Gut microbiome, metabolites, and tissue metabolism in graft-versus-host disease
Gut microbiome, metabolites, and tissue metabolism in graft-versus-host disease
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移植物抗宿主病中的肠道微生物组、代谢物和组织代谢
DOI：
10.11406/rinketsu.63.286
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Fujiwara Hideaki
中科院分区：
文献类型：
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作者：
Suzuki Junya;Shimizu Yuuki;Hayashi Takumi;Che Yiyang;Pu Zhongyue;Tsuzuki Kazuhito;Narita Shingo;Shibata Rei;Ishii Isao;Calvert John W.;Murohara Toyoaki;Fujiwara Hideaki
免疫反应不仅促进移植物抗肿瘤事件，而且促进以T细胞和抗原呈递细胞活化为特征的移植物抗宿主病（GVHD）。近年来的研究揭示了微生物植物群在GVHD中的作用，提出了免疫细胞以外的机制。组织内源性因子的作用有助于靶组织的恢复、修复和再生，并在不改变同种异体反应性免疫细胞的情况下减轻GVHD的严重程度。抗生素、特定细菌和低微生物群多样性被确定为GVHD和死亡率的风险因素。目前的焦点已经转移到GVHD的靶组织稳态。大多数肠道微生物群共生地定居在肠道中，这种稳态在胃肠道中得到很好的调节，胃肠道具有由厌氧生物主导的相对缺氧的环境。因此，肠上皮细胞（IEC）是唯一适应这种缺氧环境，并通过“生理性缺氧”编程的细胞调节与肠道细菌的屏障功能。allo-HCT后IEC的代谢变化可影响肠道环境，导致生态失调。本文综述了在移植物抗宿主病环境中，微生物群和微生物代谢产物在IEC代谢中的作用，以促进组织耐受性。
Immune reactions promote not only graft-versus-tumor events but also graft-versus-host disease (GVHD) characterized by the activation of T-cells and antigen-presenting cells. Recent studies have unveiled the effects of microbial flora on GVHD and brought the mechanism other than immune cells. The role of tissue-intrinsic factors contributes to target-tissue resilience, repair, and regeneration and mitigates the severity of GVHD without altering alloreactive immune cells. Antibiotics, specific bacteria, and low microbiota diversity are identified as risk factors for GVHD and mortality. The current focus has shifted to target-tissue homeostasis in GVHD. Most of the gut microbiota symbiotically colonize the gut, and this homeostasis is finely tuned in the gastrointestinal tract, which has a relatively hypoxic environment dominated by anaerobic organisms. Therefore, intestinal epithelial cells (IECs) are uniquely adapted to this hypoxic environment, and cells programmed by" physiological hypoxia" tonally regulate barrier function with commensal bacteria. Metabolic changes in IECs post allo-HCT can affect the gut environment, leading to dysbiosis. This review focuses on the role of metabolism in IECs with microbiota and microbial metabolites in the GVHD setting to promote tissue tolerance.