The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD
The microbe-derived short-chain fatty acids butyrate and propionate are associated with protection from chronic GVHD
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DOI：
10.1182/blood.2019003369
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发表时间：
2020-07-02
期刊：
影响因子：
20.3
通讯作者：
van den Brink, Marcel R. M.
中科院分区：
文献类型：
--
作者：
Markey, Kate A.;Schluter, Jonas;van den Brink, Marcel R. M.
胃肠道菌群与异基因造血干细胞移植（allo-HCT）结果之间关系的研究迄今主要集中在早期并发症，主要是感染和急性移植物抗宿主病（GVHD）。我们使用病例对照研究设计，通过分析allo-HCT后后期收集的粪便和血浆样本，研究了微生物组与慢性GVHD（cGVHD）的潜在关系。我们发现，在移植患者的初始病例对照队列和来自独立移植中心的进一步横断面队列中，与未发生cGVHD的患者相比，发生cGVHD的患者第100天血浆样本中微生物源性短链脂肪酸（SCFA）丙酸盐和丁酸盐的循环浓度较低。分析了来自第三家移植中心的额外横断面患者队列;然而，血清（而非血浆）可用，并且未概括血浆样本中观察到的SCFA差异。总之，我们对主要病例对照队列和2个横断面队列中的1个队列的研究结果表明，胃肠道微生物组可能在allo-HCT患者中发挥免疫调节作用，至少部分原因是控制了微生物源性SCFA的全身浓度。
Studies of the relationship between the gastrointestinal microbiota and outcomes in allogeneic hematopoietic stem cell transplantation (allo-HCT) have thus far largely focused on early complications, predominantly infection and acute graft-versus-host disease (GVHD). We examined the potential relationship of the microbiome with chronic GVHD (cGVHD) by analyzing stool and plasma samples collected late after allo-HCT using a case-control study design. We found lower circulating concentrations of the microbe-derived short-chain fatty acids (SCFAs) propionate and butyrate in day 100 plasma samples from patients who developed cGVHD, compared with those who remained free of this complication, in the initial case-control cohort of transplant pa-tients and in a further cross-sectional cohort from an independent transplant center. An additional cross-sectional patient cohort from a third transplant center was analyzed; however, serum (rather than plasma) was available, and the differences in SCFAs observed in the plasma samples were not recapitulated. In sum, our findings from the primary case-control cohort and 1 of 2 cross-sectional cohorts explored suggest that the gastrointestinal microbiome may exert immuno-modulatory effects in allo-HCT patients at least in part due to control of systemic concentrations of microbe-derived SCFAs.