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Zhang B, Xu K, Deng W, Liu C, Xu Q, Sheng H, Feng J, Yuan Q. Protective effects of Sulforaphene on kidney damage and gut dysbiosis in high-fat diet plus streptozotocin-induced diabetic mice. Food Chem 2025; 469:142558. [PMID: 39709924 DOI: 10.1016/j.foodchem.2024.142558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Revised: 12/09/2024] [Accepted: 12/16/2024] [Indexed: 12/24/2024]
Abstract
Diabetic nephropathy (DN) is one of the most serious and prevalent complications associated with diabetes. Consequently, antidiabetic drugs or foods potentially protecting the kidneys are of significant therapeutic value. Sulforaphene (SFE) is a natural isothiocyanate derived from radish seeds, known for its anti-inflammatory and antioxidant properties. However, no studies have investigated on the ability of SFE to prevent or treat DN. This study established a high-fat diet combined with a streptozotocin-induced type II diabetes mellitus mouse model. We administered SFE treatment to examine its protective effects on renal and intestinal homeostasis in DN mice. After 4 weeks of treatment, SFE (50 mg/kg b.w.) not only reduced blood glucose concentration (20.3 %, P < 0.001), kidney to body weight ratio (26.2 %, P < 0.01), and levels of serum total cholesterol (40.6 %, P < 0.001), triglycerides (38.2 %, P < 0.01), creatinine (36.7 %, P < 0.01), and urea nitrogen (45.0 %, P < 0.001) in DN mice compared to control mice but also increased the kidney superoxide dismutase (72.7 %, P < 0.001), catalase (51.1 %, P < 0.001), and glutathione peroxidase activities (31.6 %, P < 0.01), as well as glutathione levels (39.2 %, P < 0.01) in comparison to DN mice. Furthermore, SFE decreased levels of reactive oxygen species (55.4 %, P < 0.01), 4-hydroxyalkenals (36.9 %, P < 0.001), malondialdehyde (42.6 %, P < 0.001), and 8-hydroxy-deoxyguanosine (26.3 %, P < 0.001), accompanied by a meliorating kidney morphological abnormalities. Notably, a reduction in renal inflammatory factors was also observed in SFE-treated DN mice compared to untreated DN mice, particularly in the C-X-C motif chemokine ligand 8 factors (54.8 %, P < 0.001). Western blotting results indicated that SFE significantly down-regulated the protein expression of TLR4 and MyD88 (1.9, 1.7-fold, P < 0.001). Additionally, SFE improved gut microbiota (GM) dysbiosis and intestinal homeostasis, as evidenced by increased expression of antimicrobial peptides and tight junction proteins in colon tissue. SFE appeared to enhance the proliferation of probiotics, such as Bacteroidota, Lachnospiraceae_NK4A136_group and norank_f__Muribaculaceae, while also decreasing harmful bacteria to a greater extent compared to STZ treatment. These findings suggest that SFE modulates GM and improves intestinal homeostasis, providing a theoretical basis for its use in the treatment of DN.
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Affiliation(s)
- Bo Zhang
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
| | - Kang Xu
- School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
| | - Wenlei Deng
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
| | - Ce Liu
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
| | - Qianmin Xu
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
| | - Huakang Sheng
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
| | - Jialu Feng
- School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Qipeng Yuan
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
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Addisu ZD, Demsie DG, Tafere C, Yazie TS, Endeshaw D, Tefera BB, Berihun M, Beyene DA. Time in the therapeutic range, bleeding event, and their determinants in older patients with atrial fibrillation on warfarin in Ethiopia: multicenter cross-sectional study. Front Pharmacol 2025; 16:1541592. [PMID: 40017601 PMCID: PMC11864910 DOI: 10.3389/fphar.2025.1541592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Accepted: 01/29/2025] [Indexed: 03/01/2025] Open
Abstract
Background Atrial fibrillation (AF) poses significant thromboembolism and bleeding risks, especially in older adults. Warfarin continues to be a primary treatment option, and maintaining the Time in Therapeutic Range (TTR) is critical for ensuring its effectiveness. However, suboptimal TTR is associated with increased risks of stroke, bleeding, and mortality. Despite its importance, there is limited data on warfarin management in Ethiopian older adults with AF. Therefore, this study aimed to determine the TTR, bleeding events, and their determinants, in older patients with AF in Ethiopia receiving warfarin therapy. Method In this study, older patients with AF who were treated with warfarin and had follow-up visits between May 2021 and May 2024, and met the inclusion criteria, were included. Patients were categorized based on TTR into two groups: poor anticoagulation (TTR < 65%) and good anticoagulation quality (TTR ≥ 65%). Bivariate and Multivariate Logistic regression was performed to predict determinants of a TTR < 65% and bleeding events. Odds ratios with 95% confidence intervals (CIs) were calculated, and statistical significance was set at P < 0.05. Results In this study, 384 patients with AF were included. Of this 53.4% were female. Of these 71% of patients had a TTR below 65%, 29% achieved ≥65%, with a median TTR of 45%. Bleeding events were reported by 13.5% of patients. Poor TTR was significantly associated with age (AOR = 1.199, 95% CI: 1.109-1.297), chronic kidney disease (AOR = 27.809, 95% CI: 7.57-101.76), and infrequent INR monitoring at 31-90-day intervals (AOR = 0.15, 95% CI: 0.004-0.051). Regarding determinants of bleeding events, Patients with diabetes mellitus had a 2.6-fold higher bleeding risk (AOR = 2.585, 95% CI: 1.069-6.250), and a CHA2DS2-VASc score ≥3 significantly increased bleeding risk compared to scores ≤2 (AOR = 7.562, 95% CI: 2.770-20.640). Conclusion This study highlights suboptimal warfarin therapy among older Ethiopian patients with AF. Poor anticoagulation was associated with advanced age, chronic kidney disease, and infrequent INR monitoring, while diabetes mellitus and high CHA₂DS₂-VASc scores increased bleeding risks. Close monitoring and frequent INR checks are essential to improving outcomes.
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Affiliation(s)
- Zenaw Debasu Addisu
- Department of Clinical Pharmacy, College of Medicine and Health Sciences, Bahir University, Bahir Dar, Amhara, Ethiopia
| | - Desalegn Getnet Demsie
- Department of Pharmacology, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Amhara, Ethiopia
| | - Chernet Tafere
- Department of Pharmaceutics, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Amhara, Ethiopia
| | - Taklo Simeneh Yazie
- Pharmacology and Toxicology Unit, Department of Pharmacy, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Destaw Endeshaw
- Department of Adult Health Nursing, College of Medicine and Health Sciences, Bair Dar University, Bahir Dar, Amhara, Ethiopia
| | - Bereket Bahiru Tefera
- Department of Social Pharmacy, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Amhara, Ethiopia
| | - Malede Berihun
- Department of Clinical Pharmacy, College of Medicine and Health Sciences, Bahir University, Bahir Dar, Amhara, Ethiopia
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Fu Q, Yang Y, Tian Q, Zhu Y, Xu H, Wang J, Huang Q. Exploring the mechanism of Paotianxiong polysaccharide in the treatment of chronic kidney disease combining metabolomics and microbiomics technologies. Int J Biol Macromol 2025; 289:138629. [PMID: 39667450 DOI: 10.1016/j.ijbiomac.2024.138629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 11/30/2024] [Accepted: 12/09/2024] [Indexed: 12/14/2024]
Abstract
A close relationship between the pathogenesis of chronic kidney disease (CKD) and abnormalities in the gut-kidney axis. Paotianxiong polysaccharides (PTXP) that have demonstrated therapeutic effects on CKD. However, the specific mechanism by which PTXP ameliorates CKD through the gut-kidney axis remains to be explored. In this study, the microbiomes and metabolomics were combined to investigate the impact of PTXP on intestinal flora structure and metabolism, further unveiling the relationship through correlation analysis. The results showed that PTXP intervention significantly modulated renal function abnormalities in CKD rats and significantly modulates gut microbial disorders, evidenced by an increased abundance of Lactobacillus murinus, Bacteroides fragilis, and a decreased abundance of Bifidobacterium pseudolongum. Furthermore, PTXP reversed the changes in intestinal metabolites, such as linoleic acid and docosahexaenoic acid, induced by CKD and identified unsaturated fatty acid metabolism as a key metabolic pathway. Correlation analyses also revealed associations among gut microorganisms, metabolites, and renal function indexes, confirming that PTXP alleviated CKD through the gut-kidney axis. Moreover, the above conclusions were verified by fecal bacteria transplantation experiments. These findings provide insights into the mechanism of PTXP for the treatment of CKD and provide new targets for the treatment of CKD.
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Affiliation(s)
- Qinwen Fu
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China
| | - Yu Yang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China
| | - Qingqing Tian
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China
| | - Ying Zhu
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China
| | - Huiyuan Xu
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China
| | - Jin Wang
- College of Ethnic Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
| | - Qinwan Huang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China.
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Stepanova N, Driianska V, Korol L, Snisar L. Association between serum total indoxyl sulfate, intraperitoneal inflammation, and peritoneal dialysis technique failure: a 3-year prospective cohort study. BMC Nephrol 2024; 25:475. [PMID: 39741261 DOI: 10.1186/s12882-024-03935-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 12/27/2024] [Indexed: 01/02/2025] Open
Abstract
BACKGROUND The impact of protein-bound uremic toxins, specifically indoxyl sulfate (IS) on peritoneal dialysis (PD) complications remains controversial. This study aimed to explore the link between serum total IS (tIS) levels, proinflammatory cytokines in serum and peritoneal dialysis effluent (PDE), and PD technique survival. METHODS In this prospective cohort study, 84 patients were followed up for three years and analyzed. Stratification into low-tIS (< 22.6 µmol/L) and high-tIS (≥ 22.6 µmol/L) groups was based on the median serum tIS concentration. Logistic regression, Kaplan-Meier, receiving operation characteristic, and Cox regression analyses assessed associations between tIS levels, cytokine concentrations (IL-6, MCP-1, TNF-α), and PD technique failure. RESULTS Patients in the high-tIS group were older and had a higher prevalence of diabetes, a greater incidence of PD-related peritonitis, elevated diastolic blood pressure, and lower HDL cholesterol compared to those in the low-tIS group. They also exhibited higher peritoneal transport characteristics, lower dialysis adequacy, and reduced peritoneal creatinine clearance. Elevated tIS levels significantly correlated with higher PDE cytokine levels, without a corresponding rise in serum cytokine levels. Serum tIS levels ≥ 50 µmol/L predicted PD technique failure with 70.4% sensitivity and 87.9% specificity (p < 0.0001). The association between high tIS levels and PD technique failure remained significant after adjusting for confounders identified in logistic regression, including peritoneal weekly creatinine clearance, the D/P creatinine ratio, high peritoneal transport status, and PDE IL-6 and MCP-1 concentrations (HR 2.9, 95% CI 1.13; 8.21). CONCLUSION Our findings are the first to demonstrate a link between elevated tIS levels, peritoneal inflammation, and an increased risk of PD technique failure. Monitoring tIS levels in PD patients could be clinically relevant for risk assessment and personalized management, potentially improving long-term PD outcomes. Future research should explore interventions targeting tIS reduction to alleviate peritoneal inflammation and improve PD prognosis.
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Affiliation(s)
- Natalia Stepanova
- Head of the Department of Nephrology and Dialysis, State Institution "Institute of Nephrology National Academy of Medical Sciences of Ukraine", Degtyarivska 17 V, Kyiv, 04050, Ukraine.
- Medical Director of the Dialysis Medical Center LLC "Nephrocenter", Dovzhenka 3, Kyiv, 03057, Ukraine.
| | - Victoria Driianska
- Head of the Laboratory of Immunology, State Institution "Institute of Nephrology of the National Academy of Medical Sciences of Ukraine", Degtyarivska 17 V, Kyiv, 04050, Ukraine
| | - Lesya Korol
- Laboratory of Biochemistry, State Institution "Institute of Nephrology of the National Academy of Medical Sciences of Ukraine", Degtyarivska 17 V, Kyiv, 04050, Ukraine
| | - Lyudmyla Snisar
- Head Doctor of the Dialysis Medical Center LLC, "Nephrocenter", Dovzhenka 3, Kyiv, 03057, Ukraine
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Zheng G, Cao J, Wang XH, He W, Wang B. The gut microbiome, chronic kidney disease, and sarcopenia. Cell Commun Signal 2024; 22:558. [PMID: 39574190 PMCID: PMC11580515 DOI: 10.1186/s12964-024-01922-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 11/01/2024] [Indexed: 11/25/2024] Open
Abstract
Sarcopenia is a prevalent condition in patients with chronic kidney disease (CKD), intricately linked to adverse prognoses, heightened cardiovascular risks, and increased mortality rates. Extensive studies have found a close and complex association between gut microbiota, kidney and muscle. On one front, patients with CKD manifest disturbances in gut microbiota and alterations in serum metabolites. These abnormal microbiota composition and metabolites in turn participate in the development of CKD. On another front, altered gut microbiota and its metabolites may lead to significant changes in metabolic homeostasis and inflammation, ultimately contributing to the onset of sarcopenia. The disturbance of gut microbial homeostasis, coupled with the accumulation of toxic metabolites, exerts deleterious effects on skeletal muscles in CKD patients with sarcopenia. This review meticulously describes the alterations observed in gut microbiota and its serum metabolites in CKD and sarcopenia patients, providing a comprehensive overview of pertinent studies. By delving into the intricate interplay of gut microbiota and serum metabolites in CKD-associated sarcopenia, we aim to unveil novel treatment strategies for ameliorating their symptoms and prognosis.
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Affiliation(s)
- Guohao Zheng
- Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China
| | - Jingyuan Cao
- Institute of Nephrology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, China
| | - Xiaonan H Wang
- Department of Medicine, Renal Division, Emory University, Atlanta, Georgia
| | - Wei He
- Department of Gastroenterology, Geriatric Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Bin Wang
- Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
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Rovira J, Ramirez-Bajo MJ, Bañon-Maneus E, Ventura-Aguiar P, Arias-Guillén M, Romano-Andrioni B, Ojeda R, Revuelta I, García-Calderó H, Barberà JA, Dantas AP, Diaz-Ricart M, Crispi F, García-Pagán JC, Campistol JM, Diekmann F. Mediterranean Diet Pattern: Potential Impact on the Different Altered Pathways Related to Cardiovascular Risk in Advanced Chronic Kidney Disease. Nutrients 2024; 16:3739. [PMID: 39519573 PMCID: PMC11547550 DOI: 10.3390/nu16213739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/25/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Cardiovascular disease (CVD) remains the most common cause of mortality in chronic kidney disease (CKD) patients. Several studies suggest that the Mediterranean diet reduces the risk of CVD due to its influence on endothelial function, inflammation, lipid profile, and blood pressure. Integrating metabolomic and proteomic analyses of CKD could provide insights into the pathways involved in uremia-induced CVD and those pathways modifiable by the Mediterranean diet. METHODS We performed metabolomic and proteomic analyses on serum samples from 19 patients with advanced CKD (aCKD) and 27 healthy volunteers. The metabolites were quantified using four different approaches, based on their properties. Proteomic analysis was performed after depletion of seven abundant serum proteins (Albumin, IgG, antitrypsin, IgA, transferrin, haptoglobin, and fibrinogen). Integrative analysis was performed using MetaboAnalyst 4.0 and STRING 11.0 software to identify the dysregulated pathways and biomarkers. RESULTS A total of 135 metabolites and 75 proteins were differentially expressed in aCKD patients, compared to the controls. Pathway enrichment analysis showed significant alterations in the innate immune system pathways, including complement, coagulation, and neutrophil degranulation, along with disrupted linoleic acid and cholesterol metabolism. Additionally, certain key metabolites and proteins were altered in aCKD patients, such as glutathione peroxidase 3, carnitine, homocitrulline, 3-methylhistidine, and several amino acids and derivatives. CONCLUSIONS Our findings reveal significant dysregulation of the serum metabolome and proteome in aCKD, particularly in those pathways associated with endothelial dysfunction and CVD. These results suggest that CVD prevention in CKD may benefit from a multifaceted approach, including dietary interventions such as the Mediterranean diet.
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Affiliation(s)
- Jordi Rovira
- Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d’Investigacions Biomètiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain; (M.J.R.-B.); (E.B.-M.); (P.V.-A.); (M.A.-G.); (I.R.); (J.M.C.)
- Red de Investigación Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain
| | - María José Ramirez-Bajo
- Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d’Investigacions Biomètiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain; (M.J.R.-B.); (E.B.-M.); (P.V.-A.); (M.A.-G.); (I.R.); (J.M.C.)
- Red de Investigación Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain
| | - Elisenda Bañon-Maneus
- Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d’Investigacions Biomètiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain; (M.J.R.-B.); (E.B.-M.); (P.V.-A.); (M.A.-G.); (I.R.); (J.M.C.)
- Red de Investigación Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain
| | - Pedro Ventura-Aguiar
- Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d’Investigacions Biomètiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain; (M.J.R.-B.); (E.B.-M.); (P.V.-A.); (M.A.-G.); (I.R.); (J.M.C.)
- Red de Investigación Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain
- Department of Nephrology and Kidney Transplantation, Clínic’s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain; (B.R.-A.); (R.O.)
| | - Marta Arias-Guillén
- Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d’Investigacions Biomètiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain; (M.J.R.-B.); (E.B.-M.); (P.V.-A.); (M.A.-G.); (I.R.); (J.M.C.)
- Red de Investigación Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain
- Department of Nephrology and Kidney Transplantation, Clínic’s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain; (B.R.-A.); (R.O.)
| | - Barbara Romano-Andrioni
- Department of Nephrology and Kidney Transplantation, Clínic’s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain; (B.R.-A.); (R.O.)
| | - Raquel Ojeda
- Department of Nephrology and Kidney Transplantation, Clínic’s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain; (B.R.-A.); (R.O.)
| | - Ignacio Revuelta
- Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d’Investigacions Biomètiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain; (M.J.R.-B.); (E.B.-M.); (P.V.-A.); (M.A.-G.); (I.R.); (J.M.C.)
- Red de Investigación Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain
- Department of Nephrology and Kidney Transplantation, Clínic’s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain; (B.R.-A.); (R.O.)
| | - Héctor García-Calderó
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic_Clínic Barcelona, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Department of Medicine and Health Sciences, University of Barcelona, CSUR_EVH, 08036 Barcelona, Spain; (H.G.-C.); (J.C.G.-P.)
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), 28200 Madrid, Spain
| | - Joan Albert Barberà
- Department of Pulmonary Medicine, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain;
- Biomedical Research Networking Center on Respiratory Diseases (CIBERES), 30627 Madrid, Spain
| | - Ana Paula Dantas
- Cardiovascular Institute, Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08007 Barcelona, Spain;
| | - Maribel Diaz-Ricart
- Hematopathology, Centre Diagnòstic Biomèdic (CDB), Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08007 Barcelona, Spain;
- Barcelona Endothelium Team (BET), 08036 Barcelona, Spain
| | - Fàtima Crispi
- BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Déu, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08007 Barcelona, Spain;
- Centre for Biomedical Research on Rare Diseases (CIBER-ER), 28029 Madrid, Spain
| | - Juan Carlos García-Pagán
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic_Clínic Barcelona, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Department of Medicine and Health Sciences, University of Barcelona, CSUR_EVH, 08036 Barcelona, Spain; (H.G.-C.); (J.C.G.-P.)
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), 28200 Madrid, Spain
| | - Josep M. Campistol
- Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d’Investigacions Biomètiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain; (M.J.R.-B.); (E.B.-M.); (P.V.-A.); (M.A.-G.); (I.R.); (J.M.C.)
- Red de Investigación Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain
- Department of Nephrology and Kidney Transplantation, Clínic’s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain; (B.R.-A.); (R.O.)
| | - Fritz Diekmann
- Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d’Investigacions Biomètiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain; (M.J.R.-B.); (E.B.-M.); (P.V.-A.); (M.A.-G.); (I.R.); (J.M.C.)
- Red de Investigación Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain
- Department of Nephrology and Kidney Transplantation, Clínic’s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain; (B.R.-A.); (R.O.)
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Zhang WW, Huo JL, Xiao MD, Xu YJ, Zhou J. Exploring the potential link between gut microbiota and chronic kidney disease in causality: A 2-sample Mendelian randomization study. Medicine (Baltimore) 2024; 103:e40236. [PMID: 39470494 PMCID: PMC11521073 DOI: 10.1097/md.0000000000040236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 10/02/2024] [Accepted: 10/07/2024] [Indexed: 10/30/2024] Open
Abstract
Increasing evidence indicates a significant correlation between gut microbiota (GM) and susceptibility to chronic kidney disease (CKD). However, causal relationship presence remains uncertain. Mendelian randomization (MR) was applied to evaluate potential causal relation from GM to CKD. Genomic association analysis aggregates publicly online databases, utilizing Genome-Wide Association Study (GWAS) database focused on GM and CKD. For examination of potential causal connection from GM to CKD, a 2-way, 2-sample Mendelian randomization (MR) method was applied. Sensitivity analyses were utilized to scrutinize for heterogeneity, horizontal pleiotropy, MR outcomes resilience. Result from inverse variance weighting (IVW) method revealed that 10 microbiotas such as Porphyromonadaceae (OR = 1.351, 95% CI: 1.114-1.638, P = .002), Dorea (OR = 1.236, 95% CI: 1.040-1.468, P = .016), Ruminococcus torques group (OR = 1.290, 95% CI: 1.035-1.608, P = .024) are potential CKD risk factors. Five microbiotas, including the Prevotellaceae (OR = 0.814, 95% CI: 0.719-0.922, P = .001) are potential CKD protective factors. Sensitivity analyses reveal no horizontal pleiotropy or heterogeneity. Additionally, reverse MR results unveiled potential relation between CKD and disorders in 3 microbiotas, including Senegalimassilia. According to the investigation, MR method was employed to delve into reciprocal causal connection from GM to CKD. Our findings identified 15 types of GM causally linked to CKD, as well as CKD demonstrating causal associations with 3 types of GM. Further exploration of these associated GM types is hopeful to raise novel insights, for CKD preventing and early monitoring.
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Affiliation(s)
- Wen Wen Zhang
- First Clinical Medical College, Hubei University of Chinese Medicine, Wuhan, Hubei, China
| | - Jin Lin Huo
- College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Pudong New Area, Shanghai, China
| | - Mei Di Xiao
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, China
| | - Ya Jie Xu
- College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, China
| | - Jin Zhou
- First Clinical Medical College, Hubei University of Chinese Medicine, Wuhan, Hubei, China
- Department of Traditional Chinese Medicine, Shenzhen Second People’s Hospital, Shenzhen Municipal Health Commission Traditional Chinese Medicine Key Specialty, Shenzhen, Guangdong, China
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8
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Guldan M, Ozbek L, Topcu AU, Covic A, Kanbay M. Metabolically healthy obesity and chronic kidney disease risk: exploring the dynamics. Panminerva Med 2024; 66:293-308. [PMID: 38990212 DOI: 10.23736/s0031-0808.24.05112-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/12/2024]
Abstract
Obesity represents a prevalent global health concern with significant implications for various diseases, including chronic kidney disease (CKD). Within this landscape, the phenomenon of metabolically healthy obesity has emerged, challenging traditional notions about the health risks associated with excess weight. While traditional CKD risk factors involve obesity, metabolic syndrome, diabetes, and hypertension, the metabolically healthy obese (MHO) subgroup disrupts these assumptions. Our main objective in this study is to integrate existing literature on CKD in MHO individuals. In this endeavor, we delve into the pathophysiological foundations, the transition between obesity phenotypes and their impact on renal health, examine the implications of their metabolic resilience on mortality within a renal context, and explore potential management strategies specifically designed for MHO individuals. Offering a comprehensive overview of the pathophysiology, we cover various factors contributing to the risk of CKD in the metabolically healthy obese setting, including inflammation, cytokines, hemodynamics, and the renin-angiotensin-aldosterone system, gastrointestinal microbiota, diet, exercise, adipose distribution, and lipotoxicity. Through this synthesis, we aim to provide a comprehensive understanding of the risk of CKD in those classified as MHO.
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Affiliation(s)
| | - Lasin Ozbek
- School of Medicine, Koc University, Istanbul, Türkiye
| | - Ahmet U Topcu
- School of Medicine, Koc University, Istanbul, Türkiye
| | - Adrian Covic
- Department of Nephrology, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy of Iasi, Iasi, Romania
| | - Mehmet Kanbay
- School of Medicine, Division of Nephrology, Department of Internal Medicine, Koç University, Istanbul, Türkiye -
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9
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Wang J, Xie Y, Wu T, Chen Y, Jiang M, Li X, Ye Y, Zhou E, Yang Z. Phytic acid alleviates ochratoxin A-induced renal damage in chicks by modulating ferroptosis and the structure of the intestinal microbiota. Poult Sci 2024; 103:104027. [PMID: 39024690 PMCID: PMC11519695 DOI: 10.1016/j.psj.2024.104027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 06/20/2024] [Accepted: 06/21/2024] [Indexed: 07/20/2024] Open
Abstract
Phytic acid (PA) is a natural antioxidant with various biological activities, providing protective effects in multiple animals. Ochratoxin A (OTA) is a mold toxin commonly found in feed, which induces multi-organ damage, with kidney being the target organ of its toxicity. This study investigates the protective effects of PA on OTA-induced renal damage and its potential mechanisms in chicks. The results demonstrates that PA treatment restores OTA-induced renal pathological injuries, reverses the diminished activities of antioxidant enzymes, reduces the accumulation of malondialdehyde, and normalizes the expression of pro-inflammatory cytokines, which confirms that PA can alleviate OTA-induced renal damage. Further investigations reveal that OTA-induced renal injury accompanied by an increase in tissue iron content and the transcription levels of ferroptosis-related genes (TFR, ACSL4, and HO-1), and a decrease in the levels of SLC7A11 and GPX4. PA treatment reverses all these effects, indicating that PA mitigates OTA-induced renal ferroptosis. Moreover, PA supplementation improves intestinal morphology and mucosal function, corrects OTA-induced changes in the intestinal microbiota. Besides, PA microbiota transplantation alleviates renal inflammation and oxidative stress caused by OTA. In conclusion, PA plays a protective role against renal damage through the regulation of ferroptosis and the intestinal microbiota, possibly providing novel insights into the control and prevention of OTA-related nephrotoxicity.
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Affiliation(s)
- Jingjing Wang
- College of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528231, China
| | - Yueqing Xie
- College of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528231, China
| | - Ting Wu
- College of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528231, China
| | - Yichun Chen
- College of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528231, China
| | - Mingzhen Jiang
- College of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528231, China
| | - Xuhai Li
- College of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528231, China
| | - Yingrong Ye
- College of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528231, China
| | - Ershun Zhou
- College of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528231, China
| | - Zhengtao Yang
- College of Life Science and Engineering, Foshan University, Foshan, Guangdong, 528231, China.
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10
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Flori L, Benedetti G, Martelli A, Calderone V. Microbiota alterations associated with vascular diseases: postbiotics as a next-generation magic bullet for gut-vascular axis. Pharmacol Res 2024; 207:107334. [PMID: 39103131 DOI: 10.1016/j.phrs.2024.107334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/11/2024] [Accepted: 07/29/2024] [Indexed: 08/07/2024]
Abstract
The intestinal microbiota represents a key element in maintaining the homeostasis and health conditions of the host. Vascular pathologies and other risk factors such as aging have been recently associated with dysbiosis. The qualitative and quantitative alteration of the intestinal microbiota hinders correct metabolic homeostasis, causing structural and functional changes of the intestinal wall itself. Impairment of the intestinal microbiota, combined with the reduction of the barrier function, worsen the pathological scenarios of peripheral tissues over time, including the vascular one. Several experimental evidence, collected in this review, describes in detail the changes of the intestinal microbiota in dysbiosis associated with vascular alterations, such as atherosclerosis, hypertension, and endothelial dysfunction, the resulting metabolic disorders and how these can impact on vascular health. In this context, the gut-vascular axis is considered, for the first time, as a merged unit involved in the development and progression of vascular pathologies and as a promising target. Current approaches for the management of dysbiosis such as probiotics, prebiotics and dietary modifications act mainly on the intestinal district. Postbiotics, described as preparation of inanimate microorganisms and/or their components that confers health benefits on the host, represent an innovative strategy for a dual management of intestinal dysbiosis and vascular pathologies. In this context, this review has the further purpose of defining the positive effects of the supplementation of bacterial strains metabolites (short‑chain fatty acids, exopolysaccharides, lipoteichoic acids, gallic acid, and protocatechuic acid) restoring intestinal homeostasis and acting directly on the vascular district through the gut-vascular axis.
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Affiliation(s)
- Lorenzo Flori
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy.
| | - Giada Benedetti
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy.
| | - Alma Martelli
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa 56120, Italy; Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, Pisa 56120, Italy.
| | - Vincenzo Calderone
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa 56120, Italy; Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, Pisa 56120, Italy.
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11
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Lúcio HG, Lopes RDCSO, Gomes MJC, da Silva A, Grancieri M, Della Lucia CM, Queiroz VAV, da Silva BP, Martino HSD. A Symbiotic Meal Containing Extruded Sorghum and Probiotic ( Bifidobacterium longum) Ameliorated Intestinal Health Markers in Individuals with Chronic Kidney Disease: A Secondary Analysis of a Subsample from a Previous Randomized and Controlled Clinical Trial. Nutrients 2024; 16:1852. [PMID: 38931207 PMCID: PMC11206769 DOI: 10.3390/nu16121852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 06/07/2024] [Accepted: 06/11/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND Chronic kidney disease increases uremic toxins concentrations, which have been associated with intestinal dysbiosis. Sorghum bicolor L. Moench has dietary fiber and bioactive compounds, while Bifidobacterium longum can promote beneficial health effects. METHODS It is a controlled, randomized, and single-blind clinical trial. Thirty-nine subjects were randomly separated into two groups: symbiotic group (SG), which received 100 mL of unfermented probiotic milk with Bifidobacterium longum strain and 40 g of extruded sorghum flakes; and the control group (CG), which received 100 mL of pasteurized milk and 40 g of extruded corn flakes for seven weeks. RESULTS The uremic toxins decreased, and gastrointestinal symptoms improved intragroup in the SG group. The acetic, propionic, and butyric acid production increased intragroup in the SG group. Regarding α-diversity, the Chao1 index was enhanced in the SG intragroup. The KEGG analysis revealed that symbiotic meal increased the intragroup energy and amino sugar metabolism, in addition to enabling essential amino acid production and metabolism, sucrose degradation, and the biosynthesis of ribonucleotide metabolic pathways. CONCLUSIONS The consumption of symbiotic meal reduced BMI, improved short-chain fatty acid (SCFA) synthesis and gastrointestinal symptoms, increased diversity according to the Chao1 index, and reduced uremic toxins in chronic kidney disease patients.
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Affiliation(s)
- Haira Guedes Lúcio
- Nutrition and Health Department, Federal University of Viçosa, Campus Universitário, Av. Purdue, s/n, Viçosa 36570-900, MG, Brazil; (H.G.L.); (R.d.C.S.O.L.); (M.J.C.G.); (A.d.S.); (C.M.D.L.); (B.P.d.S.)
| | - Rita de Cassia Stampini Oliveira Lopes
- Nutrition and Health Department, Federal University of Viçosa, Campus Universitário, Av. Purdue, s/n, Viçosa 36570-900, MG, Brazil; (H.G.L.); (R.d.C.S.O.L.); (M.J.C.G.); (A.d.S.); (C.M.D.L.); (B.P.d.S.)
| | - Mariana Juste Contin Gomes
- Nutrition and Health Department, Federal University of Viçosa, Campus Universitário, Av. Purdue, s/n, Viçosa 36570-900, MG, Brazil; (H.G.L.); (R.d.C.S.O.L.); (M.J.C.G.); (A.d.S.); (C.M.D.L.); (B.P.d.S.)
| | - Alessandra da Silva
- Nutrition and Health Department, Federal University of Viçosa, Campus Universitário, Av. Purdue, s/n, Viçosa 36570-900, MG, Brazil; (H.G.L.); (R.d.C.S.O.L.); (M.J.C.G.); (A.d.S.); (C.M.D.L.); (B.P.d.S.)
| | - Mariana Grancieri
- Pharmacy and Nutrition Department, Federal University of Espírito Santo, Alto Universitário, City Center, Alegre 29500-000, ES, Brazil;
| | - Ceres Mattos Della Lucia
- Nutrition and Health Department, Federal University of Viçosa, Campus Universitário, Av. Purdue, s/n, Viçosa 36570-900, MG, Brazil; (H.G.L.); (R.d.C.S.O.L.); (M.J.C.G.); (A.d.S.); (C.M.D.L.); (B.P.d.S.)
| | | | - Bárbara Pereira da Silva
- Nutrition and Health Department, Federal University of Viçosa, Campus Universitário, Av. Purdue, s/n, Viçosa 36570-900, MG, Brazil; (H.G.L.); (R.d.C.S.O.L.); (M.J.C.G.); (A.d.S.); (C.M.D.L.); (B.P.d.S.)
| | - Hercia Stampini Duarte Martino
- Nutrition and Health Department, Federal University of Viçosa, Campus Universitário, Av. Purdue, s/n, Viçosa 36570-900, MG, Brazil; (H.G.L.); (R.d.C.S.O.L.); (M.J.C.G.); (A.d.S.); (C.M.D.L.); (B.P.d.S.)
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12
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Pires L, González-Paramás AM, Heleno SA, Calhelha RC. The Role of Gut Microbiota in the Etiopathogenesis of Multiple Chronic Diseases. Antibiotics (Basel) 2024; 13:392. [PMID: 38786121 PMCID: PMC11117238 DOI: 10.3390/antibiotics13050392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 04/23/2024] [Accepted: 04/25/2024] [Indexed: 05/25/2024] Open
Abstract
Chronic diseases (CD) may result from a combination of genetic factors, lifestyle and social behaviours, healthcare system influences, community factors, and environmental determinants of health. These risk factors frequently coexist and interact with one another. Ongoing research and a focus on personalized interventions are pivotal strategies for preventing and managing chronic disease outcomes. A wealth of literature suggests the potential involvement of gut microbiota in influencing host metabolism, thereby impacting various risk factors associated with chronic diseases. Dysbiosis, the perturbation of the composition and activity of the gut microbiota, is crucial in the etiopathogenesis of multiple CD. Recent studies indicate that specific microorganism-derived metabolites, including trimethylamine N-oxide, lipopolysaccharide and uremic toxins, contribute to subclinical inflammatory processes implicated in CD. Various factors, including diet, lifestyle, and medications, can alter the taxonomic species or abundance of gut microbiota. Researchers are currently dedicating efforts to understanding how the natural progression of microbiome development in humans affects health outcomes. Simultaneously, there is a focus on enhancing the understanding of microbiome-host molecular interactions. These endeavours ultimately aim to devise practical approaches for rehabilitating dysregulated human microbial ecosystems, intending to restore health and prevent diseases. This review investigates how the gut microbiome contributes to CD and explains ways to modulate it for managing or preventing chronic conditions.
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Affiliation(s)
- Lara Pires
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (L.P.); (S.A.H.)
- Grupo de Investigación en Polifenoles en Alimentos, Implicaciones en la Calidad y en Salud Humana, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno s/n, 37007 Salamanca, Spain;
| | - Ana M. González-Paramás
- Grupo de Investigación en Polifenoles en Alimentos, Implicaciones en la Calidad y en Salud Humana, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno s/n, 37007 Salamanca, Spain;
| | - Sandrina A. Heleno
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (L.P.); (S.A.H.)
- Laboratório Associado para Sustentabilidade e Tecnologia em Regiões de Montanha (SusTEC), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal
| | - Ricardo C. Calhelha
- Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; (L.P.); (S.A.H.)
- Laboratório Associado para Sustentabilidade e Tecnologia em Regiões de Montanha (SusTEC), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal
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13
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Huang HW, Chen MJ. Exploring the Preventive and Therapeutic Mechanisms of Probiotics in Chronic Kidney Disease through the Gut-Kidney Axis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:8347-8364. [PMID: 38571475 PMCID: PMC11036402 DOI: 10.1021/acs.jafc.4c00263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 03/25/2024] [Accepted: 03/25/2024] [Indexed: 04/05/2024]
Abstract
Gut dysbiosis contributes to deterioration of chronic kidney disease (CKD). Probiotics are a potential approach to modulate gut microbiota and gut-derived metabolites to alleviate CKD progression. We aim to provide a comprehensive view of CKD-related gut dysbiosis and a critical perspective on probiotic function in CKD. First, this review addresses gut microbial alterations during CKD progression and the adverse effects associated with the changes in gut-derived metabolites. Second, we conduct a thorough examination of the latest clinical trials involving probiotic intervention to unravel critical pathways via the gut-kidney axis. Finally, we propose our viewpoints on limitations, further considerations, and future research prospects of probiotic adjuvant therapy in alleviating CKD progression. Enhancing our understanding of host-microbe interactions is crucial for gaining precise insights into the mechanisms through which probiotics exert their effects and identifying factors that influence the effectiveness of probiotics in developing strategies to optimize their use and enhance clinical outcomes.
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Affiliation(s)
- Hsiao-Wen Huang
- Department
of Animal Science and Technology, National
Taiwan University, No. 50, Ln. 155, Section 3, Keelung Road, Taipei 10673, Taiwan
| | - Ming-Ju Chen
- Department
of Animal Science and Technology, National
Taiwan University, No. 50, Ln. 155, Section 3, Keelung Road, Taipei 10673, Taiwan
- Center
for Biotechnology, National Taiwan University, No. 81, Changxing Street, Taipei 10672, Taiwan
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14
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Liu X, Mo J, Yang X, Peng L, Zeng Y, Zheng Y, Song G. Causal relationship between gut microbiota and chronic renal failure: a two-sample Mendelian randomization study. Front Microbiol 2024; 15:1356478. [PMID: 38633704 PMCID: PMC11021586 DOI: 10.3389/fmicb.2024.1356478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 03/20/2024] [Indexed: 04/19/2024] Open
Abstract
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.
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Affiliation(s)
- Xingzheng Liu
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Jinying Mo
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Xuerui Yang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Ling Peng
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Youjia Zeng
- Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Yihou Zheng
- Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Gaofeng Song
- Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
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15
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Shi W, Li Z, Wang W, Liu X, Wu H, Chen X, Zhou X, Zhang S. Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation. J Pharm Anal 2024; 14:100931. [PMID: 38655401 PMCID: PMC11035364 DOI: 10.1016/j.jpha.2023.12.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 12/14/2023] [Accepted: 12/28/2023] [Indexed: 04/26/2024] Open
Abstract
Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis (ICGN). However, an in-depth study on this topic is currently lacking. Herein, we report an ICGN model to address this gap. ICGN was induced via the intravenous injection of cationized bovine serum albumin (c-BSA) into Sprague-Dawley (SD) rats for two weeks, after which mycophenolate mofetil (MMF) and losartan were administered orally. Two and six weeks after ICGN establishment, fecal samples were collected and 16S ribosomal DNA (rDNA) sequencing and untargeted metabolomic were conducted. Fecal microbiota transplantation (FMT) was conducted to determine whether gut normalization caused by MMF and losartan contributed to their renal protective effects. A gradual decline in microbial diversity and richness was accompanied by a loss of renal function. Approximately 18 genera were found to have significantly different relative abundances between the early and later stages, and Marvinbryantia and Allobaculum were markedly upregulated in both stages. Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN, characterized by the overproduction of indole and kynurenic acid, while the serotonin pathway was reduced. Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces. FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes (F/B) ratio but did not improve renal function. These findings indicate that ICGN induces serous gut dysbiosis, wherein an altered tryptophan metabolism may contribute to its progression. MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis, which partially contributed to their renoprotective effects.
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Affiliation(s)
- Wenying Shi
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- State Key Laboratory of Functions and Applications of Medicinal Plants, College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, 550004, China
| | - Zhaojun Li
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
- Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institute, Stockholm, 17176, Sweden
| | - Weida Wang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Xikun Liu
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Haijie Wu
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Xiaoguang Chen
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
| | - Xunrong Zhou
- Department of Pharmacy, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China
| | - Sen Zhang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
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16
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Samaey A, Vázquez-Castellanos JF, Caenepeel C, Evenepoel P, Vermeire S, Raes J, Knops N. Effects of fecal microbiota transplantation for recurrent Clostridium difficile infection in children on kidney replacement therapy: a pilot study. Pediatr Nephrol 2024; 39:1201-1212. [PMID: 37775582 DOI: 10.1007/s00467-023-06168-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 09/06/2023] [Accepted: 09/12/2023] [Indexed: 10/01/2023]
Abstract
BACKGROUND Recurrent Clostridium difficile infection (rCDI) is a rising problem in children with chronic diseases. Fecal microbiota transplantation (FMT) is a recent alternative for rCDI patients who do not respond to conventional treatment. FMT could have an additional positive effect on the intestinal dysbiosis and accumulation of uremic retention molecules (URM) associated with chronic kidney disease (CKD). Our aim was to investigate the clinical efficacy of FMT for rCDI in children with CKD together with the effect on dysbiosis and URM levels. METHODS We analyzed stool and blood samples before and until 3 months after FMT in 3 children between 4 and 8 years old with CKD and rCDI. The microbiome was analyzed by 16 s rRNA sequencing. URM were analyzed with ultra-performance liquid chromatography-tandem mass spectrometry. CRP and fecal calprotectin were analyzed as parameters for systemic and gut inflammation, respectively. RESULTS CDI resolved after FMT in all three without adverse events; one patient needed a second FMT. No significant effect on CRP and calprotectin was observed. Stool samples demonstrated a reduced richness and bacterial diversity which did not improve after FMT. We did observe a trend in the decrease of specific URM up to 3 months after FMT. CONCLUSION FMT is an effective treatment for rCDI in patients with CKD. Analysis of the microbiome showed an important intestinal dysbiosis that, besides a significant reduction in Clostridium difficile, did not significantly change after FMT. A trend for reduction was seen in some of the measured URM after FMT.
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Affiliation(s)
- An Samaey
- Department of Pediatric Nephrology and Solid Organ Transplantation, UZ Leuven, Leuven, Belgium.
| | - Jorge Francisco Vázquez-Castellanos
- Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium
- VIB-KU Leuven Center for Microbiology, Louvain, Belgium
| | - Clara Caenepeel
- Translational Research Center for Gastrointestinal Disorders (TARGID), UZ Leuven, Leuven, Belgium
| | - Pieter Evenepoel
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
- Laboratory of Nephrology, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium
| | - Séverine Vermeire
- Department of Gastroenterology &, Hepatology University Hospitals Leuven, and Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Jeroen Raes
- Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium
| | - Noël Knops
- Department of Pediatric Nephrology and Solid Organ Transplantation, UZ Leuven, Leuven, Belgium
- Department of Pediatrics, Groene Hart Ziekenhuis, Gouda, the Netherlands
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17
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Jia PP, Li Y, Zhang LC, Wu MF, Li TY, Pei DS. Metabolome evidence of CKDu risks after chronic exposure to simulated Sri Lanka drinking water in zebrafish. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 273:116149. [PMID: 38412632 DOI: 10.1016/j.ecoenv.2024.116149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/10/2024] [Accepted: 02/22/2024] [Indexed: 02/29/2024]
Abstract
It is still a serious public health issue that chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka poses challenges in identification, prevention, and treatment. What environmental factors in drinking water cause kidney damage remains unclear. This study aimed to investigate the risks of various environmental factors that may induce CKDu, including water hardness, fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM). The research focused on comprehensive metabolome analysis, and correlation with transcriptomic and gut microbiota changes. Results revealed that chronic exposure led to kidney damage and pancreatic toxicity in adult zebrafish. Metabolomics profiling showed significant alterations in biochemical processes, with enriched metabolic pathways of oxidative phosphorylation, folate biosynthesis, arachidonic acid metabolism, FoxO signaling pathway, lysosome, pyruvate metabolism, and purine metabolism. The network analysis revealed significant changes in metabolites associated with renal function and diseases, including 20-Hydroxy-LTE4, PS(18:0/22:2(13Z,16Z)), Neuromedin N, 20-Oxo-Leukotriene E4, and phenol sulfate, which are involved in the fatty acyls and glycerophospholipids class. These metabolites were closely associated with the disrupted gut bacteria of g_ZOR0006, g_Pseudomonas, g_Tsukamurella, g_Cetobacterium, g_Flavobacterium, which belonged to dominant phyla of Firmicutes and Proteobacteria, etc., and differentially expressed genes (DEGs) such as egln3, ca2, jun, slc2a1b, and gls2b in zebrafish. Exploratory omics analyses revealed the shared significantly changed pathways in transcriptome and metabolome like calcium signaling and necroptosis, suggesting potential biomarkers for assessing kidney disease.
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Affiliation(s)
- Pan-Pan Jia
- School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Yan Li
- School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Lan-Chen Zhang
- School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Ming-Fei Wu
- School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Tian-Yun Li
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China
| | - De-Sheng Pei
- School of Public Health, Chongqing Medical University, Chongqing 400016, China.
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18
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Hajra D, Kirthivasan N, Chakravortty D. Symbiotic Synergy from Sponges to Humans: Microflora-Host Harmony Is Crucial for Ensuring Survival and Shielding against Invading Pathogens. ACS Infect Dis 2024; 10:317-336. [PMID: 38170903 DOI: 10.1021/acsinfecdis.3c00554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
Gut microbiota plays several roles in the host organism's metabolism and physiology. This phenomenon holds across different species from different kingdoms and classes. Different species across various classes engage in continuous crosstalk via various mechanisms with their gut microbiota, ensuring homeostasis of the host. In this Review, the diversity of the microflora, the development of the microflora in the host, its regulations by the host, and its functional implications on the host, especially in the context of dysbiosis, are discussed across different organisms from sponges to humans. Overall, our review aims to address the indispensable nature of the microbiome in the host's survival, fitness, and protection against invading pathogens.
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Affiliation(s)
- Dipasree Hajra
- Department of Microbiology & Cell Biology, Indian Institute of Science, Bangalore, Karnataka-560012, India
| | - Nikhita Kirthivasan
- Undergraduate Programme, Indian Institute of Science, Bangalore, Karnataka-560012, India
| | - Dipshikha Chakravortty
- Department of Microbiology & Cell Biology, Indian Institute of Science, Bangalore, Karnataka-560012, India
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19
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Coutinho-Wolino KS, Melo MFS, Mota JC, Mafra D, Guimarães JT, Stockler-Pinto MB. Blueberry, cranberry, raspberry, and strawberry as modulators of the gut microbiota: target for treatment of gut dysbiosis in chronic kidney disease? From current evidence to future possibilities. Nutr Rev 2024; 82:248-261. [PMID: 37164634 DOI: 10.1093/nutrit/nuad048] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/12/2023] Open
Abstract
Gut dysbiosis is common in patients with chronic kidney disease (CKD) and is associated with uremic toxin production, inflammation, oxidative stress, and cardiovascular disease development. Therefore, healthy dietary patterns are essential modulators of gut microbiota. In this context, studies suggest that consuming berry fruits, rich in polyphenols and nutrients, may positively affect the gut microbiota, promoting the selective growth of beneficial bacteria and improving clinical status. However, studies on the effects of berry fruits on gut microbiota in CKD are scarce, and a better understanding of the possible mechanisms of action of berry fruits on gut microbiota is needed to guide future clinical studies and clinical practice in CKD. The objective was to discuss how berry fruits (blueberry, cranberry, raspberry, and strawberry) could be a therapeutic strategy to modulate the gut microbiota and possibly reverse the dysbiosis in CKD. Overall, available evidence shows that berry fruits can promote an increase in diversity by affecting the abundance of mucus-producing bacteria and short-chain fatty acids. Moreover, these fruits can increase the expression of mRNA involved in tight junctions in the gut such as occludin, tight junction protein 1 (TJP1), and mucin. Studies on the exact amount of berries leading to these effects show heterogeneous findings. However, it is known that, with 5 mg/day, it is already possible to observe some effects in animal models. Wild berries could possibly improve the uremic condition by reducing the levels of uremic toxins via modulation of the gut microbiota. In the long term, this could be an excellent strategy for patients with CKD. Therefore, clinical studies are encouraged to evaluate better these effects on CKD as well as the safe amount of these fruits in order to promote a better quality of life or even the survival of these patients.
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Affiliation(s)
- Karen S Coutinho-Wolino
- Postgraduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niterói, Rio de Janeiro, Brazil
| | - Manuela F S Melo
- Graduate Program in Nutrition, Faculty of Nutrition, Fluminense Federal University, Niterói, Brazil
| | - Jessica C Mota
- Graduate Program in Nutrition, Faculty of Nutrition, Fluminense Federal University, Niterói, Brazil
| | - Denise Mafra
- Postgraduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niterói, Rio de Janeiro, Brazil
- Postgraduate Program in Nutrition Sciences, Faculty of Nutrition, Fluminense Federal University, Niterói, Brazil
- Postgraduate Program in Medical Sciences, Faculty of Medicine, Fluminense Federal University, Niterói, Brazil
| | - Jonas T Guimarães
- Department of Food Technology, Faculty of Veterinary, Fluminense Federal University (UFF), Niterói, Rio de Janeiro, Brazil
| | - Milena B Stockler-Pinto
- Postgraduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niterói, Rio de Janeiro, Brazil
- Postgraduate Program in Nutrition Sciences, Faculty of Nutrition, Fluminense Federal University, Niterói, Brazil
- Postgraduate Program in Pathology, Faculty of Medicine, Fluminense Federal University, Niterói, Brazil
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20
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Palomo M, Moreno-Castaño AB, Salas MQ, Escribano-Serrat S, Rovira M, Guillen-Olmos E, Fernandez S, Ventosa-Capell H, Youssef L, Crispi F, Nomdedeu M, Martinez-Sanchez J, De Moner B, Diaz-Ricart M. Endothelial activation and damage as a common pathological substrate in different pathologies and cell therapy complications. Front Med (Lausanne) 2023; 10:1285898. [PMID: 38034541 PMCID: PMC10682735 DOI: 10.3389/fmed.2023.1285898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 10/30/2023] [Indexed: 12/02/2023] Open
Abstract
The endothelium is a biologically active interface with multiple functions, some of them common throughout the vascular tree, and others that depend on its anatomical location. Endothelial cells are continually exposed to cellular and humoral factors, and to all those elements (biological, chemical, or hemodynamic) that circulate in blood at a certain time. It can adapt to different stimuli but this capability may be lost if the stimuli are strong enough and/or persistent in time. If the endothelium loses its adaptability it may become dysfunctional, becoming a potential real danger to the host. Endothelial dysfunction is present in multiple clinical conditions, such as chronic kidney disease, obesity, major depression, pregnancy-related complications, septic syndromes, COVID-19, and thrombotic microangiopathies, among other pathologies, but also in association with cell therapies, such as hematopoietic stem cell transplantation and treatment with chimeric antigen receptor T cells. In these diverse conditions, evidence suggests that the presence and severity of endothelial dysfunction correlate with the severity of the associated disease. More importantly, endothelial dysfunction has a strong diagnostic and prognostic value for the development of critical complications that, although may differ according to the underlying disease, have a vascular background in common. Our multidisciplinary team of women has devoted many years to exploring the role of the endothelium in association with the mentioned diseases and conditions. Our research group has characterized some of the mechanisms and also proposed biomarkers of endothelial damage. A better knowledge would provide therapeutic strategies either to prevent or to treat endothelial dysfunction.
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Affiliation(s)
- Marta Palomo
- Hemostasis and Erythropathology Laboratory, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Institut de Recerca August Pi Sunyer, University of Barcelona, Barcelona, Spain
- Hematology External Quality Assessment Laboratory, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Ana Belén Moreno-Castaño
- Hemostasis and Erythropathology Laboratory, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Institut de Recerca August Pi Sunyer, University of Barcelona, Barcelona, Spain
| | - María Queralt Salas
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases, Hospital Clínic de Barcelona, Institut de Recerca August Pi Sunyer, Barcelona, Spain
| | - Silvia Escribano-Serrat
- Hemostasis and Erythropathology Laboratory, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Institut de Recerca August Pi Sunyer, University of Barcelona, Barcelona, Spain
| | - Montserrat Rovira
- Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Cancer and Blood Diseases, Hospital Clínic de Barcelona, Institut de Recerca August Pi Sunyer, Barcelona, Spain
| | - Elena Guillen-Olmos
- Department of Nephrology and Kidney Transplantation, Hospital Clínic de Barcelona, Centro de Referencia en Enfermedad Glomerular Compleja del Sistema Nacional de Salud (CSUR), University of Barcelona, Barcelona, Spain
| | - Sara Fernandez
- Medical Intensive Care Unit, Hospital Clínic de Barcelona, Barcelona, Spain
| | | | - Lina Youssef
- BCNatal – Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic de Barcelona and Hospital Sant Joan de Déu, Institut de Recerca August Pi Sunyer, University of Barcelona, Barcelona, Spain
- Josep Carreras Leukaemia Research Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Fatima Crispi
- BCNatal – Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Clínic de Barcelona and Hospital Sant Joan de Déu, Institut de Recerca August Pi Sunyer, University of Barcelona, Barcelona, Spain
- Centre for Biomedical Research on Rare Diseases (CIBER-ER), Madrid, Spain
| | - Meritxell Nomdedeu
- Hemostasis and Hemotherapy Department, Institute of Cancer and Blood Diseases, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Julia Martinez-Sanchez
- Hemostasis and Erythropathology Laboratory, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Institut de Recerca August Pi Sunyer, University of Barcelona, Barcelona, Spain
| | - Blanca De Moner
- Hemostasis and Erythropathology Laboratory, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Institut de Recerca August Pi Sunyer, University of Barcelona, Barcelona, Spain
- Josep Carreras Leukaemia Research Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Maribel Diaz-Ricart
- Hemostasis and Erythropathology Laboratory, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Institut de Recerca August Pi Sunyer, University of Barcelona, Barcelona, Spain
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21
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Jia PP, Chandrajith R, Junaid M, Li TY, Li YZ, Wei XY, Liu L, Pei DS. Elucidating environmental factors and their combined effects on CKDu in Sri Lanka using zebrafish. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023:121967. [PMID: 37290634 DOI: 10.1016/j.envpol.2023.121967] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 05/23/2023] [Accepted: 06/05/2023] [Indexed: 06/10/2023]
Abstract
Chronic kidney disease with uncertain etiology (CKDu) in Sri Lanka has attracted much attention as a global health issue. However, how environmental factors in local drinking water induce kidney damage in organisms is still elusive. We investigated multiple environmental factors including water hardness and fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM) to elucidate their toxic effects on CKDu risk in zebrafish. Acute exposure affected renal development and inhibited the fluorescence of Na, K-ATPase alpha1A4:GFP zebrafish kidney. Chronic exposure influenced the body weight of both genders of adult fish and induced kidney damage by histopathological analyses. Furthermore, the exposure significantly disturbed differential expression genes (DEGs), diversity and richness of gut microbiota, and critical metabolites related to renal functions. The transcriptomic analysis revealed that kidney-related DEGs were linked with renal cell carcinoma, proximal tubule bicarbonate reclamation, calcium signaling pathway, and HIF-1 signaling pathway. The significantly disrupted intestinal microbiota was closely related to the environmental factors and H&E score, which demonstrated the mechanisms of kidney risks. Notably, the Spearman correlation analysis indicated that the changed bacteria such as Pseudomonas, Paracoccus, and ZOR0006, etc were significantly connected to the DEGs and metabolites. Therefore, the assessment of multiple environmental factors provided new insights on "bio-markers" as potential therapies of the target signaling pathways, metabolites, and gut bacteria to monitor or protect residents from CKDu.
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Affiliation(s)
- Pan-Pan Jia
- School of Public Health, Chongqing Medical University, Chongqing, 400016, China
| | - Rohana Chandrajith
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China; Department of Geology, Faculty of Science, University of Peradeniya, Peradeniya, Sri Lanka
| | - Muhammad Junaid
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China
| | - Tian-Yun Li
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China
| | - Yong-Zhi Li
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China
| | - Xing-Yi Wei
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China
| | - Li Liu
- Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China
| | - De-Sheng Pei
- School of Public Health, Chongqing Medical University, Chongqing, 400016, China.
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Hayeeawaema F, Muangnil P, Jiangsakul J, Tipbunjong C, Huipao N, Khuituan P. A novel model of adenine-induced chronic kidney disease-associated gastrointestinal dysfunction in mice: The gut-kidney axis. Saudi J Biol Sci 2023; 30:103660. [PMID: 37213695 PMCID: PMC10193294 DOI: 10.1016/j.sjbs.2023.103660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 03/31/2023] [Accepted: 04/21/2023] [Indexed: 05/23/2023] Open
Abstract
Although constipation is a common complication of chronic kidney disease (CKD), there is no animal model that can be used to study the association between renal impairment and gastrointestinal function without interfering with the gastrointestinal tract of the model. Therefore, we determined whether adenine could induce CKD in association with gastrointestinal dysfunction. Six-week-old ICR mice were intraperitoneally injected with saline, 25, 50, or 75 mg adenine/kg body weight for 21 days. Blood urea nitrogen (BUN), plasma creatinine, and renal histopathology were evaluated. Defecation status was evaluated from defecation frequency and fecal water content. Colonic smooth muscle contraction was measured by the organ bath technique, and transepithelial electrical resistance (TEER) was measured using an Ussing chamber. In the 50 mg/kg treatment group, BUN and creatinine were significantly increased compared with control, and inflammatory cell infiltration, glomerular necrosis, tubular dilatation, and interstitial fibrosis were observed in renal tissues. Mice in this group also showed a significant decrease in defecation frequency, fecal water content, colonic motility index, and TEER. Overall, 50 mg/kg of adenine was the best dose to induce CKD with associated constipation and intestinal barrier impairment. Therefore, this adenine administration model can be recommended for CKD-associated gastrointestinal dysfunction research.
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Affiliation(s)
- Fittree Hayeeawaema
- Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla, Thailand
- Gut Biology and Microbiota Research Unit, Prince of Songkla University, Songkhla, Thailand
| | - Paradorn Muangnil
- Gut Biology and Microbiota Research Unit, Prince of Songkla University, Songkhla, Thailand
- Faculty of Veterinary Science, Prince of Songkla University, Thailand
| | | | - Chittipong Tipbunjong
- Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla, Thailand
- Gut Biology and Microbiota Research Unit, Prince of Songkla University, Songkhla, Thailand
| | - Nawiya Huipao
- Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla, Thailand
- Gut Biology and Microbiota Research Unit, Prince of Songkla University, Songkhla, Thailand
| | - Pissared Khuituan
- Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Songkhla, Thailand
- Gut Biology and Microbiota Research Unit, Prince of Songkla University, Songkhla, Thailand
- Corresponding author at: Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, 15 Karnjanavanich Rd., Hat Yai, Songkhla 90110, Thailand.
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23
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Fan W, Fu D, Zhang L, Xiao Z, Shen X, Chen J, Qi X. Enoxaparin sodium bone cement plays an anti-inflammatory immunomodulatory role by inducing the polarization of M2 macrophages. J Orthop Surg Res 2023; 18:380. [PMID: 37221568 DOI: 10.1186/s13018-023-03865-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 05/18/2023] [Indexed: 05/25/2023] Open
Abstract
OBJECTIVE The implantation of PMMA bone cement results in an immune response and the release of PMMA bone cement particles causes an inflammatory cascade. Our study discovered that ES-PMMA bone cement can induce M2 polarization of macrophages, which has an anti-inflammatory immunomodulatory effect. We also delved into the molecular mechanisms that underlie this process. METHODS In this study, we designed and prepared samples of bone cement. These included PMMA bone cement samples and ES-PMMA bone cement samples, which were implanted into the back muscles of rats. At 3, 7, and 14 days after the operation, we removed the bone cement and a small amount of surrounding tissue. We then performed immunohistochemistry and immunofluorescence to observe the polarization of macrophages and the expression of related inflammatory factors in the surrounding tissues. The RAW264.7 cells were exposed to lipopolysaccharide (LPS) for 24 h to establish the macrophage inflammation model. Then, each group was treated with enoxaparin sodium medium, PMMA bone cement extract medium, and ES-PMMA bone cement extract medium, respectively, and cultured for another 24 h. We collected cells from each group and used flow cytometry to detect the expressions of CD86 and CD206 in macrophages. Additionally, we performed RT-qPCR to determine the mRNA levels of three markers of M1 macrophages (TNF-α, IL-6, iNOS) and two M2 macrophage markers (Arg-1, IL-10). Furthermore, we analyzed the expression of TLR4, p-NF-κB p65, and NF-κB p65 through Western blotting. RESULTS The immunofluorescence results indicate that the ES-PMMA group exhibited an upregulation of CD206, an M2 marker, and a downregulation of CD86, an M1 marker, in comparison to the PMMA group. Additionally, the immunohistochemistry results revealed that the levels of IL-6 and TNF-α expression were lower in the ES-PMMA group than in the PMMA group, while the expression level of IL-10 was higher in the ES-PMMA group. Flow cytometry and RT-qPCR analyses revealed that the expression of M1-type macrophage marker CD86 was significantly elevated in the LPS group compared to the NC group. Additionally, M1-type macrophage-related cytokines TNF-α, IL-6, and iNOS were also found to be increased. However, in the LPS + ES group, the expression levels of CD86, TNF-α, IL-6, and iNOS were decreased, while the expression of M2-type macrophage markers CD206 and M2-type macrophage-related cytokines (IL-10, Arg-1) were increased compared to the LPS group. In comparison to the LPS + PMMA group, the LPS + ES-PMMA group demonstrated a down-regulation of CD86, TNF-α, IL-6, and iNOS expression levels, while increasing the expression levels of CD206, IL-10, and Arg-1. Western blotting results revealed a significant decrease in TLR4/GAPDH and p-NF-κB p65/NF-κB p65 in the LPS + ES group when compared to the LPS group. Additionally, the LPS + ES-PMMA group exhibited a decrease in TLR4/GAPDH and p-NF-κB p65/NF-κB p65 levels when compared to the LPS + PMMA group. CONCLUSION ES-PMMA bone cement is more effective than PMMA bone cement in down-regulating the expression of the TLR4/NF-κB signaling pathway. Additionally, it induces macrophages to polarize towards the M2 phenotype, making it a crucial player in anti-inflammatory immune regulation.
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Affiliation(s)
- Weiye Fan
- Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050035, People's Republic of China
| | - Dehao Fu
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Li Zhang
- Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050035, People's Republic of China
| | - Zhihang Xiao
- Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050035, People's Republic of China
| | - Xiaoyu Shen
- Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050035, People's Republic of China
| | - Jianchao Chen
- Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050035, People's Republic of China
| | - Xiangbei Qi
- Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050035, People's Republic of China.
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Wu HY, Lin YT, Tsai WC, Chiu YL, Ko MJ, Yang JY, Pai MF, Hsu HS, Hsu SP, Peng YS, Liao CH. Microbiota analysis in the hemodialysis population - Focusing on Enterobacteriaceae. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:311-323. [PMID: 36535841 DOI: 10.1016/j.jmii.2022.12.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 11/08/2022] [Accepted: 12/04/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Infection is a recognized risk factor for mortality among hemodialysis (HD) population, including infection caused by Enterobacteriaceae. We aimed to investigate Enterobacteriaceae in gut microbiota among HD patients and to analyze associations between microbiota and clinical parameters. METHODS This prospective study of microbiota analysis in HD patients was conducted in April-May 2019. A control group without recent antibiotic use or hospitalization was used for comparison. Stool samples underwent 16S rRNA sequencing, using Greengenes 16S rRNA database for microbiota analysis. RESULTS Among 96 hemodialysis (HD) patients, mean age was 61.9 ± 0.8 years and mean duration of HD was 6.5 ± 0.7 years. No significant differences were found in alpha diversity between HD and control groups (HD group 949.5, controls 898; p = 0.16) although significant between-group differences were found in beta diversity (p < 0.001). At phylum level, HD group had a higher abundance of Firmicutes and Proteobacteria, but lower abundance of Bacteriodetes. At genus level, Escherichia-Shigella complex increased among HD patients who had hospitalization with 1 year (median 0.024 vs 0.004, p = 0.054) and Klebsiella was associated with emergency room visit within 1 year among HD patients (p = 0.002). CONCLUSIONS Alpha diversity in HD patients is not lower than that in healthy controls but significant between-group differences are found in microbiota composition according to beta diversity, due to decreased Bacteriodetes and increased Firmicutes and Proteobacteria. Deeper microbiota analyses for Enterobacteriaceae are necessary. Whether change in dietary components can help to decrease mortality among dialysis population warrants further research.
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Affiliation(s)
- Hon-Yen Wu
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan; Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
| | - Yi-Tsung Lin
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan; Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan
| | - Wan-Chuan Tsai
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Center for General Education, Lee-Ming Institute of Technology, New Taipei City, Taiwan
| | - Yen-Ling Chiu
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Graduate Program in Biomedical Informatics, Yuan Ze University, Taoyuan City, Taiwan; Graduate Institute of Medicine, Yuan Ze University, Taoyuan City, Taiwan
| | - Mei-Ju Ko
- Department of Dermatology, Taipei City Hospital, Taipei City, Taiwan; Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
| | - Ju-Yeh Yang
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Mei-Fen Pai
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Hsin-Sui Hsu
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Shih-Ping Hsu
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; School of Life Science, National Taiwan Normal University, Taipei City, Taiwan
| | - Yu-Sen Peng
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Department of Applied Cosmetology, Lee-Ming Institute of Technology, New Taipei City, Taiwan; Department of Healthcare Administration, Asia Eastern University of Science and Technology, New Taipei City, Taiwan
| | - Chun-Hsing Liao
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan.
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Ragi N, Pallerla P, Babi Reddy Gari AR, Lingampelly SS, Ketavarapu V, Addipilli R, Chirra N, Kantevari S, Yadla M, Sripadi P. Assessment of uremic toxins in advanced chronic kidney disease patients on maintenance hemodialysis by LC-ESI-MS/MS. Metabolomics 2023; 19:14. [PMID: 36826619 DOI: 10.1007/s11306-023-01978-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 01/23/2023] [Indexed: 02/25/2023]
Abstract
INTRODUCTION In the advanced stage of chronic kidney disease (CKD), electrolytes, fluids, and metabolic wastes including various uremic toxins, accumulate at high concentrations in the patients' blood. Hemodialysis (HD) is the conventional procedure used worldwide to remove metabolic wastes. The creatinine and urea levels have been routinely monitored to estimate kidney function and effectiveness of the HD process. This study, first from in Indian perspective, aimed at the identification and quantification of major uremic toxins in CKD patients on maintenance HD (PRE-HD), and compared with the healthy controls (HC) as well as after HD (POST-HD). OBJECTIVES The study mainly focused on the identification of major uremic toxins in Indian perspective and the quantitative analysis of indoxyl sulfate and p-cresol sulfate (routinely targeted uremic toxins), and phenyl sulfate, catechol sulfate, and guaiacol sulfate (targeted for the first time), apart from creatinine and urea in PRE-HD, POST-HD, and HC groups. METHODS Blood samples were collected from 90 HD patients (both PRE-HD and POST-HD), and 74 HCs. The plasma samples were subjected to direct ESI-HRMS and LC/HRMS for untargeted metabolomics and LC-MS/MS for quantitative analysis. RESULTS Various known uremic toxins, and a few new and unknown peaks were detected in PRE-HD patients. The p-cresol sulfate and indoxyl sulfate were dominant in PRE-HD, the concentrations of phenyl sulfate, catechol sulfate, and guaiacol sulfate were about 50% of that of indoxyl sulfate. Statistical evaluation on the levels of targeted uremic toxins in PRE-HD, POST-HD, and HC groups showed a significant difference among the three groups. The dialytic clearance of indoxyl sulfate and p-cresol sulfate was found to be < 35%, while that of the other three sulfates was 50-58%. CONCLUSION LC-MS/MS method was developed and validated to evaluate five major uremic toxins in CKD patients on HD. The levels of the targeted uremic toxins could be used to assess kidney function and the effectiveness of HD.
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Affiliation(s)
- Nagarjunachary Ragi
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India
- Centre for Mass Spectrometry, Department of Analytical & Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India
| | - Pavankumar Pallerla
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India
- Centre for Mass Spectrometry, Department of Analytical & Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India
| | | | - Sai Sachin Lingampelly
- Centre for Mass Spectrometry, Department of Analytical & Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India
| | | | - Ramunaidu Addipilli
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India
- Centre for Mass Spectrometry, Department of Analytical & Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India
| | - Nagaraju Chirra
- Department of Fluoro & Agrochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India
| | - Srinivas Kantevari
- Department of Fluoro & Agrochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India
| | - Manjusha Yadla
- Department of Nephrology, Gandhi Medical College, Gandhi Hospitals, Hyderabad, Telangana, 500025, India.
| | - Prabhakar Sripadi
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India.
- Centre for Mass Spectrometry, Department of Analytical & Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India.
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Guo NK, She H, Tan L, Zhou YQ, Tang CQ, Peng XY, Ma CH, Li T, Liu LM. Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2A. Int J Nanomedicine 2023; 18:693-709. [PMID: 36816330 PMCID: PMC9930579 DOI: 10.2147/ijn.s394544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 02/02/2023] [Indexed: 02/12/2023] Open
Abstract
Background Intestinal barrier dysfunction is an important complication of sepsis, while the treatment is limited. Recently, parthenolide (PTL) has attracted much attention as a strategy of sepsis, but whether nano parthenolide (Nano PTL) is therapeutic in sepsis-induced intestinal barrier dysfunction is obscured. Methods In this study, cecal ligation and puncture (CLP)-induced sepsis rats and lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IECs) were used to investigate the effect of PTL on intestinal barrier dysfunction. Meanwhile, we synthesized Nano PTL and compared the protective effect of Nano PTL with ordinary PTL on intestinal barrier function in septic rats and IECs. Network pharmacology and serotonin 2A (5-HTR2A) inhibitor were used to explore the mechanism of PTL on the intestinal barrier function of sepsis. Results The encapsulation rate of Nano PTL was 95±1.5%, the drug loading rate was 11±0.5%, and the average uptake rate of intestinal epithelial cells was 94%. Ordinary PTL and Nano PTL improved the survival rate and survival time of septic rats, reduced the mean arterial pressure and the serum level of inflammatory cytokines, and protected the liver and kidney functions in vivo, and increased the value of transmembrane resistance (TEER) reduced the reactive oxygen species (ROS) and apoptosis in IECs in vitro through 5-HTR2A. Nano PTL had better effect than ordinary PTL. Conclusion Ordinary PTL and Nano PTL can protect the intestinal barrier function of septic rats by inhibiting apoptosis and ROS through up-regulating 5-HTR2A, Nano PTL is better than ordinary PTL.
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Affiliation(s)
- Ning-Ke Guo
- State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China,The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China
| | - Han She
- State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China
| | - Lei Tan
- State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China
| | - Yuan-Qun Zhou
- State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China
| | - Chun-Qiong Tang
- State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China
| | - Xiao-Yong Peng
- State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China
| | - Chun-Hua Ma
- State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China
| | - Tao Li
- State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China,Correspondence: Tao Li; Liang-Ming Liu, Email ;
| | - Liang-Ming Liu
- State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China
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Zheng L, Luo M, Zhou H, Chen J. Natural products from plants and microorganisms: Novel therapeutics for chronic kidney disease via gut microbiota regulation. Front Pharmacol 2023; 13:1068613. [PMID: 36733377 PMCID: PMC9887141 DOI: 10.3389/fphar.2022.1068613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 12/23/2022] [Indexed: 01/18/2023] Open
Abstract
Dysbiosis of gut microbiota plays a fundamental role in the pathogenesis and development of chronic kidney disease (CKD) and its complications. Natural products from plants and microorganisms can achieve recognizable improvement in renal function and serve as an alternative treatment for chronic kidney disease patients with a long history, yet less is known on its beneficial effects on kidney injury by targeting the intestinal microbiota. In this review, we summarize studies on the effects of natural products from plants and microorganisms, including herbal medicines and their bioactive extracts, polysaccharides from plants and microorganisms, and phytochemicals, on the prevention and treatment of chronic kidney disease through targeting gut microflora. We describe the strategies of these anti-CKD effects in animal experiments including remodulation of gut microbiota structure, reduction of uremic toxins, enhancement of short-chain fatty acid (SCFA) production, regulation of intestinal inflammatory signaling, and improvement in intestinal integrity. Meanwhile, the clinical trials of different natural products in chronic kidney disease clinical practice were also analyzed and discussed. These provide information to enable a better understanding of the renoprotective effects of these effective natural products from plants and microorganisms in the treatment of chronic kidney disease. Finally, we propose the steps to prove the causal role of the intestinal microflora in the treatment of chronic kidney disease by natural products from plants and microorganisms. We also assess the future perspective that natural active products from plants and microorganisms can beneficially delay the onset and progression of kidney disease by targeting the gut flora and highlight the remaining challenges in this area. With the continuous deepening of studies in recent years, it has been proved that gut microbiota is a potential target of natural active products derived from plants and microorganisms for chronic kidney disease treatment. Fully understanding the functions and mechanisms of gut microbiota in these natural active products from plants and microorganisms is conducive to their application as an alternative therapeutic in the treatment of chronic kidney disease.
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Affiliation(s)
- Lin Zheng
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Mingjing Luo
- Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology, Shenzhen, China
| | - Haokui Zhou
- Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institutes of Advanced Technology, Shenzhen, China
| | - Jianping Chen
- Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
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Polyphenol-rich açaí seed extract exhibits reno-protective and anti-fibrotic activities in renal tubular cells and mice with kidney failure. Sci Rep 2022; 12:20855. [PMID: 36460743 PMCID: PMC9718837 DOI: 10.1038/s41598-022-24420-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 11/15/2022] [Indexed: 12/05/2022] Open
Abstract
The main goal of this study was to evaluate the reno-protective effects of a phenolic-rich Açaí seed extract (ASE) in mice with kidney failure. Kidney failure was induced chemically with an adenine-rich diet (0.25% w/w for 4 weeks) in male CD1 Swiss mice. Mice were then provided daily with ASE (at a dose of ~ 350 mg/kg/day) in drinking water for 4 weeks. Adenine mice exhibited renal dysfunction evidenced by increased proteinuria, increased uremia, extensive tubular atrophy and kidney fibrosis associated with overexpression of pro-fibrotic genes (collagen 1a1, transforming growth factor β1, TGF-β1) and markers of tubular injury (such as Kidney injury molecule-1, KIM-1). ASE was able to beneficially counteract all these effects. ASE improved oxidative damage and fibrosis by decreasing carbonylated protein and MDA concentrations, as well as collagen deposition in renal tissue. ASE decreased the expression of TGF-β1 gene and the abundance of protein TGF-β1 in kidneys. It further decreased both expression and urinary excretion of tubular injury biomarkers, e.g., KIM-1 and Neutrophil gelatinase-associated lipocalin. CKD ASE-treated mice exhibited higher polyphenol content and total antioxidant capacity compared to control mice. ASE further prevented the expression of profibrotic genes in HK2 human tubular cells exposed to uremic toxins. Taken together, these findings suggest that ASE exerted potent reno-protective and anti-fibrotic effects through its antioxidant activity and the modulation of the TGF-β1 pathway.
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Colombo G, Astori E, Landoni L, Garavaglia ML, Altomare A, Lionetti MC, Gagliano N, Giustarini D, Rossi R, Milzani A, Dalle‐Donne I. Effects of the uremic toxin indoxyl sulphate on human microvascular endothelial cells. J Appl Toxicol 2022; 42:1948-1961. [PMID: 35854198 PMCID: PMC9796800 DOI: 10.1002/jat.4366] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/14/2022] [Accepted: 07/15/2022] [Indexed: 01/07/2023]
Abstract
Indoxyl sulphate (IS) is a uremic toxin accumulating in the plasma of chronic kidney disease (CKD) patients. IS accumulation induces side effects in the kidneys, bones and cardiovascular system. Most studies assessed IS effects on cell lines by testing higher concentrations than those measured in CKD patients. Differently, we exposed a human microvascular endothelial cell line (HMEC-1) to the IS concentrations measured in the plasma of healthy subjects (physiological) or CKD patients (pathological). Pathological concentrations reduced cell proliferation rate but did not increase long-term oxidative stress level. Indeed, total protein thiols decreased only after 24 h of exposure in parallel with an increased Nrf-2 protein expression. IS induced actin cytoskeleton rearrangement with formation of stress fibres. Proteomic analysis supported this hypothesis as many deregulated proteins are related to actin filaments organization or involved in the endothelial to mesenchymal transition. Interestingly, two proteins directly linked to cardiovascular diseases (CVD) in in vitro and in vivo studies underwent deregulation: COP9 signalosome complex subunit 9 and thrombomodulin. Future experiments will be needed to investigate the role of these proteins and the signalling pathways in which they are involved to clarify the possible link between CKD and CVD.
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Affiliation(s)
- Graziano Colombo
- Department of Biosciences (Department of Excellence 2018–2022)Università degli Studi di MilanoMilanItaly
| | - Emanuela Astori
- Department of Biosciences (Department of Excellence 2018–2022)Università degli Studi di MilanoMilanItaly
| | - Lucia Landoni
- Department of Biosciences (Department of Excellence 2018–2022)Università degli Studi di MilanoMilanItaly
| | - Maria L. Garavaglia
- Department of Biosciences (Department of Excellence 2018–2022)Università degli Studi di MilanoMilanItaly
| | - Alessandra Altomare
- Department of Pharmaceutical SciencesUniversità degli Studi di MilanoMilanItaly
| | - Maria C. Lionetti
- Department of Biosciences (Department of Excellence 2018–2022)Università degli Studi di MilanoMilanItaly
| | - Nicoletta Gagliano
- Department of Biomedical Sciences for HealthUniversità degli Studi di MilanoMilanItaly
| | - Daniela Giustarini
- Department of Life Sciences, Laboratory of Pharmacology and ToxicologyUniversity of SienaSienaItaly
| | - Ranieri Rossi
- Department of Life Sciences, Laboratory of Pharmacology and ToxicologyUniversity of SienaSienaItaly
| | - Aldo Milzani
- Department of Biosciences (Department of Excellence 2018–2022)Università degli Studi di MilanoMilanItaly
| | - Isabella Dalle‐Donne
- Department of Biosciences (Department of Excellence 2018–2022)Università degli Studi di MilanoMilanItaly
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30
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Kemp JA, Alvarenga L, Cardozo LFMF, Dai L, Stenvinkel P, Shiels PG, Hackeng TM, Schurgers LJ, Mafra D. Dysbiosis in Patients with Chronic Kidney Disease: Let Us Talk About Vitamin K. Curr Nutr Rep 2022; 11:765-779. [PMID: 36138326 DOI: 10.1007/s13668-022-00438-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/15/2022] [Indexed: 01/31/2023]
Abstract
PURPOSE OF REVIEW This narrative review aimed to summarize the current evidence on the connection between dysbiosis and vitamin K deficiency in patients with chronic kidney disease (CKD). The presence of dysbiosis (perturbations in the composition of the microbiota) has been described in several non-communicable diseases, including chronic kidney disease, and it has been hypothesized that dysbiosis may cause vitamin K deficiency. Patients with CKD present both vitamin K deficiency and gut dysbiosis; however, the relationship between gut dysbiosis and vitamin K deficiency remains to be addressed. RECENT FINDINGS Recently, few studies in animals have demonstrated that a dysbiotic environment is associated with low production of vitamin K by the gut microbiota. Vitamin K plays a vital role in blood coagulation as well as in the cardiovascular and bone systems. It serves as a cofactor for γ-glutamyl carboxylases and thus is essential for the post-translational modification and activation of vitamin K-dependent calcification regulators, such as osteocalcin, matrix Gla protein, Gla-rich protein, and proteins C and S. Additionally, vitamin K executes essential antioxidant and anti-inflammatory functions. Dietary intake is the main source of vitamin K; however, it also can be produced by gut microbiota. This review discusses the effects of uremia on the imbalance in gut microbiota, vitamin K-producing bacteria, and vitamin K deficiency in CKD patients, leading to a better understanding and raising hypothesis for future clinical studies.
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Affiliation(s)
- Julie Ann Kemp
- Graduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niterói, Brazil
| | - Livia Alvarenga
- Graduate Program in Medical Sciences, Fluminense Federal University (UFF), Niterói, Brazil
| | - Ludmila F M F Cardozo
- Graduate Program in Cardiovascular Sciences, Fluminense Federal University (UFF), Niterói, Brazil
| | - Lu Dai
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Technology and Intervention, Karolinska Institutet, Stockholm, Sweden
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Technology and Intervention, Karolinska Institutet, Stockholm, Sweden
| | - Paul G Shiels
- Wolfson Wohl Translational Research Centre, University of Glasgow, Glasgow, UK
| | - Tilman M Hackeng
- Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
| | - Leon J Schurgers
- Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
- Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
| | - Denise Mafra
- Graduate Program in Medical Sciences, Fluminense Federal University (UFF), Niterói, Brazil.
- Graduate Program in Biological Sciences, Physiology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
- Unidade de Pesquisa Clínica, Rua Marquês Do Paraná, Niterói, RJ, 30324033-900, Brazil.
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Kuznetzova AB, Prazdnova EV, Chistyakov VA, Kutsevalova OY, Batiushin MM. Are Probiotics Needed in Nephrology? NEPHROLOGY (SAINT-PETERSBURG) 2022; 26:18-30. [DOI: 10.36485/1561-6274-2022-26-4-18-30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Affiliation(s)
- A. B. Kuznetzova
- Academy of Biology and Biotechnology named after D.I. Ivanovsky, Southern Federal University
| | - E. V. Prazdnova
- Academy of Biology and Biotechnology named after D.I. Ivanovsky, Southern Federal University
| | - V. A. Chistyakov
- Academy of Biology and Biotechnology named after D.I. Ivanovsky, Southern Federal University
| | - O. Yu. Kutsevalova
- Federal State Budgetary Institution "National Medical Research Center of Oncology"
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Cigarrán Guldris S, Latorre Catalá JA, Sanjurjo Amado A, Menéndez Granados N, Piñeiro Varela E. Fibre Intake in Chronic Kidney Disease: What Fibre Should We Recommend? Nutrients 2022; 14:nu14204419. [PMID: 36297103 PMCID: PMC9612304 DOI: 10.3390/nu14204419] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 10/12/2022] [Accepted: 10/13/2022] [Indexed: 11/29/2022] Open
Abstract
Chronic kidney disease (CKD) is a major global health problem that challenges all patients' healthcare needs. Fibre consumption benefits kidney patients by acting preventively on associated risk factors, improving intestinal microbiota composition or reducing metabolic acidosis and inflammation. In this review, we focus on increasing fibre consumption and the quality of fibre to recommend, in addition to increasing the consumption of foods that naturally have it in their design, that can resort to fortified foods or fibre supplements. The Western nutritional practice, which is low in fibre and rich in animal proteins, saturated fats, sodium, and sugar, increases the risk of mortality in these patients. On the contrary, patterns with higher consumption of fibre and vegetable proteins, such as the Mediterranean, vegetarian, or Plant dominant low protein diet (PLADO), seem to have a preventive effect on the associated risk factors and influence CKD progression. Until now, the use of fibre supplements has not achieved an evident impact on clinical results. Fibre-rich foods contain other nutrients that reduce cardiovascular risk. Promoting diets richer in vegetables and guaranteeing adequate energy and protein intake is a challenge for the multidisciplinary teams involved in the standard of care for CKD.
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Affiliation(s)
- Secundino Cigarrán Guldris
- Nephrology Service, Hospital Publico da Mariña, E-27880 Burela, Spain
- Nephrology Research Unit, Hospital Publico da Mariña, E-27880 Burela, Spain
- Correspondence:
| | | | | | - Nicolás Menéndez Granados
- Nephrology Service, Hospital Publico da Mariña, E-27880 Burela, Spain
- Nephrology Research Unit, Hospital Publico da Mariña, E-27880 Burela, Spain
| | - Eva Piñeiro Varela
- Nephrology Service, Hospital Publico da Mariña, E-27880 Burela, Spain
- Nephrology Research Unit, Hospital Publico da Mariña, E-27880 Burela, Spain
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Favero C, Giordano L, Mihaila SM, Masereeuw R, Ortiz A, Sanchez-Niño MD. Postbiotics and Kidney Disease. Toxins (Basel) 2022; 14:toxins14090623. [PMID: 36136562 PMCID: PMC9501217 DOI: 10.3390/toxins14090623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 08/26/2022] [Accepted: 09/01/2022] [Indexed: 11/16/2022] Open
Abstract
Chronic kidney disease (CKD) is projected to become the fifth global cause of death by 2040 as a result of key shortcomings in the current methods available to diagnose and treat kidney diseases. In this regard, the novel holobiont concept, used to describe an individual host and its microbial community, may pave the way towards a better understanding of kidney disease pathogenesis and progression. Microbiota-modulating or -derived interventions include probiotics, prebiotics, synbiotics and postbiotics. As of 2019, the concept of postbiotics was updated by the International Scientific Association of Probiotics and Prebiotics (ISAPP) to refer to preparations of inanimate microorganisms and/or their components that confer a health benefit to the host. By explicitly excluding purified metabolites without a cellular biomass, any literature making use of such term is potentially rendered obsolete. We now review the revised concept of postbiotics concerning their potential clinical applications and research in kidney disease, by discussing in detail several formulations that are undergoing preclinical development such as GABA-salt for diet-induced hypertension and kidney injury, sonicated Lactobacillus paracasei in high fat diet-induced kidney injury, GABA-salt, lacto-GABA-salt and postbiotic-GABA-salt in acute kidney injury, and O. formigenes lysates for hyperoxaluria. Furthermore, we provide a roadmap for postbiotics research in kidney disease to expedite clinical translation.
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Affiliation(s)
- Chiara Favero
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28049 Madrid, Spain
| | - Laura Giordano
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands
| | - Silvia Maria Mihaila
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands
| | - Rosalinde Masereeuw
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands
| | - Alberto Ortiz
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28049 Madrid, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28049 Madrid, Spain
- Departamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, Spain
- Correspondence: (A.O.); (M.D.S.-N.)
| | - Maria Dolores Sanchez-Niño
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28049 Madrid, Spain
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28049 Madrid, Spain
- Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, Spain
- Correspondence: (A.O.); (M.D.S.-N.)
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Luo L, Luo J, Cai Y, Fu M, Li W, Shi L, Liu J, Dong R, Xu X, Tu L, Yang Y. Inulin-type fructans change the gut microbiota and prevent the development of diabetic nephropathy. Pharmacol Res 2022; 183:106367. [PMID: 35882293 DOI: 10.1016/j.phrs.2022.106367] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 07/17/2022] [Accepted: 07/22/2022] [Indexed: 10/16/2022]
Abstract
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease, and few treatment options that prevent the progressive loss of renal function are available. Studies have shown that dietary fiber intake improves kidney diseases and metabolism-related diseases, most likely through short-chain fatty acids (SCFAs). The present study aimed to examine the protective effects of inulin-type fructans (ITFs) on DN through 16 S rRNA gene sequencing, gas chromatographymass spectrometry (GCMS) analysis and fecal microbiota transplantation (FMT). The results showed that ITFs supplementation protected against kidney damage in db/db mice and regulated the composition of the gut microbiota. Antibiotic treatment and FMT experiments further demonstrated a key role of the gut microbiota in mediating the beneficial effects of ITFs. The ITFs treatment-induced changes in the gut microbiota led to an enrichment of SCFA-producing bacteria, especially the genera Akkermansia and Candidatus Saccharimonas, which increased the fecal and serum acetate concentrations. Subsequently, acetate supplementation improved glomerular damage and renal fibrosis by attenuating mitochondrial dysfunction and reducing toxic glucose metabolite levels. In conclusion, ITFs play a renoprotective role by modulating the gut microbiota and increasing acetate production. Furthermore, acetate mediates renal protection by regulating glucose metabolism, decreasing glycotoxic product levels and improving mitochondrial function.
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Affiliation(s)
- Liman Luo
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Division of Endocrinology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
| | - Jinlan Luo
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yueting Cai
- Division of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Menglu Fu
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Wenhua Li
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Lili Shi
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Jingrui Liu
- Division of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Ruolan Dong
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Xizhen Xu
- Division of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
| | - Ling Tu
- Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China.
| | - Yan Yang
- Division of Endocrinology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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Guthrie L, Spencer SP, Perelman D, Van Treuren W, Han S, Yu FB, Sonnenburg ED, Fischbach MA, Meyer TW, Sonnenburg JL. Impact of a 7-day homogeneous diet on interpersonal variation in human gut microbiomes and metabolomes. Cell Host Microbe 2022; 30:863-874.e4. [PMID: 35643079 PMCID: PMC9296065 DOI: 10.1016/j.chom.2022.05.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 02/17/2022] [Accepted: 05/04/2022] [Indexed: 02/06/2023]
Abstract
Gut microbiota metabolism of dietary compounds generates a vast array of microbiome-dependent metabolites (MDMs), which are highly variable between individuals. The uremic MDMs (uMDMs) phenylacetylglutamine (PAG), p-cresol sulfate (PCS), and indoxyl sulfate (IS) accumulate during renal failure and are associated with poor outcomes. Targeted dietary interventions may reduce toxic MDM generation; however, it is unclear if inter-individual differences in diet or gut microbiome dominantly contribute to MDM variance. Here, we use a 7-day homogeneous average American diet to standardize dietary precursor availability in 21 healthy individuals. During dietary homogeneity, the coefficient of variation in PAG, PCS, and IS (primary outcome) did not decrease, nor did inter-individual variation in most identified metabolites; other microbiome metrics showed no or modest responses to the intervention. Host identity and age are dominant contributors to variability in MDMs. These results highlight the potential need to pair dietary modification with microbial therapies to control MDM profiles.
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Affiliation(s)
- Leah Guthrie
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Sean Paul Spencer
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Dalia Perelman
- Stanford Prevention Research Center, Department of Medicine, Stanford School of Medicine, Stanford, CA 94305, USA
| | - Will Van Treuren
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Shuo Han
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
| | | | - Erica D Sonnenburg
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Michael A Fischbach
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; ChEM-H, Stanford University, Stanford, CA 94305, USA; Chan-Zuckerburg Biohub, San Francisco, CA 94158, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
| | - Timothy W Meyer
- Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA
| | - Justin L Sonnenburg
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Chan-Zuckerburg Biohub, San Francisco, CA 94158, USA; Center for Human Microbiome Studies, Stanford, CA 94305, USA.
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Guo H, Li X, Zhang Y, Li J, Yang J, Jiang H, Sun G, Huo T. Metabolic characteristics related to the hazardous effects of environmental arsenic on humans: A metabolomic review. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2022; 236:113459. [PMID: 35367889 DOI: 10.1016/j.ecoenv.2022.113459] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 02/18/2022] [Accepted: 03/24/2022] [Indexed: 06/14/2023]
Abstract
Arsenic (As) is a toxic metalloid exist ubiquitously in environment. Epidemiological studies and laboratory animal studies have verified that As damages multiple organs or tissues in the body and is associated with a variety of diseases. Changes in metabolites usually indicate disturbances in metabolic pathways and specific metabolites are considered as biomarkers of diseases or drugs/toxins or environmental effects. Metabolomics is the quantitative measurement of the dynamic multi-parameter metabolic responses of biological systems due to pathophysiological or genetic changes. Current years, some metabolomic studies on the hazardous effect of environmental As on humans have been reported. In this paper, we first overviewed the metabolomics studies of environmental As exposure in humans since 2011, emphasizing on the data mining process of metabolic characteristics related to the hazardous effects of environmental As on humans. Then, the relationship between metabolic characteristics and the toxic mechanism of environmental As exposure in humans were discussed, and finally, the prospects of metabolomics studies on populations exposed to environmental As were put forward. Our paper may shed light on the study of mechanisms, prevention and individualized treatment of As poisoning.
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Affiliation(s)
- Haoqi Guo
- Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang 110122, PR China
| | - Xiaohong Li
- The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China
| | - Yuwei Zhang
- Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang 110122, PR China
| | - Jian Li
- Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang 110122, PR China
| | - Jing Yang
- Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang 110122, PR China
| | - Hong Jiang
- Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang 110122, PR China; Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110122, PR China
| | - Guifan Sun
- Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110122, PR China
| | - Taoguang Huo
- Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang 110122, PR China; Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang 110122, PR China.
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Mizdrak M, Kumrić M, Kurir TT, Božić J. Emerging Biomarkers for Early Detection of Chronic Kidney Disease. J Pers Med 2022; 12:jpm12040548. [PMID: 35455664 PMCID: PMC9025702 DOI: 10.3390/jpm12040548] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/22/2022] [Accepted: 03/28/2022] [Indexed: 12/14/2022] Open
Abstract
Chronic kidney disease (CKD) is a major and serious global health problem that leads to kidney damage as well as multiple systemic diseases. Early diagnosis and treatment are two major measures to prevent further deterioration of kidney function and to delay adverse outcomes. However, the paucity of early, predictive and noninvasive biomarkers has undermined our ability to promptly detect and treat this common clinical condition which affects more than 10% of the population worldwide. Despite all limitations, kidney function is still measured by serum creatinine, cystatin C, and albuminuria, as well as estimating glomerular filtration rate using different equations. This review aims to provide comprehensive insight into diagnostic methods available for early detection of CKD. In the review, we discuss the following topics: (i) markers of glomerular injury; (ii) markers of tubulointerstitial injury; (iii) the role of omics; (iv) the role of microbiota; (v) and finally, the role of microRNA in the early detection of CKD. Despite all novel findings, none of these biomarkers have met the criteria of an ideal early marker. Since the central role in CKD progression is the proximal tubule (PT), most data from the literature have analyzed biomarkers of PT injury, such as KIM-1 (kidney injury molecule-1), NGAL (neutrophil gelatinase-associated lipocalin), and L-FABP (liver fatty acid-binding protein).
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Affiliation(s)
- Maja Mizdrak
- Department of Nephrology and Hemodialysis, University Hospital of Split, 21000 Split, Croatia;
- Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia; (M.K.); (T.T.K.)
| | - Marko Kumrić
- Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia; (M.K.); (T.T.K.)
| | - Tina Tičinović Kurir
- Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia; (M.K.); (T.T.K.)
- Department of Endocrinology, Diabetes and Metabolic Disorders, University Hospital of Split, 21000 Split, Croatia
| | - Joško Božić
- Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia; (M.K.); (T.T.K.)
- Correspondence:
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Corona R, Ordaz B, Robles-Osorio L, Sabath E, Morales T. Neuroimmunoendocrine Link Between Chronic Kidney Disease and Olfactory Deficits. Front Integr Neurosci 2022; 16:763986. [PMID: 35173591 PMCID: PMC8841736 DOI: 10.3389/fnint.2022.763986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 01/07/2022] [Indexed: 11/18/2022] Open
Abstract
Chronic kidney disease (CKD) is a multifactorial pathology that progressively leads to the deterioration of metabolic functions and results from deficient glomerular filtration and electrolyte imbalance. Its economic impact on public health is challenging. Mexico has a high prevalence of CKD that is strongly associated with some of the most common metabolic disorders like diabetes and hypertension. The gradual loss of kidney functions provokes an inflammatory state and endocrine alterations affecting several systems. High serum levels of prolactin have been associated with CKD progression, inflammation, and olfactory function. Also, the nutritional status is altered due to impaired renal function. The decrease in calorie and protein intake is often accompanied by malnutrition, which can be severe at advanced stages of the disease. Nutrition and olfactory functioning are closely interconnected, and CKD patients often complain of olfactory deficits, which ultimately can lead to deficient food intake. CKD patients present a wide range of deficits in olfaction like odor discrimination, identification, and detection threshold. The chronic inflammatory status in CKD damages the olfactory epithelium leading to deficiencies in the chemical detection of odor molecules. Additionally, the decline in cognitive functioning impairs the capacity of odor differentiation. It is not clear whether peritoneal dialysis and hemodialysis improve the olfactory deficits, but renal transplants have a strong positive effect. In the present review, we discuss whether the olfactory deficiencies caused by CKD are the result of the induced inflammatory state, the hyperprolactinemia, or a combination of both.
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Affiliation(s)
- Rebeca Corona
- Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico
| | - Benito Ordaz
- Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico
| | | | - Ernesto Sabath
- Facultad de Nutrición, Universidad Autónoma de Querétaro, Querétaro, Mexico
| | - Teresa Morales
- Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico
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Acceptability of Plant-Based Diets for People with Chronic Kidney Disease: Perspectives of Renal Dietitians. Nutrients 2022; 14:nu14010216. [PMID: 35011091 PMCID: PMC8747619 DOI: 10.3390/nu14010216] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 12/24/2021] [Accepted: 01/01/2022] [Indexed: 02/08/2023] Open
Abstract
The purpose of this study was to explore the perspective of renal dietitians regarding plant-based diets for chronic kidney disease (CKD) management and evaluate the acceptability of a hypothetical plant-based dietary prescription aiming for the consumption of 30 unique plant foods per week. This study used an exploratory mixed methods design. Forty-six renal dietitians participated in either an online survey (n = 35) or an in-depth interview (n = 11). Dietitians perceived that plant-based diets could address multiple clinical concerns relevant to CKD. Forty percent of survey respondents reported the hypothetical dietary prescription was realistic for people with CKD, 34.3% were unsure, and 25.7% perceived it as unrealistic. Strengths of the hypothetical prescription included shifting the focus to whole foods and using practical resources like recipes. Limited staffing, time, and follow-up opportunities with patients, as well as differing nutrition philosophies were the most commonly reported challenges to implementation; while a supportive multidisciplinary team was identified as an important enabler. To increase patient acceptance of plant-based dietary approaches, education about plant food benefits was recommended, as was implementing small, incremental dietary changes. Successful implementation of plant-based diets is perceived to require frequent patient contact and ongoing education and support by a dietitian. Buy-in from the multidisciplinary team was also considered imperative.
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Hassan MS, Ahmed YS, Sarhaan EI, Mehanna NS, Madbouli NN, Abdelgawad MA. Effect of dietary synbiotic supplementation on serum indoxyl sulfate in prevalent hemodialysis patients. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.1186/s43162-021-00096-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Indoxyl sulfate (IS) is produced by action of the intestinal flora on tryptophan in protein diet, and it is normally excreted by the kidney. IS is a protein-bound uremic toxin, and it is difficult to be removed by conventional hemodialysis (HD) methods; so, it accumulates in HD patients and may contribute to major cardiovascular morbidity and mortality.
Aim
To study the effect of dietary synbiotic (prebiotic and probiotic) supplementation on IS level in prevalent HD patients.
Patients and methods
This single-blind, placebo-controlled trial was conducted on 80 prevalent HD patients (between January 2017 and March 2017) in Ain Shams University Hospital. Patients were divided into 2 groups: group 1 was given synbiotic (SYN) and group 2 was given placebo for 6 weeks. Blood levels of IS, CRP, creatinine, blood urea nitrogen (BUN), sodium, potassium, calcium, and phosphorus were measured at baseline and after 6 weeks.
Results
There was a significant reduction in serum IS level in groups 1 and 2 in comparison to their baselines (P value = 0.000 and 0.019 respectively); however, the change in IS level in group 1 after SYN supplementation (64% with IR 72.38–33.33) was more than that shown in group 2 (did not receive SYN) (18.47% with IR 26.75–26.75) with a highly significant P value, 0.000. Also, there were significant reductions in the levels of creatinine, BUN, phosphorus (P values < 0.001), and CRP (P values 0.002) in group 1 respectively with no similar changes noticed in group 2.
Conclusion
SYN supplementation in HD patients can reduce serum levels of IS and other uremic toxins like BUN and creatinine. Also, it may help to reduce serum phosphorus and CRP levels.
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Zhang P, Fang J, Li G, Zhang L, Lai X, Xu L, Liu L, Xiong Y, Li L, Zhang T, Wan J, Xu H, Chen R, Zhang W, Ma J, Chen Z. Sex Differences in Fecal Microbiota Correlation With Physiological and Biochemical Indices Associated With End-Stage Renal Disease Caused by Immunoglobulin a Nephropathy or Diabetes. Front Microbiol 2021; 12:752393. [PMID: 34899638 PMCID: PMC8661007 DOI: 10.3389/fmicb.2021.752393] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 10/29/2021] [Indexed: 12/29/2022] Open
Abstract
This study investigated the sex-specific differences in the correlation between intestinal microbiota and end-stage renal disease. Here, we compared the differences in the gut microbiota of male and female healthy controls (HC) and patients with end-stage renal disease (ESRD) caused by immunoglobulin A (IgA) nephropathy (ESRD-IgAN) or type-2 diabetes mellitus (ESRD-T2DM) using high-throughput sequencing of the 16S rRNA gene. We also analyzed the correlation between gut microbiota and clinical immune indicators. We assigned 8, 10, 5, 7, 11, and 20 volunteers to female HC, ESRD-IgAN, and ESRD-T2DM, and male HC, ESRD-IgAN, and ESRD-T2DM, respectively. The results showed sex-specific differences in both physiological and biochemical indices and intestinal microbiota composition, as well as the correlation between them. The correlations between physiological and biochemical indices in men were significantly lower than those in women, especially for indices related to immunity, blood glucose, and cardiac color sonography. Urine output, lymphocyte ratio, serum albumin, blood calcium, dialysis status, serum urea nitrogen, urine protein, and diabetes significantly correlated with male fecal microbiota composition, whereas only creatinine and 2-h post-prandial blood glucose significantly correlated with female fecal microbiota composition. The top 50 dominant operational taxonomic units showed a stronger correlation with physiological and biochemical indices in samples obtained from females than from males. These differences highlight sex-specific differences in the effectiveness of ESRD prevention and treatments via regulating intestinal microbiota.
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Affiliation(s)
- Peng Zhang
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jiali Fang
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Guanghui Li
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Lei Zhang
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xingqiang Lai
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Lu Xu
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Luhao Liu
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yunyi Xiong
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Li Li
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Tao Zhang
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jiao Wan
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Hailin Xu
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Rongxin Chen
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Weiting Zhang
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Junjie Ma
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Zheng Chen
- Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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Mertowska P, Mertowski S, Wojnicka J, Korona-Głowniak I, Grywalska E, Błażewicz A, Załuska W. A Link between Chronic Kidney Disease and Gut Microbiota in Immunological and Nutritional Aspects. Nutrients 2021; 13:3637. [PMID: 34684638 PMCID: PMC8540836 DOI: 10.3390/nu13103637] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 10/14/2021] [Accepted: 10/15/2021] [Indexed: 02/07/2023] Open
Abstract
Chronic kidney disease (CKD) is generally progressive and irreversible, structural or functional renal impairment for 3 or more months affecting multiple metabolic pathways. Recently, the composition, dynamics, and stability of a patient's microbiota has been noted to play a significant role during disease onset or progression. Increasing urea concentration during CKD can lead to an acceleration of the process of kidney injury leading to alterations in the intestinal microbiota that can increase the production of gut-derived toxins and alter the intestinal epithelial barrier. A detailed analysis of the relationship between the role of intestinal microbiota and the development of inflammation within the symbiotic and dysbiotic intestinal microbiota showed significant changes in kidney dysfunction. Several recent studies have determined that dietary factors can significantly influence the activation of immune cells and their mediators. Moreover, dietary changes can profoundly affect the balance of gut microbiota. The aim of this review is to present the importance and factors influencing the differentiation of the human microbiota in the progression of kidney diseases, such as CKD, IgA nephropathy, idiopatic nephropathy, and diabetic kidney disease, with particular emphasis on the role of the immune system. Moreover, the effects of nutrients, bioactive compounds on the immune system in development of chronic kidney disease were reviewed.
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Affiliation(s)
- Paulina Mertowska
- Department of Experimental Immunology, Medical University of Lublin, 4a Chodzki Street, 20-093 Lublin, Poland; (P.M.); (S.M.); (E.G.)
| | - Sebastian Mertowski
- Department of Experimental Immunology, Medical University of Lublin, 4a Chodzki Street, 20-093 Lublin, Poland; (P.M.); (S.M.); (E.G.)
| | - Julia Wojnicka
- Department of Pathobiochemistry and Interdisciplinary Applications of Ion Chromatography, Medical University of Lublin, 1 Chodzki Street, 20-093 Lublin, Poland; (J.W.); (A.B.)
| | - Izabela Korona-Głowniak
- Department of Pharmaceutical Microbiology, Medical University of Lublin, 1 Chodzki Street, 20-093 Lublin, Poland
| | - Ewelina Grywalska
- Department of Experimental Immunology, Medical University of Lublin, 4a Chodzki Street, 20-093 Lublin, Poland; (P.M.); (S.M.); (E.G.)
| | - Anna Błażewicz
- Department of Pathobiochemistry and Interdisciplinary Applications of Ion Chromatography, Medical University of Lublin, 1 Chodzki Street, 20-093 Lublin, Poland; (J.W.); (A.B.)
| | - Wojciech Załuska
- Department of Nephrology, Medical University of Lublin, 8 Jaczewskiego Street, 20-954 Lublin, Poland;
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Lv Y, Ren G, Ren X. Changes of Intestinal Flora and Lymphocyte Subsets in Patients with Chronic Renal Failure. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:4288739. [PMID: 34764999 PMCID: PMC8577924 DOI: 10.1155/2021/4288739] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 09/15/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To explore the changes of intestinal flora and lymphocyte subsets in patients with chronic renal failure (CRF). METHODS 60 CRF patients who were treated from June 2018 to June 2019 were selected; 60 healthy persons were selected as the control group. 16S rDNA was used to detect the expression of Lactobacillus, Enterobacteriaceae, Enterococcus, Bacteroides, Clostridium, and Bifidobacterium in the feces of the two groups. Illumina Miseq sequencing (Solexa sequencing technology) method was used to analyze the structural differences and species diversity of intestinal flora, including species richness index (Chao) and diversity index (Shannon, Simpson). Flow cytometry was used to detect the levels of lymphocytes and their subgroups of the two groups. Pearson correlation analysis was used to analyze the correlation between Chao and lymphocyte subsets. RESULTS The number of Enterobacteriaceae and Enterococcus in CRF group were higher than those in the control group (P < 0.05), while the Lactobacillus, Bacteroides, Clostridium, and Bifidobacterium were opposite (P < 0.05). The Simpson index of the CRF group was lower than that of the control group, while the Chao index and Shannon index were opposite (P < 0.05). The levels of CD3+, CD4+, CD8+, and CD4+/CD8+ in the CRF group were lower than those in the control group, while the levels of CD14+, CD19+, and CD16+/CD56+ were opposite (P < 0.05). The intestinal flora Chao index of CRF group was negatively correlated with the levels of CD3+, CD4+, and CD8+ (r = -0.692, P=0.019; r = -0.669, P=0.021; r = -0.603, P=0.028). The intestinal flora Chao of CRF group is positively correlated with the level of CD14+ and CD16+/CD56+ (r = 0.615, P=0.026; r = 0.758, P=0.016). CONCLUSION There are intestinal flora disorder and the imbalance of immune function in CRF patients, which are mainly manifested in the change of intestinal flora structure, the increase of richness and diversity of intestinal flora, and the decrease of lymphocyte subgroups. There is correlation between the imbalance of intestinal colony and the imbalance of immune function.
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Affiliation(s)
- Yan Lv
- Department of Nephrology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China
| | - Gang Ren
- Department of Neurology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China
| | - Xiaojun Ren
- Department of Nephrology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China
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Zaky A, Glastras SJ, Wong MYW, Pollock CA, Saad S. The Role of the Gut Microbiome in Diabetes and Obesity-Related Kidney Disease. Int J Mol Sci 2021; 22:9641. [PMID: 34502562 PMCID: PMC8431784 DOI: 10.3390/ijms22179641] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 12/12/2022] Open
Abstract
Diabetic kidney disease (DKD) is a progressive disorder, which is increasing globally in prevalence due to the increased incidence of obesity and diabetes mellitus. Despite optimal clinical management, a significant number of patients with diabetes develop DKD. Hence, hitherto unrecognized factors are likely to be involved in the initiation and progression of DKD. An extensive number of studies have demonstrated the role of microbiota in health and disease. Dysregulation in the microbiota resulting in a deficiency of short chain fatty acids (SCFAs) such as propionate, acetate, and butyrate, by-products of healthy gut microbiota metabolism, have been demonstrated in obesity, type 1 and type 2 diabetes. However, it is not clear to date whether such changes in the microbiota are causative or merely associated with the diseases. It is also not clear which microbiota have protective effects on humans. Few studies have investigated the centrality of reduced SCFA in DKD development and progression or the potential therapeutic effects of supplemental SCFAs on insulin resistance, inflammation, and metabolic changes. SCFA receptors are expressed in the kidneys, and emerging data have demonstrated that intestinal dysbiosis activates the renal renin-angiotensin system, which contributes to the development of DKD. In this review, we will summarize the complex relationship between the gut microbiota and the kidney, examine the evidence for the role of gut dysbiosis in diabetes and obesity-related kidney disease, and explore the mechanisms involved. In addition, we will describe the role of potential therapies that modulate the gut microbiota to prevent or reduce kidney disease progression.
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Affiliation(s)
- Amgad Zaky
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia; (A.Z.); (S.J.G.); (M.Y.W.W.); (C.A.P.)
| | - Sarah J. Glastras
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia; (A.Z.); (S.J.G.); (M.Y.W.W.); (C.A.P.)
- Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
| | - May Y. W. Wong
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia; (A.Z.); (S.J.G.); (M.Y.W.W.); (C.A.P.)
- Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
| | - Carol A. Pollock
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia; (A.Z.); (S.J.G.); (M.Y.W.W.); (C.A.P.)
- Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
| | - Sonia Saad
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia; (A.Z.); (S.J.G.); (M.Y.W.W.); (C.A.P.)
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Yeh H, Chiang CC, Yen TH. Hepatocellular carcinoma in patients with renal dysfunction: Pathophysiology, prognosis, and treatment challenges. World J Gastroenterol 2021; 27:4104-4142. [PMID: 34326614 PMCID: PMC8311541 DOI: 10.3748/wjg.v27.i26.4104] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/17/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
The population of patients with hepatocellular carcinoma (HCC) overlaps to a high degree with those for chronic kidney disease (CKD) and end-stage renal disease (ESRD). The degrees of renal dysfunction vary, from the various stages of CKD to dialysis-dependent ESRD, which often affects the prognosis and treatment choice of patients with HCC. In addition, renal dysfunction makes treatment more difficult and may negatively affect treatment outcomes. This study summarized the possible causes of the high comorbidity of HCC and renal dysfunction. The possible mechanisms of CKD causing HCC involve uremia itself, long-term dialysis status, immunosuppressive agents for postrenal transplant status, and miscellaneous factors such as hormone alterations and dysbiosis. The possible mechanisms of HCC affecting renal function include direct tumor invasion and hepatorenal syndrome. Finally, we categorized the risk factors that could lead to both HCC and CKD into four categories: Environmental toxins, viral hepatitis, metabolic syndrome, and vasoactive factors. Both CKD and ESRD have been reported to negatively affect HCC prognosis, but more research is warranted to confirm this. Furthermore, ESRD status itself ought not to prevent patients receiving aggressive treatments. This study then adopted the well-known Barcelona Clinic Liver Cancer guidelines as a framework to discuss the indicators for each stage of HCC treatment, treatment-related adverse renal effects, and concerns that are specific to patients with pre-existing renal dysfunction when undergoing aggressive treatments against CKD and ESRD. Such aggressive treatments include liver resection, simultaneous liver kidney transplantation, radiofrequency ablation, and transarterial chemoembolization. Finally, focusing on patients unable to receive active treatment, this study compiled information on the latest systemic pharmacological therapies, including targeted and immunotherapeutic drugs. Based on available clinical studies and Food and Drug Administration labels, this study details the drug indications, side effects, and dose adjustments for patients with renal dysfunction. It also provides a comprehensive review of information on HCC patients with renal dysfunction from disease onset to treatment.
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Affiliation(s)
- Hsuan Yeh
- Department of Nephrology, Chang Gung Memorial Hospital and Chang Gung University, Taipei 105, Taiwan
| | - Chun-Cheng Chiang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Tzung-Hai Yen
- Department of Nephrology, Chang Gung Memorial Hospital and Chang Gung University, Taipei 105, Taiwan
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The Herbal Formula Granule Prescription Mahuang Decoction Ameliorated Chronic Kidney Disease Which Was Associated with Restoration of Dysbiosis of Intestinal Microbiota in Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:4602612. [PMID: 34257680 PMCID: PMC8249121 DOI: 10.1155/2021/4602612] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 08/05/2020] [Accepted: 06/11/2021] [Indexed: 12/01/2022]
Abstract
Chronic kidney disease (CKD) has become a global health issue, and there is increasing evidence showing the beneficial roles of traditional Chinese medicine (TCM) in CKD treatment. Here, we studied the renoprotective role of Mahuang decoction, a famous TCM prescription, in a rat CKD model induced with the combination of doxorubicin and adenine. Our data showed that intragastric administration of Mahuang decoction inhibited the loss of bodyweight and attenuated proteinuria, serum creatinine, and blood urea nitrogen in CKD rats. Kidney histological analysis revealed decreased tubulointerstitial injury and fibrosis in CKD rats treated with Mahuang decoction accompanied with suppressed expression of TGF-β1 and phosphorylated NF-κB/P65 (p-P65) as indicated by immunohistochemistry. ELISA analysis demonstrated reduced serum levels of proinflammatory cytokines TNFα and IL-6. Most importantly, intestinal microbiota analysis by 16s rRNA-seq showed that Mahuang decoction restored the impaired richness and diversity of intestinal microflora and recovered the disrupted microbial community through reducing the abundance of deleterious microbes and promoting the expansion of beneficial microbes in CKD rats. Collectively, our findings demonstrated that Mahuang decoction mitigated kidney functional and structural impairment in CKD rats which were associated with the restoration of dysbiosis of intestinal microbiota, implying its potential in clinical CKD treatment.
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Li D, Yang Y, Li Y, Li Z, Zhu X, Zeng X. Changes induced by chronic exposure to high arsenic concentrations in the intestine and its microenvironment. Toxicology 2021; 456:152767. [PMID: 33813003 DOI: 10.1016/j.tox.2021.152767] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 03/17/2021] [Accepted: 03/24/2021] [Indexed: 01/07/2023]
Abstract
The perturbation of intestinal microbes may serve as a mechanism by which arsenic exposure causes or exacerbates diseases in humans. However, the changes in the intestinal microbiome and metabolome induced by long-term exposure to high concentrations of arsenic have not been extensively studied. In this study, C57BL/6 mice were exposed to sodium arsenite (As) (50 ppm) for 6 months. Our results show that long-term exposure to high As concentrations changed the structure of intestinal tissues and the expression of As resistance related genes in intestinal microbes. In addition, 16S rRNA gene sequencing revealed that As exposure significantly affected the Beta diversity of intestinal flora but had no significant effect on the Alpha diversity (except ACE index). Moreover, As exposure altered the composition of the intestinal microbiota from phylum to species. Non-targeted metabolomics profiling revealed that As exposure significantly changed the composition of metabolites, specifically those related to phenylalanine metabolism. Correlation analysis demonstrated that the changes in microbial communities and metabolites were highly correlated under As exposure. Overall, this study demonstrates that long-term exposure to high As concentrations disrupted the intestinal microbiome and metabolome, which may indicate the role of As exposure at inducing human diseases under similar conditions.
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Affiliation(s)
- Dong Li
- College of Environmental Science and Engineering, China West Normal University, Nanchong, Sichuan, 637009, China; College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan, 625014, China
| | - Yan Yang
- College of Environmental Science and Engineering, China West Normal University, Nanchong, Sichuan, 637009, China
| | - Yunxiang Li
- College of Environmental Science and Engineering, China West Normal University, Nanchong, Sichuan, 637009, China
| | - Zeqin Li
- College of Environmental and Civil Engineering, Chengdu University of Technology, Chengdu, Sichuan, 610059, China
| | - Xiaohua Zhu
- College of Environmental Science and Engineering, China West Normal University, Nanchong, Sichuan, 637009, China; College of Environmental and Civil Engineering, Chengdu University of Technology, Chengdu, Sichuan, 610059, China.
| | - Xianyin Zeng
- College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan, 625014, China.
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Rysz J, Franczyk B, Ławiński J, Olszewski R, Ciałkowska-Rysz A, Gluba-Brzózka A. The Impact of CKD on Uremic Toxins and Gut Microbiota. Toxins (Basel) 2021; 13:toxins13040252. [PMID: 33807343 PMCID: PMC8067083 DOI: 10.3390/toxins13040252] [Citation(s) in RCA: 143] [Impact Index Per Article: 35.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/23/2021] [Accepted: 03/28/2021] [Indexed: 12/11/2022] Open
Abstract
Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an "imbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota". The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD.
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Affiliation(s)
- Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.)
| | - Beata Franczyk
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.)
| | - Janusz Ławiński
- Department of Urology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-055 Rzeszow, Poland;
| | - Robert Olszewski
- Department of Gerontology, Public Health and Didactics, Rheumatology and Rehabilitation, National Institute of Geriatrics, 02-637 Warsaw, Poland;
- Department of Ultrasound, Institute of Fundamental Technological Research, Polish Academy of Sciences, 02-637 Warsaw, Poland
| | | | - Anna Gluba-Brzózka
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (J.R.); (B.F.)
- Correspondence: ; Tel.: +48-42-6393750
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Portolés J, Martín L, Broseta JJ, Cases A. Anemia in Chronic Kidney Disease: From Pathophysiology and Current Treatments, to Future Agents. Front Med (Lausanne) 2021; 8:642296. [PMID: 33842503 PMCID: PMC8032930 DOI: 10.3389/fmed.2021.642296] [Citation(s) in RCA: 110] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 03/01/2021] [Indexed: 12/19/2022] Open
Abstract
Anemia is a common complication in chronic kidney disease (CKD), and is associated with a reduced quality of life, and an increased morbidity and mortality. The mechanisms involved in anemia associated to CKD are diverse and complex. They include a decrease in endogenous erythropoietin (EPO) production, absolute and/or functional iron deficiency, and inflammation with increased hepcidin levels, among others. Patients are most commonly managed with oral or intravenous iron supplements and with erythropoiesis stimulating agents (ESA). However, these treatments have associated risks, and sometimes are insufficiently effective. Nonetheless, in the last years, there have been some remarkable advances in the treatment of CKD-related anemia, which have raised great expectations. On the one hand, a novel family of drugs has been developed: the hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). These agents induce, among other effects, an increase in the production of endogenous EPO, improve iron availability and reduce hepcidin levels. Some of them have already received marketing authorization. On the other hand, recent clinical trials have elucidated important aspects of iron supplementation, which may change the treatment targets in the future. This article reviews the current knowledge of the pathophysiology CKD-related anemia, current and future therapies, the trends in patient management and the unmet goals.
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Affiliation(s)
- Jose Portolés
- Department of Nephrology, Puerta de Hierro Majadahonda University Hospital, Madrid, Spain
- Anemia Working Group Spanish Society of Nephrology, Madrid, Spain
| | - Leyre Martín
- Department of Nephrology, Puerta de Hierro Majadahonda University Hospital, Madrid, Spain
- Anemia Working Group Spanish Society of Nephrology, Madrid, Spain
| | - José Jesús Broseta
- Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
| | - Aleix Cases
- Anemia Working Group Spanish Society of Nephrology, Madrid, Spain
- Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
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Salvadori M, Tsalouchos A. Microbiota, renal disease and renal transplantation. World J Transplant 2021; 11:16-36. [PMID: 33816144 PMCID: PMC8009061 DOI: 10.5500/wjt.v11.i3.16] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/06/2021] [Accepted: 02/12/2021] [Indexed: 02/06/2023] Open
Abstract
Aim of this frontier review has been to highlight the role of microbiota in healthy subjects and in patients affected by renal diseases with particular reference to renal transplantation. The microbiota has a relevant role in conditioning the healthy status and the diseases. In particular gut microbiota is essential in the metabolism of food and has a relevant role for its relationship with the immune system. The indigenous microbiota in patients with chronic renal failure is completely different than that of the healthy subjects and pathobionts appear. This abnormality in microbiota composition is called dysbiosis and may cause a rapid deterioration of the renal function both for activating the immune system and producing large quantity of uremic toxins. Similarly, after renal trans-plantation the microbiota changes with the appearance of pathobionts, principally in the first period because of the assumption of immunosuppressive drugs and antibiotics. These changes may deeply interfere with the graft outcome causing acute rejection, renal infections, diarrhea, and renal interstitial fibrosis. In addition, change in the microbiota may modify the metabolism of immuno-suppressive drugs causing in some patients the need of modifying the immunosuppressant dosing. The restoration of the indigenous microbiota after transplantation is important, either to avoiding the complications that impair the normal renal graft, and because recent studies have documented the role of an indigenous microbiota in inducing tolerance towards the graft. The use of prebiotics, probiotics, smart bacteria and diet modification may restore the indigenous microbiota, but these studies are just at their beginning and more data are needed to draw definitive conclusions.
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Affiliation(s)
- Maurizio Salvadori
- Department of Transplantation Renal Unit, Careggi University Hospital, Florence 50139, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
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