Altered gut microbiome in FUT2 loss-of-function mutants in support of personalized medicine for inflammatory bowel diseases

Sijing Cheng; Jun Hu; Xianrui Wu; Ji-An Pan; Na Jiao; Yichen Li; Yibo Huang; Xutao Lin; Yifeng Zou; Yuan Chen; Lixin Zhu; Min Zhi; Ping Lan

doi:10.1016/j.jgg.2021.08.003

Volume 48 Issue 9

Sep. 2021

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Article Navigation > Journal of Genetics and Genomics > 2021 > 48(9): 771-780

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Altered gut microbiome in FUT2 loss-of-function mutants in support of personalized medicine for inflammatory bowel diseases

doi: 10.1016/j.jgg.2021.08.003

a. Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China;
b. School of Medicine, Sun Yat-sen University, Shenzhen 510080, China;
c. Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China

Funds:

The authors thank Dr. Lishuo Shi (the Clinical Research Center, the Sixth Affiliated Hospital of Sun Yat-Sen University) for providing valuable advices on statistical analysis. This work was supported by Guangdong Province "Pearl River Talent Plan" Innovation and Entrepreneurship Team Project 2019ZT08Y464 (to L.Z.), the National Natural Science Foundation of China 81770571 (to L.Z.), 82000536 (to N.J.), National Postdoctoral Program for Innovative Talents of China BX20190393 (to N.J.), China Postdoctoral Science Foundation 2019M663252 (to N.J.), Fundamental Research Funds for the Central Universities 19ykzd01 (to L.Z.), and 20kypy07 (to N.J.).

Received Date: 2021-07-18
Accepted Date: 2021-08-05
Rev Recd Date: 2021-08-03
Publish Date: 2021-08-20

Abstract

Abstract

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.
- FUT2,
- Inflammatory bowel diseases,
- Crohn's disease,
- Ulcerative colitis,
- Secretor

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References(51)

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