Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats.
BACKGROUND
The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development.


RESULTS
Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin.


CONCLUSIONS
It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data suggest that the gut and the gut microbiota are potential agents of influence in type 1 diabetes development. These data also support therapeutic efforts that seek to modify gut microbiota as a means to modulate development of this disorder.
Valladares
Ricardo
R
Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, United States of America.
Sankar
Dhyana
D
Li
Nan
N
Williams
Emily
E
Lai
Kin-Kwan
KK
Abdelgeliel
Asmaa Sayed
AS
Gonzalez
Claudio F
CF
Wasserfall
Clive H
CH
Larkin
Joseph
J
Schatz
Desmond
D
Atkinson
Mark A
MA
Triplett
Eric W
EW
Neu
Josef
J
Lorca
Graciela L
GL
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000382:microbiology* / Q000473:pathology*; D005247:Feeding Behavior; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology / Q000473:pathology; D015994:Incidence; D018836:Inflammation Mediators / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007778:Lactobacillus / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D054892:Metagenome; D018384:Oxidative Stress / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB; D019108:Tight Junctions / Q000378:metabolism; D014886:Weaning
D016207:Cytokines; D018836:Inflammation Mediators; D008565:Membrane Proteins; D012333:RNA, Messenger
Int J Androl. 2003 Oct;26(5):271-8
14511215
Inflamm Bowel Dis. 2009 Aug;15(8):1183-9
19235886
Curr Opin Gastroenterol. 2004 Nov;20(6):565-71
15703684
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16731-6
18936492
J Pediatr Gastroenterol Nutr. 2005 May;40(5):589-95
15861021
Diabetologia. 2005 Aug;48(8):1565-75
15986236
J Clin Microbiol. 2004 Jul;42(7):3128-36
15243071
Biofactors. 2004;21(1-4):315-9
15630218
Diabetes. 2008 Oct;57(10):2555-62
18820210
Free Radic Biol Med. 2004 Dec 1;37(11):1864-74
15528045
Diabetologia. 2006 Sep;49(9):2105-8
16816951
Microbiol Res. 2008;163(6):663-70
19216105
FEBS Lett. 1993 Aug 9;328(1-2):9-12
7688327
Diabetologia. 2007 Jan;50(1):220-1
17119915
N Engl J Med. 2001 Mar 1;344(9):655-64
11228281
Pediatr Res. 2008 Mar;63(3):303-7
18091354
Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5179-84
16547141
Life Sci. 2007 Apr 17;80(19):1729-37
17383680
ISME J. 2009 May;3(5):536-48
19225551
Metabolism. 2003 Mar;52(3):333-7
12647272
Am J Physiol. 1999 Apr;276(4):G941-50
10198338
Appl Environ Microbiol. 2009 Apr;75(7):1961-9
19201979
Diabetologia. 1984 Apr;26(4):297-9
6376238
Ann Surg. 2002 Jul;236(1):56-66
12131086
Int J Biochem Cell Biol. 2006;38(5-6):794-803
16442834
Am J Physiol Cell Physiol. 2002 Jan;282(1):C144-52
11742807
Am J Physiol. 1996 Jun;270(6 Pt 1):C1581-7
8764139
J Exp Med. 1997 Dec 15;186(12):2023-31
9396771
Am J Trop Med Hyg. 1999 Apr;60(4 Suppl):10-5
10344672
Appl Environ Microbiol. 2009 Aug;75(15):5018-24
19502437
J Mol Med (Berl). 2000;78(3):121-9
10868474
Appl Environ Microbiol. 2007 Jan;73(1):32-9
17071791
BMC Neurosci. 2006 Dec 01;7:78
17137520
Lett Appl Microbiol. 2008 Nov;47(5):367-73
19146523
Acta Physiol Scand. 2002 Mar;174(3):265-74
11906326
J Immunol. 2004 Jul 15;173(2):1327-35
15240727
Diabetologia. 2009 Jul;52(7):1445-7
19396422
Free Radic Biol Med. 2006 Jul 15;41(2):177-84
16814095
Ann N Y Acad Sci. 2009 May;1165:294-300
19538319
Am J Pathol. 2003 Dec;163(6):2513-22
14633623
J Cereb Blood Flow Metab. 2009 May;29(5):944-52
19259110
Oncogene. 2007 Mar 29;26(14):2071-81
17016440
Br J Pharmacol. 2003 Sep;140(1):71-80
12967936
Cell Tissue Res. 2002 Nov;310(2):169-75
12397372