NDLI: Prevention of virus-induced type 1 diabetes with antibiotic therapy.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hara, Naoko Ir, Diana Alkanani, Aimon K. Robertson, Charles E. Wagner, Brandie D. Zipris, Danny Frank, Daniel N.
Description	Country affiliation: United States Author Affiliation: Hara N ( Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA.)
Abstract	Microbes were hypothesized to play a key role in the progression of type 1 diabetes (T1D). We used the LEW1.WR1 rat model of Kilham rat virus (KRV)-induced T1D to test the hypothesis that the intestinal microbiota is involved in the mechanism leading to islet destruction. Treating LEW1.WR1 rats with KRV and a combination of trimethoprim and sulfamethoxazole (Sulfatrim) beginning on the day of infection protected the rats from insulitis and T1D. Pyrosequencing of bacterial 16S rRNA and quantitative RT-PCR indicated that KRV infection resulted in a transient increase in the abundance of Bifidobacterium spp. and Clostridium spp. in fecal samples from day 5- but not day 12-infected versus uninfected animals. Similar alterations in the gut microbiome were observed in the jejunum of infected animals on day 5. Treatment with Sulfatrim restored the level of intestinal Bifidobacterium spp. and Clostridium spp. We also observed that virus infection induced the expression of KRV transcripts and the rapid upregulation of innate immune responses in Peyer's patches and pancreatic lymph nodes. However, antibiotic therapy reduced the virus-induced inflammation as reflected by the presence of lower amounts of proinflammatory molecules in both the Peyer's patches and pancreatic lymph nodes. Finally, Sulfatrim treatment reduced the number of B cells in Peyer's patches and downmodulated adaptive immune responses to KRV, but did not interfere with antiviral Ab responses or viral clearance from the spleen, pancreatic lymph nodes, and serum. The data suggest that gut microbiota may be involved in promoting virus-induced T1D in the LEW1.WR1 rat model.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	8
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-10-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Diabetes Mellitus, Experimental Prevention & Control Virology Diabetes Mellitus, Type 1 Parvovirus Immunology Animals Microbiology Drug Combinations Inflammation Mediators Administration & Dosage Islets Of Langerhans Pathology Mice Mice, Inbred C57bl Peyer's Patches Rats, Inbred Lew Sulfadoxine Sulfamethoxazole Analogs & Derivatives Trimethoprim Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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