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FUT2 deficiency may influence the pathogenesis of inflammatory bowel diseases through gut microbiome
Author(s) -
Cheng Sijing,
Hu Jun,
Wu Xianrui,
Jiao Na,
Li Yichen,
Huang Yibo,
Zhu Ruixin,
Zhi Min,
Zhu Lixin,
Lan Ping
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02866
Subject(s) - pathogenesis , microbiome , ruminococcus , inflammatory bowel disease , ulcerative colitis , gut flora , immunology , biology , medicine , disease , genetics
Background & Aims Non‐functional fucosyltransferase 2 (FUT2) polymorphisms are associated with inflammatory bowel diseases (IBDs). FUT2 is required for the proper production of oligosaccharides and glycoproteins. These free or attached oligosaccharides have a large impact on the gut microbiota. In this study, we investigated the role of the gut microbiota in IBD pathogenesis with FUT2 deficiency. Method We recruited 56 Crohn’s disease (CD) and 25 ulcerative colitis (UC) patients with endoscopically confirmed disease from the IBD clinic in 6th Affiliated Hospital of Sun Yat‐sen University in Guangzhou, China between March 2016 and July 2018. Individuals were asked to provided stool and blood samples respectively. To determine the genotypes of the patients at rs1047781 (A418T) and rs601338 (G461A) of the FUT2 gene, blood DNA was extracted and FUT2 coding sequence was sequenced. For microbiome study, fecal DNA was collected and the V5–V6 region of the 16S rDNA was sequenced with a MiSeq platform. Result The incidence of wild‐type, heterozygous and homozygous non‐functional mutations of FUT2, were found to be 32% (26), 49% (40) and 18% (15), respectively, in IBD patients. Significant structural and functional difference were observed at every taxonomic levels among these three groups. Interestingly, the abundance of butyrate producing Dorea, Coprococcus and Ruminococcus was significantly higher in the group carrying homozygous non‐functional FUT2 than those of the other groups (wild‐type and heterozygous non‐functional FUT2, P<0.05). The PICRUSt functional analysis based on the 16S data showed that several carbohydrate synthesis pathways including UDP‐2,3‐diacetamido‐2,3‐dideoxy‐α‐D‐mannuronate biosynthesis and sucrose biosynthesis pathways were enriched in IBD patients with homozygous non‐functional mutation of FUT2 (P<0.05). Discussion Our results indicated that FUT2 non‐functional mutation was associated with elevated butyrate producing microbiota, which is in concert with elevated gut microbial capacity for carbohydrate production. FUT2 homozygous mutations may lead to the compensatory increase of carbohydrate production, providing fermentation substrate for the production of short‐chain fatty acids by intestinal flora. Our results may provide a theoretical basis for IBD treatment based on microbiome intervention. Support or Funding Information 1.National Natural Science Foundation of China 81774152, 31200986, 41530105, 81770571,81970452. 2.Guangzhou laboratory clinical innovation project 2018GZR0201005. 3.National Postdoctoral Program for Innovative Talents of China BX20190393. 4.Natural Science Foundation of Shanghai 16ZR1449800. 5.the University at Buffalo Community of Excellence in Genome, Environment and Microbiome (GEM).