Presentation Authors: Kunjie Wang*, Yu Liu, Liang Zhou, Yi Li, Qun Sun, Zude Chen, Qingyao Jiang, Liang Cheng, Lei Tian, Hong Li, Chengdu, China, People's Republic of
Introduction: Calcium oxalate stone (60%-90%) is the most common type of nephrolithiasis, while the etiology is still unclear. Emerging evidence has linked the gut microbiome to nephrolithiasis. Some studies found that Oxalobacter formigenes, a member of the human gut microbiome, can degrade oxalate and obtain energy from it, which may decrease the level of oxalate in serum and urine. However, several prospective researches indicated that patients with calcium oxalate stones showed no significant change in urinary oxalate after oral administration of O. formigenes. Thus, the objectives of the study were to continually explore the gut microbiome and their metabolite which may play a major role in the formation of calcium oxalate stones.
Methods: We performed microbiome analysis using 16S ribosomal RNA (rRNA) amplicon sequencing on fecal samples from 160 Chinese individuals, including 23 with recurrent renal calcium oxalate stones (RS), 53 with single stones (SS) and 84 non-stones (NS) people. The Î± and Î² diversity analyses were performed with Mothur and QIIME, respectively. LefSe analysis was also employed to filter out significant gut bacteria between patients with nephrolithiasis and healthy people. Random forests analysis was used to find which Operational Taxonomic Units (OTUs) are of vital roles in predicting stone/non-stone status. Furthermore, we fed stoneâ€‘forming Spragueâ€“Dawley rats with or without acetic acid and examined the change of amount of crystal in kidney.
Results: We identified that RS (Chao1 index 3057.7Â±915.67 vs 2371.1Â±1233.6, p=0.015) and SS patients (Chao1 index 2899Â±1081.5 vs 2371.1Â±1233.6, p=0.012) both exhibited higher fecal microbial diversity than controls. We also found significant associations between total community composition and disease status by assessing Î² diversity. At phylum level, Firmicutes-Bacteroidetes ratio in RS group (3.595) was the highest, followed by OS (2.789) and NS group (2.646). At genus level, the abundance of Blautia, Lachnospiraceae, [Eubacterium] hallii and Faecalibacterium, all producing short chain fatty acids (SCFAs) (like acetic acid, propionic acid and butyric acid), were significantly lower in stone patientsâ€™ gut microbiome, while Megamonasc, Lachnoclostridium, Acinetobacter, Halomonas, Empedobacter, Cellulosilyticum, Brevinema, Anaerosalibacter, Nocardia, Syntrophobacter were higher. By random forests analysis, we found 43 bacteria of great importance and then formed a predicting model based on them (area under curve = 0.76). In addition, the percentage of stone-forming rats who had kidney crystal decreased from 60% to 20% after oral administration of acetic acid.
Conclusions: Our findings revealed association between gut microbiome alterations and renal calcium oxalate stones. SCFAs may prevent stone formation while the underlying mechanism is still unknown. It may be possible to prevent kidney stones by regulating gut microbiome composition and SCFAs production. We are likely to predict the formation of calcium oxalate stones by analyzing the composition of gut microbiome; however, further large-scale, multi-center researches are required to optimize the predicting model.
Source of Funding: This study was supported by the National Natural Science Foundation of China (81770703, 81800667), Project of Science and Technology Department of Sichuan Province (2018SZ0118) and 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan