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Maternal treatment with short-chain fatty acids modulates the intestinal microbiota and immunity and ameliorates type 1 diabetes in the offspring.

Maternal treatment with short-chain fatty acids modulates the intestinal microbiota and immunity and ameliorates type 1 diabetes in the offspring.
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Needell JC, Ir D, Robertson CE, Kroehl ME, Frank DN, Zipris D,


Needell JC, Ir D, Robertson CE, Kroehl ME, Frank DN, Zipris D, (click to view)

Needell JC, Ir D, Robertson CE, Kroehl ME, Frank DN, Zipris D,

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PloS one 2017 09 0812(9) e0183786 doi 10.1371/journal.pone.0183786
Abstract

We recently hypothesized that the intestinal microbiota and the innate immune system play key roles in the mechanism of Kilham Rat Virus-induced type 1 diabetes in the LEW1.WR1 rat. We used this animal model to test the hypothesis that maternal therapy with short-chain fatty acids can modulate the intestinal microbiota and reverse virus-induced proinflammatory responses and type 1 diabetes in rat offspring. We observed that administration of short-chain fatty acids to rat breeders via drinking water prior to pregnancy and further treatment of the offspring with short-chain fatty acids after weaning led to disease amelioration. In contrast, rats that were administered short-chain fatty acids beginning at weaning were not protected from type 1 diabetes. Short-chain fatty acid therapy exerted a profound effect on the intestinal microbiome in the offspring reflected by a reduction and an increase in the abundances of Firmicutes and Bacteroidetes taxa, respectively, on day 5 post-infection, and reversed virus-induced alterations in certain bacterial taxa. Principal component analysis and permutation multivariate analysis of variance tests further revealed that short-chain fatty acids induce a distinct intestinal microbiota compared with uninfected animals or rats that receive the virus only. Short-chain fatty acids downregulated Kilham Rat Virus-induced proinflammatory responses in the intestine. Finally, short-chain fatty acids altered the B and T cell compartments in Peyer’s patches. These data demonstrate that short-chain fatty acids can reshape the intestinal microbiota and prevent virus-induced islet autoimmunity and may therefore represent a useful therapeutic strategy for disease prevention.

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