Altered gut microbiome in FUT2 loss-of-function mutants in support of personalized medicine for inflammatory bowel diseases
Altered gut microbiome in FUT2 loss-of-function mutants in support of personalized medicine for inflammatory bowel diseases
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DOI：
10.1016/j.jgg.2021.08.003
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发表时间：
2021-09-01
影响因子：
5.9
通讯作者：
Lan, Ping
中科院分区：
文献类型：
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作者：
Cheng, Sijing;Hu, Jun;Lan, Ping
FUT2功能丧失突变非常普遍，与炎症性肠病（IBD）相关。为了研究FUT2功能缺失突变对IBD患者肠道微生物群的影响，对81例经内镜检查确诊的IBD患者进行基因分型，并将其分为3组：功能性FUT2基因纯合（SeSe）、具有一个非功能性FUT2基因拷贝（Sese）或非功能性FUT2基因纯合（Sese）。大肠埃希氏菌，附着于岩藻糖基化糖复合物，是唯一的丰富的属，在sese患者中表现出丰度下降。与SeSe或Sese患者相比，Sese患者在诱导Alistipe和Phascolarctobacterium的CD8（+）和诱导丹毒丝菌科UCG-003的Th17中表现出更高的丰度。与直觉相反的是，产丁酸菌在sese患者中更丰富。同样，代谢组学分析发现sese患者的丁酸水平较高。我们的数据支持FUT2功能丧失突变通过减少粘附细菌的结合位点从而改变肠道微生物群参与IBD发病机制的假设。粘附细菌的丰度降低可能允许诱导炎性T细胞的细菌过度生长，导致肠道炎症。由于FUT2功能缺失突变非常普遍，因此在这些患者中鉴定T细胞诱导细菌对于IBD的个性化微生物干预的发展可能是有价值的。中国科学院遗传与发育生物学研究所版权所有（C）2021由爱思唯尔有限公司和科学出版社出版。All rights reserved.
The FUT2 loss-of-function mutations are highly prevalent and are associated with inflammatory bowel disease (IBD). To investigate the impact of FUT2 loss-of-function mutation on the gut microbiota in patients with IBD, 81 endoscopically confirmed IBD patients were genotyped and divided into 3 groups: homozygous for functional FUT2 genes (SeSe), with one copy of non-functional FUT2 gene (Sese), or homozygous for non-functional FUT2 genes (sese). Escherichia, which attaches to fucosylated glycoconjugates, was the only abundant genus exhibiting decreased abundance in sese patients. Compared with SeSe or Sese patients, sese patients exhibited higher abundance in CD8(+) inducing Alistipe and Phascolarctobacterium and Th17 inducing Erysipelotrichaceae UCG-003. Counter-intuitively, butyrate-producing bacteria were more abundant in sese patients. Consistently, metabolomics analysis found higher levels of butyrate in sese patients. Our data support the hypothesis that FUT2 loss-of-function mutation participates in the IBD pathogenesis by decreasing binding sites for adherent bacteria and thus altering the gut microbiota. Decreased abundances of adherent bacteria may allow the overgrowth of bacteria that induce inflammatory T cells, leading to intestinal inflammation. As FUT2 loss-of-function mutations are highly prevalent, the identification of T cell inducing bacteria in sese patients could be valuable for the development of personalized microbial intervention for IBD. Copyright (C) 2021, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.