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肠道微生物群与人类免疫细胞动力学有关。

The gut microbiota is associated with immune cell dynamics in humans.

机构信息

Institute for Computational Medicine, NYU Langone Health, New York, NY, USA.

Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

出版信息

Nature. 2020 Dec;588(7837):303-307. doi: 10.1038/s41586-020-2971-8. Epub 2020 Nov 25.

Abstract

The gut microbiota influences development and homeostasis of the mammalian immune system, and is associated with human inflammatory and immune diseases as well as responses to immunotherapy. Nevertheless, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans, where the difficulty of direct experimentation makes inference challenging. Here we study hundreds of hospitalized-and closely monitored-patients with cancer receiving haematopoietic cell transplantation as they recover from chemotherapy and stem-cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, enabling the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and more than 10,000 longitudinal microbiota samples revealed consistent associations between gut bacteria and immune cell dynamics. High-resolution clinical metadata and Bayesian inference allowed us to compare the effects of bacterial genera in relation to those of immunomodulatory medications, revealing a considerable influence of the gut microbiota-together and over time-on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.

摘要

肠道微生物群影响哺乳动物免疫系统的发育和稳态,与人类炎症和自身免疫性疾病以及对免疫治疗的反应有关。然而,我们对肠道细菌如何调节免疫系统的理解仍然有限,特别是在人类中,由于直接实验的难度使得推断具有挑战性。在这里,我们研究了数百名接受造血细胞移植的住院患者和密切监测的癌症患者,他们在化疗和干细胞移植后正在康复。这种激进的治疗方法导致循环免疫细胞和微生物群的大量转移,使两者之间的关系能够同时研究。对观察到的循环中性粒细胞、淋巴细胞和单核细胞计数的日常变化以及超过 10000 个纵向微生物样本的分析显示,肠道细菌与免疫细胞动力学之间存在一致的关联。高分辨率的临床元数据和贝叶斯推理允许我们比较细菌属的作用与免疫调节药物的作用,揭示了肠道微生物群——以及随着时间的推移——对全身免疫细胞动力学的相当大的影响。我们的分析建立并量化了肠道微生物群与人类免疫系统之间的联系,这对基于微生物群的免疫调节具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/335a/7725892/14bc5a8439c3/nihms-1634150-f0004.jpg

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