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

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          Abstract

          In pigs, the alpha-(1,2) fucosyltransferase ( FUT1) gene has been highlighted for its properties in controlling the intestinal expression of enterotoxigenic E. coli (ETEC) F18 receptors; a pathogen causing edema disease and post-weaning diarrhoea. In this study, we hypothesized that pigs with different genotypes (ETEC F18 resistant ( FUT1 AA) versus susceptible ( FUT1 AG)) differed in following systemic and enteric responses: growth performance, plasma metabolic profiles, expression of candidate genes for intestinal mucosal homeostasis and immunity, number of selected bacteria and the concentration of short-chain fatty acids (SCFA) in faeces and digesta in piglets pre and post-weaning, and on the ETEC F18 adherence ex vivo. Genotype had the strongest impact on plasma metabolomic profile on day 7 and 28 of age. FUT1 AG piglets had higher level of N-methyl-2-pyrrolidinone, hippuric acid, oxindole, and 3-oxo-5-beta-chol-7-en-24-oic acid on day 7, and a higher level of guanosine on day 28 than that in the FUT1 AA piglets. FUT1 AA piglets had a higher level of betaine on day 7 and 3-methylguanine on day 28. On day 34 of age, the FUT1 AA pigs had higher levels of S-2-hydroxyglutarate, L-phenylalanine, tauroursodeoxycholic acid and an undetermined PC/LysoPC, while Ile Glu Phe Gly peptide and genistein 5-O-glucuronide, and PC (18:0/0:0) were at higher levels in the FUT1 AG piglets. FUT1 genotype did not affect the growth performance and expression of candidate genes. FUT1 AG piglets had a higher number of haemolytic bacteria in faeces and in digesta than that in FUT1 AA at 34 days of age. The colonic acetic acid concentration was highest in FUT1 AG piglets. FUT1 genotype may influence not only the expression of E. coli F18 receptors but could potentially impact the gut homeostasis and metabotype of piglets pre and post-weaning. Further investigations on the relation between FUT1 genotype and these aspects including the intestinal commensal microbiota will expand the knowledge on factors affecting the intestinal ecosystem.

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          Mucins in cancer: protection and control of the cell surface.

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            Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases.

            Abnormal host-microbe interactions are implicated in the pathogenesis of inflammatory bowel diseases. Previous 16S rRNA sequence analysis of intestinal tissues demonstrated that a subset of Crohn's disease (CD) and ulcerative colitis (UC) samples exhibited altered intestinal-associated microbial compositions characterized by depletion of Bacteroidetes and Firmicutes (particularly Clostridium taxa). We hypothesize that NOD2 and ATG16L1 risk alleles may be associated with these alterations. To test this hypothesis, we genotyped 178 specimens collected from 35 CD, 35 UC, and 54 control patients for the three major NOD2 risk alleles (Leu 1007fs, R702W, and G908R) and the ATG16L1T300A risk allele, that had undergone previous 16S rRNA sequence analysis. Our statistical models incorporated the following independent variables: 1) disease phenotype (CD, UC, non-IBD control); 2) NOD2 composite genotype (NOD2(R) = at least one risk allele, NOD2(NR) = no risk alleles); 3) ATG16L1T300A genotype (ATG16L1(R/R), ATG16L1(R/NR), ATG16L1(NR/NR)); 4) patient age at time of surgery and all first-order interactions. The dependent variable(s) were the relative frequencies of bacterial taxa classified by applying the RDP 2.1 classifier to previously reported 16S rRNA sequence data. Disease phenotype, NOD2 composite genotype and ATG16L1 genotype were significantly associated with shifts in microbial compositions by nonparametric multivariate analysis of covariance (MANCOVA). Shifts in the relative frequencies of Faecalibacterium and Escherichia taxa were significantly associated with disease phenotype by nonparametric ANCOVA. These results support the concept that disease phenotype and genotype are associated with compositional changes in intestinal-associated microbiota. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.
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              Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness

              Systemic infection induces conserved physiological responses that include both resistance and ‘tolerance of infection’ mechanisms 1 . Temporary anorexia associated with an infection is often beneficial 2,3 reallocating energy from food foraging towards resistance to infection 4 or depriving pathogens of nutrients 5 . It imposes, however, a stress on intestinal commensals, as they also experience reduced substrate availability and impacting host fitness due to the loss of caloric intake and colonization resistance (protection from additional infections) 6 . We hypothesized that the host might utilize internal resources to support the gut microbiota during the acute phase of the disease. Here we show that systemic exposure to Toll-like receptor (TLR) ligands causes rapid α1,2-fucosylation of the small intestine epithelial cells (IEC), which requires sensing of TLR agonists and production of IL-23 by dendritic cells, activation of innate lymphoid cells and expression of α1,2-Fucosyltransferase-2 (Fut2) by IL-22-stimulated IECs. Fucosylated proteins are shed into the lumen and fucose is liberated and metabolized by the gut microbiota, as shown by reporter bacteria and community-wide analysis of microbial gene expression. Fucose affects the expression of microbial metabolic pathways and reduces the expression of bacterial virulence genes. It also improves host tolerance of the mild pathogen Citrobacter rodentium. Thus, rapid IEC fucosylation appears to be a protective mechanism that utilizes the host's resources to maintain host-microbial interactions during pathogen-induced stress.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Writing – original draft
                Role: Formal analysis
                Role: Formal analysis
                Role: ConceptualizationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                27 August 2018
                2018
                : 13
                : 8
                : e0202970
                Affiliations
                [1 ] Aarhus University, Faculty of Science and Technology, Department of Animal Science, Tjele, Denmark
                [2 ] Department of Agricultural and Food Sciences (DISTAL), Alma Mater Studiorum—University of Bologna, Bologna, Italy
                [3 ] Diponegoro University, Faculty of Animal and Agricultural Sciences, Semarang, Central Java, Indonesia
                National Cancer Institute, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-7864-7822
                Article
                PONE-D-17-38620
                10.1371/journal.pone.0202970
                6110508
                30148866
                062165c4-eebf-4092-9388-f6f724a2b18c
                © 2018 Riis Poulsen et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 October 2017
                : 13 August 2018
                Page count
                Figures: 2, Tables: 5, Pages: 19
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100007605, Aarhus Universitet;
                Award Recipient :
                Funding for the experimental work and paper drafting was made possible through a Ph.D.-scholarship obtained from the Graduate School of Science and Technology, Aarhus University, Denmark, for main author Ann-Sofie Riis Poulsen, and a Short Term Scientific Mission grant for main author Diana Luise from the COST Action FA1401 (PiGutNet), supported by COST (European Cooperation in Science and Technology). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Swine
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolomics
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Colon
                Medicine and Health Sciences
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                Digestive System
                Gastrointestinal Tract
                Colon
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Metabolites
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Small Intestine
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Small Intestine
                Biology and Life Sciences
                Genetics
                Gene Expression
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Stomach
                Medicine and Health Sciences
                Anatomy
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                Gastrointestinal Tract
                Stomach
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                All relevant data are within the manuscript and its Supporting Information files.

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