Unraveling the role of gut microbiota by fecal microbiota transplantation in rat model of kidney stone disease.

Emerging research on the microbiome highlights the significant role of gut health in the development of kidney stones, indicating that an imbalance in gut bacteria or dysbiosis can influence the formation of stones by altering oxalate metabolism and urinary metabolite profiles. In particular, the overabundance of specific bacteria such as Enterococcus and Oxalobacter spp., which are known to affect oxalate absorption, is observed in patients with urolithiasis. This study investigates the effects of gut dysbiosis on urolithiasis through fecal microbiota transplantation (FMT) from patients to rats and its impact on urinary mineral excretion and stone formation. Fecal samples from eight patients with calcium oxalate stones and ten healthy volunteers were collected to assess the gut microbiome. These samples were then transplanted to antibiotic-pretreated Wistar rats for a duration of four weeks. After transplantation, we evaluated changes in the fecal gut microbiome profile, urinary mineral excretion rates, and expression levels of intestinal zonula occluden-1 (ZO-1), SLC26A6 and renal NF-κB. In humans, patients with urolithiasis exhibited increased urinary calcium and oxalate levels, along with decreased citrate excretion and increased urinary supersaturation index. The fecal microbiota showed a notable abundance of Bacteroidota. In rodents, urolithiasis-FMT rats showed urinary disturbances similar to patients, including elevated pH, oxalate level, and supersaturation index, despite negative renal pathology. In addition, a slight elevation in the expression of renal NF-κB, a significant intestinal SLC26A6, and a reduction in ZO-1 expression were observed. The gut microbiome of urolithiasis-FMT rats showed an increased abundance of Bacteroidota, particularly Muribaculaceae, compared to their healthy FMT counterparts. In conclusion, the consistent overabundance of Bacteroidota in both urolithiasis patients and urolithiasis-FMT rats is related to altered intestinal barrier function, hyperoxaluria, and renal inflammation. These findings suggest that gut dysbiosis, characterized by an overgrowth of Bacteroidota, plays a crucial role in the pathogenesis of calcium oxalate urolithiasis, underscoring the potential of targeting the gut microbiota as a therapeutic strategy.

The Role of the Gut Microbiome in Kidney Stone Disease.

Microbiome dysbiosis is closely related to the etiology of kidney stone disease (KSD) and influences a multitude of pathways. Due to our knowledge gaps on this topic, it is still unclear if microbiome interventions can be translated to demonstrate clinical efficacy. Current evidence suggests that the enhancement of butyrate-producing pathways should be the next step for KSD research. While we are not yet at a point where we can make clinical recommendations for KSD, there are many simple dietary or supplement-based approaches that could be applied in the future for prophylaxis or treatment of KSD.

The direct inhibitory effects of Lactobacillus acidophilus, a commensal urinary bacterium, on calcium oxalate stone development.

BACKGROUND: Lactobacillus acidophilus is a commensal urinary bacterium found more abundantly in healthy individuals than in stone patients. Hence, it has been proposed to play an inhibitory role in kidney stone disease (KSD) but with unclear mechanisms. We therefore investigated the direct effects of L. acidophilus on calcium oxalate (CaOx) stone development compared with Escherichia coli, which is known to promote CaOx stone formation. RESULTS: L. acidophilus at 1 × 103 CFU/ml  significantly reduced the abundance of newly formed crystals, enlargement and aggregation of seeded crystals, and crystal adhesion on renal cell membranes. By contrast, E. coli at 1 × 103 CFU/ml significantly enhanced crystal growth and aggregation but did not affect crystallization and crystal-cell adhesion. Oxalate consumption assay showed that neither L. acidophilus nor E. coli significantly reduced the remaining oxalate level after 1 - 3 h incubation. However, both of them adhered to CaOx crystals. Surface component detection revealed that only L. acidophilus expressed S-layer protein, whereas only E. coli exhibited flagella on their surfaces. Removal of L. acidophilus S-layer protein and E. coli flagella completely abolished the inhibitory and promoting effects of L. acidophilus and E. coli, respectively. CONCLUSIONS: L. acidophilus inhibits CaOx stone development by hampering crystallization, growth, aggregation and cell-adhesive ability of CaOx. By contrast, E. coli enhances CaOx stone development by promoting CaOx growth and aggregation. Their contradictory effects are most likely from differential surface components (i.e., S-layer protein on L. acidophilus and flagella on E. coli) not from oxalate-degrading ability. Video Abstract.

Species-level characterization of gut microbiota and their metabolic role in kidney stone formation using full-length 16S rRNA sequencing.

The critical role of the human gut microbiota in kidney stone formation remains largely unknown, due to the low taxonomic resolution of previous sequencing technologies. Therefore, this study aimed to explore the gut microbiota using high-throughput sequencing to provide valuable insights and identify potential bacterial species and metabolite roles involved in kidney stone formation. The overall gut bacterial community and its potential functions in healthy participants and patients were examined using PacBio sequencing targeting the full-length 16S rRNA gene, coupled with stone and statistical analyses. Most kidney stones comprised calcium oxalate and calcium phosphate (75%), pure calcium oxalate (20%), and calcium phosphate and magnesium phosphate (5%), with higher content of Ca (130,510.5 ± 108,362.7 ppm) followed by P (18,746.4 ± 23,341.2 ppm). The microbial community structure was found to be weaker in patients' kidney stone samples, followed by patients' stool samples, than in healthy participants' stool samples. The most abundant bacterial species in kidney stone samples was uncultured Morganella, whereas that in patient and healthy participant stool samples was Bacteroides vulgatus. Similarly, Akkermansia muciniphila was significantly enriched in patient stool samples at the species level, whereas Bacteroides plebeius was significantly enriched in kidney stone samples than that in healthy participant stool samples. Three microbial metabolic pathways, TCA cycle, fatty acid oxidation, and urea cycle, were significantly enriched in kidney stone patients compared to healthy participants. Inferring bacteria at the species level revealed key players in kidney stone formation, enhancing the clinical relevance of gut microbiota.

The urinary microbiota composition and functionality of calcium oxalate stone formers.

Background: Accumulated evidences indicate that dysbiosis of the urinary microbiota is associated with kidney stone formation. In the present study, we aimed to investigate the urinary microbiota composition and functionality of patients with calcium oxalate stones and compare it with those of healthy individuals. Method: We collected bladder urine samples from 68 adult patients with calcium oxalate stones and 54 age-matched healthy controls by transurethral catheterization. 16S rRNA gene and shotgun sequencing were utilized to characterize the urinary microbiota and functionality associated with calcium oxalate stones. Results: After further exclusion, a total of 100 subjects was finally included and analyzed. The diversity of the urinary microbiota in calcium oxalate stone patients was not significantly different from that of healthy controls. However, the urinary microbiota structure of calcium oxalate stone formers significantly differed from that of healthy controls (PERMANOVA, r = 0.026, P = 0.019). Differential representation of bacteria (e.g., Bifidobacterium) and several enriched functional pathways (e.g., threonine biosynthesis) were identified in the urine of calcium oxalate stone patients. Conclusion: Our results showed significantly different urinary microbiota structure and several enriched functional pathways in calcium oxalate stone patients, which provide new insight into the pathogenesis of calcium oxalate stones.

Deficient butyrate metabolism in the intestinal microbiome is a potential risk factor for recurrent kidney stone disease.

Intestinal microbiome dysbiosis is a known risk factor for recurrent kidney stone disease (KSD) with prior data suggesting a role for dysfunctional metabolic pathways other than those directly utilizing oxalate. To identify alternative mechanisms, the current study analyzed differences in the metabolic potential of intestinal microbiomes of patients (n = 17) and live-in controls (n = 17) and determined their relevance to increased risk for KSD using shotgun metagenomic sequencing. We found no differences in the abundance of genes associated with known oxalate degradation pathways, supporting the notion that dysfunction in other metabolic pathways plays a role in KSD. Further analysis showed decreased abundance of key enzymes involved in butyrate biosynthesis in patient intestinal microbiomes. Furthermore, de novo construction of microbial genomes showed that the majority of genes significantly enriched in non-stone formers are affiliated with Faecalibacterium prausnitzii, a major butyrate producer. Specifically pertaining to butyrate metabolism, the majority of abundant genes mapped back to F. prausnitzii, Alistipes spp., and Akkermansia muciniphila. No differences were observed in ascorbate or glyoxylate metabolic pathways. Collectively, these data suggest that impaired bacterial-associated butyrate metabolism may be an oxalate-independent mechanism that contributes to an increased risk for recurrent KSD. This indicates that the role of the intestinal microbiome in recurrent KSD is multi-factorial, which is representative of the highly intertwined metabolic nature of this complex environment. Future bacteria-based treatments must not be restricted to targeting only oxalate metabolism.

Synergistic effect of doxycycline and aqueous extract of irradiated khella on structure of nanobacteria isolated from kidney stones: In vitro and in vivo studies.

Kidney stones have been associated with an increased risk of chronic kidney diseases, end-stage renal failure. This study is devoted to isolate nanobacteria from patients with active urolithiasis and investigate the in vitro and in vivo antinanobacterial activity of some antibiotics alone or in combination with extracts of irradiated herbs from certain medicinal plants. Nanobacteria were detected using scanning (SEM) and transmission (TEM) electron microscopy, protein electrophoresis (SDS-PAGE) and DNA profile. The antimicrobial susceptibility of some biofilm-producing nanobacterial isolates was evaluated. The effect of medicinal plant extracts on growth was tested. A combination treatment between the most potent extracts and antibiotics was tested on biofilm production, protein profile, release of 260 nm absorbing material, protein content, and ultrastructure of the strongest biofilm producers. In vivo study of nanobacteria and its treatment by the most potent agents was evaluated on male rats. Renal function was measured in serum; histological examination and oxidative stress parameters were determined in kidney tissues. Results showed that streptomycin, trimethoprim/sulfamethoxazole, doxycycline, and water extracts of irradiated khella at 6 kGy had antinanobacterial activity. Meanwhile, the synergistic effect of the aqueous extract of irradiated Khella and doxycycline showed higher inhibition activity on microbial growth and biofilm production. They affected dramatically the strength of its cell membrane and subsequently its ultrastructure. Moreover, these results are confirmed by ameliorations in renal function and histological alterations. It could be concluded that the combination of DO and an aqueous extract of irradiated khella has an antinephrotoxic effect against nanobacteria-induced renal toxicity.

Gut microbiota in patients with kidney stones: a systematic review and meta-analysis.

BACKGROUND: Mounting evidence indicates that the gut microbiome (GMB) plays an essential role in kidney stone (KS) formation. In this study, we conducted a systematic review and meta-analysis to compare the composition of gut microbiota in kidney stone patients and healthy individuals, and further understand the role of gut microbiota in nephrolithiasis. RESULTS: Six databases were searched to find taxonomy-based comparison studies on the GMB until September 2022. Meta-analyses were performed using RevMan 5.3 to estimate the overall relative abundance of gut microbiota in KS patients and healthy subjects. Eight studies were included with 356 nephrolithiasis patients and 347 healthy subjects. The meta-analysis suggested that KS patients had a higher abundance of Bacteroides (35.11% vs 21.25%, Z = 3.56, P = 0.0004) and Escherichia_Shigella (4.39% vs 1.78%, Z = 3.23, P = 0.001), and a lower abundance of Prevotella_9 (8.41% vs 10.65%, Z = 4.49, P < 0.00001). Qualitative analysis revealed that beta-diversity was different between the two groups (P < 0.05); Ten taxa (Bacteroides, Phascolarctobacterium, Faecalibacterium, Flavobacterium, Akkermansia, Lactobacillus, Escherichia coli, Rhodobacter and Gordonia) helped the detection of kidney stones (P < 0.05); Genes or protein families of the GMB involved in oxalate degradation, glycan synthesis, and energy metabolism were altered in patients (P < 0.05). CONCLUSIONS: There is a characteristic gut microbiota dysbiosis in kidney stone patients. Individualized therapies like microbial supplementation, probiotic or synbiotic preparations and adjusted diet patterns based on individual gut microbial characteristics of patients may be more effective in preventing stone formation and recurrence.

Characterization of Biofilm Producer Nanobacteria Isolated from Kidney Stones of Some Egyptian Patients.

<b>Background and Objective:</b> Nanobacteria (NB) appear to contribute to many calcifying diseases including kidney stones which represent a common problem with inadequate prevention exist. NB framing itself with a mineral coat that assists as a primary defence shield against the immune system, antibiotics. This study aims to collect and detect nanobes from different kidney stones from patients with active urolithiasis then investigated the anti-nano-bacterial activity of some antibiotics alone or in combination with extracts of irradiated herbs of certain medicinal plants which will represent a new approach to therapy for patients with kidney stones. <b>Materials and Methods:</b> Total of 32 nanobes were isolated from 54 kidney stones. Fourier Transforms Infrared Spectroscopy (FTIR) revealed that calcium and phosphate are the main components of stones. Scanning Electron Microscopy (SEM) with Energy-dispersive X-ray spectroscopy (EDX) and Transmission Electron Microscope (TEM), showed that nanobes were Gram-ve cocci with size ranged from (375:600 nm). The biofilm production ability of nanobes was estimated qualitatively and quantitatively. <b>Results:</b> The results revealed that all were strong biofilm producers. Further, the antibiotic susceptibility test indicates their resistance towards most of the tested antibiotics. Molecular identification of the strong biofilm producer isolates by ribosomal ribonucleic acid (rRNA) revealed that it is indicated by 85.37% to <i>Bartonella apis</i> strain PEB0122. <b>Conclusion:</b> The findings of the current study evidenced that combination treatment between Doxycycline (DO) and water extract of khella exhibited a significant reduction in biofilm formation ability of the strongest producers nanobes. Therefore, this treatment can play a role in enhancing public health, especially with patients who suffer from recurrent kidney stone formation.

Recent advances on the mechanisms of kidney stone formation (Review).

Kidney stone disease is one of the oldest diseases known to medicine; however, the mechanisms of stone formation and development remain largely unclear. Over the past decades, a variety of theories and strategies have been developed and utilized in the surgical management of kidney stones, as a result of recent technological advances. Observations from the authors and other research groups suggest that there are five entirely different main mechanisms for kidney stone formation. Urinary supersaturation and crystallization are the driving force for intrarenal crystal precipitation. Randall's plaques are recognized as the origin of calcium oxalate stone formation. Sex hormones may be key players in the development of nephrolithiasis and may thus be potential targets for new drugs to suppress kidney stone formation. The microbiome, including urease­producing bacteria, nanobacteria and intestinal microbiota, is likely to have a profound effect on urological health, both positive and negative, owing to its metabolic output and other contributions. Lastly, the immune response, and particularly macrophage differentiation, play crucial roles in renal calcium oxalate crystal formation. In the present study, the current knowledge for each of these five aspects of kidney stone formation is reviewed. This knowledge may be used to explore novel research opportunities and improve the understanding of the initiation and development of kidney stones for urologists, nephrologists and primary care.

Secondary stone formation 8 weeks after percutaneous nephrolithotomy treatment: A case report.

INTRODUCTION: This work reports a patient with recurrent renal calculi subjected to three surgeries in half a year to be in the same position, and the high-throughput sequencing data showed different species in the renal pus and urine samples, which suggested that partial renal infection or stone formation can be judged by the bacteria in urine. PATIENT CONCERNS: The female patient aged 43 years was referred to the authors' department on April 13, 2020, due to left waist pain and fever for 3 days. DIAGNOSIS: Kidney stones and hydronephrosis were determined by a urinary system computed tomography scan. INTERVENTIONS: On April 20, 2020 and June 15, 2020, the patient was successfully treated with left percutaneous nephrolithotomy twice under general anesthesia. An investigation on the health and eating habits of the patient within 6 months was completed at the last admission. The components of the second renal calculus sample were analyzed with an infrared spectrum analyzer. The third renal stone (renal pus, triplicates) was subjected to microbial metagenome sequencing, and urine samples before and after surgery were subjected to 16S RNA sequencing by SEQHEALTH (Wuhan, China). OUTCOMES: After percutaneous nephrolithotomy, the left kidney stones were basically cleared, stone analysis revealed that the main components were calcium oxalate monohydrate, silica, and a small amount of calcium oxalate dehydrate. Although the urine samples exhibited differences, the renal pus and urine sample shared a single species. CONCLUSION: It is not clear that the prospects of partial renal infection or stone formation can be judged by the bacteria in urine.

Patients' poor performance status is an independent risk factor for urosepsis induced by kidney and ureteral stones.

This study was aimed to identify the risk factors for urosepsis caused by kidney and ureteral stones. One hundred and nine patients who had kidney or ureteral stones and who were treated with trans-ureteral lithotripsy (TUL) at our institution from 2016 to 2020 were included. We investigated the risk factors for urosepsis caused by kidney or ureteral stones that occurred prior to TUL. Thirty patients (28%) had urosepsis prior to TUL. Patients were divided into a urosepsis group (n = 30, 28%) and a non-urosepsis group (n = 79, 72%). Patients' characteristics (gender, age, performance status [PS] score, presence of diabetes mellitus, and skeletal muscle mass), as well as their stone and urine characteristics (stone size, presence of obstructive ureteral stones, stone composition, and urine and stone cultures), were compared between the two groups. When compared to the non-urosepsis group, patients with urosepsis were more likely to be older (p < 0.001), female (p < 0.001), with lower skeletal muscle mass (p < 0.001) and with poor PSs (p < 0.001). For stone and urine characteristics, infection stones (p = 0.01), positive urine (p < 0.001) and stone culture (p = 0.007) were more often detected in patients with urosepsis. A multivariate analysis showed patients' poor PS to be an independent risk factor for urosepsis due to kidney and ureteral stones (OR = 15.7; 95% CI = 2.2-115, p = 0.007). Our study revealed that the most significant risk factor for urosepsis caused by kidney and ureteral stones was the patients' poor PS.

Intestinal dysbacteriosis leads to kidney stone disease.

The formation and physicochemical properties of kidney stones (KSs) are closely associated with diet. In view of the differences in ethnicity and dietary composition between Chinese and Western populations, the present study aimed to investigate the association between intestinal dysbacteriosis and KSs in China. The current study examined the differences in intestinal microbes between the KS disease (KSD) and the healthy control (HLT) groups, and statistically significant differences based on 16s rRNA gene amplicons were identified using a Student's t­test or one­way ANOVA. In addition, the calcium oxalate KS (COKS), uric acid KS (UAKS) and carbonate apatite KS(CCKS) groups were compared with a non­parametric statistical test. Determination of bacterial abundance was performed via the analysis of 16s rRNA marker gene sequences using next­generation sequencing. Firmicutes (F) and Bacteroides (B) levels were significantly higher in the KSD group compared with the HLT group (B/F=0.67 vs. 0.08; P<0.001), as were the overall levels of B (6.19­fold higher compared with the HLT group; 22.2 vs. 3.6%; P<0.001). The Prevotella­9 abundance levels in the KSD group were 4.65­fold higher compared with those in the HLT group (8.8 vs. 1.9%; P<0.001). The levels of Blautia and Lachnoclostridium were significantly decreased in the KSD group (13.3 vs. 6.0%; and 5.0 vs. 7.9%; both P<0.05). Moreover, Prevotella­9 levels were higher in non­calciferous KSs (UAKS) compared with calciferous KSs (COKS and CCKS). Therefore, the findings of the present study indicated a key association between specific KS components and intestinal flora, providing a theoretical basis for new treatment methods for KSs. Moreover, differences and interactions between these bacteria could initially predict specific types of urolithiasis.

Preoperative risk factors for complications of percutaneous nephrolithotomy.

This study was conducted to evaluate preoperative risk factors for development of complications of percutaneous nephrolithotomy (PCNL). All consecutive patients aged ≥ 16 years who underwent PCNL during 2015 were retrospectively reviewed. Non-contrast CT (NCCT) was performed for all patients to evaluate stone complexity. The technique of PCNL was the same for all patients. Intra-operative and postoperative complications were recorded and classified based on modified Clavien system. The differences in preoperative data (patients, renal and stone characteristics including Guy's and STONE scores) between complicated and uncomplicated cases were compared using univariate and multivariate statistical analyses for detection of independent risk factors. The study included 1178 patients (61% were males). Mean age was 50 ± 12 years, and mean BMI was 30.7 ± 5.7 kg/m2. Complicated group included 166 patients (14.1%). Independent risk factors on multivariate analysis were infected preoperative urine culture (RR: 2.098, P 0.001, 95%CI: 1.380-3.189), largest stones diameter 30 mm or more (RR: 2.481, P > 0.001, 95%CI: 1.697-3.627) and number of calyces affected by the stones (RR: 2.431, P 0.002, 95%CI: 1.400-4.222 for affection of two calyces and RR: 2.778, P 0.005, 95%CI: 1.357-5.684 for affection of three calyces). While two scoring systems (Guy's and STONE) were not predictive of complications after PCNL, preoperative risk factors were infected preoperative urine culture, distribution of the stones or stone branches in two or three calyceal groups and stone size 30 mm or more.

Renal pelvis urine Gram stain as a traditional, but new marker in predicting postoperative fever and stone culture positivity in percutaneous nephrolithotomy: an observational, prospective, non-randomized cohort study.

PURPOSE: The aim of this study was to evaluate the diagnostic value of renal pelvis urine Gram staining (RPUGS) in predicting postoperative fever and renal stone culture (RSC) positivity in percutaneous nephrolithotomy (PCNL). METHODS: Totally 141 consecutive patients undergoing PCNL for renal stone were included between January 2018 and December 2019. The RPUGS and renal pelvis urine culture (RPUC) were performed using urine sample from renal collecting system, while RSC was performed using stone fragments. Patients were divided into two groups as Group 1 (n = 119) without postoperative fever (< 38 °C) and Group 2 (n = 22) with postoperative fever (≥ 38 °C). Stone culture and Gram staining models were created for predicting postoperative fever using constant covariates of the presence of residual stone, hydronephrosis, and stone burden. RESULTS: A significantly higher number of patients in Group 2 had RPUGS, RSC, and RPUC positivity (p < 0.001, for each). The sensitivity, specificity, positive predictive value, and negative predictive value of RPUGS in predicting postoperative fever were 72.7%, 89.9%, 57.1%, and 94.7%, respectively. It was observed that both models had similar predictive values and diagnostic performances. Although RSC and RPUGS had a similar diagnostic value in predicting postoperative fever in univariable analysis, both were found to be independent predictors in multivariable analysis (OR: 10.6, 95% CI 4.07-27.9, p < 0.001 and OR: 15.0, 95% CI 5.4-41.2, p < 0.001, respectively). CONCLUSIONS: In conclusion, RPUGS is as effective as RSC in predicting fever after PCNL. We recommend RPUGS during PCNL to manage post-PCNL infectious complications.

The pelvis urinary microbiome in patients with kidney stones and clinical associations.

BACKGROUND: The long-held notion that, without urinary tract or circulatory infection, bladder urine and blood are sterile biofluids has been disproven. There have been no previous reports on the kidney pelvis urinary microbiome after bladder disinfection in kidney stone patients. This study aimed to determine whether a kidney pelvis urinary microbiome is present after eliminating the influence of the bladder urinary microbiome, whether the microbiome composition is different in patients with stone kidney pelvis (SKP) and non-stone kidney pelvis (NSKP), and the correlation between SKP and patient clinical characteristics. RESULTS: Comparisons of bacterial diversity and community structure exhibited that urine in bladder was similar to SKP and NSKP. However, the comparisons showed that urine samples were different from blood. The most common operational taxonomic units were shared by all three types of urine samples. Corynebacterium was significantly higher in SKP compared to NSKP. Several bacteria were associated with patient characteristics, including Lactobacillus, which was positively correlated with fasting blood glucose, and Prevotella was negatively correlated with BMI. Lactobacillus was significantly higher in SKP compared to blood but not in NSKP compared to blood. CONCLUSIONS: The composition of the kidney pelvis urinary microbiome after disinfection of the bladder and its similarity to the bladder microbiome indicate that bladder urine can be used to replace kidney pelvis urine in microbiome research. Additionally, the comparison of SKP and NSKP and clinical associations suggest that the occurrence of kidney stones is responsible for the SKP urinary microbiome.

The relationship between gut microbiota and short chain fatty acids in the renal calcium oxalate stones disease.

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.

Optimal perioperative antibiotic strategy for kidney stone patients treated with percutaneous nephrolithotomy.

OBJECTIVE: To assess the relevance of urine test (UT), urine culture (UC) and stone culture (SC) for postoperative infections and to investigate the optimal perioperative antibiotic treatment strategy in association with percutaneous nephrolithotomy (PCNL) in patients with renal calculi. MATERIALS AND METHODS: Between September 2016 and September 2018 1,060 patients treated with PCNL were included in the study. The results of UT, UC and SC were reviewed. The details of perioperatively administered antibiotics and postoperative infections were recorded. RESULTS: A positive UT was associated with an increased incidence of infection; this was also the case in patients with negative UC (p < 0.05). There was no significant difference in incidence of infection between patients who were given a single dose of antibiotics compared with those given multiple doses when UC was negative, whether UT was positive or negative (all p > 0.05). The incidence of infection was decreased when pre-operative antibiotics were administered according to the sensitivity pattern based on UC (p < 0.05). This outcome was particularly evident when the treatment duration exceeded 7 days (p < 0.05). A positive SC was associated with increased incidence of infection, even if the patient had a negative UC and UT (p < 0.05). The incidence of infection was significantly decreased when antibiotic treatment was administered based on the results of SC (p < 0.05). CONCLUSION: Pre-operative prophylaxis with a single-dose antibiotic was sufficient in patients with negative UC, whether UT was positive or negative. Pre-operative treatment with antibiotics according to the bacterial sensitivity pattern should be administered for ≥7 days in patients with positive UC. The postoperative antibiotic treatment strategy should be tailored according to the SC results.

The gut microbiota profile of adults with kidney disease and kidney stones: a systematic review of the literature.

BACKGROUND: There is mounting evidence that individuals with kidney disease and kidney stones have an abnormal gut microbiota composition. No studies to date have summarised the evidence to categorise how the gut microbiota profile of these individuals may differ from controls. Synthesis of this evidence is essential to inform future clinical trials. This systematic review aims to characterise differences of the gut microbial community in adults with kidney disease and kidney stones, as well as to describe the functional capacity of the gut microbiota and reporting of diet as a confounder in these studies. METHODS: Included studies were those that investigated the gut microbial community in adults with kidney disease or kidney stones and compared this to the profile of controls. Six scientific databases (CINHAL, Medline, PubMed, Scopus, Web of Science and Cochrane Library), as well as selected grey literature sources, were searched. Quality assessment was undertaken independently by three authors. The system of evidence level criteria was employed to quantitatively evaluate the alteration of microbiota by strictly considering the number, methodological quality and consistency of the findings. Additional findings relating to altered functions of the gut microbiota, dietary intakes and dietary methodologies used were qualitatively summarised. RESULTS: Twenty-five articles met the eligibility criteria and included data from a total of 892 adults with kidney disease or kidney stones and 1400 controls. Compared to controls, adults with kidney disease had increased abundances of several microbes including Enterobacteriaceae, Streptococcaceae, Streptococcus and decreased abundances of Prevotellaceae, Prevotella, Prevotella 9 and Roseburia among other taxa. Adults with kidney stones also had an altered microbial composition with variations to Bacteroides, Lachnospiraceae NK4A136 group, Ruminiclostridium 5 group, Dorea, Enterobacter, Christensenellaceae and its genus Christensenellaceae R7 group. Differences in the functional potential of the microbial community between controls and adults with kidney disease or kidney stones were also identified. Only three of the 25 articles presented dietary data, and of these studies, only two used a valid dietary assessment method. CONCLUSIONS: The gut microbiota profile of adults with kidney disease and kidney stones differs from controls. Future study designs should include adequate reporting of important confounders such as dietary intake to assist with interpretation of findings.

Perturbations of the Gut Microbiome and Metabolome in Children with Calcium Oxalate Kidney Stone Disease.

BACKGROUND: The relationship between the composition and function of gut microbial communities and early-onset calcium oxalate kidney stone disease is unknown. METHODS: We conducted a case-control study of 88 individuals aged 4-18 years, which included 44 individuals with kidney stones containing ≥50% calcium oxalate and 44 controls matched for age, sex, and race. Shotgun metagenomic sequencing and untargeted metabolomics were performed on stool samples. RESULTS: Participants who were kidney stone formers had a significantly less diverse gut microbiome compared with controls. Among bacterial taxa with a prevalence >0.1%, 31 taxa were less abundant among individuals with nephrolithiasis. These included seven taxa that produce butyrate and three taxa that degrade oxalate. The lower abundance of these bacteria was reflected in decreased abundance of the gene encoding butyryl-coA dehydrogenase (P=0.02). The relative abundance of these bacteria was correlated with the levels of 18 fecal metabolites, and levels of these metabolites differed in individuals with kidney stones compared with controls. The oxalate-degrading bacterial taxa identified as decreased in those who were kidney stone formers were components of a larger abundance correlation network that included Eggerthella lenta and several Lactobacillus species. The microbial (α) diversity was associated with age of stone onset, first decreasing and then increasing with age. For the individuals who were stone formers, we found the lowest α diversity among individuals who first formed stones at age 9-14 years, whereas controls displayed no age-related differences in diversity. CONCLUSIONS: Loss of gut bacteria, particularly loss of those that produce butyrate and degrade oxalate, associates with perturbations of the metabolome that may be upstream determinants of early-onset calcium oxalate kidney stone disease.