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Kathya Gutiérrez-Huante, Roberta Salinas-Marín, Héctor M Mora Montes, Ramón A Gonzalez, Iván Martínez-Duncker
Certain viral infections are known to modify the glycosylation profile of infected cells through the overexpression of specific host cell fucosyltransferases (FUTs). Infection with CMV (cytomegalovirus), HCV (hepatitis C virus), HSV-1 (herpes simplex virus type-1) and VZV (varicella-zoster virus) increase the expression of fucosylated epitopes, including antigens sLex (Siaα2-3 Galβ1-4(Fucα1-3)GlcNAcβ1-R) and Ley (Fucα1-2 Galβ1-4(Fucα1-3)GlcNAcβ1-R). The reorganization of the glycocalyx induced by viral infection may favor the spread of viral progeny, and alter diverse biological functions mediated by glycans, including recognition by the adaptive immune system...
March 14, 2019: Glycobiology
Norbert Sprenger, Aristea Binia, Sean Austin
Human milk oligosaccharides (HMOs) are elongations of the milk sugar lactose by galactose, N-acetylglucosamine, fucose; and sialic acid. The HMO composition of breast milk is strongly influenced by polymorphisms of the maternal fucosyltransferases, FUT2 and FUT3, and by the stage of lactation. Clinical observational studies with breastfed infant-mother dyads associate specific HMOs with infant gut microbiota, morbidity, infectious diarrhea, and allergies. Observational and basic research data suggest that HMOs influence the establishment of early-life microbiota and mucosal immunity and inhibit pathogens, thereby contributing to protection from infections...
2019: Nestlé Nutrition Institute Workshop Series
Tai-Yu Lai, I-Ju Chen, Ruey-Jen Lin, Guo-Shiou Liao, Hui-Ling Yeo, Ching-Liang Ho, Jen-Chine Wu, Nai-Chuan Chang, Andy Chi-Lung Lee, Alice L Yu
FUT1 and FUT2 encode alpha 1, 2-fucosyltransferases which catalyze the addition of alpha 1, 2-linked fucose to glycans. Glycan products of FUT1 and FUT2, such as Globo H and Lewis Y, are highly expressed on malignant tissues, including breast cancer. Herein, we investigated the roles of FUT1 and FUT2 in breast cancer. Silencing of FUT1 or FUT2 by shRNAs inhibited cell proliferation in vitro and tumorigenicity in mice. This was associated with diminished properties of cancer stem cell (CSC), including mammosphere formation and CSC marker both in vitro and in xenografts...
2019: Cell Death Discovery
Johan Nordgren, Lennart Svensson
Noroviruses are the most common etiological agent of acute gastroenteritis worldwide. Despite their high infectivity, a subpopulation of individuals is resistant to infection and disease. This susceptibility is norovirus genotype-dependent and is largely mediated by the presence or absence of human histo-blood group antigens (HBGAs) on gut epithelial surfaces. The synthesis of these HBGAs is mediated by fucosyl- and glycosyltransferases under the genetic control of the FUT2 (secretor), FUT3 (Lewis) and ABO(H) genes...
March 6, 2019: Viruses
Marcia Terezinha Baroni de Moraes, Alberto Ignácio Olivares Olivares, Alexandre Madi Fialho, Fábio Correia Malta, Sergio da Silva E Mouta Junior, Romanul de Souza Bispo, Alvaro Jorge Velloso, Gabriel Azevedo Leitão, Carina Pacheco Cantelli, Johan Nordgren, Lennart Svenson, Marize Pereira Miagostovich, José Paulo Gagliardi Leite
The Histo-blood group antigens (HBGA) are host genetic factors associated with susceptibility to rotavirus (RV) and human norovirus (HuNoV), the major etiological agents of viral acute gastroenteritis (AGE) worldwide. The FUT2 gene expressing the alpha-1, 2-L- fucosyltransferase enzyme is important for gut HBGA expression, and also provides a composition of the phenotypic profile achieved through mutations occurring in populations with different evolutionary histories; as such, it can be considered a genetic population marker...
February 18, 2019: Infection, Genetics and Evolution
Josh M Colston, Ruthly Francois, Nora Pisanic, Pablo Peñataro Yori, Benjamin J J McCormick, Maribel Paredes Olortegui, Md Amran Gazi, Erling Svensen, Mondar Maruf Moin Ahmed, Esto Mduma, Jie Liu, Eric R Houpt, Robert Klapheke, Julia W Schwarz, Robert L Atmar, Robert E Black, Margaret N Kosek
BACKGROUND: Histo blood group antigens (HBGAs) such as fucosyltransferase FUT2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their offspring to pediatric enteric infections. METHODS: In three community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. qPCR panels tested 3,663 diarrheal and 18,148 asymptomatic stool samples for 29 enteropathogens. Cumulative diarrhea and infection incidence were compared by child (n=520) and mothers' (n=519) HBGA status and hazard ratios (HRs) derived for all-cause diarrhea and specific enteropathogens...
February 15, 2019: Journal of Infectious Diseases
João Piedade, Johan Nordgren, Filipa Esteves, Aida Esteves, Rosa Teodósio, Lennart Svensson, Claudia Istrate
Norovirus (NoV) and rotavirus group A (RVA) are major agents of acute gastroenteritis worldwide. This study aimed to investigate their epidemiological profile in Portuguese elderly living in long-term care facilities and to assess the host genetic factors mediating infection susceptibility. From November 2013 to June 2015, 636 faecal specimens from 169 elderly, mainly asymptomatic, living in nursing homes in Greater Lisbon and Faro district, Portugal, were collected. NoV and RVA were detected by real-time PCR and NoV genotyped by phylogenetic analysis...
February 8, 2019: Journal of Medical Virology
Yaqiang Bai, Jia Tao, Jiaorui Zhou, Qingjie Fan, Man Liu, Yuqi Hu, Yao Xu, Lilong Zhang, Jieli Yuan, Wenzhe Li, Xiaolei Ze, Patrice Malard, Zhimou Guo, Jingyu Yan, Ming Li
The milk glycobiome has a significant impact on the gut microbiota of infants, which plays a pivotal role in health and development. Fucosylated human milk oligosaccharides (HMOs) and N-glycans on milk proteins are beneficial for the development of healthy gut microbiota, and the fucosylation levels of these glycans can be affected by the maternal fucosyltransferase 2 gene ( FUT2 ). Here, we present results of longitudinal research on paired milk and stool samples from 56 Chinese mothers (CMs) and their breast-fed children...
November 2018: MSystems
Jovanka R King, Jezabel Varadé, Lennart Hammarström
Background: Single-nucleotide polymorphisms (SNPs) in the fucosyltransferase genes FUT2 and FUT3 have been associated with susceptibility to various infectious and inflammatory disorders. FUT variations influence the expression of human histo-blood group antigens (HBGAs) (H-type 1 and Lewis), which are highly expressed in the gut and play an important role in microbial attachment, metabolism, colonization, and shaping of the microbiome. In particular, FUT polymorphisms confer susceptibility to specific rotavirus and norovirus genotypes, which has important global health implications...
December 9, 2018: Journal of the Pediatric Infectious Diseases Society
Raul Cabrera-Rubio, Clemens Kunz, Silvia Rudloff, Izaskun García-Mantrana, Elena Crehuá-Gaudiza, Cecilia Martínez-Costa, M Carmen Collado
BACKGROUND AND OBJECTIVES: Breast milk contains several bioactive factors including human milk oligosaccharides (HMOs) and microbes that shape the infant gut microbiota. HMO profile is determined by secretor status; however, their influence on milk microbiota is still uncovered. This study is aimed to determine the impact of the FUT2 genotype on the milk microbiota during the first month of lactation and the association with HMO. METHODS: Milk microbiota from 25 healthy lactating women was determined by quantitative polymerase chain reaction and 16S gene pyrosequencing...
February 2019: Journal of Pediatric Gastroenterology and Nutrition
Regie Lyn P Santos-Cortez, Charlotte M Chiong, Daniel N Frank, Allen F Ryan, Arnaud P J Giese, Tori Bootpetch Roberts, Kathleen A Daly, Matthew J Steritz, Wasyl Szeremeta, Melquiadesa Pedro, Harold Pine, Talitha Karisse L Yarza, Melissa A Scholes, Erasmo Gonzalo D V Llanes, Saira Yousaf, Norman Friedman, Ma Leah C Tantoco, Todd M Wine, Patrick John Labra, Jeanne Benoit, Amanda G Ruiz, Rhodieleen Anne R de la Cruz, Christopher Greenlee, Ayesha Yousaf, Jonathan Cardwell, Rachelle Marie A Nonato, Dylan Ray, Kimberly Mae C Ong, Edward So, Charles E Robertson, Jordyn Dinwiddie, Sheryl Mae Lagrana-Villagracia, Samuel P Gubbels, Rehan S Shaikh, Stephen P Cass, Elisabet Einarsdottir, Nanette R Lee, David A Schwartz, Teresa Luisa I Gloria-Cruz, Michael J Bamshad, Ivana V Yang, Juha Kere, Generoso T Abes, Jeremy D Prager, Saima Riazuddin, Abner L Chan, Patricia J Yoon, Deborah A Nickerson, Eva Maria Cutiongco-de la Paz, Sven-Olrik Streubel, Maria Rina T Reyes-Quintos, Herman A Jenkins, Petri Mattila, Kenny H Chan, Karen L Mohlke, Suzanne M Leal, Lena Hafrén, Tasnee Chonmaitree, Michele M Sale, Zubair M Ahmed
Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗ ) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p...
November 1, 2018: American Journal of Human Genetics
Sheila J Barton, Robert Murray, Karen A Lillycrop, Hazel M Inskip, Nicholas C Harvey, Cyrus Cooper, Neerja Karnani, Irma Silva Zolezzi, Norbert Sprenger, Keith M Godfrey, Aristea Binia
Background: Fucosyltransferase 2 (FUT2) controls the production of digestive and respiratory epithelia of histo-blood group antigens involved in the attachment of pathogens. The aim of our study was to relate FUT2 variants to reported gastrointestinal and respiratory illnesses in infancy. Methods: In the Southampton Women's Survey, FUT2 genetic variants (single-nucleotide polymorphisms [SNPs] rs601338 and rs602662) were genotyped in 1831 infants and related to infant illnesses, after adjustment for sex, breastfeeding duration, and potential confounders...
October 30, 2018: Journal of Infectious Diseases
Zhengchang Wu, Haiyue Feng, Yue Cao, Yanjie Huang, Chaohui Dai, Shenglong Wu, Wenbin Bao
Escherichia coli ( E. coli ) F18 is the main pathogen responsible for post-weaning diarrhea (PWD) in piglets. Resistance to E. coli F18 depends on the expression of the cognate receptors in the intestinal epithelial cells. However, the molecular mechanism of E. coli F18 resistance in weaned piglets remains unclear. Here, we performed a comparative transcriptome study of the duodenal tissue from Sutai E. coli F18 sensitive and resistant pigs by RNA-seq, and pig α(1,2) fucosyltransferase 2 ( FUT2 ) was identified as a host differentially expressed gene controlling the E...
October 24, 2018: International Journal of Molecular Sciences
Meghan B Azad, Kaitlin H Wade, Nicholas J Timpson
Background: The FUT2 (fucosyltransferase 2) gene encodes alpha (1,2) fucosyltransferase, which determines blood group secretor status. Being homozygous for the inactive "non-secretor" rs601338(A) allele appears to confer resistance to certain infections (e.g. Norovirus , Rotavirus and Helicobacter pylori ) and susceptibility to others (e.g. Haemophilus influenza and Streptococcus pneumonia ). Non-secretors also have an increased risk of type 1 diabetes and inflammatory bowel disease. We aimed to determine the association of the FUT2 secretor genotype with infections and chronic conditions in the population-based Avon Longitudinal Study of Parents and Children (ALSPAC)...
2018: Wellcome Open Research
Helene Gellert-Kristensen, Nawar Dalila, Sune Fallgaard Nielsen, Børge Grønne Nordestgaard, Anne Tybjaerg-Hansen, Stefan Stender
Gallstone disease is a common complex disease that confers a substantial economic burden on society. The genetic underpinnings of gallstone disease remain incompletely understood. We aimed to identify new genetic associations with gallstone disease using publicly available data from the UK Biobank and two large Danish cohorts. We extracted genetic associations with gallstone disease from the Global Biobank Engine (GBE), an online browser of genomewide associations in UK Biobank participants (14,940 cases and 322,268 controls)...
October 16, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Khadija El Jellas, Bente B Johansson, Karianne Fjeld, Aristotelis Antonopoulos, Heike Immervoll, Man H Choi, Dag Hoem, Mark E Lowe, Dominique Lombardo, Pål R Njølstad, Anne Dell, Eric Mas, Stuart M Haslam, Anders Molven
Carboxyl-ester lipase (CEL) is a pancreatic fat-digesting enzyme associated with human disease. Rare mutations in the CEL gene cause a syndrome of pancreatic exocrine and endocrine dysfunction denoted MODY8, whereas a recombined CEL allele increases the risk for chronic pancreatitis. Moreover, CEL has been linked to pancreatic ductal adenocarcinoma (PDAC) through a postulated oncofetal CEL variant termed feto-acinar pancreatic protein (FAPP). The monoclonal antibody mAb16D10 was previously reported to detect a glycotope in the highly O-glycosylated, mucin-like C-terminus of CEL/FAPP...
October 12, 2018: Journal of Biological Chemistry
Edward P K Parker, Helena Whitfield, Chudarkodi Baskar, Sidhartha Giri, Jacob John, Nicholas C Grassly, Gagandeep Kang, Ira Praharaj
The FUT2 gene determines whether histo-blood group antigens are secreted at mucosal surfaces. Secretor status influences susceptibility to enteric viruses, potentially including oral poliovirus vaccine (OPV). We performed a nested case-control study to determine the association between FUT2 genotype (SNPs G428A, C302T, and A385T) and seroconversion among Indian infants who received a single dose of monovalent type 3 OPV. Secretor prevalence was 89/118 (75%) in infants who seroconverted and 97/122 (80%) in infants who failed to seroconvert (odds ratio 0...
September 19, 2018: Journal of Infectious Diseases
Katri Korpela, Anne Salonen, Brandon Hickman, Clemens Kunz, Norbert Sprenger, Kaarina Kukkonen, Erkki Savilahti, Mikael Kuitunen, Willem M de Vos
One of the most abundant components in human milk is formed by oligosaccharides, which are poorly digested by the infant. The oligosaccharide composition of breast milk varies between mothers, and is dependent on maternal secretor (FUT2) genotype. Secretor mothers produce milk containing α1-2 fucosylated human milk oligosaccharides, which are absent in the milk of non-secretor mothers. Several strains of bacteria in the infant gut have the capacity to utilise human milk oligosaccharides (HMOs). Here we investigate the differences in infant gut microbiota composition between secretor (N = 76) and non-secretor (N = 15) mothers, taking into account birth mode...
September 13, 2018: Scientific Reports
Wei Liang, Feng Cai, Liang Yang, Zhe Zhang, Zhicheng Wang
Background: The para-Bombay phenotype is characterized by a lack of ABH antigens on red cells, but ABH substances are found in saliva. Molecular genetic analysis was performed for seven Chinese individuals serologically typed as para-Bombay in Blood Station Center of Ningbo, Zhejiang Province, Ningbo, China from 2011 to 2014. Methods: RBCs' phenotype was characterized by standard serologic technique. Genomic DNA was sequenced with primers that amplified the coding sequence of α (1, 2)-fucosyltransferase genes FUT1 (or H ) and FUT2 (or Se ), respectively...
August 2018: Iranian Journal of Public Health
Yasuhiro Omata, Reiji Aoki, Ayako Aoki-Yoshida, Keiko Hiemori, Atsushi Toyoda, Hiroaki Tateno, Chise Suzuki, Yoshiharu Takayama
Psychological stress can cause dysfunction of the gastrointestinal tract by regulating its interaction with central nervous system (brain-gut axis). Chronic social defeat stress (CSDS) is widely used to produce a rodent model of stress-induced human mood disorders and depression. We previously showed that CSDS significantly affects the intestinal ecosystem including cecal and fecal microbiota, intestinal gene expression profiles and cecal metabolite profiles. Here, we investigated whether the glycosylation pattern in the intestinal epithelium was affected in C57BL/6 mice exposed to CSDS (hereinafter referred to as CSDS mice)...
September 4, 2018: Scientific Reports
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