Miller Aaron W, Dale Colin, Dearing M Denise
Departments of Urology and Immunology, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Biology, University of Utah, Salt Lake City, Utah, USA.
mSystems. 2017 Sep 26;2(5). doi: 10.1128/mSystems.00088-17. eCollection 2017 Sep-Oct.
For mammals, oxalate enters the body through the diet or is endogenously produced by the liver; it is removed by microbial oxalate metabolism in the gut and/or excretion in feces or urine. Deficiencies in any one of the these pathways can lead to complications, such as calcium oxalate urinary stones. While considerable research has been conducted on individual oxalate-degrading bacterial isolates, interactions between oxalate and the gut microbiota as a whole are unknown. We examined the reduction in oxalate excretion in a rat model following oral administration of fecal microbes from a mammalian herbivore adapted to a high oxalate diet or to fecal transplants consisting of two different formulations of mixed oxalate-degrading isolates. While all transplants elicited a significant reduction in oxalate excretion initially, the greatest effect was seen with fecal microbial transplants, which persisted even in the absence of dietary oxalate. The reduction in oxalate excretion in animals given fecal transplants corresponded with the establishment of diverse bacteria, including known oxalate-degrading bacteria and a cohesive network of bacteria centered on oxalate-degrading specialists from the family. Results suggested that the administration of a complete community of bacteria facilitates a cohesive balance in terms of microbial interactions. Our work offers important insights into the development of targeted bacteriotherapies intended to reduce urinary oxalate excretion in patients at risk for recurrent calcium oxalate stones as well as bacteriotherapies targeting other toxins for elimination. Oxalate is a central component in 80% of kidney stones. While mammals do not possess the enzymes to degrade oxalate, many gastrointestinal bacteria are efficient oxalate degraders. We examined the role of cohesive microbial networks for oxalate metabolism, using Sprague-Dawley rats as a model host. While the transplantation of oxalate-degrading bacteria alone to the Sprague-Dawley hosts did increase oxalate metabolism, fecal transplants from a wild mammalian herbivore, , had a significantly greater effect. Furthermore, the boost for oxalate metabolism persisted only in animals that received fecal transplants. Animals receiving fecal transplants had a more diverse and cohesive network of bacteria associated with the , a family known to consist of specialist oxalate-degrading bacteria, than did animals that received oxalate-degrading bacteria alone. Our results indicate that fecal transplants are more effective at transferring specific functions than are microbial specialists alone, which has broad implications for the development of bacteriotherapies.
对于哺乳动物来说，草酸盐通过饮食进入体内，或由肝脏内源性产生；它通过肠道内微生物对草酸盐的代谢和/或随粪便或尿液排出体外而被清除。这些途径中任何一条出现缺陷都可能导致并发症，比如草酸钙尿路结石。虽然对单个草酸盐降解细菌分离株已经进行了大量研究，但草酸盐与整个肠道微生物群之间的相互作用尚不清楚。我们在大鼠模型中研究了口服来自适应高草酸盐饮食的哺乳动物食草动物的粪便微生物或由两种不同配方的混合草酸盐降解分离株组成的粪便移植后草酸盐排泄量的减少情况。虽然所有移植最初都引起了草酸盐排泄量的显著减少，但粪便微生物移植的效果最为显著，即使在没有饮食草酸盐的情况下这种效果仍然持续。接受粪便移植的动物草酸盐排泄量的减少与多种细菌的定植相对应，这些细菌包括已知的草酸盐降解细菌以及以该科草酸盐降解专家为中心的紧密细菌网络。结果表明，给予完整的细菌群落有助于在微生物相互作用方面实现紧密的平衡。我们的工作为开发旨在减少复发性草酸钙结石风险患者尿草酸盐排泄的靶向细菌疗法以及针对其他毒素清除的细菌疗法提供了重要见解。草酸盐是80%肾结石的核心成分。虽然哺乳动物不具备降解草酸盐的酶，但许多胃肠道细菌是高效的草酸盐降解者。我们以Sprague-Dawley大鼠作为模型宿主，研究了紧密微生物网络在草酸盐代谢中的作用。虽然单独将草酸盐降解细菌移植到Sprague-Dawley宿主中确实增加了草酸盐代谢，但来自野生哺乳动物食草动物的粪便移植效果显著更强。此外，草酸盐代谢的增强仅在接受粪便移植的动物中持续存在。接受粪便移植的动物与一个已知由草酸盐降解专家组成的科相关的细菌网络比仅接受草酸盐降解细菌移植的动物更加多样化和紧密。我们的结果表明，粪便移植在转移特定功能方面比单独的微生物专家更有效，这对细菌疗法的发展具有广泛的意义。
