Microbiota-dysbiosis-induced gut leakage is a pathophysiologic change in chronic kidney disease (CKD), leading to the production of several uremic toxins and their absorption into the bloodstream to worsen the renal complications. We evaluate the benefits of resistant maltodextrin (RMD) and chitosan oligosaccharide (COS) supplements in cell culture and CKD-induced rats. The RMD exerted a significant anti-inflammatory effect in vitro and intestinal occludin and zonula occluden-1 up-regulation in CKD rats compared with inulin and COS. While all prebiotics slightly improved gut dysbiosis, RMD remarkably promoted the relative abundance and the combined abundance of Lactobacillus, Bifidobacteria, Akkermansia, and Roseburia in CKD rats. Supplements of RMD should be advantageous in the treatment of gut leakage and microbiota dysbiosis in CKD.

Chronic kidney disease (CKD) affects more than 850 million people worldwide, contributing to morbidity and mortality, particularly through cardiovascular disease (CVD). The altered composition in CKD patients leads to increased production and absorption of uremic toxins such as trimethylamine (TMA) and its oxidized form, trimethylamine N-oxide (TMAO), which are associated with cardiovascular risks. This study investigated the potential of supplementary interventions with high-carotenoid-content gac fruit extract and probiotics to mitigate serum TMAO by modulating the gut microbiota. We conducted an animal study involving 48 male Wistar rats, divided into six groups: the control, CKD control, and four treatment groups receiving gac fruit extract, carotenoid extract, or combinations with Ligilactobacillus salivarius and Lactobacillus crispatus and Lactobacillus casei as a standard probiotic. CKD was induced in rats using cisplatin and they were supplemented with choline to enhance TMA production. The measures included serum creatinine, TMAO levels, gut microbiota composition, and the expression of fecal TMA lyase and intestinal zonula occluden-1 (ZO-1). CKD rats showed increased TMA production and elevated serum levels of TMAO. Treatment with gac fruit extract and selective probiotics significantly altered the composition of the gut microbiota by decreasing Actinobacteriota abundance and increasing the abundance of Bacteroides. This combination effectively promoted ZO-1 expression, reduced fecal TMA lyase, and subsequently lowered serum TMAO levels, demonstrating the therapeutic potential of these interventions. Our results highlight the benefits of gac fruit extract combined with probiotics for the effective reduction in serum TMAO levels in rats with CKD, supporting the further exploration of dietary and microbial interventions to improve outcomes in patients with CKD.

Background: Recurrent urolithiasis is a major clinical challenge, with more than 50% of patients experiencing recurrence within 5 years. While potassium citrate effectively reduces recurrence, poor adherence due to cost and gastrointestinal side effects limits its long-term use. Citrus-based interventions, such as lime juice, have shown potential in enhancing urinary citrate and alkalinity but require further validation. This study evaluated the efficacy of a lime-based phytochemical-rich regimen (LPR) in preventing stone recurrence and reducing urinary inflammation in post-operative urolithiasis patients. Objective: This multicenter, double-blind, randomized controlled trial aimed to evaluate the efficacy and safety of a novel lime-based preparation called LPR in preventing kidney stone recurrence over 24 months. Methods: In a double-blind, randomized, placebo-controlled, multicenter trial, 173 patients with calcium oxalate urolithiasis who had undergone successful stone removal were enrolled from six hospitals in Thailand. Participants were randomized to receive either LPR or placebo for 24 months. The primary outcome was the incidence of stone recurrence confirmed by computerized topography (CT). Secondary outcomes included changes in urinary protein excretion and urinary interleukin-8 (IL-8) level, a pro-inflammatory cytokine implicated in renal inflammation and stone formation. Kaplan–Meier survival analysis and multivariate Cox regression were used to assess recurrence risk. Results: Of 173 enrolled participants, 151 completed the study. The recurrence rate at 2 years was significantly lower in the LPR group (14%) compared to placebo (45%) (p < 0.001). Kaplan–Meier analysis demonstrated a hazard ratio (HR) of 0.24 (95% CI: 0.13–0.44; log-rank p < 0.0001) favoring LPR. Among completers, LPR significantly reduced urinary IL-8 level (p = 0.017) and 24-hour urinary protein excretion (p = 0.032) compared to baseline and placebo. No serious adverse events were reported, and adherence was high in both groups. Conclusion: LPR, a lime-based supplement rich in citrate and flavonoids, significantly reduced the 2-year recurrence rate of calcium oxalate stones by approximately 76%. This effect may be mediated by increased urinary citrate excretion, alkalinization, and attenuation of renal inflammation, as evidenced by reduced urinary IL-8 and proteinuria. LPR was well tolerated, with minimal adverse effects, and may serve as a safe, cost-effective adjunct for secondary prevention in patients intolerant to conventional alkali therapy.