912:
Intestinal Microbial-Derived Sphingolipids Are Associated with Childhood Food Allergy
Monday, March 5, 2018: 2:30 PM
S330GH (Convention Center)
Kathleen Lee-Sarwar, MD, , , , , , , , , , , , , , , , ,
RATIONALE: Investigation of the early-life intestinal microenvironment may provide insight into food allergy pathophysiology. We performed an untargeted analysis of the infant gut metabolome and bacterial microbiome of childhood food allergy in this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART).

METHODS: Metabolomic and bacterial microbial composition profiling was performed on infant fecal samples from 14 subjects who developed food sensitization and clinical food allergy by age 3 years, 32 with food sensitization but no clinical food allergy, and 37 controls. We identified modules of correlated metabolites that were associated with food allergy or sensitization, including sphingolipid biosynthetic metabolites. As invariant natural killer T (iNKT) cells are activated by selected glycosphingolipids, we tested iNKT cell activation by fecal lipid fractions and evaluated associations of lipid activity with phenotype, sphingolipid metabolite and Bacteroides spp. relative abundances.

RESULTS: Sphingolipid biosynthetic metabolites had higher relative abundances in subjects with food sensitization vs allergy (adjusted logistic regression p=0.01) and controls (p=0.02), and were associated with Bacteroides spp. iNKT cell activity of fecal lipid fractions was positively associated with relative abundances of several sphingolipid metabolites, Bacteroides fragilis (Spearman rho=0.50, p<0.001), and food sensitization vs allergy (Wilcoxon test p=0.03). Additional metabolite modules were inversely associated with food allergy, including anti-inflammatory fatty acids and metabolites associated with the microbe Ruminococcus gnavus.

CONCLUSIONS: Profiling of the human early-life gut microenvironment identified new molecular pathways associated with food allergy. Bacteroides-derived sphingolipids are inversely associated with food allergy among sensitized subjects, possibly indicating a protective effect of early-life iNKT cell activation.