Effects of Child and Maternal Histo-Blood Group Antigen Status on Symptomatic and Asymptomatic Enteric Infections in Early Childhood

Abstract

Background Histo-blood group antigens (HBGAs) such as fucosyltransferase (FUT)2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their offspring to pediatric enteric infections. Methods In 3 community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. Quantitative polymerase chain reaction panels tested 3663 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. Results Children of secretor (FUT2 positive) mothers had a 38% increased adjusted risk of all-cause diarrhea (HR = 1.38; 95% confidence interval (CI), 1.15–1.66) and significantly reduced time to first diarrheal episode. Child FUT2 and FUT3 positivity reduced the risk for all-cause diarrhea by 29% (HR = 0.81; 95% CI, 0.71–0.93) and 27% (HR = 0.83; 95% CI, 0.74–0.92), respectively. Strong associations between HBGAs and pathogen-specific infection and diarrhea were observed, particularly for noroviruses, rotaviruses, enterotoxigenic Escherichia coli , and Campylobacter jejuni / coli . Conclusions Histo-blood group antigens affect incidence of all-cause diarrhea and enteric infections at magnitudes comparable to many common disease control interventions. Studies measuring impacts of interventions on childhood enteric disease should account for both child and mothers’ HBGA status.

Genetic Manipulation of Human Intestinal Enteroids Demonstrates the Necessity of a Functional Fucosyltransferase 2 Gene for Secretor-Dependent Human Norovirus Infection

“…HIEs provide an excellent tool for future studies on intestinal enzymes involved in glycosylation and how glycosylation alters glycoprotein localization. An association of enteric commensals and pathogens with host secretor status has led to increased recognition of secretor glycans being susceptibility factors important in infection and disease outcomes (30,31). The exact role played by the glycans in these infections is not fully understood.…”

Use of earth observation-derived hydrometeorological variables to model and predict rotavirus infection (MAL-ED): a multisite cohort study

“…Future analyses could adjust for easily measured, non-environmental exposures (such as breastfeeding status and sanitation) to increase predictive power. However, identification of the individual-level factors most likely to ascertain disease risk (such as fucosyltransferase 2 phenotype 39 ) might be unfeasible at this scale. Modelling interactions between hydrometeorological variables can produce modest improvements, as demonstrated by the increase in COD for the interaction models relative to the main effects.…”

Enteropathogenic Infections: Organoids Go Bacterial

“…Preliminary data unveiled a predilection of π -class Std fimbriae encoded by the Std operon of Salmonella enterica serotype typhimurium ( S. typhimurium ) for binding terminal α 1,2-fucose residues [ 57 ]. This enzyme catalyzes the addition of fucose sugar to host membrane-bound glycans crucial to the expression of ABH and Lewis histo-blood group antigens on mucosal membranes and in body fluids [ 58 ]. This adherence strategy has been further corroborated by in vitro studies on intestinal organoids grown from α 1,2-fucosyl transferase 2 WT mice.…”