Zn2+ regulates human oxalate metabolism by manipulating oxalate decarboxylase to treat calcium oxalate stones.

A high concentration of oxalate is associated with an increased risk of kidney calcium oxalate (CaOx) stones, and the degradation of exogenous oxalate mostly depends on oxalate-degrading enzymes from the intestinal microbiome. We found that zinc gluconate supplement to patients with CaOx kidney stones could significantly improve the abundance of oxalate metabolizing bacteria in humans through clinical experiments on patients also subjected to antibiotic treatment. The analysis of clinical samples revealed that an imbalance of Lactobacillus and oxalate decarboxylase (OxDC) was involved in the formation of CaOx kidney stones. Then, we identified that Zn2+ could be used as an external factor to improve the activity of OxDC and promote Lactobacillus in the intestinal flora, and this treatment achieved a therapeutic effect on rats with stones aggravated by antibiotics. Finally, by analyzing the three-dimensional structure of OxDC and completing in vitro experiments, we propose a model of the Zn2+-induced reduction of CaOx kidney stone symptoms in rats by increasing the metabolism of oxalate through the positive effects of Zn2+ on Lactobacillus and OxDC.

Anti-urolithiatic Activity of Daidzin in Ethylene Glycol-Induced Urolithiasis in Rats.

Urolithiasis is a common urological disorder, which causes considerable morbidity in both genders at all age groups worldwide. Though treatment options such as diuretics and non-invasive techniques to disintegrate the deposits are available, but often they are found less effective in the clinics. In this work, we planned to investigate the ameliorative effects of daidzin against the ethylene glycol (EG)-induced urolithiasis in rats. The male albino rats were distributed into four groups (n = 6) as control (group I), urolithiasis induced by the administration of 0.75% EG (group II), urolithiasis induced rats treated with 50 mg/kg of daidzin (group III), and urolithiasis rats treated with standard drug 750 mg/kg of cystone (group IV). The urine volume, pH, and total protein in the urine were assessed. The activities of marker enzymes in both plasma and kidney tissues were analyzed using assay kits. The levels of kidney function markers such as calcium, oxalate, urea, creatinine, uric acid, magnesium, BUN, and phosphorous were estimated using assay kits. The status of antioxidants and inflammatory cytokines were also examined using kits. The renal tissues were examined by histopathological analysis. Our results revealed that the daidzin treatment effectively decreased the urine pH and protein level and increased the urine volume in the urolithiasis rats. Daidzin decreased the calcium, oxalate, uric acid, and urea, creatinine, and BUN levels and also improved the magnesium and phosphorus in the urolithiasis rats. The activities of AST, ALT, ALP, GGT, and LDH were effectively reduced by the daidzin in both serum and renal tissue. Daidzin also reduced the inflammatory marker and increased the antioxidant levels. Histopathology results also proved the therapeutic effects of daidzin. Together, our results displayed that daidzin is effective in the amelioration of EG-induced urolithiasis in rats.

Insights into the cytoprotective potential of Bergenia ligulata against oxalate-induced oxidative stress and epithelial-mesenchymal transition (EMT) via TGFß1/p38MAPK pathway in human renal epithelial cells.

Oxalate exposure to human renal epithelial cells triggers a vicious cycle of oxidative stress leading to cellular injury and deposition of calcium oxalate crystals on the injured cells. This results in further oxidative damage causing inflammation and loss of cell-cell adhesion factors, ultimately leading to irreparable kidney damage. However, these events can be attenuated or prevented by plants rich in antioxidants used in the traditional system of medicine for treatment of kidney stones. To delineate the mechanism by which Bergenia ligulata extract exerts its cytoprotective role in oxalate-induced injury we designed this study. Our results revealed that oxalate-injured HK2 cells cotreated with ethanolic extract of Bergenia ligulata displayed increased viability, reduced oxidative stress due to lowered production of intracellular reactive oxygen species (ROS) and decreased apoptosis. We also observed lowered markers of inflammation, along with increased expression of epithelial marker E-cadherin and decreased expression of mesenchymal markers Vimentin, F-actin, Transforming growth factor beta 1 (TGF-ß1) and EMT-related proteins in renal tubular epithelial cells through immunocytochemistry, real-time PCR and western blotting. Our findings collectively suggest that by reducing oxidative stress, modulating crystal structure and preventing crystal-cell adhesion, B. ligulata inhibits the EMT pathway by downregulating the various mediators and thereby exerts its cytoprotective effect.

Effect of Black Tea Consumption on Urinary Risk Factors for Kidney Stone Formation.

Copious fluid intake is the most essential nutritional measure in the treatment of urolithiasis, and is suggested to be a protective factor in the primary prevention of urinary stone formation. Although the intake of black tea contributes to daily fluid intake, the high oxalate content could outweigh the beneficial effect of urine dilution. The present study investigated the effect of black tea consumption on urinary risk factors for kidney stone formation. Ten healthy men received a standardized diet for a period of ten days. Subjects consumed 1.5 L/day of fruit tea (0 mg/day oxalate) during the 5-day control phase, which was replaced by 1.5 L/day of black tea (86 mg/day oxalate) during the 5-day test phase. Fractional and 24-h urines were obtained. The intake of black tea did not significantly alter 24-h urinary oxalate excretion. Urinary citrate, an important inhibitor of calcium stone formation, increased significantly, while the relative supersaturation of calcium oxalate, uric acid, and struvite remained unchanged. No significantly increased risk for kidney stone formation could be derived from the ingestion of black tea in normal subjects. Further research is needed to evaluate the impact of black tea consumption in kidney stone patients with intestinal hyperabsorption of oxalate.

Calcium and Vitamin D Supplementation and Their Association with Kidney Stone Disease: A Narrative Review.

Kidney stone disease is a multifactorial condition influenced by both genetic predisposition and environmental factors such as lifestyle and dietary habits. Although different monogenic polymorphisms have been proposed as playing a causal role for calcium nephrolithiasis, the prevalence of these mutations in the general population and their complete pathogenetic pathway is yet to be determined. General dietary advice for kidney stone formers includes elevated fluid intake, dietary restriction of sodium and animal proteins, avoidance of a low calcium diet, maintenance of a normal body mass index, and elevated intake of vegetables and fibers. Thus, balanced calcium consumption protects against the risk for kidney stones by reducing intestinal oxalate availability and its urinary excretion. However, calcium supplementation given between meals might increase urinary calcium excretion without the beneficial effect on oxalate. In kidney stone formers, circulating active vitamin D has been found to be increased, whereas higher plasma 25-hydroxycholecalciferol seems to be present only in hypercalciuric patients. The association between nutritional vitamin D supplements and the risk for stone formation is currently not completely understood. However, taken together, available evidence might suggest that vitamin D administration worsens the risk for stone formation in patients predisposed to hypercalciuria. In this review, we analyzed and discussed available literature on the effect of calcium and vitamin D supplementation on the risk for kidney stone formation.

Effect of a Probiotic Supplement Containing Lactobacillus Acidophilus and Bifidobacterium Animalis Lactis on Urine Oxalate in Calcium Stone Formers with Hyperoxaluria: A Randomized, Placebo-controlled, Double-blind and In-vitro Trial.

PURPOSE: To determine the effect of a probiotic supplement containing native Lactobacillus acidophilus (L. acidophilus) and Bifidobacterium animalis lactis (B. lactis) on 24-hour urine oxalate in recurrent calcium stone formers with hyperoxaluria. Moreover, the in-vitro oxalate degradation capacity and the intestinal colonization of consumed probiotics were evaluated. MATERIALS AND METHODS: The oxalate degrading activity of L. acidophilus and B. lactis were evaluated in-vitro. The presence of oxalyl-CoA decarboxylase (oxc) gene in the probiotic species was assessed. One hundred patients were randomized to receive the probiotic supplement or placebo for four weeks. The 24-hour urine oxalate and the colonization of consumed probiotics were assessed after weeks four and eight. RESULTS: Although the oxc gene was present in both species, only L. acidophilus had a good oxalate degrading activity, in-vitro. Thirty-four patients from the probiotic and thirty patients from the placebo group finished the study. The urine oxalate changes were not significantly different between groups (57.21 ± 11.71 to 49.44 ± 18.14 mg/day for probiotic, and 56.43 ± 9.89 to 50.47 ± 18.04 mg/day for placebo) (P = .776). The probiotic consumption had no significant effect on urine oxalate, both in univariable (P = .771) and multivariable analyses (P = .490). The consumed probiotics were not detected in the stool samples of most participants. CONCLUSION: Our results showed that the consumption of a probiotic supplement containing L. acidophilus and B. lactis did not affect urine oxalate. The results may be due to a lack of bacterial colonization in the intestine.

Effect of alanine supplementation on oxalate synthesis.

The Primary Hyperoxalurias (PH) are rare disorders of metabolism leading to excessive endogenous synthesis of oxalate and recurring calcium oxalate kidney stones. Alanine glyoxylate aminotransferase (AGT), deficient in PH type 1, is a key enzyme in limiting glyoxylate oxidation to oxalate. The affinity of AGT for its co-substrate, alanine, is low suggesting that its metabolic activity could be sub-optimal in vivo. To test this hypothesis, we examined the effect of L-alanine supplementation on oxalate synthesis in cell culture and in mouse models of Primary Hyperoxaluria Type 1 (Agxt KO), Type 2 (Grhpr KO) and in wild-type mice. Our results demonstrated that increasing L-alanine in cells decreased synthesis of oxalate and increased viability of cells expressing GO and AGT when incubated with glycolate. In both wild type and Grhpr KO male and female mice, supplementation with 10% dietary L-alanine significantly decreased urinary oxalate excretion ~30% compared to baseline levels. This study demonstrates that increasing the availability of L-alanine can increase the metabolic efficiency of AGT and reduce oxalate synthesis.

Collapsing Focal Segmental Glomerulosclerosis and Acute Oxalate Nephropathy in a Patient With COVID-19: A Double Whammy.

As COVID-19 (coronavirus disease 2019) spreads across the world multiple therapeutic interventions have been tried to reduce morbidity and mortality. We describe a case of collapsing focal sclerosing glomerulosclerosis (FSGS) and acute oxalate nephropathy in a patient treated with high-dose intravenous vitamin C for severe COVID-19 infection. Collapsing FSGS has been described in patients with COVID-19 infection associated with APOL-1; however, this case had collapsing FSGS developing in low-risk heterozygous APOL-1 variant, and we postulate that the intensity of the COVID-19 cytokine storm overwhelmed the protective state of APOL-1 heterozygosity. This case illustrates the importance of assessing the risk and benefit of planned therapeutic interventions on a case-by-case basis especially when there are still so many unknowns in the management of COVID-19 infection. Strong consideration should be given for performing a renal biopsy in patients who develop multifactorial acute kidney injury.

[Primary hyperoxaluria: case report and therapeutic perspectives].

Primary hyperoxaluria (PH) is a rare genetic disorder with autosomal recessive transmission, characterized by high endogenous production and markedly excessive urinary excretion of oxalate (Ox). It causes the accumulation of calcium oxide crystals in organs and tissues including bones, heart, arteries, skin and kidneys, where it may cause oxalo-calcic nephrolithiasis, nephrocalcinosis and chronic renal failure. Some forms are secondary to enteric diseases, drugs or dietetic substances, while three primitive forms, caused by various enzymatic defects, are currently known: PH1, PH2 and PH3. An early diagnosis, with the aid of biochemical and genetic investigations, helps prevent complications and establish a therapeutic strategy that often includes liver and liver-kidney transplantation, improving the prognosis of these patients. In this work we describe the clinical case of a patient with PH1 undergoing extracorporeal hemodialysis treatment and we report the latest research results that could change the life of patients with PH.

Aspergillus niger enhances oxalate production as a response to phosphate deficiency induced by aluminium(III).

This paper investigates Aspergillus niger's behaviour in the presence of mobile Al3+ species by evaluating the changes in oxalate exudation at various aluminium contents. When the fungus was exposed to Al3+, no significant changes in oxalate production were observed until 100 mg.L-1 aluminium was reached resulting in oxalate production decrease by 18.2%. By stripping the culture medium completely of phosphate, even more prominent decrease by 34.8% and 67.1% at 10 and 100 mg.L-1 aluminium was observed, respectively, indicating the phosphate's significance instead of Al3+ in oxalate production. Our results suggest that the low phosphate bioavailability, which most likely resulted from its interaction with Al3+, stimulated the overproduction of oxalate by A. niger. Furthermore, when the fungus was incubated in aluminium-free media supplemented with 0.1 mM of phosphate, oxalate production increased up to 281.5 µmol.g-1, while at 1.85 mM of available phosphate only 80.7 µmol.g-1 of oxalate was produced. This indicates that oxalic acid is produced by fungus not as a mean to detoxify aluminium, but as an attempt to gain access to additional phosphate.

Metabolomic profiling of oxalate-degrading probiotic Lactobacillus acidophilus and Lactobacillus gasseri.

Oxalate, a ubiquitous compound in many plant-based foods, is absorbed through the intestine and precipitates with calcium in the kidneys to form stones. Over 80% of diagnosed kidney stones are found to be calcium oxalate. People who form these stones often experience a high rate of recurrence and treatment options remain limited despite decades of dedicated research. Recently, the intestinal microbiome has become a new focus for novel therapies. Studies have shown that select species of Lactobacillus, the most commonly included genus in modern probiotic supplements, can degrade oxalate in vitro and even decrease urinary oxalate in animal models of Primary Hyperoxaluria. Although the purported health benefits of Lactobacillus probiotics vary significantly between species, there is supporting evidence for their potential use as probiotics for oxalate diseases. Defining the unique metabolic properties of Lactobacillus is essential to define how these bacteria interact with the host intestine and influence overall health. We addressed this need by characterizing and comparing the metabolome and lipidome of the oxalate-degrading Lactobacillus acidophilus and Lactobacillus gasseri using ultra-high-performance liquid chromatography-high resolution mass spectrometry. We report many species-specific differences in the metabolic profiles of these Lactobacillus species and discuss potential probiotic relevance and function resulting from their differential expression. Also described is our validation of the oxalate-degrading ability of Lactobacillus acidophilus and Lactobacillus gasseri, even in the presence of other preferred carbon sources, measuring in vitro 14C-oxalate consumption via liquid scintillation counting.

Targeting kidney inflammation as a new therapy for primary hyperoxaluria?

The primary hyperoxalurias (PHs) are inborn errors of glyoxylate metabolism characterized by endogenous oxalate overproduction in the liver, and thus elevated urinary oxalate excretion. The urinary calcium-oxalate (CaOx) supersaturation and the continuous renal accumulation of insoluble CaOx crystals yield a progressive decline in renal function that often ends with renal failure. In PH Type 1 (AGXT mutated), the most frequent and severe condition, patients typically progress to end-stage renal disease (ESRD); in PH Type 2 (GRHPR mutated), 20% of patients develop ESRD, while only one patient with PH Type 3 (HOGA1 mutated) has been reported with ESRD so far. Patients with ESRD undergo frequent maintenance (haemo)dialysis treatment, and finally must receive a combined liver-kidney transplantation as the only curative treatment option available in PH Type 1. In experimental models using oxalate-enriched chow, CaOx crystals were bound to renal tubular cells, promoting a pro-inflammatory environment that led to fibrogenesis in the renal parenchyma by activation of a NACHT, LRR and PYD domains-containing protein 3 (NALP3)-dependent inflammasome in renal dendritic cells and macrophages. Chronic fibrogenesis progressively impaired renal function. Targeting the inflammatory response has recently been suggested as a therapeutic strategy to treat not only oxalate-induced crystalline nephropathies, but also those characterized by accumulation of cystine and urate in other organs. Herein, we summarize the pathogenesis of PH, revising the current knowledge of the CaOx-mediated inflammatory response in animal models of endogenous oxalate overproduction. Furthermore, we highlight the possibility of modifying the NLRP3-dependent inflammasome as a new and complementary therapeutic strategy to treat this severe and devastating kidney disease.

A GH family 28 endo-polygalacturonase from the brown-rot fungus Fomitopsis palustris: Purification, gene cloning, enzymatic characterization and effects of oxalate.

Brown-rot fungi are the wood-decay basidiomycetes and have ability to break down plant cell wall carbohydrates. It has been suggested that degradation of pectin is important for the initial stages of brown rot. We purified an endo-polygalacturonase (FpPG28A) from the brown-rot fungus Fomitopsis palustris, analysis of the predicted amino acid sequence indicated that FpPG28A belongs to GH family 28. The highest activity of purified FpPG28A was observed at 60 °C in 50 mM sodium acetate buffer (pH 5.0); this activity was highly specific for polygalacturonic acid chains. However, calcium polygalacturonate gel was not degraded by FpPG28A under those optimal conditions. We observed that calcium polygalacturonate gel was readily degraded by the enzyme in the oxalate buffer. Furthermore, the thermostability of FpPG28A was elevated in oxalate buffer at pH 3.0. These results indicated that oxalate has an important role in the degradation of woody pectin by FpPG28A.

Renal lithiasis and inflammatory bowel diseases, an update on pediatric population.

BACKGROUND AND AIM OF THE WORK: Historical studies have demonstrated that the prevalence of symptomatic nephrolithiasis is higher in patients with inflammatory bowel disease (IBD), compared to general population. The aim of the review was to analyze literature data in order to identify the main risk conditions described in literature and the proposed treatment. METHODS: A research on the databases PubMed, Medline, Embase and Google Scholar was performed by using the keywords "renal calculi/lithiasis/stones" and "inflammatory bowel diseases". A research on textbooks of reference for Pediatric Nephrology was also performed, with focus on secondary forms of nephrolithiasis. RESULTS: Historical studies have demonstrated that the prevalence of symptomatic nephrolithiasis is higher in patients with inflammatory bowel disease (IBD), compared to general population, typically in patients who underwent extensive small bowel resection or in those with persistent severe small bowel inflammation. In IBD, kidney stones may arise from chronic inflammation, changes in intestinal absorption due to inflammation, surgery or intestinal malabsorption. Kidney stones are more closely associated with Crohn's Disease (CD) than Ulcerative Colitis (UC) in adult patients for multiple reasons: mainly for malabsorption, but in UC intestinal resection may be an additional risk. Nephrolithiasis is often under-diagnosed and might be a rare but noticeable extra-intestinal presentation of pediatric IBD. Secondary enteric hyperoxaluria the main risk factor of UL in IBD, this has been mainly studied in CD, whether in UC has not been completely explained. In the long course of CD recurrent urolithiasis and calcium-oxalate deposition may cause severe chronic interstitial nephritis and, as a consequence, chronic kidney disease. ESRD and systemic oxalosis often develop early, especially in those patients with multiple bowel resections. Even if we consider that many additional factors are present in IBD as hypomagnesuria, acidosis, hypocitraturia, and others, the secondary hyperoxaluria seems to finally have a central role. Some medications as parenteral vitamin D, long-term and high dose steroid treatment, sulfasalazine are reported as additional risk factors. Hydration status may also play an important role in this process. Intestinal surgery is a widely described independent risk factor. Patients with ileostomy post bowel resection may have relative dehydration from liquid stool, which, added to the acidic pH from bicarbonate loss, is responsible for this process. In this acidic pH, the urinary citrate level excretion reduces. The stones most commonly seen in these patients contain uric acid or are mixed. In addition, the risk of calcium containing stones also increases with ileostomy. The treatment of UL in IBD involves correction of the basic gastrointestinal tract inflammation, restricted dietary oxalate intake, and, at times, increased calcium intake. Citrate therapy that increases both urine pH and urinary citrate could also provide an additional therapeutic benefit. Finally, patients with IBD in a pediatric study had less urologic intervention for their calculosis compared with pediatric patients without IBD.

Remediation of lead-contaminated water by geological fluorapatite and fungus Penicillium oxalicum.

Phosphate-solubilizing fungi (PSF) can secrete large amounts of organic acids. In this study, the application of the fungus Penicillium oxalicum and geological fluorapatite (FAp) to lead immobilization was investigated. The formation and morphology of the lead-related minerals were analyzed by ATR-IR, XRD, Raman, and SEM. The quantity of organic acids secreted by P. oxalicum reached the maximum on the fourth day, which elevated soluble P concentrations from 0.4 to 108 mg/L in water. The secreted oxalic acid dominates the acidity in solution. P. oxalicum can survive in the solution with Pb concentration of ~ 1700 mg/L. In addition, it was shown that ~ 98% lead cations were removed while the fungus was cultured with Pb (~ 1700 mg/L) and FAp. The mechanism is that the released P from FAp (enhanced by organic acids) can react with Pb2+ to form the stable pyromorphite mineral [Pb5(PO4)3F]. The precipitation of lead oxalate also contributes to Pb immobilization. However, lead oxalate is more soluble due to its relatively high solubility. P. oxalicum has a higher rate of organic acid secretion compared with other typical PSF, e.g., Aspergillus niger. This study sheds light on bright future of applying P. oxalicum in Pb remediation.

Evaluation of aluminium mobilization from its soil mineral pools by simultaneous effect of Aspergillus strains' acidic and chelating exometabolites.

This contribution investigates aluminium mobilization from main aluminium pools in soils, phyllosilicates and oxyhydroxides, by acidic and chelating exometabolites of common soil fungi Aspergillus niger and A. clavatus. Their exometabolites' acidity as well as their ability to extract aluminium from solid mineral phases differed significantly during incubation. While both strains are able to mobilize aluminium from boehmite and aluminium oxide mixture to some extent, A. clavatus struggles to mobilize any aluminium from gibbsite. Furthermore, passive and active fungal uptake of aluminium enhances its mobilization from boehmite, especially in later growth phase, with strong linear correlation between aluminium bioaccumulated fraction and increasing culture medium pH. We also provide data on concentrations of oxalate, citrate and gluconate which are synthesized by A. niger and contribute to aluminium mobilization. Compared to boehmite-free treatment, fungus reduces oxalate production significantly in boehmite presence to restrict aluminium extraction efficiency. However, in presence of high phyllosilicates' dosages, aluminium is released to an extent that acetate and citrate is overproduced by fungus. Our results also highlight fungal capability to significantly enhance iron and silicon mobility as these elements are extracted from mineral lattice of phyllosilicates by fungal exometabolites alongside aluminium.

Role of gut microbiota against calcium oxalate.

Nephrolithiasis is a condition marked by the presence or formation of stones in kidneys. Several factors contribute to kidney stones development such as environmental conditions, type of dietary intake, gender and gastrointestinal flora. Most of the kidney stones are composed of calcium phosphate and calcium oxalate, which enter in to the body through diet. Both sources of oxalates become dangerous when normal flora of gastrointestinal tract is disturbed. Oxalobacter and Lactobacillus species exist symbiotically in the human gut and prevent stone formation by altering some biochemical pathways through production of specific enzymes which help in the degradation of oxalate salts. Both Oxalobacter and Lactobacillus have potential probiotic characteristics for the prevention of kidney stone formation and this avenue should be further explored.

Effects of Juice Processing on Oxalate Contents in Carambola Juice Products.

Effects of processing methods including pressing, enzyme-assisted extraction, lactic acid fermentation by Lactobacillus acidophilus, and alcohol fermentation by Saccharomyces cerevisiae on total and soluble oxalate contents of carambola juices were studied. In comparison with pressing, the use of enzyme increased juice yields (15.89-17.29%), but resulted in higher total oxalate (1.60-1.73 times) and soluble oxalate contents (1.16-1.49 times). In addition, extension of enzyme incubation periods led to an increase in soluble oxalate contents in the products (p < 0.05). On the other hand, alcohol fermentation with Saccharomyces cerevisiae from 1 to 5 weeks reduced 37-58% of total oxalate and 39-59% of soluble oxalate contents. Prolonged fermentation also demonstrated better reduction of oxalate contents. Meanwhile, lactic acid fermentation using Lactobacillus acidophilus had no effects on total and soluble oxalate contents in carambola juices. These results suggested that carambola juice products should only be consumed moderately, and that alcohol fermentation could be a potential method to reduce oxalate contents in foods in order to prevent the risks of forming kidney stones.

Hyperoxaluria in a Model of Mini-Gastric Bypass Surgery in Rats.

BACKGROUND: Bariatric surgery is associated with hyperoxaluria hence predisposing to nephrolithiasis. The present study aimed to investigate the underlying mechanisms contributing to increased urinary oxalate in a mini-gastric bypass (MGB) surgery model in rats under different dietary conditions. The expression of intestinal oxalate transporters was also evaluated. METHODS: Male rats underwent MGB (n = 21) or Sham procedure (n = 21) and after recovery were fed a standard or high-fat diet with or without oxalate for 8 weeks. Stool and urine were collected before surgery (baseline) and at the end of protocol (final), when intestinal fragments were harvested for expression of Slc26a3 and Slc26a6 oxalate transporters. RESULTS: MGB groups fed with fat, irrespective of oxalate supplementation, presented steatorrhea. In MGB animals fed with fat and oxalate (Fat + Ox), final values of urinary oxalate and calcium oxalate supersaturation risk were markedly and significantly increased versus baseline or Sham animals under the same diet, as well as MGB groups under other diets. Slc26a3 was decreased in biliopancreatic limbs of MGB rats, probably reflecting a physiological adaptation to the restriction of food passage. Slc26a6 was not altered in any harvested intestinal fragment. CONCLUSIONS: A high-fat and oxalate diet induced hyperoxaluria and elevation in calcium oxalate supersaturation risk in a MGB rat model. The presence of fat malabsorption and increased dietary oxalate absorption, but not modifications of Slc26a3 and Slc26a6 oxalate transporters, accounted for these findings, suggesting that bariatric patients may benefit from a low-fat and low-oxalate diet.

Effect of Dietary Oxalate on the Gut Microbiota of the Mammalian Herbivore Neotoma albigula.

Diet is one of the primary drivers that sculpts the form and function of the mammalian gut microbiota. However, the enormous taxonomic and metabolic diversity held within the gut microbiota makes it difficult to isolate specific diet-microbe interactions. The objective of the current study was to elucidate interactions between the gut microbiota of the mammalian herbivore Neotoma albigula and dietary oxalate, a plant secondary compound (PSC) degraded exclusively by the gut microbiota. We quantified oxalate degradation in N. albigula fed increasing amounts of oxalate over time and tracked the response of the fecal microbiota using high-throughput sequencing. The amount of oxalate degraded in vivo was linearly correlated with the amount of oxalate consumed. The addition of dietary oxalate was found to impact microbial species diversity by increasing the representation of certain taxa, some of which are known to be capable of degrading oxalate (e.g., Oxalobacter spp.). Furthermore, the relative abundances of 117 operational taxonomic units (OTU) exhibited a significant correlation with oxalate consumption. The results of this study indicate that dietary oxalate induces complex interactions within the gut microbiota that include an increase in the relative abundance of a community of bacteria that may contribute either directly or indirectly to oxalate degradation in mammalian herbivores.