RT Journal Article
SR Electronic
T1 Persistent alterations in plasma lipid profiles prior to introduction of gluten in the diet associate with progression to celiac disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 419416
DO 10.1101/419416
A1 Partho Sen
A1 Cecilia Carlsson
A1 Suvi M. Virtanen
A1 Satu Simell
A1 Heikki Hyöty
A1 Jorma Ilonen
A1 Jorma Toppari
A1 Riitta Veijola
A1 Tuulia Hyötyläinen
A1 Mikael Knip
A1 Matej Orešič
YR 2018
UL http://biorxiv.org/content/early/2018/09/18/419416.abstract
AB 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.