Increasing evidence supports the role of early-life gut microbiota in developing atopic diseases, but ecological changes to gut microbiota during infancy in relation to food sensitization remain unclear. We aimed to characterize and associate these changes with the development of food sensitization in children.In this observational study, using 16S rRNA amplicon sequencing, we characterized the composition of 2844 fecal microbiota in 1422 Canadian full-term infants. Atopic sensitization outcomes were measured by skin prick tests at age 1 year and 3 years. The association between gut microbiota trajectories, based on longitudinal shifts in community clusters, and atopic sensitization outcomes at age 1 and 3 years was determined. Ethnicity and early life exposures influencing microbiota trajectories were initially examined, and post hoc analyses were conducted.Four identified developmental trajectories of gut microbiota were shaped by birth mode and varying by ethnicity. The trajectory with persistently-low Bacteroides abundance and high Enterobacteriaceae/Bacteroidaceae ratio throughout infancy increased the risk of sensitization to food allergens, particularly peanut at age 3 years by 3-fold (adjusted OR, 2.82; 95% CI, 1.13-7.01); a much higher likelihood for peanut sensitization was found if infants with this trajectory were born to Asian mothers (adjusted OR, 7.87; 95% CI, 2.75-22.55). It was characterized by a deficiency in sphingolipid metabolism and persistent C. difficile colonization. Importantly, this trajectory of depleted Bacteroides abundance mediated the association between Asian ethnicity and food sensitization.This study documented an association between persistently-low gut Bacteroides abundance throughout infancy and sensitization to peanut in childhood. It is the first to show a mediation role for infant gut microbiota in ethnicity-associated development of food sensitization.
Hein M Tun, Ye Peng, Bolin Chen, Theodore B Konya, Nadia P Morales-Lizcano, Radha Chari, Catherine J Field, David S Guttman, Allan B Becker, Piush J Mandhane, Theo J Moraes, Malcolm R Sears, Stuart E Turvey, Padmaja Subbarao, Elinor Simons, James A Scott, Anita L Kozyrskyj