利用宏基因组学技术探讨特发性草酸钙结石患者肠道菌群与结石形成危险因素的相关性研究

urolithiasis is the most common disease of urology.Calcium oxalate is the most common composition of urinary stones and idiopathic calcium oxalate stones are the most common type with unknown etiology and high recurrence rate.The prevention of idiopathic calcium oxalate stones is difficult because of unknown etiology,but were influenced by various genes and factors,such as hyperoxaluria,hypocitraturia,hypercalciuria,hyperuricosuria,which is the most important risk factors of stone formation. Previous study showed that the indigestion and absorption of oxalate in gut influence oxalate concentration in urine.Some bacteria with potency of oxalate degradation in gut influence hyperoxaluria.But up to day there was no study on relationship between gut flora in patients with idiopathic calcium oxalate stone and stone formation risk factors from overall level. In order to investigate the etiology of idiopathic calcium oxalate stone,the relationship between the gut flora and stone formation risk factors is the key factor. 60 idiopathic calcium oxalate stone patients（proved by infrared spectroscopy）will be recruited into the study，the gut flora was analyzed by metagenomic sequencing technology,and the urine concentration of oxalic acid, citric acid, uric acid were detected by ion chromatography.To explore the relationship between specific gut flora from patients with idiopathic calcium oxalate stone and stone formation factors,such as hyperoxaluria,hypocitraturia,hypercalciuria, hyperuricosuria,which will provide a new way to explore the etiology and prevention of calcium oxalate stones.

尿路结石是泌尿外科最常见疾病之一，草酸钙结石是最常见的尿路结石成份，绝大多数草酸钙结石缺乏明确病因故命名为特发性草酸钙结石。特发性草酸钙结石复发率高，难以预防是由于特发性高草酸钙结石病因不明，目前认为是多基因多因素作用的结果，而各种原因导致的高草酸尿、高钙尿、高尿酸尿、低枸橼酸尿石最重要的成石危险因素。现有研究表明胃肠道内草酸代谢和吸收对尿草酸排泄有重要影响，包括我们前期研究在内的众多研究工作发现肠道内存在可代谢草酸并对尿草酸排泄产生影响的菌群。另有研究表明草酸钙结石患者肠道内菌群与正常人存在明显差异，提示肠道菌群与结石发病可能有关，但未有研究从整体角度探讨肠道菌群与成石危险因素相关，因此本课题拟通过宏基因组学技术对60名特发性草酸钙结石患者肠道菌群及功能基因进行测序，并按成石危险因素分组分析肠道菌群差异和特点，为特发性草酸钙结石病因探索提供新思路。

尿路结石是泌尿外科最常见疾病之一，草酸钙结石是最常见的尿路结石成份，绝大多数草酸钙结石缺乏明确病因故命名为特发性草酸钙结石。特发性草酸钙结石复发率高，难以预防是由于特发性高草酸钙结石病因不明，目前认为是多基因多因素作用的结果。现有研究表明胃肠道内草酸代谢和吸收对尿草酸排泄有重要影响，包括我们前期研究在内的众多研究工作发现肠道内存在可代谢草酸并对尿草酸排泄产生影响的菌群。另有研究表明草酸钙结石患者肠道内菌群与正常人存在明显差异，提示肠道菌群与结石发病可能有关，但未有研究从整体角度探讨肠道菌群与成石危险因素相关，因此本课题通过宏基因组学技术对60名特发性草酸钙结石患者肠道菌群及功能基因进行测序，并按成石危险因素分组分析肠道菌群差异和特点。我们成功的收集了特发性高草酸钙患者的粪便标本和尿样标本，并对患者结石进行了成分分析，随后对粪便标本进行了测序，结果提示：与对照组比较，大量肠道微生物基因为患者所特有，这些特有的微生物基因可能是特发性草酸钙结石的致病或者保护基因；患者组或健康对照组肠道微生物在目科属水平上均有显著差异；teroides_coprocola_CAG_162，g_Paraprevotella，s_Clostridium_sp_ CAG_7可以作为生物标记物种；egNOG分析提示患者组或健康对照组之间存在较多的直系同源簇，这些蛋白可能行使致病或者保护功能。总之，该课题揭示了患者和健康人群在微生物总体基因构成、物种组成和微生物功能组成上均有显著差异，为特发性草酸钙结石在病因、治疗及预防方面提供了新的策略。