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Persistent alterations in plasma lipid profiles prior to introduction of gluten in the diet associate with progression to celiac disease

View ORCID ProfilePartho Sen, Cecilia Carlsson, Suvi M. Virtanen, Satu Simell, Heikki Hyöty, Jorma Ilonen, Jorma Toppari, Riitta Veijola, Tuulia Hyötyläinen, Mikael Knip, View ORCID ProfileMatej Orešič
doi: https://doi.org/10.1101/419416
Partho Sen
1Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland
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  • ORCID record for Partho Sen
Cecilia Carlsson
2Department of Chemistry, Örebro University, 702 81 Örebro, Sweden
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Suvi M. Virtanen
3National Institute for Health and Welfare, Public Health Promotion Unit, Helsinki, Helsinki, Finland
4Faculty of Social Sciences/Health, University of Tampere, Tampere, Finland
5Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland
6Science Centre, Tampere University Hospital, Tampere, Finland
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Satu Simell
7Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland
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Heikki Hyöty
8Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
9Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland
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Jorma Ilonen
10Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
11Clinical Microbiology, Turku University Hospital, Turku, Finland
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Jorma Toppari
7Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland
12Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
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Riitta Veijola
13Department of Paediatrics, PEDEGO Research Unit, Medical Research Centre, University of Oulu, Oulu, Finland
14Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
15Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
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Tuulia Hyötyläinen
2Department of Chemistry, Örebro University, 702 81 Örebro, Sweden
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Mikael Knip
16Children’s Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, 00290 Helsinki, Finland
17Tampere Centre for Child Health Research, Tampere University Hospital, Tampere, Finland
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  • For correspondence: mikael.knip@helsinki.fi matej.oresic@utu.fi
Matej Orešič
1Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland
18School of Medical Sciences, Örebro University, 702 81 Örebro, Sweden
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  • For correspondence: mikael.knip@helsinki.fi matej.oresic@utu.fi
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ABSTRACT

Background and Aims Celiac disease (CD) is a chronic enteropathy characterized by an autoimmune reaction in the small intestine in genetically-susceptible individuals. Gluten is the required environmental trigger of clinical CD, but the underlying causes of the autoimmune reaction remain unknown. Herein, we apply lipidomics to elucidate the early events preceding clinical CD in a prospective study of children observed from birth until diagnosis of CD and subsequent introduction of a gluten-free diet.

Methods Mass spectrometry–based lipidomics profiling was applied to a longitudinal series of 233 plasma samples from the Type 1 Diabetes Prediction and Prevention (DIPP) study, spanning the period between birth and the introduction of a gluten–free diet following CD diagnosis (n=23 CD progressors, n=23 controls matched for gender, HLA risk, period of birth, and age).

Results 23 children progressed to CD at a mean age of 4.8 years. They showed increased amounts of triacylglycerols (TGs) of low carbon number and double bond count and a decreased level of phosphatidylcholines by 3 months of age as compared to controls. These differences were exacerbated with age but were not observed at birth. No significant differences were observed in essential (dietary) TGs such as those containing polyunsaturated fatty acids.

Conclusion Our findings suggest that abnormal lipid metabolism associated with development of clinical CD may occur prior to the introduction of gluten to the diet. Moreover, our data suggest that the specific TGs found elevated in CD progressors may be due to a host response to compromised intake of essential lipids in the small intestine, requiring de novo lipogenesis.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 18, 2018.
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Persistent alterations in plasma lipid profiles prior to introduction of gluten in the diet associate with progression to celiac disease
Partho Sen, Cecilia Carlsson, Suvi M. Virtanen, Satu Simell, Heikki Hyöty, Jorma Ilonen, Jorma Toppari, Riitta Veijola, Tuulia Hyötyläinen, Mikael Knip, Matej Orešič
bioRxiv 419416; doi: https://doi.org/10.1101/419416
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Persistent alterations in plasma lipid profiles prior to introduction of gluten in the diet associate with progression to celiac disease
Partho Sen, Cecilia Carlsson, Suvi M. Virtanen, Satu Simell, Heikki Hyöty, Jorma Ilonen, Jorma Toppari, Riitta Veijola, Tuulia Hyötyläinen, Mikael Knip, Matej Orešič
bioRxiv 419416; doi: https://doi.org/10.1101/419416

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