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.

Fig. 1.

Distribution of the major phyla with respect to disease status and genotype (error bars indicate SD). The corresponding results of the statistical analyses are presented in Table S2. CON, control.

Fig. 2.

Ordination of individuals using CCA of disease status and its interaction with genotype, conditioned by the factors age and sex. The ordination includes only nonredundant factors that were validated by variance inflation scores ranging between 1.1 and 3.6. Only axes that significantly contribute to the explained variance (expl. var.) are displayed (CCA1: expl. var. = 3.34%, P = 0.007; CCA2: expl. var. = 2.66%, P = 0.03; CCA3: expl. var. = 2.44%, P = 0.171; CCA4: expl. var. = 2.19%, P = 0.476; CCA5: expl. var. = 1.76%, P = 0.944).

Fig. 3.

Abundance of species-level OTUs identified by indicator species analysis with respect to genotype within disease status. Numbers in parentheses indicate the total read number in the normalized dataset (1,000 reads per individual).