Long term effect of gut microbiota transfer on diabetes development.
The composition of the gut microbiome represents a very important environmental factor that influences the development of type 1 diabetes (T1D). We have previously shown that MyD88-deficient non-obese diabetic (MyD88-/-NOD) mice, that were protected from T1D development, had a different composition of gut microbiota compared to wild type NOD mice. The aim of our study was to investigate whether this protection could be transferred. We demonstrate that transfer of gut microbiota from diabetes-protected MyD88-deficient NOD mice, reduced insulitis and significantly delayed the onset of diabetes. Gut bacteria from MyD88-deficient mice, administered over a 3-week period, starting at 4 weeks of age, stably altered the family composition of the gut microbiome, with principally Lachnospiraceae and Clostridiaceae increased and Lactobacillaceae decreased. The transferred mice had a higher concentration of IgA and TGFβ in the lumen that was accompanied by an increase in CD8(+)CD103(+) and CD8αβ T cells in the lamina propria of the large intestine. These data indicate not only that gut bacterial composition can be altered after the neonatal/weaning period, but that the composition of the microbiome affects the mucosal immune system and can delay the development of autoimmune diabetes. This result has important implications for the development of probiotic treatment for T1D.
Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Jian
J
Peng
Section of Infectious Disease, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Sukanya
S
Narasimhan
Cardiff School of Biosciences, Main Building, Museum Avenue, Cardiff University, Cardiff, UK; Centre for Digestive and Gut Health, Imperial College London, London, UK.
Julian R
JR
Marchesi
Department of Food Science and Technology, University of Nebraska, Lincoln, NE, USA.
Andrew
A
Benson
Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK.
F Susan
FS
Wong
Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: li.wen@yale.edu.
Li
L
Wen
D000818:Animals; D001419:Bacteria / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D019936:Probiotics / Q000494:pharmacology*
C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88
Gut microbiota; Innate immunity; Mucosal immunology; Type 1 diabetes