prevotella-dominant and Streptococcus-dominant lymphotypes were more frequent in dTBLs whereas a Corynebacterium-dominant lymphotype and a fifth lymphotype (no dominant taxon) were more frequent in nTBLs. When restricted to dTBLs, clustering identified a Mycobacterium-dominant lymphotype with low α-diversity and non-Mycobacterium-dominated lymphotypes (termed Prevotella-Corynebacterium, Prevotella-Streptococcus). The Mycobacterium dTBL lymphotype was associated with HIV-positivity and features characteristic of severe lymphadenitis (eg, larger nodes). dTBL microbial communities were enriched with potentially proinflammatory microbial short-chain fatty acid metabolic pathways (propanoate, butanoate) vs nTBLs. 11% (7/61) of nTBLs had Mycobacterium reads BLAST-confirmed as Mycobacterium tuberculosis complex. TBL at the site-of-disease is not microbially homogeneous. Distinct microbial community clusters exist that, in our setting, are associated with different clinical characteristics, and immunomodulatory potentials. Non-Mycobacterium-dominated dTBL lymphotypes, which contain taxa potentially targeted by TB treatment, were associated with milder, potentially earlier stage disease. These investigations lay foundations for studying the microbiome’s role in lymphatic TB. The long-term clinical significance of these lymphotypes requires prospective validation.
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