Maternal and child FUT2 secretor status affect gastroenteritis risk and gut microbiota composition in early life

OBJECTIVES: To investigate associations between maternal and child secretor status and early-life gastroenteritis risk, considering the roles of gut microbiota, breastfeeding, and daycare attendance.

METHODS: In the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort (n = 700), parents recorded gastroenteritis episodes during the first 3 years of life. Secretor status, rs601338 in the FUT2 gene, was genotyped in both parents and children. The association between secretor status and gastroenteritis was assessed using quasi-Poisson regression. Faecal samples were collected at 1 week, 1 month, 1 year after birth. The interaction between secretor status, breastfeeding and daycare attendance were analysed through Cox regression.

RESULTS: Maternal secretor status increased first-year gastroenteritis risk (incidence rate ratio [IRR] = 1.48, 95% CI: 1.05-2.16, p 0.033); child status increased second-year risk (IRR = 1.56, 95% CI: 1.11-2.27, p 0.015), especially after daycare attendance (interaction p 0.006). Maternal status associated with microbiota differences at 1 week (weighted UniFrac F = 2.4, R 2 = 0.47%, p 0.048) and 1 month (F = 3.3, R 2 = 0.62%, p 0.026); child status at 1 year (F = 2.5, R 2 = 0.45%, p 0.027). Secretor children showed lower Bacteroides vulgatus (median [interquartile range (IQR)]: 1.00% [0.04-12.92] vs. 5.00% [0.09-24.80], p 0.023) but higher Escherichia/Shigella (1.35% [IQR: 0.28-7.42] vs. 0.56% [IQR: 0.13-2.62], p 0.002). B. vulgatus mediated 14% of child status effects (average causal mediation effect IRR = 0.95, 95% CI: 0.89-0.99, p 0.014).

DISCUSSION: Maternal and child FUT2 status demonstrates age-specific impacts on gastroenteritis and microbiota in early life, providing new insights into gastrointestinal health genetics and host-microbiome dynamics.