Document Detail


Promotion of autoimmune diabetes by cereal diet in the presence or absence of microbes associated with gut immune activation, regulatory imbalance and altered cathelicidin antimicrobial peptide.
MedLine Citation:
PMID:  23349499     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
We are exposed to millions of microbial and dietary antigens via the gastrointestinal tract, which likely plays a key role in type 1 diabetes (T1D). We differentiated the effects of these two major environmental factors on gut immunity and T1D. Diabetes-prone BioBreeding (BBdp) rats were housed in specific pathogen-free (SPF) or germ-free (GF) conditions and weaned onto diabetespromoting cereal diets or a protective low antigen hydrolyzed casein (HC) diet and T1D incidence was monitored. Fecal microbiota 16S rRNA genes, immune cell distribution, and gene expression in jejunum were analyzed. T1D was highest in cereal-SPF (65%) and cereal-GF rats (53%) but inhibited and delayed in HC-fed counterparts. Nearly all HC-GF rats remained diabetes-free whereas HC-fed SPF rats were less protected (7% vs. 29%). Bacterial communities differed in SPF rats fed cereal compared with HC. Cereal-SPF rats displayed increased gut CD3(+)and CD8α+ lymphocytes, ratio of Ifng/Il4 mRNA, and Lck expression, indicating T cellactivation. The ratio of CD3(+) T cells expressing the T(reg) marker Foxp3(+) was highest in HC-GF and lowest in cereal-SPF rats. Resident CD163(+) M2 macrophages were increased in HC-protected rats. The cathelicidin antimicrobial peptide (Camp) gene was upregulated in the jejunum of HC diet-protected rats and CAMP(+) cells co-localized with CD163. A cereal diet was a stronger promoter of T1D than gut microbes in association with impaired gut immune homeostasis.
Authors:
Fraser W Scott; Christopher Patrick; Gen-Sheng Wang; David E Lefebvre; Jennifer A Crookshank; Brigitte Sonier; Chandra E Eberhard; Majid Mojibian; Christopher R Kennedy; Stephen P J Brooks; Martin L Kalmokoff; Mariantonia Maglio; Riccardo Troncone; Philippe Poussier
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Diabetes     Volume:  -     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University of Ottawa, Biochemistry, Microbiology and Immunology, Ottawa, Ontario, Canada.
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