AUTHOR=Hao Sijia , Fan Qingjie , Bai Yaqiang , Fang Hui , Zhou Jiaorui , Fukuda Tomohiko , Gu Jianguo , Li Ming , Li Wenzhe 

TITLE=Core Fucosylation of Intestinal Epithelial Cells Protects Against Salmonella Typhi Infection via Up-Regulating the Biological Antagonism of Intestinal Microbiota

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01097

DOI=10.3389/fmicb.2020.01097

ISSN=1664-302X

ABSTRACT=<p>The fucosylated carbohydrate moieties on intestinal epithelial cells (IECs) are involved in the creation of an environmental niche for commensal and pathogenic bacteria. Core fucosylation catalyzed by fucosyltransferase 8 (Fut8) is the major fucosylation pattern on the <italic>N</italic>-glycans of the surface glycoproteins on IECs, however, the role of IECs core fucosylation during infection remains unclear. This study was conducted to investigate the interaction between IECs core fucosylation and gut microbiota, and the effects of this interaction on protecting <italic>Salmonella enterica</italic> subsp. <italic>enterica</italic> serovar Typhi (<italic>S.</italic> Typhi) infection. Firstly, the <italic>Fut8</italic><sup>+/+</sup> and <italic>Fut8</italic><sup>+/–</sup> mice were infected with <italic>S.</italic> Typhi. The level of IECs core fucosylation and protein expression of intestinal mucosa were then detected by LCA blot and Western blot, respectively. The gut microbiota of <italic>Fut8</italic><sup>+/+</sup> and <italic>Fut8</italic><sup>+/–</sup> mice before and after <italic>S.</italic> Typhi infection was assessed by 16S rRNA sequencing. Our results showed that core fucosylation was ubiquitous expressed on the intestinal mucosa of mice and had significant effects on their gut microbiota. Fut8<sup>+/–</sup> mice was more susceptive to <italic>S.</italic> Typhi infection than Fut8<sup>+/+</sup> mice. Interestingly, infection of <italic>S.</italic> Typhi upregulated the core fucosylation level of IECs and increased the abundances of beneficial microorganisms such as <italic>Lactobacillus</italic> and <italic>Akkermansia</italic> spp. Further <italic>in vitro</italic> and <italic>in vivo</italic> studies demonstrated that Wnt/β-catenin signaling pathway mediated the elevation of IECs core fucosylation level upon infection of <italic>S.</italic> Typhi. Taken together, our data in this study revealed that the IECs core fucosylation plays an important role in protecting against <italic>S.</italic> Typhi infection via up-regulating the biological antagonism of intestinal microbiota.</p>