Weagley James, Makimaa Heyde, Cárdenas Luis Alberto Chica, Romani Ana, Sullender Meagan, Aggarwal Somya, Hogarty Michael, Rodgers Rachel, Kennedy Elizabeth, Foster Lynne, Schriefer Lawrence A, Baldridge Megan T
Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
bioRxiv. 2025 Jan 15:2025.01.15.633206. doi: 10.1101/2025.01.15.633206.
Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transplantation of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of fecal or cecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, fecal transplantation, and cecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored microbial populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR, and shotgun sequencing of viral-like particles. As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transplanted control mice. While all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. This study provides valuable insights into microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transplantation in mouse models.
小鼠模型是用于辨别宿主和微生物遗传学对疾病相对贡献的重要工具，通常需要在不同小鼠品系之间进行微生物群移植。移植方法包括对受体进行抗生素处理，以及通过与供体合笼饲养或移植粪便或盲肠供体材料进行定殖。然而，这些方法在用供体微生物重建受体方面的效率和动态变化尚未得到充分了解。因此，我们直接比较了合笼饲养、粪便移植和盲肠移植方法。来自Taconic Biosciences的供体小鼠拥有独特的微生物群落，作为来自Jackson Laboratories的受体小鼠的微生物来源，受体小鼠接受抗生素处理以破坏其原生微生物群。我们在抗生素治疗和重建过程中，使用16S rRNA基因测序、定量PCR和病毒样颗粒的鸟枪法测序对微生物种群进行纵向监测。正如预期的那样，抗生素治疗迅速消耗了微生物生物量和多样性，未移植的对照小鼠的微生物群自然恢复缓慢且不完全。虽然所有移植方法都用供体微生物群重建了受体小鼠，但合笼饲养在细菌和病毒群落方面都能更快地实现这一点。这项研究为微生物移植方法提供了有价值的见解，提高了可重复性，并为小鼠模型中微生物群移植的最佳实践提供了参考。
