Hyperoxaluria, including primary and secondary hyperoxaluria, is a disorder characterized by increased urinary oxalate excretion and could lead to recurrent calcium oxalate kidney stones, nephrocalcinosis and eventually end stage renal disease. For secondary hyperoxaluria, high dietary oxalate (HDOx) or its precursors intake is a key reason. Recently, accumulated studies highlight the important role of gut microbiota in the regulation of oxalate homeostasis. However, the underlying mechanisms involving gut microbiota and metabolite disruptions in secondary hyperoxaluria remain poorly understood. Here, we investigated the therapeutic efficacy of fecal microbiota transplantation (FMT) sourced from healthy rats fed with standard pellet diet against urinary oxalate excretion, renal damage and calcium oxalate (CaOx) crystal depositions via using hyperoxaluria rat models. We observed dose-dependent increases in urinary oxalate excretion and CaOx crystal depositions due to hyperoxaluria, accompanied by significant reductions in gut microbiota diversity characterized by shifts in Ruminococcaceae_UCG-014 and Parasutterella composition. Metabolomic analysis validated these findings, revealing substantial decreases in key metabolites associated with these microbial groups. Transplanting microbes from healthy rats effectively reduced HDOx-induced urinary oxalate excretion and CaOx crystal depositions meanwhile restoring Ruminococcaceae_UCG-014 and Parasutterella populations and their associated metabolites. Furthermore, FMT treatment could significantly decrease the urinary oxalate excretion and CaOx crystal depositions in rat kidneys via, at least in part, upregulating the expressions of intestinal barrier proteins and oxalate transporters in the intestine. In conclusion, our study emphasizes the effectiveness of FMT in countering HDOx-induced hyperoxaluria by restoring gut microbiota and related metabolites. These findings provide insights on the complex connection between secondary hyperoxaluria caused by high dietary oxalate and disruptions in gut microbiota, offering promising avenues for targeted therapeutic strategies.

The human gut microbiota, a complex and diverse community of microorganisms, plays a crucial role in maintaining overall health by influencing various physiological processes, including digestion, immune function, and disease susceptibility. The balance between beneficial and harmful bacteria is essential for health, with dysbiosis - disruption of this balance - linked to numerous conditions such as metabolic disorders, autoimmune diseases, and cancers. This review highlights key genera such as Enterococcus, Ruminococcus, Bacteroides, Bifidobacterium, Escherichia coli, Akkermansia muciniphila, Firmicutes (including Clostridium and Lactobacillus), and Roseburia due to their well-established roles in immune regulation and metabolic processes, but other bacteria, including Clostridioides difficile, Salmonella, Helicobacter pylori, and Fusobacterium nucleatum, are also implicated in dysbiosis and various diseases. Pathogenic bacteria, including Escherichia coli and Bacteroides fragilis, contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues. The potential for microbiota-based therapies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, to improve health outcomes is examined. Future research directions in the integration of multi-omics, the impact of diet and lifestyle on microbiota composition, and advancing microbiota engineering techniques are also discussed. Understanding the gut microbiota's role in health and disease is essential for formulating personalized, efficacious treatments and preventive strategies, thereby enhancing health outcomes and progressing microbiome research.

Urolithiasis represents one of the most common urologic diseases, and its incidence demonstrates, globally, an increasing trend. The application of preventive measures is an established strategy to reduce urolithiasis-related morbidity, and it is based mostly on the adaptation of lifestyle factors and pharmacotherapy. Furthermore, other research areas demonstrate promising results, such as the research on the microbiome. In the current review, we searched for the latest data on lifestyle-based prevention and microbiome alterations in urolithiasis patients. The majority of the proposed lifestyle measures are already included in the urological guidelines, while additional factors, such as vitamin D supplementation, seem to have a putative positive effect. From the microbiome studies, several microbial composition patterns and metabolic pathways demonstrated an inhibiting or promoting role in lithogenesis. Up to the present, stone prevention has not shown satisfying results, which suggests that lifestyle measures are not adequate. Moreover, microbiome studies are prone to bias, since microbes are strongly affected by numerous clinical factors, while the analysis procedures are not standardized yet. Analysis standardization and data pooling from extensive registration of clinical and microbiome data are essential steps in order to improve the existing prevention strategy with targeted microbiome manipulations.

This study aimed to assess the impact of radish sprouts on the gut microbiota of healthy individuals. Radish sprout additives, subjected to short-term storage and steam treatment, were used to intervene in an in vitro culture of human gut microbiota. The influence of radish sprouts on the gut microbiota was evaluated by monitoring short-chain fatty acid (SCFA) content and proportion in the fermentation broth, and microbial diversity was assessed using 16S rDNA amplicon sequencing. The results indicated that the gut microbiota produced a substantial amount of SCFA within 48 h of fermentation, with a right-skewed distribution across all groups. The addition of both digestates enhanced Firmicutes diversity, while Bacteroidetes and Proteobacteria diversity remained stable between the control and fresh sprout groups. The 30 s steam treatment group showed an increase in Bacteroidetes and a decrease in Proteobacteria diversity. The abundance of Bacilli, Bacillaceae, and Bacillus was significantly higher in both the fresh and steam-treated groups compared to the control. Both fresh and steam-treated radish sprout digestates enriched gut microbiota diversity, with steam treatment showing superior effects. These findings suggest that radish sprout consumption may positively influence gut microbiota, with steam treatment potentially enhancing these benefits.

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.

Urinary system stones are a common clinical disease, with significant differences in incidence and recurrence rates between different countries and regions. The etiology and pathogenesis of urinary system stones have not been fully elucidated, but many studies have found that some bacteria and fungi that are difficult to detect in urine constitute a unique urinary microbiome. This special urinary microbiome is closely related to the occurrence and development of urinary system stones. By analyzing the urinary microbiome and its metabolic products, early diagnosis and treatment of urinary system stones can be carried out.

This article reviews the relationship between the urinary microbiome and urinary system stones, discusses the impact of the microbiome on the formation of urinary system stones and its potential therapeutic value, with the aim of providing a reference for the early diagnosis, prevention, and treatment of urinary system stones.

(i) Urinary stones are a common and recurrent disease, and there is no good way to prevent them. (ii) With advances in testing technology, studies have found that healthy human urine also contains various types of bacteria. (iii) Is there a potential connection between the urinary microbiota and urinary stones, and if so, can understanding these connections offer fresh perspectives and strategies for the diagnosis, treatment, and prevention of urinary stones?

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.

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.

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.

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.

Infectious urolithiasis is a type of urolithiasis, that is caused by infections of the urinary tract by bacteria producing urease such as Proteus mirabilis. Lactobacillus spp. have an antagonistic effect against many pathogens by secreting molecules, including organic acids. The aim of the study was to determine the impact of Lactobacillus strains isolated from human urine on crystallization of urine components caused by P. mirabilis by measuring bacterial viability (CFU/mL), pH, ammonia release, concentration of crystallized salts and by observing crystals by phase contrast microscopy. Moreover, the effect of lactic acid on the activity of urease was examined by the kinetic method and in silico study. In the presence of selected Lactobacillus strains, the crystallization process was inhibited. The results indicate that one of the mechanisms of this action was the antibacterial effect of Lactobacillus, especially in the presence of L. gasseri, where ten times less P. mirabilis bacteria was observed, compared to the control. It was also demonstrated that lactic acid inhibited urease activity by a competitive mechanism and had a higher binding affinity to the enzyme than urea. These results demonstrate that Lactobacillus and lactic acid have a great impact on the urinary stones development, which in the future may help to support the treatment of this health problem.

Inquiry of microbiota involvement in kidney stone disease (KSD) has largely focussed on potential oxalate handling abilities by gut bacteria and the increased association with antibiotic exposure. By systematically comparing the gut, urinary, and oral microbiota of 83 stone formers (SF) and 30 healthy controls (HC), we provide a unified assessment of the bacterial contribution to KSD.

Amplicon and shotgun metagenomic sequencing approaches were consistent in identifying multi-site microbiota disturbances in SF relative to HC. Biomarker taxa, reduced taxonomic and functional diversity, functional replacement of core bioenergetic pathways with virulence-associated gene markers, and community network collapse defined SF, but differences between cohorts did not extend to oxalate metabolism.

We conclude that multi-site microbiota alteration is a hallmark of SF, and KSD treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics where applicable to prevent stone recurrence. Video Abstract.

The goal of this systematic review was to examine the current literature on the urinary microbiome and its associations with noninfectious, nonmalignant, urologic diseases. Secondarily, we aimed to describe the most common bioinformatics used to analyze the urinary microbiome.

A comprehensive literature search of Ovid MEDLINE using the keywords "microbiota" AND "prostatic hyperplasia," "microbiota" AND "urinary bladder, overactive," "microbiota" AND "pelvic pain," and "microbiota" AND "urolithiasis" OR "nephrolithiasis" OR "urinary calculi" AND "calcium oxalate" was performed to identify relevant clinical microbiome studies associated with noninfectious benign urological conditions published from 2010 to 2022. We included human studies that evaluated the urinary, stone, or semen microbiota, or any combination of the above-mentioned locations.

A total of 25 human studies met the inclusion criteria: 4 on benign prostatic hyperplasia (BPH), 9 on overactive bladder (OAB), 8 on calcium oxalate stones, and 4 on chronic pelvic pain syndrome (CPPS). Specific taxonomic profiles in the urine microbiome were associated with each pathology, and evaluation of alpha- and beta-diversity and relative abundance was accounted for most of the studies. Symptom prevalence and severity were also analyzed and showed associations with specific microbes.

The study of the urogenital microbiome is rapidly expanding in urology. Noninfectious benign urogenital diseases, such as BPH, calcium oxalate stones, CPPS, and OAB were found to be associated with specific microbial taxonomies. Further research with larger study populations is necessary to solidify the knowledge of the urine microbiome in these conditions and to facilitate the creation of microbiome-based diagnostic and therapeutic approaches.

The human gut microbiota (GM) is a complex microbial ecosystem that colonises the gastrointestinal tract (GIT) and is comprised of bacteria, viruses, fungi, and protozoa. The GM has a symbiotic relationship with its host that is fundamental for body homeostasis. The GM is not limited to the scope of the GIT, but there are bidirectional interactions between the GM and other organs, highlighting the concept of the "gut-organ axis". Any deviation from the normal composition of the GM, termed "microbial dysbiosis", is implicated in the pathogenesis of various diseases. Only a few studies have demonstrated a relationship between GM modifications and disease phenotypes, and it is still unknown whether an altered GM contributes to a disease or simply reflects its status. Restoration of the GM with probiotics and prebiotics has been postulated, but evidence for the effects of prebiotics is limited. Prebiotics are substrates that are "selectively utilized by host microorganisms, conferring a health benefit". This study highlights the bidirectional relationship between the gut and vital human organs and demonstrates the relationship between GM dysbiosis and the emergence of certain representative diseases. Finally, this article focuses on the potential of prebiotics as a target therapy to manipulate the GM and presents the gaps in the literature and research.

Oxalate is a metabolic end-product whose systemic concentrations are highly variable among individuals. Genetic (primary hyperoxaluria) and non-genetic (e.g., diet, microbiota, renal and metabolic disease) reasons underlie elevated plasma concentrations and tissue accumulation of oxalate, which is toxic to the body. A classic example is the triad of primary hyperoxaluria, nephrolithiasis, and kidney injury. Lessons learned from this example suggest further investigation of other putative factors associated with oxalate dysmetabolism, namely the identification of precursors (glyoxylate, aromatic amino acids, glyoxal and vitamin C), the regulation of the endogenous pathways that produce oxalate, or the microbiota's contribution to oxalate systemic availability. The association between secondary nephrolithiasis and cardiovascular and metabolic diseases (hypertension, type 2 diabetes, and obesity) inspired the authors to perform this comprehensive review about oxalate dysmetabolism and its relation to cardiometabolic toxicity. This perspective may offer something substantial that helps advance understanding of effective management and draws attention to the novel class of treatments available in clinical practice.

Chronic kidney disease (CKD) refers to a range of various pathophysiological processes correlated with abnormal renal function and a progressive loss in GFR. Just as dysbiosis and altered pathology of the gut are accompanied with hypertension, which is a significant CKD risk factor. Gut dysbiosis in CKD patients is associated with an elevated levels of uremic toxins, which in turn increases the CKD progression. According to research results, the gut-kidney axis has a role in the formation of kidney stones, also in IgAN. A number of researchers have categorized the gut microbiota as enterotypes, and others, skeptical of theory of enterotypes, have suggested biomarkers to describe taxa that related to lifestyle, nutrition, and disease status. Metabolome-microbiome studies have been used to investigate the interactions of host-gut microbiota in terms of the involvement of metabolites in these interactions and are yielded promising results. The correlation between gut microbiota and CKD requires further multi-omic researches. Also, with regard to systems biology, studies on the communication network of proteins and transporters such as SLC and ABC, can help us achieve a deeper understanding of the gut-liver-kidney axis communication and can thus provide promising new horizons in the treatment of CKD patients. Probiotic-based treatment is an approach to reduce uremic poisoning, which is accomplished by swallowing microbes those can catalyze URS in the gut. If further comprehensive studies are carried out, we will know about the probiotics impact in slowing the renal failure progression and reducing inflammatory markers.

Several reports in recent years have found an association between gut microbiota and upper urinary urolithiasis. However, the causal relationship between them remains to be clarified.

Genetic variation is used as a tool in Mendelian randomization for inference of whether exposure factors have a causal effect on disease outcomes. We selected summary statistics from a large genome-wide association study of the gut microbiome published by the MiBioGen consortium with a sample size of 18,340 as an exposure factor and upper urinary urolithiasis data from FinnGen GWAS with 4,969 calculi cases and 213,445 controls as a disease outcome. Then, a two-sample Mendelian randomization analysis was performed by applying inverse variance-weighted, MR-Egger, maximum likelihood, and weighted median. In addition, heterogeneity and horizontal pleiotropy were excluded by sensitivity analysis.

IVW results confirmed that class Deltaproteobacteria (OR = 0.814, 95% CI: 0.666-0.995, P = 0.045), order NB1n (OR = 0.833, 95% CI: 0.737-0.940, P = 3.15 × 10^-3), family Clostridiaceae1 (OR = 0.729, 95% CI: 0.581-0.916, P = 6.61 × 10^-3), genus Barnesiella (OR = 0.695, 95% CI: 0.551-0.877, P = 2.20 × 10^-3), genus Clostridium sensu_stricto_1 (OR = 0.777, 95% CI: 0.612-0.986, P = 0.0380), genus Flavonifractor (OR = 0.711, 95% CI: 0.536-0.944, P = 0.0181), genus Hungatella (OR = 0.829, 95% CI: 0.690-0.995, P = 0.0444), and genus Oscillospira (OR = 0.758, 95% CI: 0.577-0.996, P = 0.0464) had a protective effect on upper urinary urolithiasis, while Eubacterium xylanophilum (OR =1.26, 95% CI: 1.010-1.566, P = 0.0423) had the opposite effect. Sensitivity analysis did not find outlier SNPs.

In summary, a causal relationship was found between several genera and upper urinary urolithiasis. However, we still need further randomized controlled trials to validate.

Microbiota are ecological communities of commensal, symbiotic, and pathogenic microorganisms. The microbiome could be involved in kidney stone formation through hyperoxaluria and calcium oxalate supersaturation, biofilm formation and aggregation, and urothelial injury. Bacteria bind to calcium oxalate crystals, which causes pyelonephritis and leads to changes in nephrons to form Randall's plaque. The urinary tract microbiome, but not the gut microbiome, can be distinguished between cohorts with urinary stone disease (USD) and those without a history of the disease. In the urine microbiome, the role is known of urease-producing bacteria (Proteus mirabilis, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Providencia stuartii, Serratia marcescens, and Morganella morganii) in stone formation. Calcium oxalate crystals were generated in the presence of two uropathogenic bacteria (Escherichia coli and K. pneumoniae). Non-uropathogenic bacteria (S. aureus and Streptococcus pneumoniae) exhibit calcium oxalate lithogenic effects. The taxa Lactobacilli and Enterobacteriaceae best distinguished the healthy cohort from the USD cohort, respectively. Standardization is needed in urine microbiome research for urolithiasis. Inadequate standardization and design of urinary microbiome research on urolithiasis have hampered the generalizability of results and diminished their impact on clinical practice.

The process of renal stone formation is complex, multifactorial, and variable depending on the type of stone. The microbiome, whether by direct or indirect action, is a factor that both promotes the formation and protects from developing of renal stones. It is a highly variable factor due to the great interindividual and intraindividual variability that it presents. In recent years, with the incorporation of nonculture-based techniques such as the high-throughput sequencing of 16S rRNA bacterian gene, both intestinal and urinary microbiota have been deeply studied in various diseases such as the kidney stone disease.

This review has examined the new insights on the influence of the intestinal and urinary microbiome in nephrolithiasis disease and its usefulness as a diagnostic and prognostic tool, highlighting its contribution to the pathogenesis, its ability to modulate it and to influence disease development.

The incidence of urolithiasis has been increasing considerably. These patients represent a significant expense for national health systems. With the knowledge of the influence of the urobiome and intestinal microbiota on the urolithiasis, it could be possible to modulate it to interrupt its development.

With the dogma of sterile urine no longer held as truth, numerous studies have implicated distinct changes in microbial diversity and composition to diseased subgroups in both benign and malignant urological diseases, ranging from overactive bladder to bladder and prostate cancer. Further facilitated by novel and effective techniques of urine culture and sequencing, analysis of the genitourinary microbiome holds high potential to identify biomarkers for disease and prognosis. However, the low biomass of samples included in microbiome studies of the urinary tract challenge researchers to draw definitive conclusions, confounded by technical and procedural considerations that must be addressed. Lack of samples and adequate true negative controls can lead to overestimation of microbial influence with clinical relevance. As such, results from currently available studies and assessment of their limitations required a thorough understanding. The purpose of this narrative review was to summarize notable microbiome studies in the field of urology with a focus on significant findings and limitations of study design. Methodological considerations in future research are also discussed.