The Relationship between Gut Microbiota and Short Chain Fatty Acids in the Renal Calcium Oxalate Stones Disease

Abstract

Background: 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. Methods: 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). Findings: 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. Interpretation: Depletion of gut microbiota promoted the formation of renal crystals. Fecal SCFAs dominant patients, with altered gut microbiota composition and the functional metagenome, were associated with oxalate synthesis. Funding Statement: This work was supported by the National Natural Science Foundation of China [81770703, 81970602]; the Foundation of Science & Technology Department of Sichuan Province [2018SZ0118]; and the 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University [ZYGD18011, ZYJC18015, ZY2016104]. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: The animal experiment was performed in accordance with the policies of the West China Hospital of Sichuan University Medical Research Ethics Committee (2017063A). This study was approved by the West China Hospital of Sichuan University Medical Research Ethics Committee (2018182), and informed consents were obtained from each participant.