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结核分枝杆菌感染后全身炎症与 HIV 未感染者的肠道微生物组有关。

Systemic proinflammation after Mycobacterium tuberculosis infection was correlated to the gut microbiome in HIV-uninfected humans.

机构信息

Institution of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.

Division of Infectious Disease, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.

出版信息

Eur J Clin Invest. 2019 May;49(5):e13068. doi: 10.1111/eci.13068. Epub 2019 Mar 15.

DOI:10.1111/eci.13068
PMID:30620398
Abstract

BACKGROUND

The dysbiosis of gut microbiome and interaction with host immunity after Mycobacterium tuberculosis (MTB) infection are under investigation. We had found fatigue symptom concurrent with dysbiosis by decreasing the ratio of Firmicutes to Bacteroidetes (F/B ratio) in active tuberculosis (TB). The study aims to assess the inflammatory biomarkers and their interaction with gut microbiome in active TB and latent TB infection before starting anti-TB regimens.

MATERIALS AND METHOD

Interleukin-1 beta (IL-1B), IL-4, IL-6, IL-10, CD3+, CD4+, CD8+ T cells and interferon-gamma (IFN-γ) releasing assay (IGRA) were measured in 25 active TB patients, 32 LTBI subjects and 23 healthy controls (HC). Gut microbiome profiles were obtained using 16S rRNA MiSeq sequencing method.

RESULTS

The leucocytosis (7032 ± 387 cell/cum, P < 0.05), increase in IL-6 (229.7 ± 104 µg/dL, P < 0.05), and decrease in IL-4 (0.27 µg/dL ± 0.1, P < 0.05) were presented in active TB. The proportion of polymorphic neutrophil (PMN) in peripheral blood was positively related to the relative abundance of Bacteroidetes in LTBI and active TB (R  = 0.23, P < 0.05). The F/B ratio was positively related to the detectable IL-1B in TB (R  = 0.97, P < 0.01) and to the IL-4 in LTBI (R  = 0.27, P < 0.05). In LTBI, the relative abundances of Coriobacteriaceae were positively related to the secretion of IFN-gamma against MTB-antigens more likely associated with of CD4+ T cell (R  = 0.42, P < 0.05).

CONCLUSION

In active TB, dysbiosis with higher relative abundances of Bacteroidetes in stool and low F/B ratio was related to systemic proinflammation. In LTBI, dose-response relationship between peripheral PMN and relative abundances of Bacteroidetes was remained but not leads to systemic inflammation.

摘要

背景

分枝杆菌(Mycobacterium tuberculosis,MTB)感染后肠道微生物组的失调及其与宿主免疫的相互作用正在研究中。我们发现,在活动性肺结核(TB)中,随着厚壁菌门与拟杆菌门(Firmicutes to Bacteroidetes,F/B)比值的降低,出现了疲劳症状。本研究旨在评估活动性 TB 和潜伏性 TB 感染开始抗结核治疗前的炎症生物标志物及其与肠道微生物组的相互作用。

材料与方法

对 25 例活动性 TB 患者、32 例 LTBI 患者和 23 例健康对照者(HC)进行白细胞介素-1β(IL-1β)、IL-4、IL-6、IL-10、CD3+、CD4+、CD8+T 细胞和干扰素-γ(IFN-γ)释放测定(IGRA)。采用 16S rRNA MiSeq 测序方法获得肠道微生物组图谱。

结果

活动性 TB 患者表现为白细胞增多(7032±387 个细胞/µL,P<0.05)、IL-6 升高(229.7±104µg/dL,P<0.05)和 IL-4 降低(0.27µg/dL±0.1,P<0.05)。外周血多形核中性粒细胞(PMN)的比例与 LTBI 和活动性 TB 中拟杆菌的相对丰度呈正相关(R=0.23,P<0.05)。F/B 比值与 TB 中可检测到的 IL-1B(R=0.97,P<0.01)和 LTBI 中的 IL-4(R=0.27,P<0.05)呈正相关。在 LTBI 中,柯里氏菌科的相对丰度与针对 MTB 抗原的 IFN-γ分泌呈正相关,这可能与 CD4+T 细胞有关(R=0.42,P<0.05)。

结论

在活动性 TB 中,粪便中拟杆菌相对丰度较高、F/B 比值较低的肠道微生态失调与全身炎症反应有关。在 LTBI 中,外周血 PMN 与拟杆菌相对丰度之间存在剂量反应关系,但不会导致全身炎症。

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