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キーワード:
B4galnt2; blood group; glycosylation; intestine; microbiota; mouse
要旨:
Glycans on mucosal surfaces have an important role in host–microbe interactions. The locus
encoding the blood-group-related glycosyltransferase b-1,4-N-acetylgalactosaminyltransferase 2
(B4galnt2) is subject to strong selective forces in natural house-mouse populations that contain a
common allelic variant that confers loss of B4galnt2 gene expression in the gastrointestinal (GI)
tract. We reasoned that altered glycan-dependent intestinal host–microbe interactions may underlie
these signatures of selection. To determine whether B4galnt2 influences the intestinal microbial
ecology, we profiled the microbiota of wild-type and B4galnt2-deficient siblings throughout the GI
tract using 16S rRNA gene pyrosequencing. This revealed both distinct communities at different
anatomic sites and significant changes in composition with respect to genotype, indicating a
previously unappreciated role of B4galnt2 in host–microbial homeostasis. Among the numerous
B4galnt2-dependent differences identified in the abundance of specific bacterial taxa, we
unexpectedly detected a difference in the pathogenic genus, Helicobacter, suggesting Helicobacter
spp. also interact with B4galnt2 glycans. In contrast to other glycosyltransferases, we found that the
host intestinal B4galnt2 expression is not dependent on presence of the microbiota. Given the longterm
maintenance of alleles influencing B4galnt2 expression by natural selection and the GI
phenotypes presented here, we suggest that variation in B4galnt2 GI expression may alter
susceptibility to GI diseases such as infectious gastroenteritis.
