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.
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.
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