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Chafekar D. Optimizing chronic kidney disease management: The potential of a multi-strain probiotic formulation. World J Nephrol 2025; 14:101515. [DOI: 10.5527/wjn.v14.i1.101515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/21/2024] [Accepted: 12/03/2024] [Indexed: 01/20/2025] Open
Abstract
Chronic kidney disease (CKD), which represents a significant global health concern, is characterized by a gradual decline in kidney function, leading to complications such as electrolyte imbalance, cardiovascular disease, and immune dysfunction. Standard CKD management includes dietary modifications, ketoanalogues supplementation, blood pressure and blood glucose control, hydration maintenance, and treatment of the underlying causes. Emerging evidence has indicated a significant role of the gut microbiota in CKD, and that dysbiosis of the gut microbiota contributes to the progression of CKD towards end-stage renal disease. Probiotics and prebiotics have recently garnered attention owing to their potential to enhance gastrointestinal health and well-being by restoring the balance of the gut microbiota. Specific probiotic strains, including Lactobacillus and Bifidobacterium, promote beneficial bacterial growth, suppress harmful bacteria, and exert anti-inflammatory, antihypertensive, and antidiabetic effects. The combination of Streptococcus thermophilus, Lactobacillus acidophilus, Bifidobacterium longum, and Bacillus coagulans has demonstrated potential as a therapeutic formulation for CKD management in various studies, highlighting its promise in treating CKD; however, supporting evidence remains limited, making it crucial to conduct further investigations to determine the specific effects of different probiotic formulations on outcomes in patients with CKD.
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Affiliation(s)
- Deodatta Chafekar
- Dr V N Pawar Medical College, Director Supreme Kidney Care, Nashik 422005, Mahārāshtra, India
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Ribeiro FPB, de Luna Freire MO, de Oliveira Coutinho D, de Santana Cirilo MA, de Brito Alves JL. Gut Dysbiosis and Probiotic Therapy in Chronic Kidney Disease: A Comprehensive Review. Probiotics Antimicrob Proteins 2024:10.1007/s12602-024-10427-9. [PMID: 39668321 DOI: 10.1007/s12602-024-10427-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/06/2024] [Indexed: 12/14/2024]
Abstract
Chronic kidney disease (CKD) is a multifactorial disease affecting more than 13.4% of the world's population and is a growing public health problem. It is silent in its early stages and leads to irreversible kidney damage as the disease progresses. A key factor in this progression is the bidirectional relationship between CKD and gut dysbiosis, which creates an imbalance that promotes the accumulation of uremic toxins (UTs), contributing to renal fibrosis, endothelial dysfunction, and decreased glomerular filtration rate. In addition, CKD itself exacerbates gut dysbiosis by altering the composition of the gut microbiota (GM) and promoting the growth of pathogenic microorganisms. Therefore, it is crucial to explore new therapeutic strategies, and the use of probiotics and synbiotics has shown promise in modulating the GM. Numerous preclinical studies have shown that the use of probiotics in CKD has a beneficial effect on the kidney by reducing UTs, apoptosis, inflammation, and oxidative stress. Probiotic treatment has also been associated with restoration of intestinal integrity, modulation of microbial composition and diversity, and increased production of short-chain fatty acids (SCFAs). These positive results have also been observed in patients at different stages of CKD, where the use of probiotics and/or synbiotics was able to improve creatinine levels and uremic parameters and alleviate abdominal discomfort, in addition to modulating GM and reducing serum endotoxin levels. Although recent studies have explored the benefits of probiotics in the treatment of CKD, further research is needed to determine their long-term efficacy and clinical relevance. This review focuses on the factors driving gut dysbiosis in CKD, its role in disease progression, and the potential of probiotics as a therapeutic strategy.
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Affiliation(s)
- Fernanda Priscila Barbosa Ribeiro
- Department of Nutrition, Health Sciences Center, Federal University of Paraíba, Campus I - Jd, Cidade Universitária, João Pessoa, 58051-900, Brazil
| | - Micaelle Oliveira de Luna Freire
- Department of Nutrition, Health Sciences Center, Federal University of Paraíba, Campus I - Jd, Cidade Universitária, João Pessoa, 58051-900, Brazil
| | - Daniella de Oliveira Coutinho
- Department of Nutrition, Health Sciences Center, Federal University of Paraíba, Campus I - Jd, Cidade Universitária, João Pessoa, 58051-900, Brazil
| | | | - José Luiz de Brito Alves
- Department of Nutrition, Health Sciences Center, Federal University of Paraíba, Campus I - Jd, Cidade Universitária, João Pessoa, 58051-900, Brazil.
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Zhang A, Chen S, Zhu Y, Wu M, Lu B, Zhou X, Zhu Y, Xu X, Liu H, Zhu F, Lin R. Intestinal microbiome changes and mechanisms of maintenance hemodialysis patients with constipation. Front Cell Infect Microbiol 2024; 14:1495364. [PMID: 39588509 PMCID: PMC11586350 DOI: 10.3389/fcimb.2024.1495364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 10/18/2024] [Indexed: 11/27/2024] Open
Abstract
Background Constipation is a common symptom in maintenance hemodialysis patients and greatly affects the quality of survival of hemodialysis patients. Fecal microbiota transplantation and probiotics are feasible treatments for functional constipation, but there is still a gap in the research on the characteristics of gut flora in patients with maintenance hemodialysis combined with constipation. The aim of this study is to clarify the characteristics of the intestinal flora and its changes in maintenance hemodialysis patients with constipation. Methods Fecal samples were collected from 45 participants, containing 15 in the maintenance hemodialysis constipation group,15 in the maintenance hemodialysis non-constipation group and 15 in the healthy control group. These samples were analyzed using 16S rRNA gene sequencing. The feature of the intestinal microbiome of maintenance hemodialysis constipation group and the microbiome differences among the three groups were elucidated by species annotation analysis, α-diversity analysis, β-diversity analysis, species difference analysis, and predictive functional analysis. Results The alpha diversity analysis indicated that maintenance hemodialysis constipation group was less diverse and homogeneous than maintenance hemodialysis non-constipation group and healthy control group. At the genus level, the top ten dominant genera in maintenance hemodialysis constipation group patients were Enterococcus, Escherichia-Shigella, Bacteroides, Streptococcus, Bifidobacterium, Ruminococcus_gnavus_group, Lachnospiraceae_unclassified, Faecalibacterium, Akkermansia and UCG-002. Compared with non-constipation group, the Enterococcus, Rhizobiales_unclassified, Filomicrobium, Eggerthella, Allobaculum, Prevotella_7, Gordonibacter, Mitochondria_unclassified, Lachnoanaerobaculum were significantly higher in constipation group (p<0.05). Compared with non-constipation group, the Kineothrix, Rhodopirellula, Weissella were significantly lower in constipation group (p<0.05). The predictive functional analysis revealed that compared with non-constipation group, constipation group was significantly enriched in pathways associated with pyruate metabolism, flavonoid biosynthesis. Conclusions This study describes for the first time the intestinal microbiome characteristics of maintenance hemodialysis patients with constipation. The results of this study suggest that there is a difference in the intestinal flora between maintenance hemodialysis patients with constipation and maintenance hemodialysis patients without constipation.
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Affiliation(s)
- Aiping Zhang
- Department of nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Shilei Chen
- Department of General Medicine, Hangzhou Xihu District Zhuantang Street Community Health Service Centre, Hangzhou, Zhejiang, China
| | - Yanqin Zhu
- Department of nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Mengqi Wu
- Department of nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Bin Lu
- Department of nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xin Zhou
- Department of nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yan Zhu
- Department of nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xinyu Xu
- Department of Oncology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Hong Liu
- Department of nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Fenggui Zhu
- Department of nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Riyang Lin
- Department of nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang, China
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Vanholder R, Snauwaert E, Verbeke F, Glorieux G. Future of Uremic Toxin Management. Toxins (Basel) 2024; 16:463. [PMID: 39591217 PMCID: PMC11598275 DOI: 10.3390/toxins16110463] [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: 09/10/2024] [Revised: 10/10/2024] [Accepted: 10/16/2024] [Indexed: 11/28/2024] Open
Abstract
During the progression of chronic kidney disease (CKD), the retention of uremic toxins plays a key role in the development of uremic syndrome. Knowledge about the nature and biological impact of uremic toxins has grown exponentially over the past decades. However, the science on reducing the concentration and effects of uremic toxins has not advanced in parallel. Additionally, the focus has remained for too long on dialysis strategies, which only benefit the small fraction of people with CKD who suffer from advanced kidney disease, whereas uremic toxicity effects are only partially prevented. This article reviews recent research on alternative methods to counteract uremic toxicity, emphasizing options that are also beneficial in the earlier stages of CKD, with a focus on both established methods and approaches which are still under investigation or at the experimental stage. We will consequently discuss the preservation of kidney function, the prevention of cardiovascular damage, gastro-intestinal interventions, including diet and biotics, and pharmacologic interventions. In the final part, we also review alternative options for extracorporeal uremic toxin removal. The future will reveal which of these options are valid for further development and evidence-based assessment, hopefully leading to a more sustainable treatment model for CKD than the current one.
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Affiliation(s)
- Raymond Vanholder
- Nephrology Section, Department of Internal Medicine and Pediatrics, Ghent University Hospital, 9000 Gent, Belgium; (F.V.); (G.G.)
| | - Evelien Snauwaert
- Pediatric Nephrology Section, Department of Internal Medicine and Pediatrics, Ghent University Hospital, 9000 Ghent, Belgium;
- European Reference Network for Rare Kidney Diseases (ERKNet)
| | - Francis Verbeke
- Nephrology Section, Department of Internal Medicine and Pediatrics, Ghent University Hospital, 9000 Gent, Belgium; (F.V.); (G.G.)
| | - Griet Glorieux
- Nephrology Section, Department of Internal Medicine and Pediatrics, Ghent University Hospital, 9000 Gent, Belgium; (F.V.); (G.G.)
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Matar A, Damianos JA, Jencks KJ, Camilleri M. Intestinal Barrier Impairment, Preservation, and Repair: An Update. Nutrients 2024; 16:3494. [PMID: 39458489 PMCID: PMC11509958 DOI: 10.3390/nu16203494] [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: 09/19/2024] [Revised: 10/10/2024] [Accepted: 10/11/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES Our objective was to review published studies of the intestinal barrier and permeability, the deleterious effects of dietary components (particularly fat), the impact of altered intestinal permeability in disease models and human diseases, the role of the microbiome and epigenomics in control of barrier function, and the opportunities to restore normal barrier function with dietary interventions and products of the microbiota. METHODS We conducted a literature review including the following keywords alone or in combination: intestinal barrier, permeability, microbiome, epigenomics, diet, irritable bowel syndrome, inflammatory bowel disease, probiotics. RESULTS Intestinal permeability is modified by a diet including fat, which increases permeability, and nutrients such as fiber, glutamine, zinc, vitamin D, polyphenols, emulsifiers, and anthocyanins, which decrease permeability. There is significant interaction of the microbiome and barrier function, including the inflammatory of luminal/bacterial antigens, and anti-inflammatory effects of commensals or probiotics and their products, including short-chain fatty acids. Epigenomic modification of barrier functions are best illustrated by effects on junction proteins or inflammation. Detailed documentation of the protective effects of diet, probiotics, prebiotics, and microbiota is provided. CONCLUSION intestinal permeability is a critical factor in protection against gastrointestinal diseases and is impacted by nutrients that preserve or heal and repair the barrier and nurture anti-inflammatory effects.
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Affiliation(s)
| | | | | | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; (A.M.); (J.A.D.)
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Nie HY, Ge J, Huang GX, Liu KG, Yue Y, Li H, Lin HG, Zhang T, Yan HF, Xu BX, Sun HW, Yang JW, Si SY, Zhou JL, Cui Y. New insights into the intestinal barrier through "gut-organ" axes and a glimpse of the microgravity's effects on intestinal barrier. Front Physiol 2024; 15:1465649. [PMID: 39450142 PMCID: PMC11499591 DOI: 10.3389/fphys.2024.1465649] [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: 07/16/2024] [Accepted: 09/02/2024] [Indexed: 10/26/2024] Open
Abstract
Gut serves as the largest interface between humans and the environment, playing a crucial role in nutrient absorption and protection against harmful substances. The intestinal barrier acts as the initial defense mechanism against non-specific infections, with its integrity directly impacting the homeostasis and health of the human body. The primary factor attributed to the impairment of the intestinal barrier in previous studies has always centered on the gastrointestinal tract itself. In recent years, the concept of the "gut-organ" axis has gained significant popularity, revealing a profound interconnection between the gut and other organs. It speculates that disruption of these axes plays a crucial role in the pathogenesis and progression of intestinal barrier damage. The evaluation of intestinal barrier function and detection of enterogenic endotoxins can serve as "detecting agents" for identifying early functional alterations in the heart, kidney, and liver, thereby facilitating timely intervention in the disorders. Simultaneously, consolidating intestinal barrier integrity may also present a potential therapeutic approach to attenuate damage in other organs. Studies have demonstrated that diverse signaling pathways and their corresponding key molecules are extensively involved in the pathophysiological regulation of the intestinal barrier. Aberrant activation of these signaling pathways and dysregulated expression of key molecules play a pivotal role in the process of intestinal barrier impairment. Microgravity, being the predominant characteristic of space, can potentially exert a significant influence on diverse intestinal barriers. We will discuss the interaction between the "gut-organ" axes and intestinal barrier damage, further elucidate the signaling pathways underlying intestinal barrier damage, and summarize alterations in various components of the intestinal barrier under microgravity. This review aims to offer a novel perspective for comprehending the etiology and molecular mechanisms of intestinal barrier injury as well as the prevention and management of intestinal barrier injury under microgravity environment.
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Affiliation(s)
- Hong-Yun Nie
- Department of General Surgery, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Jun Ge
- Clinical laboratory, The Ninth Medical Center of the PLA General Hospital, Beijing, China
| | - Guo-Xing Huang
- 306th Clinical College of PLA, The Fifth Clinical College, Anhui Medical University, Beijing, China
| | - Kai-Ge Liu
- Department of General Surgery, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Yuan Yue
- Department of Disease Control and Prevention, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Hao Li
- Department of General Surgery, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Hai-Guan Lin
- Department of General Surgery, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Tao Zhang
- Department of General Surgery, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Hong-Feng Yan
- Department of General Surgery, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Bing-Xin Xu
- Special Medical Laboratory Center, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Hong-Wei Sun
- Department of General Surgery, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Jian-Wu Yang
- Department of General Surgery, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Shao-Yan Si
- Special Medical Laboratory Center, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Jin-Lian Zhou
- Department of Pathology, The Ninth Medical Center of PLA General Hospital, Beijing, China
| | - Yan Cui
- Department of General Surgery, The Ninth Medical Center of PLA General Hospital, Beijing, China
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Młynarska E, Budny E, Saar M, Wojtanowska E, Jankowska J, Marciszuk S, Mazur M, Rysz J, Franczyk B. Does the Composition of Gut Microbiota Affect Chronic Kidney Disease? Molecular Mechanisms Contributed to Decreasing Glomerular Filtration Rate. Int J Mol Sci 2024; 25:10429. [PMID: 39408756 PMCID: PMC11477184 DOI: 10.3390/ijms251910429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/16/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
Chronic kidney disease (CKD) is a very prevalent and insidious disease, particularly with initially poorly manifested symptoms that progressively culminate in the manifestation of an advanced stage of the condition. The gradual impairment of kidney function, particularly decreased filtration capacity, results in the retention of uremic toxins and affects numerous molecular mechanisms within the body. The dysbiotic intestinal microbiome plays a crucial role in the accumulation of protein-bound uremic toxins such as p-cresol (pC), indoxyl sulfate (IS), and p-cresyl sulfate (p-CS) through the ongoing fermentation process. The described phenomenon leads to an elevated level of oxidative stress and inflammation, subsequently resulting in tissue damage and complications, particularly an increase in cardiovascular risk, representing the predominant cause of mortality in chronic kidney disease (CKD). Therefore, exploring methods to reduce uremic toxins is currently a pivotal therapeutic strategy aimed at reducing the risk of organ damage in patients with chronic kidney disease (CKD). This review aims to summarize recent discoveries on modifying the composition of the intestinal microbiota through the introduction of special probiotic and synbiotic supplements for CKD therapy. The potential to connect the gut microbiota with CKD opens the possibility for further extensive research in this area, which could lead to the incorporation of synbiotics and probiotics into the fundamental treatment and prevention of CKD.
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Affiliation(s)
- Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (M.M.)
| | - Emilian Budny
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (M.M.)
| | - Maciej Saar
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (M.M.)
| | - Ewa Wojtanowska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (M.M.)
| | - Justyna Jankowska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (M.M.)
| | - Szymon Marciszuk
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (M.M.)
| | - Marcin Mazur
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (M.M.)
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland (M.M.)
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Messing M, Torres JA, Holznecht N, Weimbs T. Trigger Warning: How Modern Diet, Lifestyle, and Environment Pull the Trigger on Autosomal Dominant Polycystic Kidney Disease Progression. Nutrients 2024; 16:3281. [PMID: 39408247 PMCID: PMC11479178 DOI: 10.3390/nu16193281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/10/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
Understanding chronic kidney disease (CKD) through the lens of evolutionary biology highlights the mismatch between our Paleolithic-optimized genes and modern diets, which led to the dramatically increased prevalence of CKD in modern societies. In particular, the Standard American Diet (SAD), high in carbohydrates and ultra-processed foods, causes conditions like type 2 diabetes (T2D), chronic inflammation, and hypertension, leading to CKD. Autosomal dominant polycystic kidney disease (ADPKD), a genetic form of CKD, is characterized by progressive renal cystogenesis that leads to renal failure. This review challenges the fatalistic view of ADPKD as solely a genetic disease. We argue that, just like non-genetic CKD, modern dietary practices, lifestyle, and environmental exposures initiate and accelerate ADPKD progression. Evidence shows that carbohydrate overconsumption, hyperglycemia, and insulin resistance significantly impact renal health. Additionally, factors like dehydration, electrolyte imbalances, nephrotoxin exposure, gastrointestinal dysbiosis, and renal microcrystal formation exacerbate ADPKD. Conversely, carbohydrate restriction, ketogenic metabolic therapy (KMT), and antagonizing the lithogenic risk show promise in slowing ADPKD progression. Addressing disease triggers through dietary modifications and lifestyle changes offers a conservative, non-pharmacological strategy for disease modification in ADPKD. This comprehensive review underscores the urgency of integrating diet and lifestyle factors into the clinical management of ADPKD to mitigate disease progression, improve patient outcomes, and offer therapeutic choices that can be implemented worldwide at low or no cost to healthcare payers and patients.
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Affiliation(s)
| | | | | | - Thomas Weimbs
- Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA 93106, USA; (M.M.); (J.A.T.); (N.H.)
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Liu C, Yang L, Wei W, Fu P. Efficacy of probiotics/synbiotics supplementation in patients with chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials. Front Nutr 2024; 11:1434613. [PMID: 39166132 PMCID: PMC11333927 DOI: 10.3389/fnut.2024.1434613] [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: 05/18/2024] [Accepted: 07/17/2024] [Indexed: 08/22/2024] Open
Abstract
Background Chronic kidney disease (CKD) is a serious and steadily growing health problem worldwide. Probiotic and synbiotic supplementation are expected to improve kidney function in CKD patients by altering imbalanced intestinal flora, regulating microbiota metabolites, modulating the brain-gut axis, and reducing inflammation. Objectives Our aim is to report the latest and largest pooled analyses and evidence updates to explore whether probiotic and synbiotic have beneficial effects on renal function and general conditions in patients with CKD. Methods We conducted a systematic literature search using PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from inception until 1 December 2023. Eligible literatures were screened according to inclusion and exclusion criteria, data were extracted, and a systematic review and meta-analysis was performed. Measurements included renal function-related markers, inflammatory markers, uremic toxins, lipid metabolism-related markers and electrolytes levels. Results Twenty-one studies were included. The results showed that probiotic/synbiotic significantly reduced blood urea nitrogen (BUN) (standardized mean difference (SMD), -0.23, 95% confidence interval (CI) -0.41, -0.04; p = 0.02, I2 = 10%) and lowered c-reactive protein level (CRP) (SMD: -0.34; 95% CI: -0.62, -0.07; p = 0.01, I2 = 37%) in CKD patients, compared with the control group. Conclusion In summary, probiotic/synbiotic supplementation seems to be effective in improving renal function indices and inflammation indices in CKD patients. Subgroup analyses suggested that longer-term supplementation is more favorable for CKD patients, but there is a high degree of heterogeneity in the results of partial subgroup analyses. The efficacy of probiotic/synbiotic in treating CKD needs to be supported by more evidence from large-scale clinical studies. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024526836, Unique identifier: CRD42024526836.
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Affiliation(s)
| | | | | | - Ping Fu
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, Chengdu, China
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Lee S, Choi SP, Choi HJ, Jeong H, Park YS. A comprehensive review of synbiotics: an emerging paradigm in health promotion and disease management. World J Microbiol Biotechnol 2024; 40:280. [PMID: 39060821 DOI: 10.1007/s11274-024-04085-w] [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] [Accepted: 07/14/2024] [Indexed: 07/28/2024]
Abstract
Synbiotics are complex preparations of prebiotics that can be selectively utilized by live microorganisms to improve host health. Synbiotics are divided into complementary synbiotics, which consist of probiotics and prebiotics with independent functions, and synergistic synbiotics, which consist of prebiotics that are selectively used by gut microorganisms. Complementary synbiotics used in human clinical trials include Lactobacillus spp. and Bifidobacterium spp. as probiotics, and fructooligosaccharides, galactooligosaccharides, and inulin as prebiotics. Over the past five years, synbiotics have been most commonly used in patients with metabolic disorders, including obesity, and immune and gastrointestinal disorders. Several studies have observed alterations in the microbial community; however, these changes did not lead to significant improvements in disease outcomes or biochemical and hematological markers. The same synbiotics have been applied to individuals with different gut environments. As a result, even with the same synbiotics, there are non-responders who do not respond to the applied synbiotics due to the different intestinal environment for each individual. Therefore, to obtain meaningful results, applying different synbiotics depending on the individual is necessary. Synergistic synbiotics are one solution to circumvent this problem, as they combine elements that can effectively improve health, even in non-responders. This review aims to explain the concept of synbiotics, highlight recent human clinical trials, and explore the current state of research on synergistic synbiotics.
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Affiliation(s)
- Sulhee Lee
- Kimchi Functionality Research Group, World Institute of Kimchi, Gwangju, 61755, Republic of Korea
| | - Sang-Pil Choi
- Kimchi Functionality Research Group, World Institute of Kimchi, Gwangju, 61755, Republic of Korea
| | - Hak-Jong Choi
- Kimchi Functionality Research Group, World Institute of Kimchi, Gwangju, 61755, Republic of Korea
| | - Huijin Jeong
- Department of Food Science and Biotechnology, Gachon University, Seongnam, 13120, Republic of Korea
| | - Young-Seo Park
- Department of Food Science and Biotechnology, Gachon University, Seongnam, 13120, Republic of Korea.
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Wakamatsu T, Yamamoto S, Yoshida S, Narita I. Indoxyl Sulfate-Induced Macrophage Toxicity and Therapeutic Strategies in Uremic Atherosclerosis. Toxins (Basel) 2024; 16:254. [PMID: 38922148 PMCID: PMC11209365 DOI: 10.3390/toxins16060254] [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: 04/14/2024] [Revised: 05/18/2024] [Accepted: 05/29/2024] [Indexed: 06/27/2024] Open
Abstract
Cardiovascular disease (CVD) frequently occurs in patients with chronic kidney disease (CKD), particularly those undergoing dialysis. The mechanisms behind this may be related to traditional risk factors and CKD-specific factors that accelerate atherosclerosis and vascular calcification in CKD patients. The accumulation of uremic toxins is a significant factor in CKD-related systemic disorders. Basic research suggests that indoxyl sulfate (IS), a small protein-bound uremic toxin, is associated with macrophage dysfunctions, including increased oxidative stress, exacerbation of chronic inflammation, and abnormalities in lipid metabolism. Strategies to mitigate the toxicity of IS include optimizing gut microbiota, intervening against the abnormality of intracellular signal transduction, and using blood purification therapy with higher efficiency. Further research is needed to examine whether lowering protein-bound uremic toxins through intervention leads to a reduction in CVD in patients with CKD.
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Affiliation(s)
- Takuya Wakamatsu
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; (T.W.); (S.Y.); (I.N.)
- Ohgo Clinic, Maebashi 371-0232, Japan
| | - Suguru Yamamoto
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; (T.W.); (S.Y.); (I.N.)
| | - Shiori Yoshida
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; (T.W.); (S.Y.); (I.N.)
| | - Ichiei Narita
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; (T.W.); (S.Y.); (I.N.)
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Meijers B, Zadora W, Lowenstein J. A Historical Perspective on Uremia and Uremic Toxins. Toxins (Basel) 2024; 16:227. [PMID: 38787079 PMCID: PMC11126090 DOI: 10.3390/toxins16050227] [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: 04/05/2024] [Revised: 05/12/2024] [Accepted: 05/14/2024] [Indexed: 05/25/2024] Open
Abstract
Uremia, also known as uremic syndrome, refers to the clinical symptoms in the final stage of renal failure. The definition of the term has changed over time due to an improved comprehension of the kidney's function and the advancement of dialysis technology. Here, we aim to present an overview of the various concepts that have developed regarding uremia throughout the years. We provide a comprehensive review of the historical progression starting from the early days of Kolff and his predecessors, continuing with the initial research conducted by Niwa et al., and culminating in the remote sensing hypothesis of Nigam. Additionally, we explore the subsequent investigation into the function of these toxins as signaling molecules in various somatic cells.
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Affiliation(s)
- Björn Meijers
- Nephrology and Transplantation Unit, University Hospitals Leuven, 30000 Leuven, Belgium; (B.M.); (W.Z.)
- Laboratory of Nephrology, Katholieke Universiteit Leuven, 30000 Leuven, Belgium
| | - Ward Zadora
- Nephrology and Transplantation Unit, University Hospitals Leuven, 30000 Leuven, Belgium; (B.M.); (W.Z.)
- Laboratory of Nephrology, Katholieke Universiteit Leuven, 30000 Leuven, Belgium
| | - Jerome Lowenstein
- Nephrology Division, NYU Langone Medical Center, New York, NY 10016, USA
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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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Tsai CW, Huang HW, Lee YJ, Chen MJ. Investigating the Efficacy of Kidney-Protective Lactobacillus Mixture-Containing Pet Treats in Feline Chronic Kidney Disease and Its Possible Mechanism. Animals (Basel) 2024; 14:630. [PMID: 38396596 PMCID: PMC10886156 DOI: 10.3390/ani14040630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/26/2024] [Accepted: 02/13/2024] [Indexed: 02/25/2024] Open
Abstract
Microbiota-based strategies are a novel auxiliary therapeutic and preventative way of moderating chronic kidney disease (CKD). Lactobacillus mixture (Lm) was previously demonstrated to exert a renal-protective function in the CKD mice model. The efficacy of probiotics in pet foods is a relatively new area of study, and thus verifying the potential health benefits is necessary. This study evaluated the efficacy of Lm treats in feline CKD and elucidated the mechanisms underlying host-microbe interactions. CKD cats (2 and 3 stages) were administrated probiotic pet treats daily (10 g) for 8 weeks. The results demonstrated that during the eight weeks of Lm administration, creatinine was reduced or maintained in all cats with CKD. Similarly, gut-derived uremic toxin (GDUT), indoxyl sulfate (IS), were potential clinical significance in IS after Lm treatment (confidence intervals = 90%). The life quality of the cats also improved. Feline gut microbiome data, metabolic functional pathway, and renal function indicator analyses revealed the possible mechanisms involved in modulating CKD feline microbial composition. Further regulation of the microbial functions in amino acid metabolism after Lm administration contributed to downregulating deleterious GDUTs. The current study provides potential adjuvant therapeutic insights into probiotic pet foods or treats for pets with CKD.
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Affiliation(s)
- Ching-Wen Tsai
- Department of Animal Science and Technology, National Taiwan University, Taipei 106037, Taiwan; (C.-W.T.); (H.-W.H.)
| | - Hsiao-Wen Huang
- Department of Animal Science and Technology, National Taiwan University, Taipei 106037, Taiwan; (C.-W.T.); (H.-W.H.)
| | - Ya-Jane Lee
- Institute of Veterinary Clinical Science, School of Veterinary Medicine, National Taiwan University, Taipei 106328, Taiwan;
- Department of Internal Medicine, National Taiwan University Veterinary Hospital, Taipei 106319, Taiwan
| | - Ming-Ju Chen
- Department of Animal Science and Technology, National Taiwan University, Taipei 106037, Taiwan; (C.-W.T.); (H.-W.H.)
- Center for Biotechnology, National Taiwan University, Taipei 106038, Taiwan
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Ye XY, Chen JY, Wu LH, Luo DP, Ye XH, Wu LQ, He XX. Washed microbiota transplantation improves symptoms and intestinal barrier function in patients with functional bowel disorders: a propensity-score matching analysis. BMC Gastroenterol 2024; 24:45. [PMID: 38262980 PMCID: PMC10804514 DOI: 10.1186/s12876-024-03131-z] [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: 03/28/2023] [Accepted: 01/09/2024] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND Alterations in the intestinal microbiota may play a role in the pathogenesis of functional bowel disorders (FBDs). Probiotics are widely used to improve intestinal dysbacteriosis in FBDs. In the context of FBDs, washed microbiota transplantation (WMT) appear to be a promising therapeutic option. We aimed to compare probiotics with WMT by using a propensity-score matching analysis (PSMA). METHODS We conducted a retrospective investigation of 103 patients with FBDs, including irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FDr), functional abdominal bloating (FAB). Patients were divided into the WMT group or probiotics group (taking probiotics capsules). Data on the following parameters were matched for PSMA: age; sex; disease course; body mass index; anxiety; insomnia; tobacco smoking; alcohol consumption; and levels of D-lactate, diamine oxidase, and lipopolysaccharide. Intestinal barrier function (IBF) and symptoms were evaluated both before and after treatment initiation. Prognostic factors were assessed by Cox proportional hazards regression analysis. RESULTS PSMA identified in 34 matched pairs (11 IBS, 12 FC, 7 FDr, and 4 FAB in the probiotics group and 14 IBS, 13 FC, 5 FDr, and 2 FAB in the WMT group. Improvement of FBD symptoms was greater with WMT than probiotics (P = 0.002). The WMT group had significantly fewer patients with intestinal barrier damage than the probiotics group (38.2% vs. 67.6%, P = 0.041). This improvement of FBD with WMT was further reflected as a reduction in D-lactate levels (P = 0.031). Increased D-lactate levels which were identified as a prognostic factor for FBDs (HR = 0.248, 95%CI 0.093-0.666, P = 0.006) in multivariate Cox regression analysis. CONCLUSION WMT could improve symptoms and IBF in patients with FBDs. Increased D-lactate levels in patients with FBDs may predict a favorable response to WMT treatment.
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Affiliation(s)
- Xiao-Yan Ye
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China
| | - Jun-Yi Chen
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China
| | - Li-Hao Wu
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China
| | - Dan-Ping Luo
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China
| | - Xiao-Huo Ye
- Department of Pharmacy, Heyuan Health School, 517000, Heyuan, Guangdong Province, China
| | - Li-Quan Wu
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China
| | - Xing-Xiang He
- Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, 510030, Guangzhou, Guangdong Province, China.
- Department of Gastroenterology, Research Center for Engineering Techniques of Microbiota -Targeted Therapies of Guangdong Province, 510030, Guangzhou, Guangdong Province, China.
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Cabała S, Ożgo M, Herosimczyk A. The Kidney-Gut Axis as a Novel Target for Nutritional Intervention to Counteract Chronic Kidney Disease Progression. Metabolites 2024; 14:78. [PMID: 38276313 PMCID: PMC10819792 DOI: 10.3390/metabo14010078] [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: 12/20/2023] [Revised: 01/17/2024] [Accepted: 01/19/2024] [Indexed: 01/27/2024] Open
Abstract
A well-balanced diet is integral for overall health, aiding in managing key risk factors for kidney damage like hypertension while supplying necessary precursors for metabolite production. Dietary choices directly influence the composition and metabolic patterns of the gut microbiota, showing promise as therapeutic tools for addressing various health conditions, including chronic kidney diseases (CKD). CKD pathogenesis involves a decline in the glomerular filtration rate and the retention of nitrogen waste, fostering gut dysbiosis and the excessive production of bacterial metabolites. These metabolites act as uremic toxins, contributing to inflammation, oxidative stress, and tissue remodeling in the kidneys. Dietary interventions hold significance in reducing oxidative stress and inflammation, potentially slowing CKD progression. Functional ingredients, nutrients, and nephroprotective phytoconstituents could modulate inflammatory pathways or impact the gut mucosa. The "gut-kidney axis" underscores the impact of gut microbes and their metabolites on health and disease, with dysbiosis serving as a triggering event in several diseases, including CKD. This review provides a comprehensive overview, focusing on the gut-liver axis, and explores well-established bioactive substances as well as specific, less-known nutraceuticals showing promise in supporting kidney health and positively influencing CKD progression.
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Affiliation(s)
| | | | - Agnieszka Herosimczyk
- Department of Physiology, Cytobiology and Proteomics, Faculty of Biotechnology and Animal Husbandry, West Pomeranian University of Technology Szczecin, Klemensa Janickiego 29, 71-270 Szczecin, Poland; (S.C.); (M.O.)
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Nakayama M, Kabayama S, Miyazaki M. Application of Electrolyzed Hydrogen Water for Management of Chronic Kidney Disease and Dialysis Treatment-Perspective View. Antioxidants (Basel) 2024; 13:90. [PMID: 38247514 PMCID: PMC10812465 DOI: 10.3390/antiox13010090] [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: 12/22/2023] [Revised: 01/09/2024] [Accepted: 01/09/2024] [Indexed: 01/23/2024] Open
Abstract
Chronic kidney disease (CKD), which is globally on the rise, has become an urgent challenge from the perspective of public health, given its risk factors such as end-stage renal failure, cardiovascular diseases, and infections. The pathophysiology of CKD, including dialysis patients, is deeply associated with enhanced oxidative stress in both the kidneys and the entire body. Therefore, the introduction of a safe and widely applicable antioxidant therapy is expected as a measure against CKD. Electrolyzed hydrogen water (EHW) generated through the electrolysis of water has been confirmed to possess chemical antioxidant capabilities. In Japan, devices producing this water have become popular for household drinking water. In CKD model experiments conducted to date, drinking EHW has been shown to suppress the progression of kidney damage related to hypertension. Furthermore, clinical studies have reported that systemic oxidative stress in patients undergoing dialysis treatment using EHW is suppressed, leading to a reduction in the incidence of cardiovascular complications. In the future, considering EHW as one of the comprehensive measures against CKD holds significant importance. The medical utility of EHW is believed to be substantial, and further investigation is warranted.
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Affiliation(s)
- Masaaki Nakayama
- Kidney Center, St. Luke’s International Hospital, Tokyo 104-8560, Japan
- Division of Blood Purification, Tohoku University Hospital, Sendai 980-8574, Japan; (S.K.); (M.M.)
| | - Shigeru Kabayama
- Division of Blood Purification, Tohoku University Hospital, Sendai 980-8574, Japan; (S.K.); (M.M.)
- Graduate School of Science, Technology & Innovation, Kobe University, Kobe 657-8501, Japan
- Nihon Trim Co., Ltd., Osaka 530-0001, Japan
| | - Mariko Miyazaki
- Division of Blood Purification, Tohoku University Hospital, Sendai 980-8574, Japan; (S.K.); (M.M.)
- Division of Nephrology, Rheumatology and Endocrinology, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan
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Liu F, Liu Y, Lv X, Lun H. Effects of prebiotics, probiotics and synbiotics on serum creatinine in non-dialysis patients: a meta-analysis of randomized controlled trials. Ren Fail 2023; 45:2152693. [PMID: 36636981 PMCID: PMC9848283 DOI: 10.1080/0886022x.2022.2152693] [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] [Indexed: 01/14/2023] Open
Abstract
OBJECTIVE Serum creatinine level are influenced by many factors. Although accumulated data suggested that prebiotics, probiotics and synbiotics supplements could affect serum creatinine level, the results remained controversial. The aim of the present paper was to evaluate the effects of prebiotics, probiotics and synbiotics on serum creatinine in non-dialysis patients. METHODS PubMed, EMBASE (Excerpta Medica Database) and the Cochrane Library databases were searched for eligible randomized, controlled trials (RCTs) which were limited to English language studies until 30 September 2022. A random-effects model was performed to analyze the impact of pooled trials. RESULT Twelve randomized, controlled trial studies were included in the meta-analysis. Prebiotics, probiotics or synbiotics supplementation did not significantly decrease the serum creatinine levels in non-dialysis patients compared to placebo [standardized mean difference (SMD) = 0.05; 95% confidence interval (CI): (-0.21, 0.31); p = 0.72; I2 = 61%]. CONCLUSION The present meta-analysis indicated that supplementation with prebiotics, probiotics and synbiotics could not act as promising adjuvant therapies to decrease the serum creatinine levels in non-dialysis patients.
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Affiliation(s)
- Fenfen Liu
- Department of Nephrology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China
| | - Yang Liu
- Senior Department of Cardiology, the Sixth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xueai Lv
- Department of Nephrology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China
| | - Hengzhong Lun
- Department of Clinical Laboratory, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China,CONTACT Hengzhong Lun Department of Clinical Laboratory, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China
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Denman CR, Park SM, Jo J. Gut-brain axis: gut dysbiosis and psychiatric disorders in Alzheimer's and Parkinson's disease. Front Neurosci 2023; 17:1268419. [PMID: 38075261 PMCID: PMC10704039 DOI: 10.3389/fnins.2023.1268419] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Accepted: 10/30/2023] [Indexed: 02/17/2025] Open
Abstract
Gut dysbiosis and psychiatric symptoms are common early manifestations of Alzheimer's disease (AD) and Parkinson's disease (PD). These diseases, characterised by progressive neuron loss and pathological protein accumulation, impose debilitating effects on patients. Recently, these pathological proteins have been linked with gut dysbiosis and psychiatric disorders. The gut-brain axis links the enteric and central nervous systems, acting as a bidirectional communication pathway to influence brain function and behavior. The relationship triad between gut dysbiosis, psychiatric disorders, and neurodegeneration has been investigated in pairs; however, evidence suggests that they are all interrelated and a deeper understanding is required to unravel the nuances of neurodegenerative diseases. Therefore, this review aims to summarise the current literature on the roles of gut dysbiosis and psychiatric disorders in pathological protein-related neurodegenerative diseases. We discussed how changes in the gut environment can influence the development of psychiatric symptoms and the progression of neurodegeneration and how these features overlap in AD and PD. Moreover, research on the interplay between gut dysbiosis, psychiatric disorders, and neurodegeneration remains in its early phase. In this review, we highlighted potential therapeutic approaches aimed at mitigating gastrointestinal problems and psychiatric disorders to alter the rate of neurodegeneration. Further research to assess the molecular mechanisms underlying AD and PD pathogenesis remains crucial for developing more effective treatments and achieving earlier diagnoses. Moreover, exploring non-invasive, early preventive measures and interventions is a relatively unexplored but important avenue of research in neurodegenerative diseases.
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Affiliation(s)
- Charlotte R. Denman
- Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan
| | - Sang Myun Park
- Department of Pharmacology, Ajou University School of Medicine, Suwon, Republic of Korea
- Center for Convergence Research of Neurological Disorders, Ajou University School of Medicine, Suwon, Republic of Korea
- Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Junghyun Jo
- Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan
- Department of Pharmacology, Ajou University School of Medicine, Suwon, Republic of Korea
- Center for Convergence Research of Neurological Disorders, Ajou University School of Medicine, Suwon, Republic of Korea
- Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea
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Cooper TE, Khalid R, Chan S, Craig JC, Hawley CM, Howell M, Johnson DW, Jaure A, Teixeira-Pinto A, Wong G. Synbiotics, prebiotics and probiotics for people with chronic kidney disease. Cochrane Database Syst Rev 2023; 10:CD013631. [PMID: 37870148 PMCID: PMC10591284 DOI: 10.1002/14651858.cd013631.pub2] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
Abstract
BACKGROUND Chronic kidney disease (CKD) is a major public health problem affecting 13% of the global population. Prior research has indicated that CKD is associated with gut dysbiosis. Gut dysbiosis may lead to the development and/or progression of CKD, which in turn may in turn lead to gut dysbiosis as a result of uraemic toxins, intestinal wall oedema, metabolic acidosis, prolonged intestinal transit times, polypharmacy (frequent antibiotic exposures) and dietary restrictions used to treat CKD. Interventions such as synbiotics, prebiotics, and probiotics may improve the balance of the gut flora by altering intestinal pH, improving gut microbiota balance and enhancing gut barrier function (i.e. reducing gut permeability). OBJECTIVES This review aimed to evaluate the benefits and harms of synbiotics, prebiotics, and probiotics for people with CKD. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 9 October 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA We included randomised controlled trials (RCTs) measuring and reporting the effects of synbiotics, prebiotics, or probiotics in any combination and any formulation given to people with CKD (CKD stages 1 to 5, including dialysis and kidney transplant). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS Data extraction was independently carried out by two authors using a standard data extraction form. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS Forty-five studies (2266 randomised participants) were included in this review. Study participants were adults (two studies in children) with CKD ranging from stages 1 to 5, with patients receiving and not receiving dialysis, of whom half also had diabetes and hypertension. No studies investigated the same synbiotic, prebiotic or probiotic of similar strains, doses, or frequencies. Most studies were judged to be low risk for selection bias, performance bias and reporting bias, unclear risk for detection bias and for control of confounding factors, and high risk for attrition and other biases. Compared to prebiotics, it is uncertain whether synbiotics improve estimated glomerular filtration rate (eGFR) at four weeks (1 study, 34 participants: MD -3.80 mL/min/1.73 m², 95% CI -17.98 to 10.38), indoxyl sulfate at four weeks (1 study, 42 participants: MD 128.30 ng/mL, 95% CI -242.77 to 499.37), change in gastrointestinal (GI) upset (borborymgi) at four weeks (1 study, 34 participants: RR 15.26, 95% CI 0.99 to 236.23), or change in GI upset (Gastrointestinal Symptom Rating Scale) at 12 months (1 study, 56 participants: MD 0.00, 95% CI -0.27 to 0.27), because the certainty of the evidence was very low. Compared to certain strains of prebiotics, it is uncertain whether a different strain of prebiotics improves eGFR at 12 weeks (1 study, 50 participants: MD 0.00 mL/min, 95% CI -1.73 to 1.73), indoxyl sulfate at six weeks (2 studies, 64 participants: MD -0.20 μg/mL, 95% CI -1.01 to 0.61; I² = 0%) or change in any GI upset, intolerance or microbiota composition, because the certainty of the evidence was very low. Compared to certain strains of probiotics, it is uncertain whether a different strain of probiotic improves eGFR at eight weeks (1 study, 30 participants: MD -0.64 mL/min, 95% CI -9.51 to 8.23; very low certainty evidence). Compared to placebo or no treatment, it is uncertain whether synbiotics improve eGFR at six or 12 weeks (2 studies, 98 participants: MD 1.42 mL/min, 95% CI 0.65 to 2.2) or change in any GI upset or intolerance at 12 weeks because the certainty of the evidence was very low. Compared to placebo or no treatment, it is uncertain whether prebiotics improves indoxyl sulfate at eight weeks (2 studies, 75 participants: SMD -0.14 mg/L, 95% CI -0.60 to 0.31; very low certainty evidence) or microbiota composition because the certainty of the evidence is very low. Compared to placebo or no treatment, it is uncertain whether probiotics improve eGFR at eight, 12 or 15 weeks (3 studies, 128 participants: MD 2.73 mL/min, 95% CI -2.28 to 7.75; I² = 78%), proteinuria at 12 or 24 weeks (1 study, 60 participants: MD -15.60 mg/dL, 95% CI -34.30 to 3.10), indoxyl sulfate at 12 or 24 weeks (2 studies, 83 participants: MD -4.42 mg/dL, 95% CI -9.83 to 1.35; I² = 0%), or any change in GI upset or intolerance because the certainty of the evidence was very low. Probiotics may have little or no effect on albuminuria at 12 or 24 weeks compared to placebo or no treatment (4 studies, 193 participants: MD 0.02 g/dL, 95% CI -0.08 to 0.13; I² = 0%; low certainty evidence). For all comparisons, adverse events were poorly reported and were minimal (flatulence, nausea, diarrhoea, abdominal pain) and non-serious, and withdrawals were not related to the study treatment. AUTHORS' CONCLUSIONS We found very few studies that adequately test biotic supplementation as alternative treatments for improving kidney function, GI symptoms, dialysis outcomes, allograft function, patient-reported outcomes, CVD, cancer, reducing uraemic toxins, and adverse effects. We are not certain whether synbiotics, prebiotics, or probiotics are more or less effective compared to one another, antibiotics, or standard care for improving patient outcomes in people with CKD. Adverse events were uncommon and mild.
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Affiliation(s)
- Tess E Cooper
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
| | - Rabia Khalid
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Samuel Chan
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
| | - Jonathan C Craig
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Carmel M Hawley
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
| | - Martin Howell
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - David W Johnson
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia
| | - Allison Jaure
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Armando Teixeira-Pinto
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
| | - Germaine Wong
- Sydney School of Public Health, The University of Sydney, Sydney, Australia
- Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- Centre for Transplant and Renal Research, Westmead Hospital, Westmead, Australia
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Martínez-Hernández SL, Muñoz-Ortega MH, Ávila-Blanco ME, Medina-Pizaño MY, Ventura-Juárez J. Novel Approaches in Chronic Renal Failure without Renal Replacement Therapy: A Review. Biomedicines 2023; 11:2828. [PMID: 37893201 PMCID: PMC10604533 DOI: 10.3390/biomedicines11102828] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/28/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open
Abstract
Chronic kidney disease (CKD) is characterized by renal parenchymal damage leading to a reduction in the glomerular filtration rate. The inflammatory response plays a pivotal role in the tissue damage contributing to renal failure. Current therapeutic options encompass dietary control, mineral salt regulation, and management of blood pressure, blood glucose, and fatty acid levels. However, they do not effectively halt the progression of renal damage. This review critically examines novel therapeutic avenues aimed at ameliorating inflammation, mitigating extracellular matrix accumulation, and fostering renal tissue regeneration in the context of CKD. Understanding the mechanisms sustaining a proinflammatory and profibrotic state may offer the potential for targeted pharmacological interventions. This, in turn, could pave the way for combination therapies capable of reversing renal damage in CKD. The non-replacement phase of CKD currently faces a dearth of efficacious therapeutic options. Future directions encompass exploring vaptans as diuretics to inhibit water absorption, investigating antifibrotic agents, antioxidants, and exploring regenerative treatment modalities, such as stem cell therapy and novel probiotics. Moreover, this review identifies pharmaceutical agents capable of mitigating renal parenchymal damage attributed to CKD, targeting molecular-level signaling pathways (TGF-β, Smad, and Nrf2) that predominate in the inflammatory processes of renal fibrogenic cells.
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Affiliation(s)
- Sandra Luz Martínez-Hernández
- Departamento de Microbiología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Ags, Mexico
| | - Martín Humberto Muñoz-Ortega
- Departamento de Química, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Ags, Mexico
| | - Manuel Enrique Ávila-Blanco
- Departamento de Morfología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Ags, Mexico
| | - Mariana Yazmin Medina-Pizaño
- Departamento de Morfología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Ags, Mexico
| | - Javier Ventura-Juárez
- Departamento de Morfología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Ags, Mexico
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22
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Mafra D, Kemp JA, Borges NA, Wong M, Stenvinkel P. Gut Microbiota Interventions to Retain Residual Kidney Function. Toxins (Basel) 2023; 15:499. [PMID: 37624256 PMCID: PMC10467110 DOI: 10.3390/toxins15080499] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/01/2023] [Accepted: 08/08/2023] [Indexed: 08/26/2023] Open
Abstract
Residual kidney function for patients with chronic kidney disease (CKD) is associated with better quality of life and outcome; thus, strategies should be implemented to preserve kidney function. Among the multiple causes that promote kidney damage, gut dysbiosis due to increased uremic toxin production and endotoxemia need attention. Several strategies have been proposed to modulate the gut microbiota in these patients, and diet has gained increasing attention in recent years since it is the primary driver of gut dysbiosis. In addition, medications and faecal transplantation may be valid strategies. Modifying gut microbiota composition may mitigate chronic kidney damage and preserve residual kidney function. Although various studies have shown the influential role of diet in modulating gut microbiota composition, the effects of this modulation on residual kidney function remain limited. This review discusses the role of gut microbiota metabolism on residual kidney function and vice versa and how we could preserve the residual kidney function by modulating the gut microbiota balance.
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Affiliation(s)
- Denise Mafra
- Graduate Program in Nutrition Sciences, Fluminense Federal University (UFF), Niteroi 24020-140, Brazil;
- Graduate Program in Biological Sciences—Physiology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
| | - Julie A. Kemp
- Graduate Program in Nutrition Sciences, Fluminense Federal University (UFF), Niteroi 24020-140, Brazil;
| | - Natalia A. Borges
- Institute of Nutrition, Rio de Janeiro State University (UERJ), Rio de Janeiro 20550-170, Brazil;
| | - Michelle Wong
- Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, BC V6T 1Z1, Canada;
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23
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Vacca M, Celano G, Calabrese FM, Rocchetti MT, Iacobellis I, Serale N, Calasso M, Gesualdo L, De Angelis M. In vivo evaluation of an innovative synbiotics on stage IIIb-IV chronic kidney disease patients. Front Nutr 2023; 10:1215836. [PMID: 37396126 PMCID: PMC10311028 DOI: 10.3389/fnut.2023.1215836] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 05/30/2023] [Indexed: 07/04/2023] Open
Abstract
Background Microbiota unbalance has been proven to affect chronic kidney disease (CKD) patients and, noteworthy, microbiota composition and activity are implicated in CKD worsening. The progression of kidney failure implies an exceeding accumulation of waste compounds deriving from the nitrogenous metabolism in the intestinal milieu. Therefore, in the presence of an altered intestinal permeability, gut-derived uremic toxins, i.e., indoxyl sulfate (IS) and p-cresyl sulfate (PCS), can accumulate in the blood. Methods In a scenario facing the nutritional management as adjuvant therapy, the present study assessed the effectiveness of an innovative synbiotics for its ability to modulate the patient gut microbiota and metabolome by setting a randomized, single-blind, placebo-controlled, pilot trial accounting for IIIb-IV stage CKD patients and healthy controls. Metataxonomic fecal microbiota and fecal volatilome were analyzed at the run-in, after 2 months of treatment, and after 1 month of wash out. Results Significant changes in microbiota profile, as well as an increase of the saccharolytic metabolism, in feces were found for those CKD patients that were allocated in the synbiotics arm. Conclusions Noteworthy, the here analyzed data emphasized a selective efficacy of the present synbiotics on a stage IIIb-IV CKD patients. Nonetheless, a further validation of this trial accounting for an increased patient number should be considered. Clinical trial registration https://clinicaltrials.gov/, identifier NCT03815786.
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Affiliation(s)
- Mirco Vacca
- Department of Soil Plant and Food Sciences, University of Bari, Bari, Italy
| | - Giuseppe Celano
- Department of Soil Plant and Food Sciences, University of Bari, Bari, Italy
| | | | | | - Ilaria Iacobellis
- Department of Soil Plant and Food Sciences, University of Bari, Bari, Italy
| | - Nadia Serale
- Department of Soil Plant and Food Sciences, University of Bari, Bari, Italy
| | - Maria Calasso
- Department of Soil Plant and Food Sciences, University of Bari, Bari, Italy
| | - Loreto Gesualdo
- Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Bari, Italy
| | - Maria De Angelis
- Department of Soil Plant and Food Sciences, University of Bari, Bari, Italy
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24
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Böhler H, Orth-Alampour S, Baaten C, Riedner M, Jankowski J, Beck T. Assembly of chemically modified protein nanocages into 3D materials for the adsorption of uremic toxins. J Mater Chem B 2022; 11:55-60. [PMID: 36504125 DOI: 10.1039/d2tb02386e] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hemodialysis fails to remove protein-bound uremic toxins that are attributed with high cardiovascular risk. Application of adsorption materials is a viable strategy, but suitable biocompatible adsorbents are still not available. Here, we demonstrate that adsorbents based on the bottom-up assembly of the intrinsically biocompatible protein cage ferritin are applicable for toxin adsorption. Due to the size-exclusion effect of its pores, only small molecules such as uremic toxins can enter the protein cage. Protein redesign techniques that target selectively the inner surface were used to introduce anchor sites for chemical modification. Porous crystalline adsorbents were fabricated by bottom-up assembly of the protein cage. Linkage of up to 96 phenylic or aliphatic molecules per container was verified by ESI-MS. Materials based on unmodified ferritin cages can already adsorb the uremic toxins. The adsorption capacity could be increased by about 50% through functionalization with hydrophobic molecules reaching 458 μg g-1 for indoxyl sulfate. The biohybrid materials show no contamination with endotoxins and do not activate blood platelets. These findings demonstrate the great potential of protein-based adsorbents for the clearance of uremic toxins: modifications enhance toxin adsorption without diminishing the biocompatibility of the final protein-based material.
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Affiliation(s)
- Hendrik Böhler
- Universität Hamburg, Department of Chemistry, Institute of Physical Chemistry, Grindelallee 117, Hamburg 20146, Germany.
| | - Setareh Orth-Alampour
- Universitätsklinikum Aachen, Institute for Molecular Cardiovascular Research IMCAR, Pauwelsstraße, 30, Aachen 52074, Germany
| | - Constance Baaten
- Universitätsklinikum Aachen, Institute for Molecular Cardiovascular Research IMCAR, Pauwelsstraße, 30, Aachen 52074, Germany.,Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht 6229 ER, The Netherlands
| | - Maria Riedner
- Universität Hamburg, Technology Platform Mass Spectrometry, Mittelweg 177, Hamburg 20148, Germany
| | - Joachim Jankowski
- Universitätsklinikum Aachen, Institute for Molecular Cardiovascular Research IMCAR, Pauwelsstraße, 30, Aachen 52074, Germany
| | - Tobias Beck
- Universität Hamburg, Department of Chemistry, Institute of Physical Chemistry, Grindelallee 117, Hamburg 20146, Germany. .,The Hamburg Centre of Ultrafast Imaging, Hamburg, Germany
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25
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The effects of synbiotics on indoxyl sulphate level, constipation, and quality of life associated with constipation in chronic haemodialysis patients: a randomized controlled trial. BMC Nephrol 2022; 23:259. [PMID: 35869437 PMCID: PMC9308250 DOI: 10.1186/s12882-022-02890-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 07/15/2022] [Indexed: 11/24/2022] Open
Abstract
Background Gut microbiota dysbiosis in patients with chronic kidney disease on haemodialysis (CKD-HD) creates an increase in proteolytic bacteria activity, leading to an increase in the production of uraemic toxins, such as indoxyl sulphate, worsening of constipation symptoms and reducing patients’ quality of life. Improving gut microbiota dysbiosis is expected to improve this condition. This study aimed to evaluate the effect of synbiotics on indoxyl sulphate levels, constipation symptoms, and constipation-related quality of life in haemodialysis patients. Methods This was a double-blinded randomized controlled clinical trial with a parallel design involving haemodialysis patients. We included chronic haemodialysis patients with gastrointestinal complaints, difficulty defecating, faeces with hard consistency, or a bowel movement frequency of fewer than three times per week. Patients were randomly divided into two groups (synbiotics (Lactobacillus acidophilus and Bifidobacterium longum 5x109 CFU) and placebo) for 60 days of oral intervention. All participants, caregivers, and outcome assessors were blinded to group assignment. The primary outcome was a decrease in indoxyl sulphate toxin levels. Meanwhile, improvement in constipation symptoms (measured using the Patient Assessment of Constipation: Symptoms (PAC-SYM) questionnaire) and improvement in constipation-related quality of life (measured using the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire) were assessed as secondary outcomes. Results We included 60 patients (30 intervention; median age of 51.23 (13.57) years, 33.3% male; 30 control; median age of 52.33 (11.29) years, 36.7% male). There was no significant difference in terms of pre- and postintervention indoxyl sulphate toxin levels in the synbiotics group compared to the placebo group (p=0.438). This study found an improvement in constipation symptoms (p = 0.006) and constipation-related quality of life (p=0.001) after synbiotic administration. Conclusion Two months of synbiotic supplementation did not lower indoxyl sulphate toxin levels. Nevertheless, it had a major effect in improving constipation and quality of life affected by constipation in patients undergoing chronic haemodialysis. Trial registration NCT04527640 (date of first registration: 26/08/2020) Supplementary Information The online version contains supplementary material available at 10.1186/s12882-022-02890-9.
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26
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Tian N, Li L, Ng JKC, Li PKT. The Potential Benefits and Controversies of Probiotics Use in Patients at Different Stages of Chronic Kidney Disease. Nutrients 2022; 14:4044. [PMID: 36235699 PMCID: PMC9571670 DOI: 10.3390/nu14194044] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 09/17/2022] [Accepted: 09/19/2022] [Indexed: 11/24/2022] Open
Abstract
The therapeutic modulation of the gut microbiome has been suggested to be one of the tools in the integrated management of chronic kidney disease (CKD) in recent years. Lactobacillus and Bifidobacterium genera are the two most commonly used probiotics strains. Most of the probiotics used in studies are mixed formulation. There is no consensus on the dose and duration of the probiotic administration for CKD patients Increasing evidence indicates that patients with early stage (1-2) CKD have an altered quantitative and qualitative microbiota profile. However, there was a dearth of prospective controlled studies on the use of probiotics in the early stage of the CKD population. The association between gut microbiota disturbance and advanced CKD was reported. Most randomized controlled trials on probiotic treatment used in CKD stage 3-5ND patients reported positive results. The metabolites of abnormal gut microbiota are directly involved in the pathogenetic mechanisms of cardiovascular disease and inflammation. We summarized 13 studies performed in the dialysis population, including 10 in hemodialysis (HD) patients and 3 in peritoneal dialysis (PD). Some controversial results were concluded on the decreasing plasma concentration of uremic toxin, symptoms, inflammation, and cardiovascular risk. Only three randomized controlled trials on PD were reported to show the potential beneficial effects of probiotics on inflammation, uremic toxins and gastrointestinal symptoms. There is still no standard in the dosage and duration of the use of probiotics in CKD patients. Overall, the probiotic administration may have potential benefit in improving symptoms and quality of life, reducing inflammation, and delaying the progression of kidney failure. Further research studies using a larger sample size with longer follow-up durations and a greater focus on clinical outcomes-including survival-are warranted to elucidate the significant clinical impact of the use of probiotics in CKD patients.
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Affiliation(s)
- Na Tian
- Department of Nephrology, General Hospital of Ningxia Medical University, Yinchuan 750004, China
| | - Lu Li
- Department of Nephrology, General Hospital of Ningxia Medical University, Yinchuan 750004, China
| | - Jack Kit-Chung Ng
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing St., Shatin, Hong Kong, China
- Carol and Richard Yu Peritoneal Dialysis Research Centre, The Chinese University of Hong Kong, Ngan Shing St., Shatin, Hong Kong, China
| | - Philip Kam-Tao Li
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing St., Shatin, Hong Kong, China
- Carol and Richard Yu Peritoneal Dialysis Research Centre, The Chinese University of Hong Kong, Ngan Shing St., Shatin, Hong Kong, China
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27
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Tan J, Zhou H, Deng J, Sun J, Zhou X, Tang Y, Qin W. Effectiveness of Microecological Preparations for Improving Renal Function and Metabolic Profiles in Patients With Chronic Kidney Disease. Front Nutr 2022; 9:850014. [PMID: 36172526 PMCID: PMC9510395 DOI: 10.3389/fnut.2022.850014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 02/28/2022] [Indexed: 12/02/2022] Open
Abstract
Background Determining whether microecological preparations, including probiotics, prebiotics, and synbiotics, are beneficial for patients with chronic kidney disease (CKD) has been debated. Moreover, determining which preparation has the best effect remains unclear. In this study, we performed a network meta-analysis of randomized clinical trials (RCTs) to address these questions. Methods MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials were searched. Eligible RCTs with patients with CKD who received intervention measures involving probiotics, prebiotics, and/or synbiotics were included. The outcome indicators included changes in renal function, lipid profiles, inflammatory factors, and oxidative stress factors. Results Twenty-eight RCTs with 1,373 patients were ultimately included. Probiotics showed greater effect in lowering serum creatinine [mean difference (MD) -0.21, 95% confidence interval (CI) -0.34, -0.09] and triglycerides (MD -9.98, 95% CI -19.47, -0.49) than the placebo, with the largest surface area under the cumulative ranking curve, while prebiotics and synbiotics showed no advantages. Probiotics were also able to reduce malondialdehyde (MDA) (MD -0.54, 95% CI -0.96, -0.13) and increase glutathione (MD 72.86, 95% CI 25.44, 120.29). Prebiotics showed greater efficacy in decreasing high-sensitivity C-reactive protein (MD -2.06, 95% CI -3.79, -0.32) and tumor necrosis factor-α (MD -2.65, 95% CI -3.91, -1.39). Synbiotics showed a partially synergistic function in reducing MDA (MD -0.66, 95% CI -1.23, -0.09) and high-sensitivity C-reactive protein (MD -2.01, 95% CI -3.87, -0.16) and increasing total antioxidant capacity (MD 145.20, 95% CI 9.32, 281.08). Conclusion The results indicated that microbial supplements improved renal function and lipid profiles and favorably affected measures of oxidative stress and inflammation in patients with CKD. After thorough consideration, probiotics provide the most comprehensive and beneficial effects for patients with CKD and might be used as the best choice for microecological preparations. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022295497, PROSPERO 2022, identifier: CRD42022295497.
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Affiliation(s)
- Jiaxing Tan
- Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Huan Zhou
- Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Jiaxin Deng
- Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Jiantong Sun
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Xiaoyuan Zhou
- West China School of Public Health, West China Forth Hospital of Sichuan University, Chengdu, China
| | - Yi Tang
- Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Wei Qin
- Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
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28
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Bartochowski P, Gayrard N, Bornes S, Druart C, Argilés A, Cordaillat-Simmons M, Duranton F. Gut–Kidney Axis Investigations in Animal Models of Chronic Kidney Disease. Toxins (Basel) 2022; 14:toxins14090626. [PMID: 36136564 PMCID: PMC9502418 DOI: 10.3390/toxins14090626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/01/2022] [Accepted: 09/01/2022] [Indexed: 11/16/2022] Open
Abstract
Chronic kidney disease (CKD) is an incurable disease in which renal function gradually declines, resulting in no noticeable symptoms during the early stages and a life-threatening disorder in the latest stage. The changes that accompany renal failure are likely to influence the gut microbiota, or the ecosystem of micro-organisms resident in the intestine. Altered gut microbiota can display metabolic changes and become harmful to the host. To study the gut–kidney axis in vivo, animal models should ideally reproduce the disorders affecting both the host and the gut microbiota. Murine models of CKD, but not dog, manifest slowed gut transit, similarly to patient. Animal models of CKD also reproduce altered intestinal barrier function, as well as the resulting leaky gut syndrome and bacterial translocation. CKD animal models replicate metabolic but not compositional changes in the gut microbiota. Researchers investigating the gut–kidney axis should pay attention to the selection of the animal model (disease induction method, species) and the setting of the experimental design (control group, sterilization method, individually ventilated cages) that have been shown to influence gut microbiota.
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Affiliation(s)
- Piotr Bartochowski
- RD Néphrologie SAS, 34090 Montpellier, France
- BC2M, Faculty of Pharmacy, University of Montpellier, 34090 Montpellier, France
| | - Nathalie Gayrard
- RD Néphrologie SAS, 34090 Montpellier, France
- BC2M, Faculty of Pharmacy, University of Montpellier, 34090 Montpellier, France
- Correspondence:
| | - Stéphanie Bornes
- Université Clermont Auvergne, Inrae, Vetagro Sup, UMRF0545, 15000 Aurillac, France
| | - Céline Druart
- Pharmabiotic Research Institute (PRI), 11100 Narbonne, France
| | - Angel Argilés
- RD Néphrologie SAS, 34090 Montpellier, France
- BC2M, Faculty of Pharmacy, University of Montpellier, 34090 Montpellier, France
| | | | - Flore Duranton
- RD Néphrologie SAS, 34090 Montpellier, France
- BC2M, Faculty of Pharmacy, University of Montpellier, 34090 Montpellier, France
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Chen L, Shi J, Ma X, Shi D, Qu H. Effects of Microbiota-Driven Therapy on Circulating Indoxyl Sulfate and P-Cresyl Sulfate in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Adv Nutr 2022; 13:1267-1278. [PMID: 34905018 PMCID: PMC9340978 DOI: 10.1093/advances/nmab149] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 11/03/2021] [Accepted: 12/02/2021] [Indexed: 12/16/2022] Open
Abstract
Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, exacerbate the deterioration of renal function and increase the risk of cardiovascular events in chronic kidney disease (CKD) patients. The effects of microbiota-driven therapy (probiotics, prebiotics, or synbiotics) on decreasing circulating IS and PCS concentrations are controversial; thus, we performed the present systematic review and meta-analysis to assess the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients. PubMed, EMBASE, and Cochrane Library databases were systematically searched from inception to 22 July, 2021, and randomized controlled trials (RCTs) investigating the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients were included. In all, 14 RCTs with 513 participants were eligible for the meta-analysis. The effects of microbiota-driven therapy on the circulating IS and PCS concentrations were evaluated with weighted mean differences (WMDs) measured by a fixed-effects model or a random-effects model. Compared with placebo, microbiota-driven therapy had no statistically significant effect on the circulating IS concentration (WMD: -1.64 mg/L; 95% CI: -3.46, 0.18 mg/L; P = 0.077) but it decreased the circulating PCS concentration (WMD: -2.42 mg/L; 95% CI: -3.81, -1.04 mg/L; P = 0.001). In the subgroup analyses, prebiotic (n = 6) and synbiotic (n = 3) supplementation significantly decreased the circulating PCS concentration, whereas probiotic (n = 3) supplementation did not. Meta-regression showed that the effects of microbiota-driven therapy were not associated with the supplementation time or the year of publication. Moreover, there was no significant evidence of publication bias. This review found that microbiota-driven therapy decreased the circulating PCS concentration in CKD patients. Additional large, well-designed RCTs with improved methodology and reporting are necessary to assess the effects of microbiota-driven therapy on circulating IS and PCS concentrations in the long term. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42021269146.
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Affiliation(s)
- Li Chen
- Xi yuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Peking University Traditional Chinese Medicine Clinical Medical School (Xi yuan), Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Junhe Shi
- Xi yuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaojuan Ma
- Xi yuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Dazhuo Shi
- Xi yuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Peking University Traditional Chinese Medicine Clinical Medical School (Xi yuan), Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Hua Qu
- Xi yuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
- National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Traditional Chinese Medicine, Beijing, China
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30
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Exploring the Probiotic Potential of Dairy Industrial-Relevant Lactobacilli. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12104989] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Usually, the search for new candidate probiotics starts from strain isolation, followed by genotypic and phenotypic characterisations. For the best candidates, the final selection criteria, i.e., an efficient biomass production and the survival to stressful conservation processes, may often represent a bottleneck. The aim of this study is to reverse this classic bottom-up approach, thereby evaluating the in vitro probiotic properties of microbes that are already commercialized and employed in the dairy sector. The major advantage of reversing the traditional scheme is to deal with strains that are already suitable for the scale-up at the industrial level. In this work, four lactobacilli strains were analysed, belonging to the species of Lactiplantibacillus plantarum (strains PLA and PLA2) and Lacticaseibacillus rhamnosus (strains PAR4 and RHM). Both L. plantarum strains showed the best survival under simulated oro-gastrointestinal stress; PLA and PAR4 had the strongest inhibitory activity against all the tested harmful bacteria, with the latter strain showing also the highest percentage of Caco-2 adhesion; RHM was the best biofilm producer on abiotic surface. Finally, cell-free surnatants from all the strain cultures exhibited anti-inflammatory action on THP-1 macrophages. For all the studied strains, it is possible to claim beneficial functional properties other than the technological ones for which they are already marketed. The possible use of the four strains in a mixture could represent a strategy to diversify and maximize their beneficial potential. Nonetheless, future studies are necessary to validate in vivo the observed beneficial properties and to evaluate any effect of the vehicle product on the probiotic aptitude.
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31
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De Mauri A, Carrera D, Bagnati M, Rolla R, Vidali M, Chiarinotti D, Pane M, Amoruso A, Del Piano M. Probiotics-Supplemented Low-Protein Diet for Microbiota Modulation in Patients with Advanced Chronic Kidney Disease (ProLowCKD): Results from a Placebo-Controlled Randomized Trial. Nutrients 2022; 14:1637. [PMID: 35458199 PMCID: PMC9025298 DOI: 10.3390/nu14081637] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 04/05/2022] [Accepted: 04/11/2022] [Indexed: 02/01/2023] Open
Abstract
The probiotics-supplemented low-protein diet in chronic kidney disease (ProLowCKD) was a single-centre, double-blind, placebo-controlled, randomised trial that was conducted to investigate whether the association between a low protein diet (LPD) and a new formulation of probiotics (Bifidobacterium longum and Lactobacillus reuteri) was effective at reducing traditional uremic, microbiota-derived, and proatherogenic toxins in sixty patients affected by advanced CKD. After 2 months of a LPD-a reduction in blood urea nitrogen (52 ± 17 vs. 46 ± 15 mg/dL, p = 0.003), total cholesterol (185 ± 41 vs. 171 ± 34 mg/dL, p = 0.001), and triglycerides (194 ± 148 vs. 161 ± 70 mg/dL, p = 0.03) was observed; 57 subjects were then randomized to receive probiotics or a placebo for the subsequent 3 months. A total of 27 patients in the placebo group showed increased serum values of total cholesterol (169 ± 36 vs. 185 ± 40 mg/dL, p = 0.01), LDL cholesterol (169 ± 36 vs. 185 ± 40 mg/dL, p = 0.02), lipoprotein-associated phospholipase A2 (155.4 ± 39.3 vs. 167.5 ± 51.4 nmol/mL/min, p = 0.006), and indoxyl-sulphate (30.1 ± 17.6 vs. 34.5 ± 20.2 μM, p = 0.026), while the 24 subjects in the probiotics group showed a trend in the reduction of microbiota toxins. A reduction of antihypertensive and diuretic medications was possible in the probiotics group. This study shows that associating probiotics to LPD may have an additional beneficial effect on the control and modulation of microbiota-derived and proatherogenic toxins in CKD patients.
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Affiliation(s)
- Andreana De Mauri
- Nephrology and Dialysis Unit, Maggiore della Carità University Hospital, 28100 Novara, Italy;
| | - Deborah Carrera
- Dietetic and Clinical Nutrition, Maggiore della Carità University Hospital, 28100 Novara, Italy;
| | - Marco Bagnati
- Clinical Chemistry Laboratory, Maggiore della Carità University Hospital, 28100 Novara, Italy; (M.B.); (R.R.)
| | - Roberta Rolla
- Clinical Chemistry Laboratory, Maggiore della Carità University Hospital, 28100 Novara, Italy; (M.B.); (R.R.)
- Department of Health Sciences, Amedeo Avogadro University of Eastern Piedmont, 28100 Novara, Italy
| | - Matteo Vidali
- Clinical Chemistry Unit, Fondazione IRCCS Ca’ Granda Maggiore Policlinico Hospital, 20122 Milano, Italy;
| | - Doriana Chiarinotti
- Nephrology and Dialysis Unit, Maggiore della Carità University Hospital, 28100 Novara, Italy;
| | - Marco Pane
- Research & Development, Probiotical Research Srl, 28100 Novara, Italy; (M.P.); (A.A.)
| | - Angela Amoruso
- Research & Development, Probiotical Research Srl, 28100 Novara, Italy; (M.P.); (A.A.)
| | - Mario Del Piano
- Past head of Clinical Research, Probiotical SpA, 28100 Novara, Italy;
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The Microbiome and Uremic Solutes. Toxins (Basel) 2022; 14:toxins14040245. [PMID: 35448854 PMCID: PMC9033124 DOI: 10.3390/toxins14040245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/07/2022] [Accepted: 03/23/2022] [Indexed: 02/05/2023] Open
Abstract
Uremic retention solutes, especially the protein-bound compounds, are toxic metabolites, difficult to eliminate with progressive renal functional decline. They are of particular interest because these uremic solutes are responsible for the pathogenesis of cardiovascular and chronic kidney diseases. Evidence suggests that the relation between uremic toxins, the microbiome, and its host is altered in patients with chronic kidney disease, with the colon’s motility, epithelial integrity, and absorptive properties also playing an important role. Studies found an alteration of the microbiota composition with differences in species proportion, diversity, and function. Since uremic toxins precursors are generated by the microbiota, multiple therapeutic options are currently being explored to address dysbiosis. While an oral adsorbent can decrease the transport of bacterial metabolites from the intestinal lumen to the blood, dietary measures, supplements (prebiotics, probiotics, and synbiotics), and antibiotics aim to target directly the gut microbiota composition. Innovative approaches, such as the modulation of bacterial enzymes, open new perspectives to decrease the plasma level of uremic toxins.
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Kocot AM, Jarocka-Cyrta E, Drabińska N. Overview of the Importance of Biotics in Gut Barrier Integrity. Int J Mol Sci 2022; 23:ijms23052896. [PMID: 35270039 PMCID: PMC8911280 DOI: 10.3390/ijms23052896] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/03/2022] [Accepted: 03/04/2022] [Indexed: 02/07/2023] Open
Abstract
Increased gut permeability is suggested to be involved in the pathogenesis of a growing number of disorders. The altered intestinal barrier and the subsequent translocation of bacteria or bacterial products into the internal milieu of the human body induce the inflammatory state. Gut microbiota maintains intestinal epithelium integrity. Since dysbiosis contributes to increased gut permeability, the interventions that change the gut microbiota and correct dysbiosis are suggested to also restore intestinal barrier function. In this review, the current knowledge on the role of biotics (probiotics, prebiotics, synbiotics and postbiotics) in maintaining the intestinal barrier function is summarized. The potential outcome of the results from in vitro and animal studies is presented, and the need for further well-designed randomized clinical trials is highlighted. Moreover, we indicate the need to understand the mechanisms by which biotics regulate the function of the intestinal barrier. This review is concluded with the future direction and requirement of studies involving biotics and gut barrier.
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Affiliation(s)
- Aleksandra Maria Kocot
- Department of Immunology and Food Microbiology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences in Olsztyn, Tuwima 10, 10-748 Olsztyn, Poland;
| | - Elżbieta Jarocka-Cyrta
- Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine, Collegium Medicum University of Warmia and Mazury, Regional Specialized Children’s Hospital, Żołnierska St. 18A, 10-561 Olsztyn, Poland;
| | - Natalia Drabińska
- Department of Chemistry and Biodynamics of Food, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland
- Correspondence:
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New Strategies for the Reduction of Uremic Toxins: How Much More We Know. Toxins (Basel) 2021; 13:toxins13120837. [PMID: 34941675 PMCID: PMC8706305 DOI: 10.3390/toxins13120837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 10/18/2021] [Accepted: 11/01/2021] [Indexed: 11/16/2022] Open
Abstract
The importance of uremic toxin (UTx) removal in chronic kidney disease (CKD) is an emerging topic in the literature, widely recognized over time as a strategy to slow-down the disease progression towards end-stage renal disease and, consequentely, the occurence of deleterious effects on cardiovascular (CV) system [...].
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Abstract
PURPOSE OF REVIEW Growing evidence show the importance of gut/kidney axis in renal diseases. Advances in gut microbiome sequencing, associated metabolites, detection of gut permeability and inflammation provide new therapeutic strategies targeting gut for kidney diseases and particularly for Immunoglobulin A (IgA) nephropathy (IgAN). RECENT FINDINGS The diversity and composition of gut flora have been recently deeply explored in kidney diseases. Modulation and depletion of microbiota in animal models allowed the understanding of molecular mechanisms involved in the crosstalk between gut, immune system and kidney. New clinical trials in order to positively modulate microbiota result in improvement of gastrointestinal disorders and inflammation in patients suffering with kidney diseases. SUMMARY The investigation of gut alterations in kidney diseases open new therapeutic strategies. In IgAN, targeted treatments for intestinal inflammation and modifications of gut microbiota seem promising.
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Affiliation(s)
- Renato C Monteiro
- INSERM UMR1149, Center of Research on Inflammation CRI, CNRS ERL8252
- Inflamex Laboratory of Excellence, Paris University
- Immunology Department, Bichat Hospital, AP-HP, DHU Apollo, Paris
| | - Laureline Berthelot
- Center of Research in Transplantation and Immunology CRTI, UMR1064, INSERM, Nantes University, Nantes, France
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Mafra D, Kalantar-Zadeh K, Moore LW. New Tricks for Old Friends: Treating Gut Microbiota of Patients With CKD. J Ren Nutr 2021; 31:433-437. [PMID: 34294553 DOI: 10.1053/j.jrn.2021.07.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 07/06/2021] [Indexed: 01/28/2023] Open
Affiliation(s)
- Denise Mafra
- Post Graduation Program in Medical Sciences and Post-Graduation Program in Cardiovascular Sciences, Federal University Fluminense, Rio de Janeiro, Brazil.
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology, Hypertension and Kidney Transplantation, University of California, Irvine, California
| | - Linda W Moore
- Department of Surgery, Houston Methodist Hospital, Houston, Texas
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