Department of Urology, Laboratory of Reconstructive Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
Department of Statistics and Probability, Michigan State University, East Lansing, MI, USA.
FASEB J. 2020 Aug;34(8):11200-11214. doi: 10.1096/fj.202000786R. Epub 2020 Jul 9.
The relationship of gut microbiota and calcium oxalate stone has been limited investigated, especially with no study of gut microbiota and short chain fatty acids (SCFAs) in nephrolithiasis. We provided Sprague Dawley rats of renal calcium oxalate stones with antibiotics and examined the renal crystals deposition. We also performed a case-control study by analyzing 16S rRNA microbial profiling, shotgun metagenomics and SCFAs in 153 fecal samples from non-kidney stone (NS) controls, patients with occasional renal calcium oxalate stones (OS) and patients with recurrent stones (RS). Antibiotics reduced bacterial load in feces and could promote the formation of renal calcium crystals in model rats. In addition, both OS and RS patients exhibited higher fecal microbial diversity than NS controls. Several SCFAs-producing gut bacteria, as well as metabolic pathways associated with SCFAs production, were considerably lower in the gut microbiota among the kidney stone patients compared with the NS controls. Representation of genes involved in oxalate degradation showed no significance difference among groups. However, fecal acetic acid concentration was the highest in RS patients with high level of urinary oxalate, which was positively correlated with genes involvement in oxalate synthesis. Administration of SCFAs reduced renal crystals. These results shed new light on bacteria and SCFAs, which may promote the development of treatment strategy in nephrolithiasis.
肠道微生物群与草酸钙结石的关系尚未得到广泛研究,尤其是在肾结石中,尚未研究过肠道微生物群与短链脂肪酸(SCFAs)的关系。我们用抗生素处理患有肾草酸钙结石的 Sprague Dawley 大鼠,并检查肾脏晶体沉积。我们还通过分析 16S rRNA 微生物谱、宏基因组和 153 份非肾结石(NS)对照、偶发性肾草酸钙结石(OS)患者和复发性结石(RS)患者的粪便样本中的 SCFAs,进行了病例对照研究。抗生素减少了粪便中的细菌负荷,并可促进模型大鼠肾脏钙晶体的形成。此外,OS 和 RS 患者的粪便微生物多样性均高于 NS 对照组。与 NS 对照组相比,肾结石患者的肠道微生物群中几种产生 SCFAs 的肠道细菌以及与 SCFAs 产生相关的代谢途径显著减少。参与草酸降解的基因在各组之间没有显著差异。然而,RS 患者粪便中的乙酸浓度最高,其尿液中的草酸水平也很高,这与参与草酸合成的基因呈正相关。SCFAs 的给药减少了肾脏晶体。这些结果为细菌和 SCFAs 提供了新的认识,这可能有助于制定肾结石的治疗策略。