Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 ( Secretor ) genotype

Abstract

The FUT2 (Secretor) gene is responsible for the presence of ABO histo-blood group antigens on the gastrointestinal mucosa and in bodily secretions. Individuals lacking a functional copy of FUT2 are known as “nonsecretors” and display an array of differences in susceptibility to infection and disease, including Crohn disease. To determine whether variation in resident microbial communities with respect to FUT2 genotype is a potential factor contributing to susceptibility, we performed 454-based community profiling of the intestinal microbiota in a panel of healthy subjects and Crohn disease patients and determined their genotype for the primary nonsecretor allele in Caucasian populations, W143X (G428A). Consistent with previous studies, we observe significant deviations in the microbial communities of individuals with Crohn disease. Furthermore, the FUT2 genotype explains substantial differences in community composition, diversity, and structure, and we identified several bacterial species displaying disease-by-genotype associations. These findings indicate that alterations in resident microbial communities may in part explain the variety of host susceptibilities surrounding nonsecretor status and that FUT2 is an important genetic factor influencing host–microbial diversity

Dietary history contributes to enterotype-like clustering and functional metagenomic content in the intestinal microbiome of wild mice

“…The 27F-338R primer pair spanning the hypervariable regions V1 and V2 was used for PCR and barcoded pyrosequencing on the 454 GS-FLX platform with Titanium sequencing chemistry, as previously described (2). Sequences were filtered using MOTHUR v1.…”

“…Numerous studies expanded upon these initial observations and identified factors, such as geography, host genetics, diet, and other environmental factors that contribute to interindividual variability in humans (2)(3)(4) and other animals (5-7). However, important questions pertaining to the nature and origins of gut microbial community structure remain to be answered.…”

Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency

“…18,19 In humans, deficiency of FUT2 -which occurs in around 20% of individuals, termed "nonsecretors" -is associated with shifts in microbial composition in the colonic mucosa, feces, and bile. [20][21][22][23] Tsyn deficiency could similarly affect microbial composition by altering nutrient sources and disrupting attachment sites for the intestinal microbiota.…”

Update on primary sclerosing cholangitis

“…how the specific genetic constitution of an individual influences the gut microbial environment is given by the FUT2 association in PSC (and Crohn's disease) [52,53]. Even in healthy individuals, homozygous state for the disease associated variant is associated with substantial alterations in gut microbial community composition [53,54]. The impact of dietary fat on IBD susceptibility represents another example of gene-environment interactions.…”

“…Additional risk loci may be defined by taking a priori knowledge on genetic associations reported in these other phenotypes into account (see [9] for further details). how the specific genetic constitution of an individual influences the gut microbial environment is given by the FUT2 association in PSC (and Crohn's disease) [52,53]. Even in healthy individuals, homozygous state for the disease associated variant is associated with substantial alterations in gut microbial community composition [53,54].…”