FUT1genetic variants impact protein glycosylation of porcine intestinal mucosa

Abstract

A massive use of antibiotics in industrial pig production is a major cause of the rapidly rising bacterial resistance to antibiotics. An enhanced understanding of infectious diseases and of host-microbe interactions has the potential to explore alternative ways to improve pig health and reduce the need for antibiotics. Host-microbe interactions depend on host-expressed glycans and microbe-carrying lectins. In this study, a G > A (nucleotide 307) missense mutation in the porcine α1,2fucosyltransferase 1 gene (FUT1), which has been reported to prevent infections by the common porcine enteric pathogen F18 fimbriated Escherichia coli, provided a unique opportunity to study glycan structures potentially involved in intestinal infections. N- and O-Linked glycans of the intestinal mucosa proteins were characterized in detail using LC-MS/MS. Relative abundances of all glycans were determined and compared between four heterozygous pigs (FUT1-307(A/G)) and four age-matched homozygous pigs from the same 2 litters carrying the missense FUT1 gene constellation (FUT1-307(A/A)). None of the characterized 48 N-linked glycans was found to be regulated by the FUT1 missense mutation, while 11 of the O-linked glycans showed significantly altered abundances between the two genotypes. The overall abundance of H-antigen carrying structures was decreased fivefold, while H-antigen precursors and sialylated structures were relatively more abundant in pigs with the FUT1 missense mutation. These results provide insight into the role of FUT1 on intestinal glycosylation, improve our understanding of how variation in FUT1 can modulate host-microbe interactions, and suggest that the FUT1 genetic variant may help to improve pig gut health.

Variations in porcine colostrum oligosaccharide composition between breeds and in association with sow maternal performance

“…To our knowledge, no study has tested the variability of FUT1 in the porcine mammary gland and we do not know if it is relevant for free OS composition in addition to O-glycans. Nevertheless, the hypothesis that different frequencies of detection of FL in different breeds could be associated with FUT1 variability is worth further consideration [25]. LNDFH was identified to deter the adhesion of several strains of norovirus in humans [26], a cause of diarrhoea in infants.…”

Effect of Mucine 4 and Fucosyltransferase 1 genetic variants on gut homoeostasis of growing healthy pigs

“…The mutation on FUT1 leads to a higher expression of FUT1 and FUT2 and an increase in the activity of the enzyme in FUT1 GG pigs. This biological mechanism results in a different level of glycosylation on the protein structure of porcine ileum mucosa (Hesselager et al, ). In accordance with the immunohistochemistry observations of Coddens et al (), our work showed that the FUT1 AA had a lower immunoreactivity score for UEA than FUT1 AG and FUT1 GG and an opposite response for the PNA immunoreactivity both in brush border and goblet cell.…”

“…Studies suggested that MUC4 and FUT1 genotypes are not only associated with piglets susceptibility to PWD but can also influence the intestinal homoeostasis. For instance, healthy piglets with different MUC4 and FUT1 genotypes are known to differ for their intestinal microbial profile ( MUC4 , Messori, Trevisi, Simongiovanni, Priori, & Bosi, ; FUT1 , Poulsen et al, ) and for their intestinal protein glycosylation (Hesselager, Everest‐Dass, Thaysen‐Andersen, Bendixen, & Packer, ). Furthermore, the intestinal mucosa of piglets with the susceptible genotype ( MUC4 CG/GG ) had an up‐regulation of genes related to antimicrobial peptide and immune function such as lipopolysaccharide binding protein ( LBPI ) and regenerating islet‐derived 3 gamma ( REG3G) compared to pigs with a resistant genotype (Trevisi et al, ).…”

Effects of alpha-(1,2)-fucosyltransferase genotype variants on plasma metabolome, immune responses and gastrointestinal bacterial enumeration of pigs pre- and post-weaning

“…The fucosylation of carbohydrate structures expressed on cell surfaces of the gut by glycoproteins, glycolipids, and proteoglycans have been associated with biological processes such as inflammation, host–pathogen interactions, and tumor metastasis [ 11 , 12 ]. A recent study by Hesselager et al (2016) showed that there are significant differences in the O-linked glycans of the intestinal mucosal proteins between FUT1 AA and FUT1 AG pigs [ 13 ]. The FUT1 AG lead a higher level of O-glycan structures that were fucosylated to show H-antigens [ 13 ].…”