TY - JOUR
T1 - Early-life fecal metabolomics of food allergy
AU - Lee-Sarwar, Kathleen A.
AU - Chen, Yih Chieh
AU - Lasky-Su, Jessica
AU - Kelly, Rachel S.
AU - Zeiger, Robert S.
AU - O'Connor, George T.
AU - Bacharier, Leonard B.
AU - Jia, Xiaojiong
AU - Beigelman, Avraham
AU - Gold, Diane R.
AU - Laranjo, Nancy
AU - Bunyavanich, Supinda
AU - Weiss, Scott T.
AU - Litonjua, Augusto A.
AU - Brennan, Patrick J.
N1 - Funding Information:
AAL has received author royalties from UpToDate, Inc. STW has received royalties from UpToDate, Inc and has invested in Histolix. LBB reports grants from NIH/NIAID and NHLBI, personal fees from GlaxoSmithKline Genentech/Novartis, DBV Technologies, Teva, Boehringer Ingelheim, AstraZeneca, WebMD/Medscape, Sanofi, Regeneron, Vectura, Circassia, Kinaset, Vertex, OM Pharma; and royalties from Elsevier outside the submitted work. AB holds stock from DBV Technologies, is a consultant for AstraZeneca and Raffa, and received speaking honoraria from AstraZenica, Novartis and Sanofi. RSZ is a consultant for AstraZeneca, DBV Technologies, Genentech, Inc., GlaxoSmithKline, Merck & Co., Novartis, Quest Diagnostics, Regeneron/Sanofi, TEVA Pharmaceuticals, and has received research support from ALK Pharmaceuticals, AstraZeneca, Genentech, Inc., GlaxoSmithKline, NHLBI, MedImmune, Merck, and Teva Pharmaceuticals. GTO has been compensated for speaking at a conference supported by Menarini, Inc. and for serving on a Data and Safety Monitoring Committee for Dicerna, Inc. JL‐S is a Scientific Advisor for Precion. KL‐S, YCC, RSK, XJ, NL, SB, PJB and DRG have nothing to disclose.
Funding Information:
VDAART was funded by U01HL091528 from the National Heart, Lung, and Blood Institute. Additional funding came from an AADCRC Early Investigator Award from the NIAID and NIH grants 1K08HL148178, R01HL108818, R01HL123915, R01HL141826, 5T32HL007427, U19AI095219, R01AI143855, ECHO grant OD023268, R01 AI147028. RSK is supported by K01HL146980 from NHLBI.
Publisher Copyright:
© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PY - 2023/2
Y1 - 2023/2
N2 - Background: Intestinal microenvironmental perturbations may increase food allergy risk. We hypothesize that children with clinical food allergy, those with food sensitization, and healthy children can be differentiated by intestinal metabolites in the first years of life. Methods: In this ancillary analysis of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we performed untargeted metabolomic profiling in 824 stool samples collected at ages 3–6 months, 1 year and 3 years. Subjects included 23 with clinical food allergy at age 3 and/or 6 years, 151 with food sensitization but no clinical food allergy, and 220 controls. We identified modules of correlated, functionally related metabolites and sought associations of metabolite modules and individual metabolites with food allergy/sensitization using regression models. Results: Several modules of functionally related intestinal metabolites were reduced among subjects with food allergy, including bile acids at ages 3–6 months and 1 year, amino acids at age 3–6 months, steroid hormones at 1 year, and sphingolipids at age 3 years. One module primarily containing diacylglycerols was increased in those with food allergy at age 3–6 months. Fecal caffeine metabolites at age 3–6 months, likely derived from breast milk, were increased in those with food allergy and/or sensitization (beta = 5.9, 95% CI 1.0–10.8, p =.02) and were inversely correlated with fecal bile acids and bilirubin metabolites, though maternal plasma caffeine levels were not associated with food allergy and/or sensitization. Conclusions: Several classes of bioactive fecal metabolites are associated with food allergy and/or sensitization including bile acids, steroid hormones, sphingolipids, and caffeine metabolites.
AB - Background: Intestinal microenvironmental perturbations may increase food allergy risk. We hypothesize that children with clinical food allergy, those with food sensitization, and healthy children can be differentiated by intestinal metabolites in the first years of life. Methods: In this ancillary analysis of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we performed untargeted metabolomic profiling in 824 stool samples collected at ages 3–6 months, 1 year and 3 years. Subjects included 23 with clinical food allergy at age 3 and/or 6 years, 151 with food sensitization but no clinical food allergy, and 220 controls. We identified modules of correlated, functionally related metabolites and sought associations of metabolite modules and individual metabolites with food allergy/sensitization using regression models. Results: Several modules of functionally related intestinal metabolites were reduced among subjects with food allergy, including bile acids at ages 3–6 months and 1 year, amino acids at age 3–6 months, steroid hormones at 1 year, and sphingolipids at age 3 years. One module primarily containing diacylglycerols was increased in those with food allergy at age 3–6 months. Fecal caffeine metabolites at age 3–6 months, likely derived from breast milk, were increased in those with food allergy and/or sensitization (beta = 5.9, 95% CI 1.0–10.8, p =.02) and were inversely correlated with fecal bile acids and bilirubin metabolites, though maternal plasma caffeine levels were not associated with food allergy and/or sensitization. Conclusions: Several classes of bioactive fecal metabolites are associated with food allergy and/or sensitization including bile acids, steroid hormones, sphingolipids, and caffeine metabolites.
KW - bile acids
KW - caffeine
KW - food allergy
KW - food sensitization
KW - metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85144060472&partnerID=8YFLogxK
U2 - 10.1111/all.15602
DO - 10.1111/all.15602
M3 - Article
C2 - 36448508
AN - SCOPUS:85144060472
SN - 0105-4538
VL - 78
SP - 512
EP - 521
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
IS - 2
ER -