Effect of Genotype and Age on a Defined Microbiota in Gnotobiotic SCID Piglets

Widmer, K. M.; Rahic-Seggerman, F.; Forster, A.; Ahrens-Kress, A.; Sauer, M.; Mooyottu, S.; Vinithakumari, A.; Dunkerson-Kurzhumov, A.; Sponseller, B.; Kiupel, M.; Schmitz-Esser, S.; Tuggle, C. K.

doi:10.1101/2024.09.03.611011

bioRxiv · 10.1101/2024.09.03.611011

Effect of Genotype and Age on a Defined Microbiota in Gnotobiotic SCID Piglets

Widmer, K. M.·Rahic-Seggerman, F.·Forster, A.·Ahrens-Kress, A.·Sauer, M.·Mooyottu, S.·Vinithakumari, A.·Dunkerson-Kurzhumov, A.·Sponseller, B.·Kiupel, M.·Schmitz-Esser, S.·Tuggle, C. K.

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Abstract

Severe combined immunodeficient (SCID) individuals lack functional T and B lymphocytes, leading to a deficient adaptive immune system. SCID pigs are a unique large animal biomedical model as they possess many similarities to humans, allowing for the collection of translatable data in regenerative medicine, cancer, and other biomedical research topics. While many studies suggest early gut microbiota development is necessary for developing the intestinal barrier and immune system, these animals are often cesarian section derived, leaving them uncolonized for normal intestinal microflora. The hypothesis was that an increase in complexity of microbiota inoculum will allow for more stability in the composition of the gut microbiota of SCID piglets. This was tested across multiple litters of SCID piglets with three different defined microbiota consortium (2-strain, 6-strain, 7-strain). All piglets received their designated defined microbiota by oral gavage immediately after birth and again 24 hours later. There was no effect of SCID genotype on the composition of the gut microbiota, but there was a significant effect due to piglet age. Additionally, all three defined microbiota consortia were deemed safe to use in SCID piglets, and the 7-strain microbiota was the most stable over time. Based on these results, the 7-strain defined microbiota will be added to the SCID pig husbandry protocol, allowing for a more reproducible model.

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Widmer, K. M., Rahic-Seggerman, F., Forster, A., Ahrens-Kress, A., Sauer, M., Mooyottu, S., Vinithakumari, A., Dunkerson-Kurzhumov, A., Sponseller, B., Kiupel, M., Schmitz-Esser, S., Tuggle, C. K.. 2024-09-07. Effect of Genotype and Age on a Defined Microbiota in Gnotobiotic SCID Piglets. https://doi.org/10.1101/2024.09.03.611011

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