This review aims to synthesize current evidence on the role of chronic stress and hypothalamic–pituitary–adrenal (HPA) axis dysregulation in the pathogenesis of chronic kidney disease (CKD). The focus is on the interplay between cortisol, oxidative stress, inflammation, and metabolic risk factors within the psycho-neuro-endocrine-immune (PNEI) system. CKD is a multifactorial disease characterized by oxidative stress, chronic low-grade inflammation, and neuroendocrine imbalance. These processes interact to accelerate renal injury and systemic complications. Pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), together with oxidative stress markers including malondialdehyde (MDA), advanced oxidation protein products (AOPPs), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), are strongly associated with disease progression. Altered cortisol dynamics—assessed in serum, saliva, and hair—further reflect chronic HPA activation and contribute to immune dysfunction, metabolic disturbances, and cardiovascular risk. By integrating experimental and clinical findings, this review highlights how stress-induced dysregulation of the PNEI system amplifies CKD progression. Understanding these interconnected mechanisms underscores the potential of combining oxidative, inflammatory, and neuroendocrine biomarkers for improved risk stratification and targeted therapeutic interventions.

Introduction: Numerous studies to date have shown that the development of dysbiotic gut microbiota is a characteristic finding in chronic kidney disease (CKD). A number of uremic toxins progressively accumulate in the course of CKD, some of them generated by the intestinal microbiome, such as indoxyl sulfate (IS) and p-cresyl sulfate (p-CS). They are found to be involved in the pathogenesis of certain complications of uremic syndrome, including low-grade chronic inflammation and oxidative stress. The aim of the present study is to research the serum concentration of IS and p-CS in end stage renal disease (ESRD) patients undergoing conventional hemodialysis, as well as to study the possibilities of influencing some markers of inflammation and oxidative stress after taking a synbiotic. Materials and Methods: Thirty patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment who were taking a synbiotic in the form of Lactobacillus acidophilus La-14 2 × 10¹¹ (CFU)/g and prebiotic fructooligosaccharides were included in the study. Serum levels of total IS, total p-CS, Interleukin-6 (IL-6), and Malondialdehyde (MDA) were measured at baseline and after 8 weeks. Results. The baseline values of the four investigated indicators in the patients were significantly higher—p-CS (29.26 ± 58.32 pg/mL), IS (212.89 ± 208.59 ng/mL), IL-6 (13.84 ± 2.02 pg/mL), and MDA (1430.33 ± 583.42 pg/mL), compared to the results obtained after 8 weeks of intake, as we found a significant decrease in the parameters compared to the baseline—p-CS (6.40 ± 0.79 pg/mL, p = 0.041), IS (47.08 ± 3.24 ng/mL, p < 0.001), IL-6 (9.14 ± 1.67 pg/mL, p < 0.001), and MDA (1003.47 ± 518.37 pg/mL, p < 0.001). Conclusions: The current study found that the restoration of the intestinal microbiota in patients with CKD significantly decreases the level of certain uremic toxins. It is likely that this favorably affects certain aspects of CKD, such as persistent low-grade inflammation and oxidative stress.

Prebiotics, gut microbiota-fermentable substances, delay the development of type I diabetes. In the present study, we investigated the effect of two prebiotics (galacto-oligosaccharides and xylo-oligosaccharides) on the antioxidant protection, lipid profile, and inflammatory activity of rats with streptozotocin-induced diabetes. The following markers were studied – malondialdehyde, 8-hydroxy-2′-deoxyguanosine, ferric reducing ability of plasma (FRAP), triacylglycerols, total cholesterol (TC), high-density lipoproteins, C-reactive protein (CRP), and interleukin-6. Diabetes was induced in male Wistar experimental rats by streptozotocin injection, while the non-diabetic controls were injected with saline. Afterward the oligosaccharides were administered orally to the experimental animals. The blood collected following the decapitation was analyzed by ELISA. A modified protocol was used only for measuring the FRAP values. The galacto-oligosaccharides and xylo-oligosaccharides lowered the malondialdehyde levels in the diabetic rats (p < 0.05). The galacto-oligosaccharides decreased the serum levels of 8-hydroxy-2′-deoxyguanosine (p = 0.01), while the xylo-oligosaccharides increased the FRAP (p < 0.05) in the experimental animals. None of the oligosaccharides affected triacylglycerol and interleukin-6 concentrations, but the galacto-oligosaccharides decreased the TC and CRP levels in the diabetic animals. Both oligosaccharides exert a beneficial effect on the antioxidant protection of the diabetic rats, but have a minor effect on their lipid and inflammatory profiles.

Background and Objectives: The worldwide prevalence of chronic kidney disease (CKD) continues to increase, representing a major concern for public health systems. CKD is associated with gut microbiota dysbiosis, which may exacerbate disease progression by increasing the levels of uremic toxins, systemic inflammation, and oxidative stress. Modulation of the gut microbiota through biotic supplementation has been proposed as a potential therapeutic strategy to slow CKD progression and mitigate its complications. This study aimed to evaluate the effect of 10-month synbiotic supplementation on estimated glomerular filtration rate (eGFR), circulating concentrations of indoxyl sulfate (IS), p-cresyl sulfate (p-CS), interleukin-6 (IL-6), and malondialdehyde (MDA) in patients with stage IV–V CKD not receiving dialysis, in comparison to placebo. Materials and Methods: Fifty non-dialysis CKD IV–V patients were assigned (n = 25 each) via matched, non-randomized allocation (age, sex, and primary disease) to synbiotic or placebo. This single-blind, placebo-controlled trial blinded participants and laboratory personnel. The synbiotic group received daily capsules containing Lactobacillus acidophilus La-14 (2 × 10¹¹ CFU/g) + fructooligosaccharides; controls received identical placebo. Adherence was monitored monthly (pill counts, diaries), with < 80% over two visits resulting in withdrawal. The eGFR, IS, p-CS, IL-6, and MDA were measured at baseline and month 10. Results: Forty-two patients (21/arm) completed the study; eight withdrew (4 per arm). At 10 months, the change in eGFR was −1.2 ± 2.5 mL/min/1.73 m² (synbiotic) vs. −3.5 ± 3.0 mL/min/1.73 m² (placebo); between-group difference in change was 2.3 mL/min/1.73 m² (95% CI: 0.5–4.1; p = 0.014; adjusted p = 0.07). IS decreased by −15.4 ± 8.2 ng/L vs. −3.1 ± 6.5 ng/L; between-group difference in change was −12.3 ng/L (95% CI: −17.8 to −6.8; p < 0.001; adjusted p = 0.005). No significant differences were observed for p-CS, IL-6, or MDA after correction. Conclusions: Synbiotic supplementation over a 10-month period resulted in a trend toward decreased serum IS levels in patients with advanced CKD, suggesting potential benefits of microbiota-targeted therapies. However, no significant effects were observed on renal function, inflammatory, or oxidative stress markers. Further large-scale studies are warranted to confirm these findings and explore the long-term impact of synbiotics in CKD management.

Objectives: Type 1 diabetes mellitus is a metabolic disease characterized by dysbiosis. Modulation of the gut microbiota by oligosaccharides and aerobic training are proposed mechanisms that ameliorate the disease through affecting host-microbiota interactions. Methods: Seventy-two male Wistar rats were randomly divided into 8 groups – 5 with streptozotocin-induced diabetes and 3 healthy controls. The effect of two oligosaccharides – xylo- and galactooligosaccharides, and of aerobic training on the blood glucose concentration, growth and diversity of the gut microbiota was evaluated in the current study. Results: The galactooligosaccharides positively affected the glycemic status of the experimental animals as the diabetic and healthy rats had lower blood glucose concentration after 6 weeks of treatment (diabetic rats: week 4 vs. week 8, p=0.047; healthy rats: week 2,4,6,10 vs. week 8, p=0.001, p=0.000, p=0.025 and p=0.001, respectively). A positive effect of the galactooligosaccharides on body weight was observed when administered to diabetic rats in comparison to the diabetic control (p=0.020). Similar results were observed for the aerobically trained diabetic rats (p=0.004). The identification of bacterial species showed preserved microbiota diversity and indicated Bifidobacterium indicum , Lactobacillus feritoshensis and E. coli as the most abundant species among the analyzed genera. Conclusions: Prebiotic treatment beneficially affected the hyperglycemia and growth of type 1 diabetic rats. The most significant effect of the aerobic training was the improvement of the morphological parameters. Oligosaccharide administration and exercise did not affect the diversity of the bacterial species.

Diabetic cardiomyopathy is a major etiological factor in heart failure in diabetic patients, characterized by mitochondrial oxidative metabolism dysfunction, myocardial fibrosis, and marked glycogen elevation. The aim of the present study is to evaluate the effect of endurance training and prebiotic xylooligosaccharide (XOS) on the activity of key oxidative enzymes, myocardial collagen, and glycogen distribution as well as some serum biochemical risk markers in streptozotocin-induced type 1 diabetic rats. Male Wistar rats (n = 36) were divided into four diabetic groups (n = 9): sedentary diabetic rats on a normal diet (SDN), trained diabetic rats on a normal diet (TDN), trained diabetic rats on a normal diet with an XOS supplement (TD-XOS), and sedentary diabetic rats with an XOS supplement (SD-XOS). The results show that aerobic training managed to increase the enzyme activity of respiratory Complex I and II and the lactate dehydrogenase in the cardiomyocytes of the diabetic rats. Furthermore, the combination of exercise and XOS significantly decreased the collagen and glycogen content. No significant effects on blood pressure, heart rate or markers of inflammation were detected. These results demonstrate the beneficial effects of exercise, alone or in combination with XOS, on the cardiac mitochondrial enzymology and histopathology of diabetic rats.