Widmer Katherine M, Rahic-Seggerman Faith, Forster Ahlea, Ahrens-Kress Amanda, Sauer Mary, Mooyottu Shankumar, Vinithakumari Akhil, Dunkerson-Kurzhumov Aaron, Sponseller Brett, Kiupel Matti, Schmitz-Esser Stephan, Tuggle Christopher K
Department of Animal Science, Iowa State University, Ames, IA 50011, USA.
Laboratory Animal Resources, Iowa State University, Ames, IA 50011, USA.
bioRxiv. 2024 Sep 7:2024.09.03.611011. doi: 10.1101/2024.09.03.611011.
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.
重症联合免疫缺陷（SCID）个体缺乏功能性T淋巴细胞和B淋巴细胞，导致适应性免疫系统缺陷。SCID猪是一种独特的大型动物生物医学模型，因为它们与人类有许多相似之处，能够在再生医学、癌症及其他生物医学研究领域收集可转化的数据。虽然许多研究表明，早期肠道微生物群的发育对于肠道屏障和免疫系统的发育是必要的，但这些动物通常通过剖腹产获得，导致它们没有正常的肠道微生物群定殖。研究假设是，增加微生物接种物的复杂性将使SCID仔猪肠道微生物群的组成更加稳定。研究人员用三种不同的特定微生物群组合（2菌株、6菌株、7菌株）对多窝SCID仔猪进行了测试。所有仔猪在出生后立即通过口服灌胃接受指定的特定微生物群，并在24小时后再次接受灌胃。SCID基因型对肠道微生物群的组成没有影响，但仔猪年龄有显著影响。此外，所有三种特定微生物群组合在SCID仔猪中使用均被认为是安全的，并且7菌株微生物群随时间推移最为稳定。基于这些结果，7菌株特定微生物群将被添加到SCID猪的饲养方案中，从而形成一个更具可重复性的模型。
