Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat. Is the gut flora involved in the development of type 1 diabetes?
OBJECTIVE
Accumulating data suggest that the gut immune system plays a role in the development of type 1 diabetes. The intestinal flora is essential for the development of the (gut) immune system and the establishment of tolerance. It has been reported that oral administration of food and bacterial antigens early in life suppresses later development of diabetes in the Bio-Breeding diabetes-prone (BB-DP) rat. This study was designed to investigate the possible relationship between the development of diabetes and the composition of intestinal flora.


METHODS
The intestinal flora of BB-DP rats, a rat model for type 1 diabetes, was characterised long before the clinical onset of diabetes by fluorescent in situ hybridisation. In a separate experiment, BB-DP rats were treated with antibiotics and the effect on diabetes incidence and level of insulitis was analysed.


RESULTS
We observed a difference in bacterial composition between rats that eventually did and those that did not develop diabetes. This difference was detectable long before clinical onset of the disease. Rats that did not develop diabetes at a later age displayed a lower amount of Bacteroides sp. Modulation of the intestinal flora through antibiotic treatment decreased the incidence and delayed the onset of diabetes. A combination of antibiotic treatment and a protective hydrolysed casein diet completely prevented diabetes in the BB-DP rat.


CONCLUSIONS
Our data suggest that the intestinal flora is involved in the development of type 1 diabetes. Factors influencing composition of the intestinal flora could be a target for therapeutic intervention.
Brugman
S
S
Department of Cell Biology, Immunology Section, University Medical Center Groningen, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Klatter
F A
FA
Visser
J T J
JT
Wildeboer-Veloo
A C M
AC
Harmsen
H J M
HJ
Rozing
J
J
Bos
N A
NA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001439:Bacteroides / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000382:microbiology / Q000517:prevention & control*; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology; D008297:Male; D008856:Microscopy, Fluorescence; D011236:Prediabetic State / Q000382:microbiology / Q000517:prevention & control; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D051381:Rats; D011913:Rats, Inbred BB
D000900:Anti-Bacterial Agents; D002364:Caseins; D012336:RNA, Ribosomal, 16S