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宿主-微生物相互作用及其在多发性骨髓瘤和造血干细胞移植中的结果。

Host-microbe interactions and outcomes in multiple myeloma and hematopoietic stem cell transplantation.

机构信息

Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA.

Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI, USA.

出版信息

Cancer Metastasis Rev. 2022 Jun;41(2):367-382. doi: 10.1007/s10555-022-10033-7. Epub 2022 Apr 29.

Abstract

Microbiota are essential to normal immune development and there is growing recognition of its importance to human health and disease and deepening understanding of the complexity of host-microbe interactions in the human gut and other tissues. Commensal microbes not only can influence host immunity locally through impacts of bioactive microbial metabolites and direct interactions with epithelial cells and innate immune receptors but also can exert systemic immunomodulatory effects via impacts on host immune cells capable of trafficking beyond the gut. Emerging data suggest microbiota influence the development of multiple myeloma (MM), a malignancy of the immune system derived from immunoglobulin-producing bone marrow plasma cells, through the promotion of inflammation. Superior treatment outcomes for MM correlate with a higher abundance of commensal microbiota capable of influencing inflammatory responses through the production of butyrate. In patients with hematologic malignancies, higher levels of diversity of the gut microbiota correlate with superior outcomes after hematopoietic stem cell transplantation. Correlative data support the impact of commensal microbiota on survival, risk of infection, disease relapse, and graft-versus-host disease (GVHD) after transplant. In this review, we will discuss the current understanding of the role of host-microbe interactions and the inflammatory tumor microenvironment of multiple myeloma, discuss data describing the key role of microbiota in hematopoietic stem cell transplantation for treatment of hematologic malignancies, and highlight several possible concepts for interventions directed at the gut microbiota to influence treatment outcomes.

摘要

微生物组对于正常的免疫发育至关重要,人们越来越认识到其对人类健康和疾病的重要性,并且深入了解了宿主-微生物在人类肠道和其他组织中的相互作用的复杂性。共生微生物不仅可以通过生物活性微生物代谢产物的影响以及与上皮细胞和先天免疫受体的直接相互作用,对局部宿主免疫产生影响,还可以通过对能够在肠道以外迁移的宿主免疫细胞的影响,发挥全身免疫调节作用。新出现的数据表明,微生物组通过促进炎症,影响多发性骨髓瘤(MM)的发展,MM 是一种源自产生免疫球蛋白的骨髓浆细胞的免疫系统恶性肿瘤。MM 的治疗结果更好与能够通过产生丁酸盐影响炎症反应的共生微生物丰度更高相关。在血液恶性肿瘤患者中,肠道微生物组多样性水平较高与造血干细胞移植后更好的结果相关。相关数据支持共生微生物组对移植后生存、感染风险、疾病复发和移植物抗宿主病(GVHD)的影响。在这篇综述中,我们将讨论宿主-微生物相互作用和多发性骨髓瘤炎症肿瘤微环境的作用的现有认识,讨论描述微生物组在血液恶性肿瘤的造血干细胞移植治疗中的关键作用的数据,并强调几个可能的针对肠道微生物组的干预概念,以影响治疗结果。

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