Natural Transmission of Helicobacter saguini Causes Multigenerational Inflammatory Bowel Disease in C57/129 IL-10-/- Mice.
Natural Transmission of Helicobacter saguini Causes Multigenerational Inflammatory Bowel Disease in C57/129 IL-10-/- Mice.
复制标题
沙吉尼螺杆菌的自然传播导致 C57/129 IL-10-/- 小鼠多代炎症性肠病。
DOI：
10.1128/msphere.00011-20
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发表时间：
2020
期刊：
影响因子：
4.8
通讯作者：
Fox,JamesG
中科院分区：
文献类型：
--
作者：
Mannion,Anthony;Shen,Zeli;Feng,Yan;Puglisi,Dylan;Muthupalani,Sureshkumar;Whary,MarkT;Fox,JamesG
棉顶绢毛猴（CTT）是人类炎症性肠病（IBD）的理想模型，因为这些动物会发展多代，下肠癌。我们以前从IBD CTT中分离并鉴定了一种新的肠肝螺杆菌，即Saguini螺杆菌，并证明H。无菌C57 BL IL-10−/−小鼠中的saguini感染重现IBD，表明H. saguini影响IBD的发病机制。在这项研究中，我们利用无菌IL-10−/−模型来说明H. Saguiniinfection可自然传播并感染四代，并引起显著的肠道炎症病理。此外，全基因组测序的代表H。从每一代IL-10−/−小鼠中分离出的saguiniisolates揭示了暗示多代进化的基因突变。总的来说，这些结果支持具有致病潜力的特定细菌物种，如H。saguini是CTT中IBD发病机制中的可传播微生物，并加强了特定微生物群在人类IBD发病机制中的重要性。重要提示虽然家族史是发生炎症性肠病（IBD）的重要危险因素，但尚不清楚来自父母的微生物群是否对其后代的疾病具有可传播影响。此外，目前还不清楚IBD相关微生物是否在多代传播和宿主中的慢性定植过程中经历基因组适应。在此，我们表明，从患有家族性IBD的非人灵长类动物中分离出的单一细菌物种，即螺杆菌saguini，在无菌IL-10−/−小鼠中可从父母传播给后代，并导致多代IBD。此外，还对H.从不同代小鼠中分离的saguini鉴定了环境相互作用、营养代谢和毒力因子基因的微进化，这表明多代传播可能促进与新宿主和慢性炎症环境中的定植和存活相关的适应。我们的研究结果强调了具有致病潜力的特定细菌物种的重要性，如H。saguini是IBD发病机制中的传播微生物。
Cotton-top tamarins (CTTs) are an ideal model of human inflammatory bowel disease (IBD) because these animals develop multigenerational, lower bowel cancer. We previously isolated and characterized a novel enterohepaticHelicobacterspecies, Helicobacter saguini, from CTTs with IBD and documented that H. saguini infection in germfree C57BL IL-10−/−mice recapitulates IBD, suggesting thatH. saguiniinfluences IBD etiopathogenesis. In this study, we utilized a germfree IL-10−/−model to illustrate thatH. saguiniinfection can naturally transmit and infect four generations and cause significant intestinal inflammatory pathology. Additionally, whole-genome sequencing of representativeH. saguiniisolates from each generation of IL-10−/−mice revealed gene mutations suggestive of multigenerational evolution. Overall, these results support that specific bacterial species with pathogenic potential, likeH. saguini, are transmissible microorganisms in the etiopathogenesis of IBD in CTTs and reinforces the importance of specific microbiota in the pathogenesis of IBD in humans.IMPORTANCEWhile family history is a significant risk factor for developing inflammatory bowel disease (IBD), it is unclear whether the microbiome from parents is a transmissible influence on disease in their offspring. Furthermore, it is unknown whether IBD-associated microbes undergo genomic adaptations during multigenerational transmission and chronic colonization in their hosts. Herein, we show that a single bacterial species, Helicobacter saguini, isolated from a nonhuman primate species with familial IBD, is transmissible from parent to offspring in germfree IL-10−/−mice and causes multigenerational IBD. Additionally, whole-genome sequence analysis ofH. saguiniisolated from different mouse generations identified microevolutions in environmental interaction, nutrient metabolism, and virulence factor genes that suggest that multigenerational transmission may promote adaptations related to colonization and survival in new hosts and chronic inflammatory environments. The findings from our study highlight the importance of specific bacterial species with pathogenic potential, likeH. saguini, as transmissible microorganisms in the etiopathogenesis of IBD.