PMID- 34087019
OWN - NLM
STAT- MEDLINE
DCOM- 20220107
LR  - 20220531
IS  - 1399-3038 (Electronic)
IS  - 0905-6157 (Linking)
VI  - 32
IP  - 8
DP  - 2021 Nov
TI  - Metabolomics reveals microbial-derived metabolites associated with immunoglobulin 
      E responses in filaggrin-related atopic dermatitis.
PG  - 1709-1717
LID - 10.1111/pai.13570 [doi]
AB  - BACKGROUND: Filaggrin (FLG) gene mutation and immunoglobulin E (IgE)-mediated 
      sensitization are the most important predictors of atopic dermatitis (AD). 
      However, a metabolomics-based approach to address the metabolic impact of FLG 
      mutations on allergic IgE responses for AD is still lacking. We, though, 
      determine the relationships of metabolic profiles in AD with FLG mutations and 
      allergic responses. METHODS: Eighty-one children with adolescent AD (n = 58) and 
      healthy controls (n = 23) were prospectively enrolled. Mutations in the filaggrin 
      gene were identified using whole-exome sequencing, and plasma metabolic profiles 
      were determined using (1) H-nuclear magnetic resonance (NMR) spectroscopy. 
      Integrative analyses of their associations related to total serum IgE levels were 
      performed, and further metabolic functional pathways for AD were also assessed. 
      RESULTS: Metabolites contributed to the separation between AD and controls were 
      identified using the supervised partial least squares discriminant analysis (Q(2) 
      /R(2)  = 0.90, P(permutation) <0.001). Nitrogen and amino acid metabolisms for 
      energy production, and microbe-related methane and propanoate metabolisms were 
      significantly associated with AD compared with healthy controls (FDR-adjusted 
      p < .05). Five of fifteen metabolites related to FLG mutations were positively 
      correlated with total serum IgE levels. Among them, dimethylamine and isopropanol 
      were strongly associated with methane metabolism and propanoate metabolism, 
      respectively, in AD with FLG mutations (FDR-adjusted p < .01). CONCLUSION: A 
      strong correlation of microbial-derived metabolites, dimethylamine and 
      isopropanol, with FLG mutations and IgE allergic reactions provides the influence 
      of host genetics on the microbiome to regulate susceptibility to allergic 
      responses in the pathogenesis of AD.
CI  - (c) 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
FAU - Chiu, Chih-Yung
AU  - Chiu CY
AUID- ORCID: 0000-0002-6454-968X
AD  - Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Chang Gung 
      University, Taoyuan, Taiwan.
AD  - Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital at Linkou, 
      Taoyuan, Taiwan.
FAU - Lin, Gigin
AU  - Lin G
AD  - Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital at Linkou, 
      Taoyuan, Taiwan.
AD  - Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at 
      Linkou, Chang Gung University, Taoyuan, Taiwan.
FAU - Wang, Chia-Jung
AU  - Wang CJ
AD  - Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Chang Gung 
      University, Taoyuan, Taiwan.
FAU - Hung, Shuen-Iu
AU  - Hung SI
AD  - Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial 
      Hospital, Chang Gung University, Taoyuan, Taiwan.
FAU - Chung, Wen-Hung
AU  - Chung WH
AD  - Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, 
      Chang Gung Memorial Hospital, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210705
PL  - England
TA  - Pediatr Allergy Immunol
JT  - Pediatric allergy and immunology : official publication of the European Society 
      of Pediatric Allergy and Immunology
JID - 9106718
RN  - 0 (FLG protein, human)
RN  - 0 (Filaggrin Proteins)
RN  - 0 (Intermediate Filament Proteins)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adolescent
MH  - Case-Control Studies
MH  - Child
MH  - *Dermatitis, Atopic/genetics
MH  - *Filaggrin Proteins
MH  - Humans
MH  - Immunoglobulin E
MH  - Intermediate Filament Proteins/genetics
MH  - Metabolomics
MH  - Mutation
OTO - NOTNLM
OT  - IgE
OT  - atopic dermatitis
OT  - filaggrin mutations
OT  - microbial-derived metabolites
EDAT- 2021/06/05 06:00
MHDA- 2022/01/08 06:00
CRDT- 2021/06/04 17:39
PHST- 2021/05/23 00:00 [revised]
PHST- 2021/01/06 00:00 [received]
PHST- 2021/05/31 00:00 [accepted]
PHST- 2021/06/05 06:00 [pubmed]
PHST- 2022/01/08 06:00 [medline]
PHST- 2021/06/04 17:39 [entrez]
AID - 10.1111/pai.13570 [doi]
PST - ppublish
SO  - Pediatr Allergy Immunol. 2021 Nov;32(8):1709-1717. doi: 10.1111/pai.13570. Epub 
      2021 Jul 5.