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Background: Hyperuricemia (HUA) is a prevalent metabolic disorder whose development is associated with intestinal microbiota. Therefore, probiotics have emerged as a potential and safe approach for lowering uric acid (UA) levels. However, the underlying mechanisms of many effective probiotic strains remain unknown. Methods and Results: C57BL/6 mice were randomly divided into two groups: control and model groups. The model group received 12 weeks of potassium oxonate. Through 16s sequencing we found that HUA resulted in a significant decrease in the total diversity of all intestinal segments. When each intestinal segment was analyzed individually, the reduction in diversity was only significant in the cecum and colon sections. RDA analysis showed that lactobacilli in the rat colon exhibited a strong correlation with model group, suggesting that Lactobacillus may play an important role in HUA. Consequently, the preventive effects of Lactobacillus johnsonii YH1136 against HUA were investigated. C57BL/6 mice were randomly divided into three groups: control, model and YH1136 groups. The results showed that administering Lactobacillus johnsonii YH1136 effectively reduced serum UA levels in vivo by inhibiting hepatic xanthine oxidase (XOD) activity and promoting renal ABCG2 transporter expression. Moreover, supplementation with Lactobacillus johnsonii YH1136 significantly ameliorated pathological damage in the kidney and liver, thereby reducing UA accumulation. Conclusion: Hyperuricemia is accompanied by an altered composition of multiple gut bacteria, of which Lactobacillus is a key genus. Lactobacillus johnsonii YH1136 may ameliorate renal involvement in HUA via the gut-kidney axis. [ABSTRACT FROM AUTHOR]

Background: Observational studies and some experimental investigations have indicated that gut microbiota are closely associated with the incidence and progression of chronic renal failure. However, the causal relationship between gut microbiota and chronic renal failure remains unclear. The present study employs a two-sample Mendelian randomization approach to infer the causal relationship between gut microbiota and chronic renal failure at the genetic level. This research aims to determine whether there is a causal effect of gut microbiota on the risk of chronic renal failure, aiming to provide new evidence to support targeted gut therapy for the treatment of chronic renal failure. Methods: Employing genome-wide association study (GWAS) data from the public MiBioGen and IEU OpenGWAS platform, a two-sample Mendelian randomization analysis was conducted. The causal relationship between gut microbiota and chronic renal failure was inferred using five different methods: Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. The study incorporated sensitivity analyses that encompassed evaluations for pleiotropy and heterogeneity. Subsequently, the results of the Mendelian randomization analysis underwent a stringent correction for multiple testing, employing the False Discovery Rate method to enhance the validity of our findings. Results: According to the results from the Inverse Variance Weighted method, seven bacterial genera show a significant association with the outcome variable chronic renal failure. Of these, Ruminococcus (gauvreauii group) (OR = 0.82, 95% CI = 0.71-0.94, p = 0.004) may act as a protective factor against chronic renal failure, while the genera Escherichia-Shigella (OR = 1.22, 95% CI = 1.08-1.38, p = 0.001), Lactococcus (OR = 1.1, 95% CI = 1.02-1.19, p = 0.013), Odoribacter (OR = 1.23, 95% CI = 1.03-1.49, p = 0.026), Enterorhabdus (OR = 1.14, 95% CI = 1.00-1.29, p = 0.047), Eubacterium (eligens group) (OR = 1.18, 95% CI = 1.02-1.37, p = 0.024), and Howardella (OR = 1.18, 95% CI = 1.09-1.28, p < 0.001) may be risk factors for chronic renal failure. However, after correction for multiple comparisons using False Discovery Rate, only the associations with Escherichia-Shigella and Howardella remain significant, indicating that the other genera have suggestive associations. Sensitivity analyses did not reveal any pleiotropy or heterogeneity. Conclusion: Our two-sample Mendelian randomization study suggests that the genera Escherichia-Shigella and Howardella are risk factors for chronic renal failure, and they may serve as potential targets for future therapeutic interventions. However, the exact mechanisms of action are not yet clear, necessitating further research to elucidate their precise roles fully. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a severe microvascular complication of diabetes, which increases the risk of renal failure and causes a high global disease burden. Due to the lack of sustainable treatment, DN has become the primary cause of end-stage renal disease worldwide. Gut microbiota and its metabolites exert critical regulatory functions in maintaining host health and are associated with many pathogenesis of aging-related chronic diseases. Currently, the theory gut– kidney axis has opened a novel angle to understand the relationship between gut microbiota and multiple kidney diseases. In recent years, accumulating evidence has revealed that the gut microbiota and their metabolites play an essential role in the pathophysiologic processes of DN through the gut–kidney axis. In this review, we summarize the current investigations of gut microbiota and microbial metabolites involvement in the progression of DN, and further discuss the potential gut microbiota-targeted therapeutic approaches for DN. [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia (HUA) is a prevalent metabolic disorder whose development is associated with intestinal microbiota. Therefore, probiotics have emerged as a potential and safe approach for lowering uric acid (UA) levels. However, the underlying mechanisms of many effective probiotic strains remain unknown., Methods and Results: C57BL/6 mice were randomly divided into two groups: control and model groups. The model group received 12 weeks of potassium oxonate. Through 16s sequencing we found that HUA resulted in a significant decrease in the total diversity of all intestinal segments. When each intestinal segment was analyzed individually, the reduction in diversity was only significant in the cecum and colon sections. RDA analysis showed that lactobacilli in the rat colon exhibited a strong correlation with model group, suggesting that Lactobacillus may play an important role in HUA. Consequently, the preventive effects of Lactobacillus johnsonii YH1136 against HUA were investigated. C57BL/6 mice were randomly divided into three groups: control, model and YH1136 groups. The results showed that administering Lactobacillus johnsonii YH1136 effectively reduced serum UA levels in vivo by inhibiting hepatic xanthine oxidase (XOD) activity and promoting renal ABCG2 transporter expression. Moreover, supplementation with Lactobacillus johnsonii YH1136 significantly ameliorated pathological damage in the kidney and liver, thereby reducing UA accumulation., Conclusion: Hyperuricemia is accompanied by an altered composition of multiple gut bacteria, of which Lactobacillus is a key genus. Lactobacillus johnsonii YH1136 may ameliorate renal involvement in HUA via the gut-kidney axis., Competing Interests: YC was employed by the Guangzhou Beneco Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Jiang, Xin, Sun, Zhao, Gan, Jiang, Gong, Li, Ma, Ni, Chen, Bai and Wang.)

Background: Observational studies and some experimental investigations have indicated that gut microbiota are closely associated with the incidence and progression of chronic renal failure. However, the causal relationship between gut microbiota and chronic renal failure remains unclear. The present study employs a two-sample Mendelian randomization approach to infer the causal relationship between gut microbiota and chronic renal failure at the genetic level. This research aims to determine whether there is a causal effect of gut microbiota on the risk of chronic renal failure, aiming to provide new evidence to support targeted gut therapy for the treatment of chronic renal failure., Methods: Employing genome-wide association study (GWAS) data from the public MiBioGen and IEU OpenGWAS platform, a two-sample Mendelian randomization analysis was conducted. The causal relationship between gut microbiota and chronic renal failure was inferred using five different methods: Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. The study incorporated sensitivity analyses that encompassed evaluations for pleiotropy and heterogeneity. Subsequently, the results of the Mendelian randomization analysis underwent a stringent correction for multiple testing, employing the False Discovery Rate method to enhance the validity of our findings., Results: According to the results from the Inverse Variance Weighted method, seven bacterial genera show a significant association with the outcome variable chronic renal failure. Of these, Ruminococcus (gauvreauii group) (OR = 0.82, 95% CI = 0.71-0.94, p = 0.004) may act as a protective factor against chronic renal failure, while the genera Escherichia-Shigella (OR = 1.22, 95% CI = 1.08-1.38, p = 0.001), Lactococcus (OR = 1.1, 95% CI = 1.02-1.19, p = 0.013), Odoribacter (OR = 1.23, 95% CI = 1.03-1.49, p = 0.026), Enterorhabdus (OR = 1.14, 95% CI = 1.00-1.29, p = 0.047), Eubacterium (eligens group) (OR = 1.18, 95% CI = 1.02-1.37, p = 0.024), and Howardella (OR = 1.18, 95% CI = 1.09-1.28, p < 0.001) may be risk factors for chronic renal failure. However, after correction for multiple comparisons using False Discovery Rate, only the associations with Escherichia-Shigella and Howardella remain significant, indicating that the other genera have suggestive associations. Sensitivity analyses did not reveal any pleiotropy or heterogeneity., Conclusion: Our two-sample Mendelian randomization study suggests that the genera Escherichia-Shigella and Howardella are risk factors for chronic renal failure, and they may serve as potential targets for future therapeutic interventions. However, the exact mechanisms of action are not yet clear, necessitating further research to elucidate their precise roles fully., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Mo, Yang, Peng, Zeng, Zheng and Song.)

Diabetic nephropathy (DN) is a severe microvascular complication of diabetes, which increases the risk of renal failure and causes a high global disease burden. Due to the lack of sustainable treatment, DN has become the primary cause of end-stage renal disease worldwide. Gut microbiota and its metabolites exert critical regulatory functions in maintaining host health and are associated with many pathogenesis of aging-related chronic diseases. Currently, the theory gut-kidney axis has opened a novel angle to understand the relationship between gut microbiota and multiple kidney diseases. In recent years, accumulating evidence has revealed that the gut microbiota and their metabolites play an essential role in the pathophysiologic processes of DN through the gut-kidney axis. In this review, we summarize the current investigations of gut microbiota and microbial metabolites involvement in the progression of DN, and further discuss the potential gut microbiota-targeted therapeutic approaches for DN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Yang, Liu, Zhang, Niu, Wang and Yu.)