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Oxalobacter formigenes colonization and oxalate excretion in calcium oxalate kidney stone disease

Oxalobacter formigenes colonization and oxalate excretion in calcium oxalate kidney stone disease
草酸钙肾结石病中产草酸杆菌的定植和草酸盐排泄
批准号:
9896806
负责人:
John Knight
金额:
$44.21万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-02-01 至 2023-01-31

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中文摘要
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英文摘要
Project Summary Calcium oxalate kidney stone disease occurs in approximately 9 % of the U.S. population and contributes significantly to health care costs. Small reductions in urinary oxalate excretion are thought to limit stone risk. Recent studies have indicated that a lack of Oxalobacter formigenes colonization is a significant risk factor for calcium oxalate kidney stone formation. Our Preliminary data shows that healthy human subjects lacking O.formigenes can be readily colonized with live preparations of O.formigenes. This ability to colonize individuals offers a powerful means of assessing responses to varying diets before and after colonization. It is still not clear under what conditions O.formigenes modifies stone risk, and much still needs to be learned about how this organism establishes and maintains gut colonization. In the previous funding cycle we identified in a mouse model conditions that influence the growth of O.formigenes in the gut, its degradation of oxalate in the gut, its effects on the amount of oxalate excreted in urine and into the intestine, and its sustainability in the absence of dietary oxalate. In this application we will extend these findings to humans by examining individuals before and after colonization with O.formigenes. Diets controlled in their contents of oxalate, calcium and other nutrients, including a diet ultra-low in oxalate, will be used to examine the interaction between diet, O.formigenes colonization and urinary oxalate excretion. This proposal will use spinach that contains carbon 13-oxalate to accurately determine whether colonization modifies the response to an oxalate-rich meal. Continuous intravenous infusions of the stable, non-radioactive oxalate isotope, 13C2- oxalate, before and after colonization will directly determine if gastrointestinal oxalate secretion occurs and whether colonization influences such secretion. Recent evidence suggests individuals are colonized with different strains and in some cases more than one strain. However, it is not known whether the biological differences between strains influence colonization persistence and urinary oxalate excretion and this will be examined in this application. If the specific aims are successfully completed they will provide valuable information about the importance of O.formigenes colonization in influencing oxalate levels, will create insight into the factors that impact O.formigenes colonization, and will help identify new strategies for modifying the gut milieu and calcium oxalate kidney stone risk.
期刊论文(7)
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会议论文
DOI: 10.1016/j.urology.2014.11.013
发表时间: 2015-03
期刊: Urology
影响因子: 2.1
作者: [Ellis ML, Shaw KJ, Jackson SB, Daniel SL, Knight J]
通讯作者: Knight J
DOI: 10.1007/s00203-016-1272-y
发表时间: 2016-12
期刊: ARCHIVES OF MICROBIOLOGY
影响因子: 2.8
作者: [Ellis, Melissa L., Dowell, Alexander E., Li, Xingsheng, Knight, John]
通讯作者: Knight, John
DOI: 10.1053/j.jrn.2021.03.011
发表时间: 2022-05
期刊: Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation
影响因子: --
作者: [Borin JF, Knight J, Holmes RP, Joshi S, Goldfarb DS, Loeb S]
通讯作者: Loeb S
DOI: 10.4172/jpb.1000384
发表时间: 2016
期刊: Journal of proteomics & bioinformatics
影响因子: --
作者: [Ellis ME, Mobley JA, Holmes RP, Knight J]
通讯作者: Knight J
Oxalate formation from ascorbic acid
Oxalate formation from ascorbic acid
Oxalate formation from ascorbic acid
Oxalobacter formigenes colonization and oxalate excretion in calcium oxalate kidney stone disease
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