Quxie Capsule Modulating Gut Microbiome and Its Association With T cell Regulation in Patients With Metastatic Colorectal Cancer: Result From a Randomized Controlled Clinical Trial.
Quxie Capsule Modulating Gut Microbiome and Its Association With T cell Regulation in Patients With Metastatic Colorectal Cancer: Result From a Randomized Controlled Clinical Trial.
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祛邪胶囊调节肠道微生物组及其与转移性结直肠癌患者T细胞调节的相关性：来自随机对照临床试验的结果。
DOI：
10.1177/1534735420969820
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发表时间：
2020-01
影响因子：
2.9
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Sun L;Yan Y;Chen D;Yang Y
祛邪胶囊（QX）是一种中药复方，已显示出对转移性结直肠癌（mCRC）患者的生存结果有益，并且可以通过免疫调节抑制肿瘤生长。本研究旨在评估这种效应是否与肠道微生物组调节有关。我们在中国中医科学院西苑医院进行了一项随机双盲安慰剂对照临床试验。所有患者被随机分配到 QX 组或安慰剂对照组。在1个月的干预前后，我们收集了患者的粪便样本，通过16s rRNA测序方法进行微生物组分析，并收集了血液样本，通过流式细胞术方法分析T淋巴细胞亚群。通过生物信息分析平台进行组间微生物组分析。该研究经西苑医院伦理委员会批准（2016XLA122-1）已在中国临床试验注册中心注册（注册号：ChiCTR2000029599）。所有患者在入组前均同意。我们随机分配了 40 名患者，最终分析了 34 名患者。其中，29%为女性，平均年龄63岁，74%有肝或肺转移。 QX治疗后CD4 T(TH)细胞和CD8 T(TC)细胞计数均增加，其中QX组TH细胞明显多于对照组(737 vs 449，P = .024)。类水平的微生物群落分析显示，对照组中放线菌的比例有所下降，但 QX 治疗后显着增加（0.83% vs 4.7%，P = .017）。 LEfSe分析显示，处理后，QX组样品与颤杆菌属、真杆菌属和毛螺菌科高度相关。 RDA 分析显示，QX 干预后，粪便样本和微生物种类与 TC/TH 细胞计数相关，但不具有统计学意义。属水平热图分析表明，QX 处理后，较高数量的 TH 细胞与 g_Bifidobacteria (coef. -0.76, P = .002)、柯林斯菌 (coef.-0.61, P = .02)、Ruminiclostridium_9 (coef. -0.64, P = .01) 丰度降低显着相关。 QX胶囊可以提高转移性结直肠癌患者的TH细胞水平，并增加肠道抗癌细菌（如放线菌）以及产丁酸细菌（如毛螺菌科）的丰度。这些结果表明QX胶囊可能具有抗肿瘤和增强免疫的双重作用，这两种作用都是由微生物介导的。
Quxie capsule(QX), a TCM compound, had shown benefit on survival outcomes for metastatic colorectal cancer(mCRC) patients and could inhibit tumor growth through immune regulation. This study aimed to evaluate whether such effect is associated with gut microbiome modulation. We conducted a randomized double-blinded placebo controlled clinical trial in Xiyuan Hospital, China Academy of Chinese Medical Sciences. All patients were randomly assigned into QX or placebo control group. Before and after 1-month interventions, we collected patients’ stool samples for microbiome analysis by 16s rRNA sequencing approaches, as well as blood samples to analyze T lymphocyte subsets by flow cytometry methods. Microbiome analysis among groups was done through bioinformation analysis platform. The study had been proved by the ethics committee of Xiyuan Hospital (2016XLA122-1) had been registered on Chinese Clinical Trial Registry (registration number: ChiCTR2000029599). All patients consented before enrollment. We randomly assigned 40 patients and 34 were finally analyzed. Among them, 29% were female, with an average age of 63 years old, and 74% had liver or lung metastasis. Both CD4 T(TH) cell and CD8 T(TC) cell counts increased after QX treatment, while TH cells were significantly more in QX than in control group (737 vs 449, P = .024). Microbiome community analysis on Class level showed that the proportion of Actinobacteria declined in the control group, but significantly increased after QX treatments (0.83% vs 4.7%, P = .017). LEfSe analysis showed that after treatments, samples from QX group were highly related with Oscillibacter, Eubacterium, and Lachnospiraceae. RDA analysis showed that after QX interventions, stool samples and microbiome species had relevance with TC/TH cells counts but were not statistically significant. Heatmap analysis on Genus level revealed that after QX treatments, higher amounts of TH cells were significantly associated with less abundance of g_Bifidobacterium (coef. −0.76, P = .002), Collinsella (coef.−0.61, P = .02), Ruminiclostridium_9 (coef. −0.64, P = .01). QX capsule could enhance TH cells level among mCRC patients and increase the abundance of gut anticancer bacteria such as Actinobacteria as well as butyrate-producing bacteria such as Lachnospiraceae. These results indicated that QX capsule might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome.
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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