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1
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Wang Y, Chen Y, Xiao Z, Shi Y, Fu C, Cao Y. Fecal microbiota transplantation modulates myeloid-derived suppressor cells and attenuates renal fibrosis in a murine model. Ren Fail 2025; 47:2480749. [PMID: 40141007 PMCID: PMC11951334 DOI: 10.1080/0886022x.2025.2480749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 03/07/2025] [Accepted: 03/09/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Renal fibrosis is a hallmark of progressive chronic kidney disease (CKD), with emerging evidence linking gut microbiota dysbiosis to disease progression. Myeloid-derived suppressor cells (MDSCs) have demonstrated renoprotective effects, yet the impact of fecal microbiota transplantation (FMT) on MDSC-mediated modulation of renal fibrosis remains unclear. METHODS C57BL/6J mice underwent unilateral ureteral obstruction (UUO) to induce renal fibrosis, followed by FMT administration via gavage. Flow cytometry was used to quantify granulocytic (G-MDSCs) and monocytic (M-MDSCs) MDSC populations in peripheral blood, kidney, and spleen. To elucidate the role of MDSCs in FMT-mediated effects, MDSCs were depleted or adoptively transferred in vivo. Renal fibrosis severity and inflammatory cytokine expression were subsequently analyzed. RESULTS FMT altered MDSC distribution, increasing M-MDSC accumulation in the blood and kidney. This was associated with downregulation of proinflammatory cytokines and attenuation of renal fibrosis. Adoptive MDSC transfer similarly produced anti-inflammatory and antifibrotic effects, reinforcing their therapeutic role in FMT-mediated renal protection. CONCLUSIONS FMT enhances M-MDSC-mediated immunomodulation, reducing inflammation and renal fibrosis in UUO-induced CKD. These findings suggest a potential therapeutic strategy targeting the gut-kidney axis in CKD management.
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Affiliation(s)
- Yajie Wang
- Department of Nephrology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
- Anesthesia Laboratory and Training Center of Wannan Medical College, Wuhu, Anhui, China
- Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu, Anhui, China
| | - Yuye Chen
- Department of Nephrology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Zihao Xiao
- Department of Nephrology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Yuanhui Shi
- Department of Nephrology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Cong Fu
- Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Yuhan Cao
- Department of Nephrology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
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2
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Duan Y, Zhao LJ, Lu YT, Li J, Li SX. Crosstalk between kidney and bones: New perspective for modulating osteoporosis. Ageing Res Rev 2025; 109:102776. [PMID: 40389172 DOI: 10.1016/j.arr.2025.102776] [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: 12/27/2024] [Revised: 05/09/2025] [Accepted: 05/16/2025] [Indexed: 05/21/2025]
Abstract
Growing evidence indicates an interesting interplay between kidney and bone. The pathophysiological condition of the skeletal system is intricately associated with the normal functioning of the kidneys. This relationship is modulated by various factors, including calcium and phosphate, 1-α-hydroxylase, erythropoietin (EPO), klotho, fibroblast growth factor 23 (FGF23), bone morphogenetic protein-7 (BMP-7), and extracellular vesicles (EVs). These interactions are notably evident in conditions such as chronic kidney disease with bone mineral density (CKD-BMD), renal osteodystrophy (ROD), and osteoporosis (OP). Furthermore, innovative methodologies such as cell co-culture, organ-on-a-chip, single-cell sequencing, and spatial transcriptomics are highlighted as instrumental in advancing the study of inter-organ interactions. This review, grounded in the pathogenesis, diagnostic and therapeutic modalities, and pharmacological treatments of OP, synthesizes evidence from molecular biology to clinical perspectives. It aims to establish a foundation for the development of more complex and physiologically relevant in vitro models and to propose potential therapeutic strategies.
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Affiliation(s)
- Yan Duan
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China; Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha, Hunan 410208, PR China; Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, Hunan 410208, PR China
| | - Li-Juan Zhao
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China; Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha, Hunan 410208, PR China; Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, Hunan 410208, PR China; College of Biology and Food Engineering, Huai Hua University, Huaihua 418000, PR China
| | - Yu-Ting Lu
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China; Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha, Hunan 410208, PR China; Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, Hunan 410208, PR China; Department of Medicine, Guangxi University of Science and Technology, Liuzhou 545005, PR China
| | - Juan Li
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China; Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha, Hunan 410208, PR China; Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, Hunan 410208, PR China.
| | - Shun-Xiang Li
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China; Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, Changsha, Hunan 410208, PR China; Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, Hunan 410208, PR China.
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3
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Pereira IM, Pereira M, Lopes JA, Gameiro J. The gut microbiome as a potential therapeutic target in IgA nephropathy. Nephrol Dial Transplant 2025; 40:641-650. [PMID: 39663206 DOI: 10.1093/ndt/gfae274] [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: 10/18/2024] [Indexed: 12/13/2024] Open
Abstract
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and a leading cause of kidney failure, with limited treatment options available. The pathophysiology of IgAN remains unclear; however, recent studies suggest that genetic, epigenetic and environmental factors play significant roles. There is also strong evidence linking the gut microbiome to the development of IgAN. In this review, we will examine the relationship between the microbiome and the pathogenesis of IgAN, as well as its potential as a target for future therapeutic interventions.
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Affiliation(s)
- Inês Miguel Pereira
- Clínica Universitária de Nefrologia, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
| | - Marta Pereira
- Serviço de Nefrologia e Transplantação Renal, ULS Santa Maria, Lisboa, Portugal
| | - José António Lopes
- Clínica Universitária de Nefrologia, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
- Serviço de Nefrologia e Transplantação Renal, ULS Santa Maria, Lisboa, Portugal
| | - Joana Gameiro
- Clínica Universitária de Nefrologia, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
- Serviço de Nefrologia e Transplantação Renal, ULS Santa Maria, Lisboa, Portugal
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4
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Zhang S, Tang S, Liu Y, Xue B, Xie Q, Zhao L, Yuan H. Protein-bound uremic toxins as therapeutic targets for cardiovascular, kidney, and metabolic disorders. Front Endocrinol (Lausanne) 2025; 16:1500336. [PMID: 39931238 PMCID: PMC11808018 DOI: 10.3389/fendo.2025.1500336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 01/02/2025] [Indexed: 02/13/2025] Open
Abstract
Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic clinical condition characterized by pathological and physiological interactions among metabolic abnormalities, chronic kidney disease, and cardiovascular diseases, leading to multi-organ dysfunction and a higher incidence of cardiovascular endpoints. Traditional approaches to managing CKM syndrome risk are inadequate in these patients, necessitating strategies targeting specific CKM syndrome risk factors. Increasing evidence suggests that addressing uremic toxins and/or pathways induced by uremic toxins may reduce CKM syndrome risk and treat the disease. This review explores the interactions among heart, kidney, and metabolic pathways in the context of uremic toxins and underscores the significant role of uremic toxins as potential therapeutic targets in the pathophysiology of these diseases. Strategies aimed at regulating these uremic toxins offer potential avenues for reversing and managing CKM syndrome, providing new insights for its clinical diagnosis and treatment.
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Affiliation(s)
| | | | | | | | | | | | - Huijuan Yuan
- Department of Endocrinology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Zhengzhou, China
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5
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Li XJ, Shan QY, Wu X, Miao H, Zhao YY. Gut microbiota regulates oxidative stress and inflammation: a double-edged sword in renal fibrosis. Cell Mol Life Sci 2024; 81:480. [PMID: 39636415 PMCID: PMC11621299 DOI: 10.1007/s00018-024-05532-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/18/2024] [Accepted: 11/24/2024] [Indexed: 12/07/2024]
Abstract
Gut microbiota is a complex and dynamic system that plays critical roles in human health and various disease. Progressive chronic kidney disease (CKD) suggests that patients irreversibly progress to end-stage kidney disease and need renal replacement treatments, including dialysis and transplantation. Ample evidence indicates that local oxidative stress and inflammation play pivotal roles in the pathogenesis and progression of CKD and dysbiosis of gut microbiota. CKD is always accompanied by intestinal inflammation and oxidative stress, which lead to rapid systemic translocation of bacterial-derived uraemic toxins, including indoxyl sulphate, phenyl sulphate and indole-3-acetic acid, and the consequent development and aggravation of renal fibrosis. Although inflammation and oxidative stress have been extensively discussed, there is a paucity of reports on the effects of gut microbiota on renal fibrosis and gut microbiota mediation of oxidative stress and inflammation. This review provides an overview of gut microbiota on inflammation and oxidative stress in renal fibrosis, briefly discusses regulation of the gut flora using microecological preparations and natural products, such as resveratrol, curcumin and emodin as treatments for CKD, and provides a clear pathophysiological rationale for the design of promising therapeutic strategies.
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Affiliation(s)
- Xiao-Jun Li
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, 310053, Zhejiang, China
| | - Qi-Yuan Shan
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, 310053, Zhejiang, China
| | - Xin Wu
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, 310053, Zhejiang, China
| | - Hua Miao
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, 310053, Zhejiang, China.
| | - Ying-Yong Zhao
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, 310053, Zhejiang, China.
- State Key Laboratory of Kidney Diseases, First Medical Center of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
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Caillard P, Bennis Y, Boudot C, Chatelain D, Rybarczyk P, Boullier A, Poirot S, Titeca-Beauport D, Bodeau S, Choukroun G, Kamel S, Six I, Maizel J. Acute kidney disease in mice is associated with early cardiovascular dysfunction. Ren Fail 2024; 46:2415510. [PMID: 39422224 PMCID: PMC11492403 DOI: 10.1080/0886022x.2024.2415510] [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: 05/28/2024] [Revised: 09/16/2024] [Accepted: 10/07/2024] [Indexed: 10/19/2024] Open
Abstract
Acute kidney injury (AKI) and chronic kidney disease (CKD) are major health concerns due to their increasing incidence and high mortality. They are interconnected syndromes; AKI without recovery evolves into acute kidney disease (AKD), which can indicate an AKI-to-CKD transition. Both AKI and CKD are associated with a risk of long-term cardiovascular complications, but whether vascular and cardiac dysfunctions can occur as early as the AKD period has not been studied extensively. In a mouse model of kidney injury (KI) with non-recovery, we performed vasoreactivity and echocardiography analyses on days 15 (D15) and 45 (D45) after KI. We determined the concentrations of two major gut-derived protein-bound uremic toxins known to induce cardiovascular toxicity-indoxyl sulfate (IS) and para-cresyl sulfate (PCS)-and the levels of inflammation and contraction markers on D7, D15, and D45. Mice with KI showed acute tubular and interstitial kidney lesions on D7 and D15 and chronic glomerulosclerosis on D45. They showed significant impairment of aorta relaxation and systolic-diastolic heart function, both on D15 and D45. Such dysfunction was associated with downregulation of the expression of two contractile proteins, αSMA and SERCA2a, with a more pronounced effect on D15 than on D45. KI was also followed by a rapid increase in IS and PCS serum concentrations and the expression induction of pro-inflammatory cytokines and endothelial adhesion molecules in serum and cardiovascular tissues. Therefore, these results highlight that AKD leads to early cardiac and vascular dysfunctions. How these dysfunctions could be managed to prevent cardiovascular events deserves further study.
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Affiliation(s)
- Pauline Caillard
- Department of Nephrology, Dialysis and Transplantation, Amiens Medical Center, Amiens, France
- MP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, France
| | - Youssef Bennis
- MP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, France
- Department of Clinical Pharmacology, Amiens Medical Center, Amiens, France
| | - Cédric Boudot
- MP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, France
| | - Denis Chatelain
- Department of Anatomopathology, Amiens Medical Center, Amiens, France
| | - Pierre Rybarczyk
- Hauts-de-France Anatomopathology Institute (i-PatH), Amiens, France
| | - Agnès Boullier
- MP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, France
- Department of Clinical Biochemistry, Amiens Medical Center, Amiens, France
| | - Sabrina Poirot
- MP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, France
| | - Dimitri Titeca-Beauport
- Department of Nephrology, Dialysis and Transplantation, Amiens Medical Center, Amiens, France
- MP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, France
| | - Sandra Bodeau
- MP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, France
- Department of Clinical Pharmacology, Amiens Medical Center, Amiens, France
| | - Gabriel Choukroun
- Department of Nephrology, Dialysis and Transplantation, Amiens Medical Center, Amiens, France
- MP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, France
| | - Saïd Kamel
- MP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, France
- Department of Clinical Biochemistry, Amiens Medical Center, Amiens, France
| | - Isabelle Six
- MP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, France
| | - Julien Maizel
- MP3CV laboratory, UR UPJV 7517, University of Picardy Jules Verne, Amiens, France
- Department of Intensive Care Medicine, Amiens Medical Center, Amiens, France
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Tong Y, Guo S, Li T, Yang K, Gao W, Peng F, Zou X. Gut microbiota and renal fibrosis. Life Sci 2024; 357:123072. [PMID: 39307181 DOI: 10.1016/j.lfs.2024.123072] [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: 06/09/2024] [Revised: 09/13/2024] [Accepted: 09/18/2024] [Indexed: 09/27/2024]
Abstract
Renal fibrosis represents a critical pathological condition in the progression of renal dysfunction, characterized by aberrant accumulation of extracellular matrix (ECM) and structural alterations in renal tissue. Recent research has highlighted the potential significance of gut microbiota and demonstrated their influence on host health and disease mechanisms through the production of bioactive metabolites. This review examines the role of alterations in gut microbial composition and their metabolites in the pathophysiological processes underlying renal fibrosis. It delineates current therapeutic interventions aimed at modulating gut microbiota composition, encompassing dietary modifications, pharmacological approaches, and probiotic supplementation, while evaluating their efficacy in mitigating renal fibrosis. Through a comprehensive analysis of current research findings, this review enhances our understanding of the bidirectional interaction between gut microbiota and renal fibrosis, establishing a theoretical foundation for future research directions and potential clinical applications in this domain.
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Affiliation(s)
- Yinghao Tong
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China
| | - Shangze Guo
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China
| | - Ting Li
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China
| | - Kexin Yang
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China
| | - Wei Gao
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China
| | - Fujun Peng
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China
| | - Xiangyu Zou
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China.
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8
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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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Fan Y, Wang Y, Xiao H, Sun H. Advancements in understanding the role of intestinal dysbacteriosis mediated mucosal immunity in IgA nephropathy. BMC Nephrol 2024; 25:203. [PMID: 38907188 PMCID: PMC11191200 DOI: 10.1186/s12882-024-03646-3] [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: 04/14/2024] [Accepted: 06/18/2024] [Indexed: 06/23/2024] Open
Abstract
IgA nephropathy, presently recognized as the foremost primary glomerular disorder, emerges as a principal contributor to renal failure globally, with its pathogenesis yet to be fully elucidated. Extensive research has highlighted the critical role of gut microbiome in the onset and progression of IgA nephropathy, underscoring its importance in accurately delineating the disease's etiology. For example, gut microbiome dysbacteriosis can lead to the production of nephritogenic IgA1 antibodies, which form immune complexes that deposit in the kidneys, causing inflammation and damage. The gut microbiome, a source of numerous bioactive compounds, interacts with the host and plays a regulatory role in gut-immune axis modulation, earning it the moniker of the "second brain." Recent investigations have particularly emphasized a significant correlation between IgA nephropathy and gut microbiome dysbacteriosis. This article offers a detailed overview of the pathogenic mechanisms of IgA nephropathy, specifically focusing on elucidating how alterations in the gut microbiome are associated with anomalies in the intestinal mucosal system in IgA nephropathy. Additionally, it describes the possible influence of gut microbiome on recurrent IgA nephropathy following kidney transplantation. Furthermore, it compiles potential therapeutic interventions, offering both theoretical and practical foundations for the management of IgA nephropathy. Lastly, the challenges currently faced in the therapeutic approaches to IgA nephropathy are discussed.
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Affiliation(s)
- Yitao Fan
- The Second Clinical Medical College of Lanzhou University, Lanzhou, 730030, Gansu, China
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China
| | - Yan Wang
- The Second Clinical Medical College of Lanzhou University, Lanzhou, 730030, Gansu, China
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China
| | - Han Xiao
- The Second Clinical Medical College of Lanzhou University, Lanzhou, 730030, Gansu, China
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China
| | - Hui Sun
- The Second Clinical Medical College of Lanzhou University, Lanzhou, 730030, Gansu, China.
- Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China.
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Yang X, Cai S, Gong J, Zhang J, Lian M, Chen R, Zhou L, Bai P, Liu B, Zhuang M, Tan H, Xu J, Li M. Characterization of gut microbiota in patients with stage 3-4 chronic kidney disease: a retrospective cohort study. Int Urol Nephrol 2024; 56:1751-1762. [PMID: 38085410 DOI: 10.1007/s11255-023-03893-7] [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: 05/09/2023] [Accepted: 11/16/2023] [Indexed: 04/09/2024]
Abstract
PURPOSE Multiple factors, such as dietary patterns, pharmaceutical interventions, and exposure to harmful substances, possess the capacity to influence gut microbiota composition. Gut microbiota dysbiosis has emerged as a significant contributor to the progression of chronic kidney disease (CKD) and its associated complications. By comprehending the intricacies of the intestinal microbiota, this research endeavor holds the potential to offer novel perspectives on potential strategies for mitigating CKD progression. METHODS In this retrospective analysis, we assessed gut microbiota composition in CKD patients. Fecal samples were collected from a cohort of 44 patients with stage 3-4 CKD, alongside a control group consisting of 132 healthy volunteers. Subsequently, 16 s rDNA sequencing was conducted to examine the composition of the gut microbiota. RESULTS Our findings revealed significant alterations in the diversity of intestinal microbiota in fecal samples between patients with stage 3-4 CKD and healthy subjects. Among the 475 bacterial genera, 164 were shared, while 242 dominant genera were exclusive to healthy subjects and 69 to CKD stages 3-4 samples. Notably, healthy volunteers exhibited a prevalence of intestinal Firmicutes and Bacteroidetes, whereas stage 3-4 CKD patients displayed higher abundance of Proteobacteria and Actinobacteria. The presence of uncultured Coprobacillus sp. notably contributed to distinguishing between the two groups. ROC curve analysis identified distinct microbiota with superior diagnostic efficacy for discriminating stage 3-4 CKD patients from healthy individuals. Metabolic pathway analysis revealed differing dominant pathways between the two groups-the NADH dehydrogenase pathway in healthy individuals and the phosphate acetyltransferase pathway in stage 3-4 CKD patients. Moreover, the CKD cohort displayed a higher proportion of Gram-negative bacteria and facultative anaerobes. CONCLUSIONS In conclusion, our study underscores the profound influence of gut microbiota dysbiosis on CKD progression. The distinct microbial profiles observed in CKD patients highlight the potential efficacy of microbiota-based interventions in mitigating CKD advancement.
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Affiliation(s)
- Xiali Yang
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Shiying Cai
- Department of Nursing, Shenzhen Hospital of Southern Medical University, Shenzhen, 518101, People's Republic of China
- School of Nursing, Southern Medical University, Guangzhou, 510515, People's Republic of China
| | - Jinsheng Gong
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Jun Zhang
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Minling Lian
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Rufu Chen
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Linghui Zhou
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Peijin Bai
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Bo Liu
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Minting Zhuang
- Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China
| | - Honghong Tan
- Department of VIP Clinic, Shanghai East Hospital, Tongji University School of Medicine, No.150 Jimo Road, Shanghai, 200120, People's Republic of China.
| | - Juan Xu
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, Fujian Province, People's Republic of China.
| | - Meizhen Li
- Department of Nutrition, The First Affiliated Hospital of Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, Fujian Province, People's Republic of China.
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11
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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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12
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Samaey A, Vázquez-Castellanos JF, Caenepeel C, Evenepoel P, Vermeire S, Raes J, Knops N. Effects of fecal microbiota transplantation for recurrent Clostridium difficile infection in children on kidney replacement therapy: a pilot study. Pediatr Nephrol 2024; 39:1201-1212. [PMID: 37775582 DOI: 10.1007/s00467-023-06168-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 09/06/2023] [Accepted: 09/12/2023] [Indexed: 10/01/2023]
Abstract
BACKGROUND Recurrent Clostridium difficile infection (rCDI) is a rising problem in children with chronic diseases. Fecal microbiota transplantation (FMT) is a recent alternative for rCDI patients who do not respond to conventional treatment. FMT could have an additional positive effect on the intestinal dysbiosis and accumulation of uremic retention molecules (URM) associated with chronic kidney disease (CKD). Our aim was to investigate the clinical efficacy of FMT for rCDI in children with CKD together with the effect on dysbiosis and URM levels. METHODS We analyzed stool and blood samples before and until 3 months after FMT in 3 children between 4 and 8 years old with CKD and rCDI. The microbiome was analyzed by 16 s rRNA sequencing. URM were analyzed with ultra-performance liquid chromatography-tandem mass spectrometry. CRP and fecal calprotectin were analyzed as parameters for systemic and gut inflammation, respectively. RESULTS CDI resolved after FMT in all three without adverse events; one patient needed a second FMT. No significant effect on CRP and calprotectin was observed. Stool samples demonstrated a reduced richness and bacterial diversity which did not improve after FMT. We did observe a trend in the decrease of specific URM up to 3 months after FMT. CONCLUSION FMT is an effective treatment for rCDI in patients with CKD. Analysis of the microbiome showed an important intestinal dysbiosis that, besides a significant reduction in Clostridium difficile, did not significantly change after FMT. A trend for reduction was seen in some of the measured URM after FMT.
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Affiliation(s)
- An Samaey
- Department of Pediatric Nephrology and Solid Organ Transplantation, UZ Leuven, Leuven, Belgium.
| | - Jorge Francisco Vázquez-Castellanos
- Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium
- VIB-KU Leuven Center for Microbiology, Louvain, Belgium
| | - Clara Caenepeel
- Translational Research Center for Gastrointestinal Disorders (TARGID), UZ Leuven, Leuven, Belgium
| | - Pieter Evenepoel
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
- Laboratory of Nephrology, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium
| | - Séverine Vermeire
- Department of Gastroenterology &, Hepatology University Hospitals Leuven, and Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Jeroen Raes
- Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium
| | - Noël Knops
- Department of Pediatric Nephrology and Solid Organ Transplantation, UZ Leuven, Leuven, Belgium
- Department of Pediatrics, Groene Hart Ziekenhuis, Gouda, the Netherlands
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13
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Liu X, Liu M, Zhao M, Li P, Gao C, Fan X, Cai G, Lu Q, Chen X. Fecal microbiota transplantation for the management of autoimmune diseases: Potential mechanisms and challenges. J Autoimmun 2023; 141:103109. [PMID: 37690971 DOI: 10.1016/j.jaut.2023.103109] [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: 01/17/2023] [Revised: 08/17/2023] [Accepted: 08/28/2023] [Indexed: 09/12/2023]
Abstract
Autoimmune diseases (AIDs) are a series of immune-mediated lethal diseases featured by over-activated immune cells attacking healthy self-tissues and organs due to the loss of immune tolerance, which always causes severe irreversible systematical organ damage and threatens human health heavily. To date, there are still no definitive cures for the treatment of AIDs due to their pathogenesis has not been clearly understood. Besides, the current clinical treatments of AIDs majorly rely on glucocorticoids and immune suppressors, which can lead to serious side effects. In the past years, there are increasing studies demonstrating that an imbalance of gut microbiota is intimately related to the pathogenesis of various AIDs, shedding light on the development of therapeutics by targeting the gut microbiota for the management of AIDs. Among all the approaches targeting the gut microbiota, fecal microbiota transplantation (FMT) has attracted increasing interest, and it has been proposed as a possible strategy to intervene in the homeostasis of gut microbiota for the treatment of various diseases. However, despite the reported good curative effects and clinical studies conducted on FMT, the detailed mechanisms of FMT for the effective treatment of those diseases have not been figured out. To fully understand the mechanisms of the therapeutic effects of FMT on AIDs and improve the therapeutic efficacy of FMT treatment, a systematic review of this topic is necessary. Hence, in this review paper, the potential mechanisms of FMT for the treatment of various AIDs were summarized, including promotion, shaping, activation, or inhibition of the host immune system via the interactions between the microorganisms and the gut immune system, gut-brain, gut-liver, gut-kidney axis, and so on. Then, applications of FMT for the treatment of various AIDs were detailed presented. Finally, the current challenges and potential solutions for the development of FMT formulations and FMT therapeutics were comprehensively discussed.
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Affiliation(s)
- Xiaomin Liu
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China
| | - Mei Liu
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China
| | - Ming Zhao
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China; Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, 421142, PR China
| | - Ping Li
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China
| | - Changxing Gao
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China
| | - Xinyu Fan
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China
| | - Guangyan Cai
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China.
| | - Qianjin Lu
- Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, PR China; Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, 421142, PR China.
| | - Xiangmei Chen
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, PR China.
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14
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André C, Bodeau S, Kamel S, Bennis Y, Caillard P. The AKI-to-CKD Transition: The Role of Uremic Toxins. Int J Mol Sci 2023; 24:16152. [PMID: 38003343 PMCID: PMC10671582 DOI: 10.3390/ijms242216152] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 10/31/2023] [Accepted: 11/06/2023] [Indexed: 11/26/2023] Open
Abstract
After acute kidney injury (AKI), renal function continues to deteriorate in some patients. In a pro-inflammatory and profibrotic environment, the proximal tubules are subject to maladaptive repair. In the AKI-to-CKD transition, impaired recovery from AKI reduces tubular and glomerular filtration and leads to chronic kidney disease (CKD). Reduced kidney secretion capacity is characterized by the plasma accumulation of biologically active molecules, referred to as uremic toxins (UTs). These toxins have a role in the development of neurological, cardiovascular, bone, and renal complications of CKD. However, UTs might also cause CKD as well as be the consequence. Recent studies have shown that these molecules accumulate early in AKI and contribute to the establishment of this pro-inflammatory and profibrotic environment in the kidney. The objective of the present work was to review the mechanisms of UT toxicity that potentially contribute to the AKI-to-CKD transition in each renal compartment.
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Affiliation(s)
- Camille André
- Department of Clinical Pharmacology, Amiens Medical Center, 80000 Amiens, France; (S.B.); (Y.B.)
- GRAP Laboratory, INSERM UMR 1247, University of Picardy Jules Verne, 80000 Amiens, France
| | - Sandra Bodeau
- Department of Clinical Pharmacology, Amiens Medical Center, 80000 Amiens, France; (S.B.); (Y.B.)
- MP3CV Laboratory, UR UPJV 7517, University of Picardy Jules Verne, 80000 Amiens, France; (S.K.); (P.C.)
| | - Saïd Kamel
- MP3CV Laboratory, UR UPJV 7517, University of Picardy Jules Verne, 80000 Amiens, France; (S.K.); (P.C.)
- Department of Clinical Biochemistry, Amiens Medical Center, 80000 Amiens, France
| | - Youssef Bennis
- Department of Clinical Pharmacology, Amiens Medical Center, 80000 Amiens, France; (S.B.); (Y.B.)
- MP3CV Laboratory, UR UPJV 7517, University of Picardy Jules Verne, 80000 Amiens, France; (S.K.); (P.C.)
| | - Pauline Caillard
- MP3CV Laboratory, UR UPJV 7517, University of Picardy Jules Verne, 80000 Amiens, France; (S.K.); (P.C.)
- Department of Nephrology, Dialysis and Transplantation, Amiens Medical Center, 80000 Amiens, France
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15
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Lambert K, Rinninella E, Biruete A, Sumida K, Stanford J, Raoul P, Mele MC, Wang AYM, Mafra D. Targeting the Gut Microbiota in Kidney Disease: The Future in Renal Nutrition and Metabolism. J Ren Nutr 2023; 33:S30-S39. [PMID: 37632511 PMCID: PMC10872791 DOI: 10.1053/j.jrn.2022.12.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 10/05/2022] [Accepted: 12/10/2022] [Indexed: 08/28/2023] Open
Abstract
There is increasing interest in the therapeutic potential of manipulating the gut microbiome of patients with chronic kidney disease (CKD). This is because there is a substantial deviation from a balanced gut microbiota profile in CKD, with many deleterious downstream effects. Nutritional interventions such as plant-based diets with reduced animal protein intake and the use of probiotics, prebiotics, and synbiotics may alter the microbiome. This article aims to briefly describe what is known about the gut microbiome in patients with CKD, factors contributing to gut dysbiosis, and outline important evidence gaps. Future potential therapies, including restoring the microbiota with food and microbiota-based and metabolomic-based therapies, are also discussed.
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Affiliation(s)
- Kelly Lambert
- School of Medical, Indigenous, and Health Sciences, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, New South Wales, Australia.
| | - Emanuele Rinninella
- Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, Rome, Italy
| | - Annabel Biruete
- Department of Nutrition Science, Purdue University, West Lafayette, Indiana, USA, Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Keiichi Sumida
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Tennessee
| | - Jordan Stanford
- School of Medical, Indigenous, and Health Sciences, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, New South Wales, Australia
| | - Pauline Raoul
- Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Maria Cristina Mele
- Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Angela Yee-Moon Wang
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China
| | - Denise Mafra
- Professor, Graduate Program in Nutrition Sciences, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil
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16
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Pantazi AC, Kassim MAK, Nori W, Tuta LA, Mihai CM, Chisnoiu T, Balasa AL, Mihai L, Lupu A, Frecus CE, Lupu VV, Chirila SI, Badescu AG, Hangan LT, Cambrea SC. Clinical Perspectives of Gut Microbiota in Patients with Chronic Kidney Disease and End-Stage Kidney Disease: Where Do We Stand? Biomedicines 2023; 11:2480. [PMID: 37760920 PMCID: PMC10525496 DOI: 10.3390/biomedicines11092480] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/26/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023] Open
Abstract
The gut microbiota (GM) plays a vital role in human health, with increasing evidence linking its imbalance to chronic kidney disease and end-stage kidney disease. Although the exact methods underlying kidney-GM crosstalk are not fully understood, interventions targeting GM were made and lay in three aspects: diagnostic, predictive, and therapeutic interventions. While these interventions show promising results in reducing uremic toxins and inflammation, challenges remain in the form of patient-specific GM variability, potential side effects, and safety concerns. Our understanding of GMs role in kidney disease is still evolving, necessitating further research to elucidate the causal relationship and mechanistic interactions. Personalized interventions focusing on specific GM signatures could enhance patient outcomes. However, comprehensive clinical trials are needed to validate these approaches' safety, efficacy, and feasibility.
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Affiliation(s)
| | | | - Wassan Nori
- College of Medicine, Mustansiriyah University, Baghdad 10052, Iraq;
| | - Liliana Ana Tuta
- Faculty of Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania (L.A.T.)
- Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Cristina Maria Mihai
- Faculty of Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania (L.A.T.)
- Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Tatiana Chisnoiu
- Faculty of Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania (L.A.T.)
- Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Adriana Luminita Balasa
- Faculty of Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania (L.A.T.)
- Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Larisia Mihai
- Faculty of Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania (L.A.T.)
- Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Ancuta Lupu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Corina Elena Frecus
- Faculty of Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania (L.A.T.)
- Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Vasile Valeriu Lupu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Sergiu Ioachim Chirila
- Faculty of Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania (L.A.T.)
| | | | - Laurentiu-Tony Hangan
- Faculty of Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania (L.A.T.)
| | - Simona Claudia Cambrea
- Faculty of Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania (L.A.T.)
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17
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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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18
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Wang F, Li N, Ni S, Min Y, Wei K, Sun H, Fu Y, Liu Y, Lv D. The Effects of Specific Gut Microbiota and Metabolites on IgA Nephropathy-Based on Mendelian Randomization and Clinical Validation. Nutrients 2023; 15:nu15102407. [PMID: 37242290 DOI: 10.3390/nu15102407] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 05/02/2023] [Accepted: 05/19/2023] [Indexed: 05/28/2023] Open
Abstract
BACKGROUND Although recent research suggests that alterations in gut microbiota and metabolites play a critical role in the pathophysiology of immunoglobulin A nephropathy (IgAN), the causal relationship between specific intestinal flora and metabolites and the risk of IgAN remains unclear. METHOD This study employed Mendelian randomization (MR) to investigate the causal association between gut microbiota and IgAN. To explore potential associations between gut microbiota and various outcomes, four MR methods were applied: inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode. If the results of the four methods are inconclusive, we prefer the IVW as the primary outcome. Additionally, MR-Egger, MR-PRESSO-Global, and Cochrane's Q tests were used to detect heterogeneity and pleiotropy. The stability of MR findings was assessed using the leave-one-out approach, and the strength of the causal relationship between exposure and outcome was tested using Bonferroni correction. Additional clinical samples were utilized to validate the results of Mendelian randomization, and the outcomes were visualized through an ROC curve, confusion matrix, and correlation analysis. RESULT This study examined a total of 15 metabolites and 211 microorganisms. Among them, eight bacteria and one metabolite were found to be associated with the risk of IgAN (p < 0.05). The Bonferroni-corrected test reveals that only Class. Actinobacteria (OR: 1.20, 95% CI: 1.07-1.36, p = 0.0029) have a significant causal relationship with IgAN. According to Cochrane's Q test, there is no substantial heterogeneity across different single-nucleotide polymorphisms (p > 0.05). Furthermore, MR-Egger and MR-PRESSO-Global tests (p > 0.05) showed no evidence of pleiotropy. No reverse causal association was found between the risk of IgAN and microbiota or metabolites (p > 0.05). Clinical specimens demonstrated the effectiveness and accuracy of Actinobacteria in distinguishing IgAN patients from those with other glomerular diseases (AUC = 0.9, 95% CI: 0.78-1.00). Additionally, our correlation analysis revealed a potential association between Actinobacteria abundance and increased albuminuria (r = 0.85) and poorer prognosis in IgAN patients (p = 0.01). CONCLUSION Through MR analysis, we established a causal link between Actinobacteria and the incidence of IgAN. Moreover, clinical validation using fecal samples indicated that Actinobacteria might be associated with the onset and poorer prognosis of IgAN. This finding could provide valuable biomarkers for early, noninvasive detection of the disease and potential therapeutic targets in IgAN.
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Affiliation(s)
- Fang Wang
- Institute of Nephrology, Liyang Hospital of Chinese Medicine, Liyang 213300, China
- Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210000, China
| | - Ning Li
- Institute of Nephrology, Southeast University School of Medicine, Nanjing 210009, China
| | - Siming Ni
- Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210000, China
| | - Yu Min
- Department of Biotherapy and National Clinical Research Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Kang Wei
- Yangzhou People's Hospital, Yangzhou University, Yangzhou 225000, China
| | - Hongbin Sun
- Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210000, China
| | - Yuqi Fu
- Institute of Nephrology, Southeast University School of Medicine, Nanjing 210009, China
| | - Yalan Liu
- Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210000, China
| | - Dan Lv
- Institute of Nephrology, Liyang Hospital of Chinese Medicine, Liyang 213300, China
- Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210000, China
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19
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Franzin R, Stasi A, Caggiano G, Squiccimarro E, Losappio V, Fiorentino M, Alfieri C, Stallone G, Gesualdo L, Castellano G. Enhancing Immune Protection in Hemodialysis Patients: Role of the Polymethyl Methacrylate Membrane. Blood Purif 2023; 52 Suppl 1:49-61. [PMID: 37075738 PMCID: PMC10210079 DOI: 10.1159/000529971] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 02/07/2023] [Indexed: 04/21/2023]
Abstract
End-stage renal disease (ESRD) is characterized by deep disorders in both innate and adaptive immune systems that imply unbalance deactivation and immunosuppression. The central, widely recognized factors responsible for this immune dysregulation are uremia, uremic toxin retention, hemodialysis membrane biocompatibility, and related cardiovascular complications. Recently, several studies strengthened the concept that dialysis membranes are not considered as a simple diffusive/adsorptive device but as a platform to personalize a dialysis approach to improve the quality of life of ESRD patients. Therefore, understanding of the molecules associated with altered immune response is crucial and could lead to therapeutically intervention or adaptation of the dialysis procedure itself for the management of immunological dysfunction of ESRD patients. The polymethyl methacrylate (PMMA)-based membrane is characterized by a symmetrical structure with large-sized pores, providing a better hydrophobic and cationic adsorption capacity compared to the other synthetic membranes. Together with hydrophobic interactions, the high adsorption rate of cytokines (i.e., IL-6) can also be enhanced by the size of nano-pores placed on the membrane surface. PMMA membranes exhibit adsorptive properties for a large amount of uremic toxins including p-cresol and indoxyl sulfate, as well as β2-microglobulin characterized by higher molecular weight, maintaining the diffusive clearance of small molecules like urea with a great biocompatibility. Besides exerting a strong anti-inflammatory effects in line with the improvement of immune responses in patients undergoing dialysis, PMMA also plays a role in modulating adaptive immune response, i.e., can clear blood from soluble CD40, a natural antagonist of the CD40/CD40L signaling that acts inhibiting immunoglobulin production by B cells. This review provides an overview of the main concepts and current understanding of immune dysfunction in hemodialysis and summarizes the recent findings regarding PMMA-based dialysis as potential strategy to restore immune balance in ESRD patients.
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Affiliation(s)
- Rossana Franzin
- Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, Bari, Italy
| | - Alessandra Stasi
- Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, Bari, Italy
| | - Gianvito Caggiano
- Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, Bari, Italy
| | - Elena Squiccimarro
- Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, Bari, Italy
| | - Vincenzo Losappio
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Science, University of Foggia, Foggia, Italy
| | - Marco Fiorentino
- Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, Bari, Italy
| | - Carlo Alfieri
- Unit of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Giovanni Stallone
- Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Science, University of Foggia, Foggia, Italy
| | - Loreto Gesualdo
- Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, Bari, Italy
| | - Giuseppe Castellano
- Unit of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
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20
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Abstract
Homeostasis is a prerequisite for health. When homeostasis becomes disrupted, dysfunction occurs. This is especially the case for the gut microbiota, which under normal conditions lives in symbiosis with the host. As there are as many microbial cells in and on our body as human cells, it is unlikely they would not contribute to health or disease. The gut bacterial metabolism generates numerous beneficial metabolites but also uremic toxins and their precursors, which are transported into the circulation. Barrier function in the intestine, the heart, and the kidneys regulates metabolite transport and concentration and plays a role in inter-organ and inter-organism communication via small molecules. This communication is analyzed from the perspective of the remote sensing and signaling theory, which emphasizes the role of a large network of multispecific, oligospecific, and monospecific transporters and enzymes in regulating small-molecule homeostasis. The theory provides a systems biology framework for understanding organ cross talk and microbe-host communication involving metabolites, signaling molecules, nutrients, antioxidants, and uremic toxins. This remote small-molecule communication is critical for maintenance of homeostasis along the gut-heart-kidney axis and for responding to homeostatic perturbations. Chronic kidney disease is characterized by gut dysbiosis and accumulation of toxic metabolites. This slowly impacts the body, affecting the cardiovascular system and contributing to the progression of kidney dysfunction, which in its turn influences the gut microbiota. Preserving gut homeostasis and barrier functions or restoring gut dysbiosis and dysfunction could be a minimally invasive way to improve patient outcomes and quality of life in many diseases, including cardiovascular and kidney disease.
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Affiliation(s)
- Griet Glorieux
- Nephrology Unit, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Gent, Belgium (G.G., R.V., F.V.)
| | - Sanjay K Nigam
- Department of Pediatrics (S.K.N.), University of California San Diego, La Jolla, CA
- Division of Nephrology, Department of Medicine (S.K.N.), University of California San Diego, La Jolla, CA
| | - Raymond Vanholder
- Nephrology Unit, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Gent, Belgium (G.G., R.V., F.V.)
| | - Francis Verbeke
- Nephrology Unit, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Gent, Belgium (G.G., R.V., F.V.)
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21
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Caggiano G, Amodio L, Stasi A, Colabufo NA, Colangiulo S, Pesce F, Gesualdo L. Gut-Derived Uremic Toxins in CKD: An Improved Approach for the Evaluation of Serum Indoxyl Sulfate in Clinical Practice. Int J Mol Sci 2023; 24:5142. [PMID: 36982216 PMCID: PMC10049313 DOI: 10.3390/ijms24065142] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/26/2023] [Accepted: 03/01/2023] [Indexed: 03/10/2023] Open
Abstract
In the past years, indoxyl sulfate has been strongly implicated in kidney disease progression and contributed to cardiovascular morbidity. Moreover, as a result of its elevated albumin affinity rate, indoxyl sulfate is not adequately cleared by extracorporeal therapies. Within this scenario, although LC-MS/MS represents the conventional approach for IS quantification, it requires dedicated equipment and expert skills and does not allow real-time analysis. In this pilot study, we implemented a fast and simple technology designed to determine serum indoxyl sulfate levels that can be integrated into clinical practice. Indoxyl sulfate was detected at the time of enrollment by Tandem MS from 25 HD patients and 20 healthy volunteers. Next, we used a derivatization reaction to transform the serum indoxyl sulfate into Indigo blue. Thanks to the spectral shift to blue, its quantity was measured by the colorimetric assay at a wavelength of 420-450 nm. The spectrophotometric analysis was able to discriminate the levels of IS between healthy subjects and HD patients corresponding to the LC-MS/MS. In addition, we found a strong linear relationship between indoxyl sulfate levels and Indigo levels between the two methods (Tandem MS and spectrophotometry). This innovative method in the assessment of gut-derived indoxyl sulfate could represent a valid tool for clinicians to monitor CKD progression and dialysis efficacy.
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Affiliation(s)
- Gianvito Caggiano
- Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, 70122 Bari, Italy
| | - Loredana Amodio
- Biofordrug S.R.L., University of Bari Spin-Off, 70019 Triggiano, Italy
| | - Alessandra Stasi
- Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, 70122 Bari, Italy
| | - Nicola Antonio Colabufo
- Biofordrug S.R.L., University of Bari Spin-Off, 70019 Triggiano, Italy
- Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70122 Bari, Italy
| | | | - Francesco Pesce
- Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, 70122 Bari, Italy
| | - Loreto Gesualdo
- Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, 70122 Bari, Italy
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22
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Sumida K, Pierre JF, Yuzefpolskaya M, Colombo PC, Demmer RT, Kovesdy CP. Gut Microbiota-Targeted Interventions in the Management of Chronic Kidney Disease. Semin Nephrol 2023; 43:151408. [PMID: 37619529 PMCID: PMC10783887 DOI: 10.1016/j.semnephrol.2023.151408] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/26/2023]
Abstract
Recent advances in microbiome research have informed the potential role of the gut microbiota in the regulation of metabolic, cardiovascular, and renal systems, and, when altered, in the pathogenesis of various cardiometabolic disorders, including chronic kidney disease (CKD). The improved understanding of gut dysbiosis in cardiometabolic pathologies in turn has led to a vigorous quest for developing therapeutic strategies. These therapeutic strategies aim to investigate whether interventions targeting gut dysbiosis can shift the microbiota toward eubiosis and if these shifts, in turn, translate into improvements in (or prevention of) CKD and its related complications, such as premature cardiovascular disease. Existing evidence suggests that multiple interventions (eg, plant-based diets; prebiotic, probiotic, and synbiotic supplementation; constipation treatment; fecal microbiota transplantation; and intestinal dialysis) might result in favorable modulation of the gut microbiota in patients with CKD, and thereby potentially contribute to improving clinical outcomes in these patients. In this review, we summarize the current understanding of the characteristics and roles of the gut microbiota in CKD and discuss the potential of emerging gut microbiota-targeted interventions in the management of CKD.
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Affiliation(s)
- Keiichi Sumida
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN.
| | - Joseph F Pierre
- Department of Nutritional Sciences, College of Agriculture and Life Science, University of Wisconsin-Madison, Madison, WI
| | - Melana Yuzefpolskaya
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York, NY
| | - Paolo C Colombo
- Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York, NY
| | - Ryan T Demmer
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY
| | - Csaba P Kovesdy
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN
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23
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Das S, Gnanasambandan R. Intestinal microbiome diversity of diabetic and non-diabetic kidney disease: Current status and future perspective. Life Sci 2023; 316:121414. [PMID: 36682521 DOI: 10.1016/j.lfs.2023.121414] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 01/09/2023] [Accepted: 01/17/2023] [Indexed: 01/21/2023]
Abstract
A significant portion of the health burden of diabetic kidney disease (DKD) is caused by both type 1 and type 2 diabetes which leads to morbidity and mortality globally. It is one of the most common diabetic complications characterized by loss of renal function with high prevalence, often leading to acute kidney disease (AKD). Inflammation triggered by gut microbiota is commonly associated with the development of DKD. Interactions between the gut microbiota and the host are correlated in maintaining metabolic and inflammatory homeostasis. However, the fundamental processes through which the gut microbiota affects the onset and progression of DKD are mainly unknown. In this narrative review, we summarised the potential role of the gut microbiome, their pathogenicity between diabetic and non-diabetic kidney disease (NDKD), and their impact on host immunity. A well-established association has already been seen between gut microbiota, diabetes and kidney disease. The gut-kidney interrelationship is confirmed by mounting evidence linking gut dysbiosis to DKD, however, it is still unclear what is the real cause of gut dysbiosis, the development of DKD, and its progression. In addition, we also try to distinguish novel biomarkers for early detection of DKD and the possible therapies that can be used to regulate the gut microbiota and improve the host immune response. This early detection and new therapies will help clinicians for better management of the disease and help improve patient outcomes.
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Affiliation(s)
- Soumik Das
- School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India
| | - Ramanathan Gnanasambandan
- School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India.
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24
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Gut microbiome studies in CKD: opportunities, pitfalls and therapeutic potential. Nat Rev Nephrol 2023; 19:87-101. [PMID: 36357577 DOI: 10.1038/s41581-022-00647-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/17/2022] [Indexed: 11/12/2022]
Abstract
Interest in gut microbiome dysbiosis and its potential association with the development and progression of chronic kidney disease (CKD) has increased substantially in the past 6 years. In parallel, the microbiome field has matured considerably as the importance of host-related and environmental factors is increasingly recognized. Past research output in the context of CKD insufficiently considered the myriad confounding factors that are characteristic of the disease. Gut microbiota-derived metabolites remain an interesting therapeutic target to decrease uraemic (cardio)toxicity. However, future studies on the effect of dietary and biotic interventions will require harmonization of relevant readouts to enable an in-depth understanding of the underlying beneficial mechanisms. High-quality standards throughout the entire microbiome analysis workflow are also of utmost importance to obtain reliable and reproducible results. Importantly, investigating the relative composition and abundance of gut bacteria, and their potential association with plasma uraemic toxins levels is not sufficient. As in other fields, the time has come to move towards in-depth quantitative and functional exploration of the patient's gut microbiome by relying on confounder-controlled quantitative microbial profiling, shotgun metagenomics and in vitro simulations of microorganism-microorganism and host-microorganism interactions. This step is crucial to enable the rational selection and monitoring of dietary and biotic intervention strategies that can be deployed as a personalized intervention in CKD.
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25
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Liver Microbiome in Healthy Rats: The Hidden Inhabitants of Hepatocytes. Cell Microbiol 2023. [DOI: 10.1155/2023/7369034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The tumor and tissue microbiota of human beings have recently been investigated. Gut permeability is known as a possible resource for the positive detection of tissue bacteria. Herein, we report that microbiota were detected in high abundance in the hepatocytes of healthy rats and that they were shared with the gut microbiota to an extent. We assessed male Sprague Dawley (SD) rats for the 16S ribosomal ribonucleic acid (rRNA) gene. After the rats were sacrificed by blood drainage from the portal vein, we extracted total deoxyribonucleic acid (DNA) from their ileal and colonic contents and liver tissues. The V3–V4 region of the 16S rRNA gene was amplified by polymerase chain reaction (PCR) and sequenced using an Illumina HiSeq 2500 platform. Sequences were assigned taxonomically by the SILVA database. We also detected bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA) in situ using immunofluorescence (IF) and western blotting and the 16S rRNA gene using fluorescent in situ hybridization (FISH). In the livers of six rats, we detected
effective tags of the 16S rRNA gene and clustered them into 1003 kinds of operational taxonomic units (OTUs;
, 729–893). Rats showed conservation of bacterial richness, abundance, and evenness. LPS and the 16S rRNA gene were detected in the nuclei of hepatocytes. The main function composition of the genomes of annotated bacteria was correlated with metabolism (
). Gram negativity was about 1.6 times higher than gram positivity. The liver microbiome was shared with both the small and large intestines but showed significantly higher richness and evenness than the gut microbiome, and the β-diversity results showed that the liver microbiome exhibited significantly higher similarity than the small and large intestines (
). Our results suggest that the bacteria in the liver microbiome are hidden intracellular inhabitants in healthy rat livers.
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26
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Caggiano G, Stasi A, Franzin R, Fiorentino M, Cimmarusti MT, Deleonardis A, Palieri R, Pontrelli P, Gesualdo L. Fecal Microbiota Transplantation in Reducing Uremic Toxins Accumulation in Kidney Disease: Current Understanding and Future Perspectives. Toxins (Basel) 2023; 15:toxins15020115. [PMID: 36828429 PMCID: PMC9965504 DOI: 10.3390/toxins15020115] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/21/2023] [Accepted: 01/27/2023] [Indexed: 02/04/2023] Open
Abstract
During the past decades, the gut microbiome emerged as a key player in kidney disease. Dysbiosis-related uremic toxins together with pro-inflammatory mediators are the main factors in a deteriorating kidney function. The toxicity of uremic compounds has been well-documented in a plethora of pathophysiological mechanisms in kidney disease, such as cardiovascular injury (CVI), metabolic dysfunction, and inflammation. Accumulating data on the detrimental effect of uremic solutes in kidney disease supported the development of many strategies to restore eubiosis. Fecal microbiota transplantation (FMT) spread as an encouraging treatment for different dysbiosis-associated disorders. In this scenario, flourishing studies indicate that fecal transplantation could represent a novel treatment to reduce the uremic toxins accumulation. Here, we present the state-of-the-art concerning the application of FMT on kidney disease to restore eubiosis and reverse the retention of uremic toxins.
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27
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Liu X, Zhang M, Wang X, Liu P, Wang L, Li Y, Wang X, Ren F. Fecal microbiota transplantation restores normal fecal composition and delays malignant development of mild chronic kidney disease in rats. Front Microbiol 2022; 13:1037257. [PMID: 36532422 PMCID: PMC9748282 DOI: 10.3389/fmicb.2022.1037257] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 11/15/2022] [Indexed: 09/29/2023] Open
Abstract
Chronic kidney disease (CKD) is associated with gut microbiome dysbiosis, but the role of intestinal flora in CKD treatment remains to be elucidated. Fecal microbiota transplantation (FMT) can be utilized to re-establish healthy gut microbiota for a variety of diseases, which offers new insight for treating CKD. First, 5/6 nephrectomy rats (Donor CKD) and sham rats (Donor Sham) were used as donors for FMT, and fecal metagenome were analyzed to explore potential therapeutic targets. Then, to assess the effect of FMT on CKD, sterilized 1/2 nephrectomy rats were transplanted with fecal microbiota from Donor sham (CKD/Sham) or Donor CKD (CKD/CKD) rats, and 1/2 nephrectomy rats without FMT (CKD) or no nephrectomy (Sham) were used as model control or normal control. Results showed that Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 were enriched in Donor CKD, while Lactobacillus johnsonii and Lactobacillus intestinalis were reduced. In addition, the increased abundance of microbial functions included tryptophan metabolism and lysine degradation contributing to the accumulation of protein-bound uremic toxins (PBUTs) in Donor CKD. Genome analysis indicated that FMT successfully differentiated groups of gut microbes and altered specific gut microbiota after 1 week of treatment, with Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 increasing in CKD/CKD group as well as Lactobacillus johnsonii and Lactobacillus intestinalis being improved in CKD/Sham group. In comparison to CKD group, substantial PBUT buildup and renal damage were observed in CKD/CKD. Interestingly, compared to CKD or CKD/CKD group, tryptophan metabolism and lysine degradation were efficiently suppressed in CKD/Sham group, while lysine biosynthesis was promoted. Therefore, FMT considerably reduced PBUTs accumulation. After FMT, PBUTs and renal function in CKD/Sham rats remained the same as in Sham group throughout the experimental period. In summary, FMT could delay the malignant development of CKD by modifying microbial amino acid metabolism through altering the microenvironment of intestinal flora, thereby providing a novel potential approach for treating CKD.
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Affiliation(s)
- Xiaoxue Liu
- Key Laboratory of Functional Dairy, Co-Constructed by Ministry of Education and Beijing Municipality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Ming Zhang
- School of Food and Chemical Engineering, Beijing Technology and Business University, Beijing, China
| | - Xifan Wang
- Key Laboratory of Functional Dairy, Co-Constructed by Ministry of Education and Beijing Municipality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Ping Liu
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Longjiao Wang
- Key Laboratory of Functional Dairy, Co-Constructed by Ministry of Education and Beijing Municipality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Yixuan Li
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Xiaoyu Wang
- Key Laboratory of Functional Dairy, Co-Constructed by Ministry of Education and Beijing Municipality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Fazheng Ren
- Key Laboratory of Functional Dairy, Co-Constructed by Ministry of Education and Beijing Municipality, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
- Food Laboratory of Zhongyuan, Luohe, Henan, China
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28
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Koppe L, Soulage CO. The impact of dietary nutrient intake on gut microbiota in the progression and complications of chronic kidney disease. Kidney Int 2022; 102:728-739. [PMID: 35870642 DOI: 10.1016/j.kint.2022.06.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 06/02/2022] [Accepted: 06/10/2022] [Indexed: 11/29/2022]
Abstract
Chronic kidney disease (CKD) has been associated with changes in the function and composition of the gut microbiota. The ecosystem of the human gut consists of trillions of microorganisms forming an authentic metabolically active organ that is fueled by nutrients to produce bioactive compounds. These microbiota-derived metabolites may be protective for kidney function (e.g. short-chain fatty acids from fermentation of dietary fibers) or deleterious (e.g. gut-derived uremic toxins such as trimethylamine N-oxide, p-cresyl sulfate, and indoxyl sulfate from fermentation of amino acids). Although diet is the cornerstone of the management of the patient with CKD, it remains a relatively underused component of the clinician's armamentarium. In this review, we describe the latest advances in understanding diet-microbiota crosstalk in a uremic context, and how this communication might contribute to CKD progression and complications. We then discuss how this knowledge could be harnessed for personalized nutrition strategies to prevent patients with CKD progressing to end-stage kidney disease and its detrimental consequences.
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Affiliation(s)
- Laetitia Koppe
- Department of Nephrology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, F-69495 Pierre-Bénite, France; Univ. Lyon, CarMeN lab, INSA-Lyon, INSERM U1060, INRA, Université Claude Bernard Lyon 1, F-69621 Villeurbanne, France.
| | - Christophe O Soulage
- Univ. Lyon, CarMeN lab, INSA-Lyon, INSERM U1060, INRA, Université Claude Bernard Lyon 1, F-69621 Villeurbanne, France
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29
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Dobrek Ł. POTENTIAL THERAPEUTIC OPTIONS TARGETING THE GUT DYSBIOSIS IN CHRONIC KIDNEY DISEASE. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2022; 75:1757-1764. [PMID: 35962694 DOI: 10.36740/wlek202207127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The gut microbiota plays an important physiological role in controlling not only the function of the gastrointestinal tract, but also in maintaining systemic homeostasis. Quantitative and /or qualitative disturbances of the gut microbiota (dysbiosis) are an important element in the complex pathogenesis of many diseases, including chronic kidney disease (CKD). In the disease, the mutual interactions between disturbed gut microbiota and the progression of CKD (pathophysiological "kidney-gut axis") have been demonstrated. The kidney failure causes water and nitrogen waste retention which leads to disturbances of motility, secretion and absorption in the gastrointestinal tract. These abnormalities contribute to the development of gut dysbiosis, accompanied by overproduction of toxic bacterial metabolites, with their translocation to the peripheral blood and development of endotoxemia. As a consequence, chronic kidney "low-grade" inflammation and oxidative stress develop, with further deterioration of kidney function in the mechanism of the "vicious cycle" of the kidney-gut axis. Considering the key role of gut dysbiosis and the kidney-gut axis, the attempts to restore the gut eubiosis seem to have an important role in the treatment of CKD and may be even regarded as a form of causal therapeutic intervention. The paper briefly discusses the basics of the pathophysiological kidney-gut axis in CKD and potential methods of modulating the abnormal gut microbiota in this disease, including the use of probiotic or prebiotic preparations, agents that absorb bacterial-derived toxins in the intestinal lumen, fecal microbiota transplantation and drugs used so far for other indications (acarbose, meclofenamate, lubiprostone).
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Affiliation(s)
- Łukasz Dobrek
- DEPARTMENT OF CLINICAL PHARMACOLOGY, WROCLAW MEDICAL UNIVERSITY, WROCLAW, POLAND
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30
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Chen R, Zhu D, Yang R, Wu Z, Xu N, Chen F, Zhang S, Chen H, Li M, Hou K. Gut microbiota diversity in middle-aged and elderly patients with end-stage diabetic kidney disease. ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:750. [PMID: 35957707 PMCID: PMC9358493 DOI: 10.21037/atm-22-2926] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 07/05/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD), but the mechanism between DKD and ESRD remains unclear. Some experts have put forward the "microbial-centered ESRD development theory", believing that the bacterial load caused by gut microecological imbalance and uremia toxin transfer are the core pathogenic links. The purpose of this study was to analyze the genomic characteristics of gut microbiota in patients with ESRD, specifically DKD or non-diabetic kidney disease (NDKD). METHODS In this cross-sectional study, patients with ESRD were recruited in a community, including 22 DKD patients and 22 NDKD patients matched using gender and age. Fecal samples of patients were collected for 16S rDNA sequencing and gut microbiota analysis. The distribution structure, diversity, and abundance of microflora in DKD patients were analyzed by constructing species evolutionary trees and analyzing alpha diversity, beta diversity, and linear discriminant analysis effect size (LEfSe). RESULTS The results of our study showed that there were statistically significant differences in the richness and species of gut microbiota at the total level between DKD patients and NDKD patients. The analysis of genus level between the two groups showed significant differences in 16 bacterial genera. Among them, Oscillibacter, Bilophila, UBA1819, Ruminococcaceae UCG-004, Anaerotruncus, Ruminococcaceae, and Ruminococcaceae NK4A214 bacteria in DKD patients were higher than those in NDKD patients. CONCLUSIONS 16S rDNA sequencing technology was used in this study to analyze the characteristics of intestinal flora in ESRD patients with or without diabetes. We found that there was a significant difference in the intestinal flora of ESRD patients caused by DKD and NDKD, suggesting that these may be potential causative bacteria for the development of ERSD in DKD patients.
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Affiliation(s)
- Rongping Chen
- School of Laboratory Medical and Biotechnology, Southern Medical University, Guangzhou, China
| | - Dan Zhu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Rui Yang
- Department of Endocrine and Metabolic Diseases, Southern Medical University, Guangzhou, China
| | - Zezhen Wu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Ningning Xu
- Department of Endocrine and Metabolic Diseases, Southern Medical University, Guangzhou, China
| | - Fengwu Chen
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Shuo Zhang
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Hong Chen
- Department of Endocrine and Metabolic Diseases, Southern Medical University, Guangzhou, China
| | - Ming Li
- School of Laboratory Medical and Biotechnology, Southern Medical University, Guangzhou, China
| | - Kaijian Hou
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Jinxia Community Health Service Centre, Shantou, China
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31
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Zheng L, Ji YY, Wen XL, Duan SL. Fecal microbiota transplantation in the metabolic diseases: Current status and perspectives. World J Gastroenterol 2022; 28:2546-2560. [PMID: 35949351 PMCID: PMC9254144 DOI: 10.3748/wjg.v28.i23.2546] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 03/14/2022] [Accepted: 05/07/2022] [Indexed: 02/06/2023] Open
Abstract
With the development of microbiology and metabolomics, the relationship between the intestinal microbiome and intestinal diseases has been revealed. Fecal microbiota transplantation (FMT), as a new treatment method, can affect the course of many chronic diseases such as metabolic syndrome, malignant tumor, autoimmune disease and nervous system disease. Although the mechanism of action of FMT is now well understood, there is some controversy in metabolic diseases, so its clinical application may be limited. Microflora transplantation is recommended by clinical medical guidelines and consensus for the treatment of recurrent or refractory Clostridium difficile infection, and has been gradually promoted for the treatment of other intestinal and extraintestinal diseases. However, the initial results are varied, suggesting that the heterogeneity of the donor stools may affect the efficacy of FMT. The success of FMT depends on the microbial diversity and composition of donor feces. Therefore, clinical trials may fail due to the selection of ineffective donors, and not to faulty indication selection for FMT. A new understanding is that FMT not only improves insulin sensitivity, but may also alter the natural course of type 1 diabetes by modulating autoimmunity. In this review, we focus on the main mechanisms and deficiencies of FMT, and explore the optimal design of FMT research, especially in the field of cardiometabolic diseases.
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Affiliation(s)
- Lie Zheng
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
| | - Yong-Yi Ji
- Department of Neurology, Xi’an Hospital of Traditional Chinese Medicine, Xi’an 710021, Shaanxi Province, China
| | - Xin-Li Wen
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
| | - Sheng-Lei Duan
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
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Bian J, Liebert A, Bicknell B, Chen XM, Huang C, Pollock CA. Faecal Microbiota Transplantation and Chronic Kidney Disease. Nutrients 2022; 14:nu14122528. [PMID: 35745257 PMCID: PMC9228952 DOI: 10.3390/nu14122528] [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: 05/25/2022] [Revised: 06/10/2022] [Accepted: 06/14/2022] [Indexed: 02/05/2023] Open
Abstract
Faecal microbiota transplantation (FMT) has attracted increasing attention as an intervention in many clinical conditions, including autoimmune, enteroendocrine, gastroenterological, and neurological diseases. For years, FMT has been an effective second-line treatment for Clostridium difficile infection (CDI) with beneficial outcomes. FMT is also promising in improving bowel diseases, such as ulcerative colitis (UC). Pre-clinical and clinical studies suggest that this microbiota-based intervention may influence the development and progression of chronic kidney disease (CKD) via modifying a dysregulated gut–kidney axis. Despite the high morbidity and mortality due to CKD, there are limited options for treatment until end-stage kidney disease occurs, which results in death, dialysis, or kidney transplantation. This imposes a significant financial and health burden on the individual, their families and careers, and the health system. Recent studies have suggested that strategies to reverse gut dysbiosis using FMT are a promising therapy in CKD. This review summarises the preclinical and clinical evidence and postulates the potential therapeutic effect of FMT in the management of CKD.
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Affiliation(s)
- Ji Bian
- Kolling Institute, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; (J.B.); (X.-M.C.)
| | - Ann Liebert
- Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia;
| | - Brian Bicknell
- College of Health and Medicine, Australian National University, Deacon, ACT 2600, Australia;
| | - Xin-Ming Chen
- Kolling Institute, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; (J.B.); (X.-M.C.)
| | - Chunling Huang
- Kolling Institute, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; (J.B.); (X.-M.C.)
- Correspondence: (C.H.); (C.A.P.); Tel.: +61-2-9926-4784 (C.H.); +61-2-9926-4652 (C.A.P.)
| | - Carol A. Pollock
- Kolling Institute, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; (J.B.); (X.-M.C.)
- Correspondence: (C.H.); (C.A.P.); Tel.: +61-2-9926-4784 (C.H.); +61-2-9926-4652 (C.A.P.)
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Lin JR, Wang ZT, Sun JJ, Yang YY, Li XX, Wang XR, Shi Y, Zhu YY, Wang RT, Wang MN, Xie FY, Wei P, Liao ZH. Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives. World J Diabetes 2022; 13:308-318. [PMID: 35582668 PMCID: PMC9052008 DOI: 10.4239/wjd.v13.i4.308] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 08/09/2021] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
Diabetic kidney disease (DKD) is one of the major chronic complications of diabetes mellitus (DM), as well as a main cause of end-stage renal disease. Over the last few years, substantial research studies have revealed a contributory role of gut microbiota in the process of DM and DKD. Metabolites of gut microbiota like lipopolysaccharide, short-chain fatty acids, and trimethylamine N-oxide are key mediators of microbial–host crosstalk. However, the underlying mechanisms of how gut microbiota influences the onset and progression of DKD are relatively unknown. Besides, strategies to remodel the composition of gut microbiota or to reduce the metabolites of microbiota have been found recently, representing a new potential remedial target for DKD. In this mini-review, we will address the possible contribution of the gut microbiota in the pathogenesis of DKD and its role as a therapeutic target.
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Affiliation(s)
- Jia-Ran Lin
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
- Department of Nephrology and Endocrinology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
| | - Zi-Ting Wang
- Department of Environmental Medicine, Karolinska Institutet, Stockholm 17165, Sweden
| | - Jiao-Jiao Sun
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Ying-Ying Yang
- Clinical Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, China
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna 17165, Sweden
| | - Xue-Xin Li
- Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17121, Sweden
| | - Xin-Ru Wang
- Department of Acupuncture and Moxibustion, First Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yue Shi
- Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yuan-Yuan Zhu
- First Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Rui-Ting Wang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Mi-Na Wang
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
- Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing 100010, China
| | - Fei-Yu Xie
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
- Department of Oncology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, China
| | - Peng Wei
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Ze-Huan Liao
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
- Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm 17177, Sweden
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Lei J, Xie Y, Sheng J, Song J. Intestinal microbiota dysbiosis in acute kidney injury: novel insights into mechanisms and promising therapeutic strategies. Ren Fail 2022; 44:571-580. [PMID: 35350960 PMCID: PMC8967199 DOI: 10.1080/0886022x.2022.2056054] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
In recent years, the clinical impact of intestinal microbiota–kidney interaction has been emerging. Experimental evidence highlighted a bidirectional evolutionary correlation between intestinal microbiota and kidney diseases. Nonetheless, acute kidney injury (AKI) is still a global public health concern associated with high morbidity, mortality, healthcare costs, and limited efficient therapy. Several studies on the intestinal microbiome have improved the knowledge and treatment of AKI. Therefore, the present review outlines the concept of the gut–kidney axis and data about intestinal microbiota dysbiosis in AKI to improve the understanding of the mechanisms of the intestinal microbiome on the modification of kidney function and response to kidney injury. We also introduced the future directions and research areas, emphasizing the intervention approaches and recent research advances of intestinal microbiota dysbiosis during AKI, thereby providing a new perspective for future clinical trials.
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Affiliation(s)
- Juan Lei
- Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Yifan Xie
- Department of Rheumatism and Immunology, Children's Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Jingyi Sheng
- Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Jiayu Song
- Department of Pediatric Nephrology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
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35
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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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Zheng L, Wen XL, Duan SL. Role of metabolites derived from gut microbiota in inflammatory bowel disease. World J Clin Cases 2022; 10:2660-2677. [PMID: 35434116 PMCID: PMC8968818 DOI: 10.12998/wjcc.v10.i9.2660] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/12/2021] [Accepted: 02/27/2022] [Indexed: 02/06/2023] Open
Abstract
Over the past two decades, it is improved gut microbiota plays an important role in the health and disease pathogenesis. Metabolites, small molecules produced as intermediate or end products of microbial metabolism, is considered as one of the major interaction way for gut microbiota with the host. Bacterial metabolisms of dietary substrates, modification of host molecules or bacteria are the major source of metabolites. Signals from microbial metabolites affect immune maturation and homeostasis, host energy metabolism as well as mucosal integrity maintenance. Based on many researches, the composition and function of the microbiota can be changed, which is also seen in the metabolite profiles of patients with inflammatory bowel disease (IBD). Additionally, some specific classes of metabolites also can trigger IBD. In this paper, definition of the key classes of microbial-derived metabolites which are changed in IBD, description of the pathophysiological basis of association and identification of the precision therapeutic modulation in the future are the major contents.
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Affiliation(s)
- Lie Zheng
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
| | - Xin-Li Wen
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
| | - Sheng-Lei Duan
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
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37
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Zheng L, Wen XL, Duan SL. Role of metabolites derived from gut microbiota in inflammatory bowel disease. World J Clin Cases 2022; 10:2658-2675. [DOI: 10.12998/wjcc.v10.i9.2658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Over the past two decades, it is improved gut microbiota plays an important role in the health and disease pathogenesis. Metabolites, small molecules produced as intermediate or end products of microbial metabolism, is considered as one of the major interaction way for gut microbiota with the host. Bacterial metabolisms of dietary substrates, modification of host molecules or bacteria are the major source of metabolites. Signals from microbial metabolites affect immune maturation and homeostasis, host energy metabolism as well as mucosal integrity maintenance. Based on many researches, the composition and function of the microbiota can be changed, which is also seen in the metabolite profiles of patients with inflammatory bowel disease (IBD). Additionally, some specific classes of metabolites also can trigger IBD. In this paper, definition of the key classes of microbial-derived metabolites which are changed in IBD, description of the pathophysiological basis of association and identification of the precision therapeutic modulation in the future are the major contents.
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Affiliation(s)
- Lie Zheng
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
| | - Xin-Li Wen
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
| | - Sheng-Lei Duan
- Department of Gastroenterology, Shaanxi Hospital of Traditional Chinese Medicine, Xi’an 710003, Shaanxi Province, China
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38
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Is There a Role for Gut Microbiome Dysbiosis in IgA Nephropathy? Microorganisms 2022; 10:microorganisms10040683. [PMID: 35456735 PMCID: PMC9031807 DOI: 10.3390/microorganisms10040683] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/18/2022] [Accepted: 03/21/2022] [Indexed: 02/06/2023] Open
Abstract
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and one of the leading causes of renal failure worldwide. The pathophysiology of IgAN involves nephrotoxic IgA1-immune complexes. These complexes are formed by galactose-deficient (Gd) IgA1 with autoantibodies against the hinge region of Gd-IgA1 as well as soluble CD89, an immune complex amplifier with an affinity for mesangial cells. These multiple molecular interactions result in the induction of the mesangial IgA receptor, CD71, injuring the kidney and causing disease. This review features recent immunological and microbiome studies that bring new microbiota-dependent mechanisms developing the disease based on data from IgAN patients and a humanized mouse model of IgAN. Dysbiosis of the microbiota in IgAN patients is also discussed in detail. Highlights of this review underscore that nephrotoxic IgA1 in the humanized mice originates from mucosal surfaces. Fecal microbiota transplantation (FMT) experiments in mice using stools from patients reveal a possible microbiota dysbiosis in IgAN with the capacity to induce progression of the disease whereas FMT from healthy hosts has beneficial effects in mice. The continual growth of knowledge in IgAN patients and models can lead to the development of new therapeutic strategies targeting the microbiota to treat this disease.
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39
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Cao C, Zhu H, Yao Y, Zeng R. Gut Dysbiosis and Kidney Diseases. Front Med (Lausanne) 2022; 9:829349. [PMID: 35308555 PMCID: PMC8927813 DOI: 10.3389/fmed.2022.829349] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 02/09/2022] [Indexed: 12/16/2022] Open
Abstract
Gut dysbiosis is defined as disorders of gut microbiota and loss of barrier integrity, which are ubiquitous on pathological conditions and associated with the development of various diseases. Kidney diseases are accompanied with gut dysbiosis and metabolic disorders, which in turn contribute to the pathogenesis and progression of kidney diseases. Microbial alterations trigger production of harmful metabolites such as uremic toxins and a decrease in the number of beneficial ones such as SCFAs, which is the major mechanism of gut dysbiosis on kidney diseases according to current studies. In addition, the activation of immune responses and mitochondrial dysfunction by gut dysbiosis, also lead to the development of kidney diseases. Based on the molecular mechanisms, modification of gut dysbiosis via probiotics, prebiotics and synbiotics is a potential approach to slow kidney disease progression. Fecal microbiota transplantation (FMT) and genetic manipulation of the gut microbiota are also promising choices. However, the clinical use of probiotics in kidney disease is not supported by the current clinical evidence. Further studies are necessary to explore the causal relationships of gut dysbiosis and kidney diseases, the efficiency and safety of therapeutic strategies targeting gut-kidney axis.
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Affiliation(s)
- Chujin Cao
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Han Zhu
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ying Yao
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Division of Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rui Zeng
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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40
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Huang Y, Xin W, Xiong J, Yao M, Zhang B, Zhao J. The Intestinal Microbiota and Metabolites in the Gut-Kidney-Heart Axis of Chronic Kidney Disease. Front Pharmacol 2022; 13:837500. [PMID: 35370631 PMCID: PMC8971625 DOI: 10.3389/fphar.2022.837500] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/21/2022] [Indexed: 12/13/2022] Open
Abstract
Emerging evidences demonstrate the involvement of gut microbiota in the progression of chronic kidney disease (CKD) and CKD-associated complications including cardiovascular disease (CVD) and intestinal dysfunction. In this review, we discuss the interactions between the gut, kidney and heart in CKD state, and elucidate the significant role of intestinal microbiota in the gut-kidney-heart axis hypothesis for the pathophysiological mechanisms of these diseases, during which process mitochondria may serve as a potential therapeutic target. Dysregulation of this axis will lead to a vicious circle, contributing to CKD progression. Recent studies suggest novel therapies targeting gut microbiota in the gut-kidney-heart axis, including dietary intervention, probiotics, prebiotics, genetically engineered bacteria, fecal microbiota transplantation, bacterial metabolites modulation, antibiotics, conventional drugs and traditional Chinese medicine. Further, the identification of specific microbial communities and their corresponding pathophysiological metabolites and the illumination of the gut-kidney-heart axis may contribute to innovative basic research, clinical trials and therapeutic strategies against CKD progression and uremic complications in CKD patients.
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Gut Microbiota Dynamics and Uremic Toxins. Toxins (Basel) 2022; 14:toxins14020146. [PMID: 35202173 PMCID: PMC8878563 DOI: 10.3390/toxins14020146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 02/09/2022] [Indexed: 01/27/2023] Open
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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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Lauriero G, Abbad L, Vacca M, Celano G, Chemouny JM, Calasso M, Berthelot L, Gesualdo L, De Angelis M, Monteiro RC. Fecal Microbiota Transplantation Modulates Renal Phenotype in the Humanized Mouse Model of IgA Nephropathy. Front Immunol 2021; 12:694787. [PMID: 34712223 PMCID: PMC8546224 DOI: 10.3389/fimmu.2021.694787] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 09/03/2021] [Indexed: 01/22/2023] Open
Abstract
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. Several observations suggest that gut microbiota could be implicated in IgAN pathophysiology. Aiming at exploring whether microbiota modulation is able to influence disease outcome, we performed fecal microbiota transplantation (FMT) from healthy controls (HC-sbjs), non-progressor (NP-pts) and progressor (P-pts) IgAN patients to antibiotic-treated humanized IgAN mice (α1KI-CD89Tg), by oral gavage. FMT was able to modulate renal phenotype and inflammation. On one hand, the microbiota from P-pts was able to induce an increase of serum BAFF and galactose deficient-IgA1 levels and a decrease of CD89 cell surface expression on blood CD11b+ cells which was associated with soluble CD89 and IgA1 mesangial deposits. On the other hand, the microbiota from HC-sbjs was able to induce a reduction of albuminuria immediately after gavage, an increased cell surface expression of CD89 on blood CD11b+ cells and a decreased expression of KC chemokine in kidney. Higher serum BAFF levels were found in mice subjected to FMT from IgAN patients. The main bacterial phyla composition and volatile organic compounds profile significantly differed in mouse gut microbiota. Microbiota modulation by FMT influences IgAN phenotype opening new avenues for therapeutic approaches in IgAN.
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Affiliation(s)
- Gabriella Lauriero
- Center for Research on Inflammation, Inflamex Laboratory of Excellence, Paris University, Paris, France.,INSERM U1149, Paris, France.,CNRS ERL8252, Paris, France.,Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari, Italy
| | - Lilia Abbad
- Center for Research on Inflammation, Inflamex Laboratory of Excellence, Paris University, Paris, France.,INSERM U1149, Paris, France.,CNRS ERL8252, Paris, France
| | - Mirco Vacca
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Bari, Italy
| | - Giuseppe Celano
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Bari, Italy
| | - Jonathan M Chemouny
- Center for Research on Inflammation, Inflamex Laboratory of Excellence, Paris University, Paris, France.,INSERM U1149, Paris, France.,CNRS ERL8252, Paris, France
| | - Maria Calasso
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Bari, Italy
| | - Laureline Berthelot
- Center for Research on Inflammation, Inflamex Laboratory of Excellence, Paris University, Paris, France
| | - Loreto Gesualdo
- Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari, Italy
| | - Maria De Angelis
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Bari, Italy
| | - Renato C Monteiro
- Center for Research on Inflammation, Inflamex Laboratory of Excellence, Paris University, Paris, France.,INSERM U1149, Paris, France.,CNRS ERL8252, Paris, France
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Abstract
The precise pathogenesis of immunoglobulin A nephropathy (IgAN) is still not clearly established but emerging evidence confirms a pivotal role for mucosal immunity. This review focuses on the key role of mucosa-associated lymphoid tissue (MALT) in promoting the onset of the disease, underlying the relationship among microbiota, genetic factors, food antigen, infections, and mucosal immune response. Finally, we evaluate potential therapies targeting microbes and mucosa hyperresponsiveness in IgAN patients.
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45
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Bokoliya SC, Dorsett Y, Panier H, Zhou Y. Procedures for Fecal Microbiota Transplantation in Murine Microbiome Studies. Front Cell Infect Microbiol 2021; 11:711055. [PMID: 34621688 PMCID: PMC8490673 DOI: 10.3389/fcimb.2021.711055] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 08/24/2021] [Indexed: 12/11/2022] Open
Abstract
Fecal microbiota transplantation (FMT) has been widely recognized as an approach to determine the microbiome’s causal role in gut dysbiosis-related disease models and as a novel disease-modifying therapy. Despite potential beneficial FMT results in various disease models, there is a variation and complexity in procedural agreement among research groups for performing FMT. The viability of the microbiome in feces and its successful transfer depends on various aspects of donors, recipients, and lab settings. This review focuses on the technical practices of FMT in animal studies. We first document crucial factors required for collecting, handling, and processing donor fecal microbiota for FMT. Then, we detail the description of gut microbiota depletion methods, FMT dosages, and routes of FMT administrations in recipients. In the end, we describe assessments of success rates of FMT with sustainability. It is critical to work under the anaerobic condition to preserve as much of the viability of bacteria. Utilization of germ- free mice or depletion of recipient gut microbiota by antibiotics or polyethylene glycol are two common recipient preparation approaches to achieve better engraftment. Oral-gastric gavage preferred by most researchers for fast and effective administration of FMT in mice. Overall, this review highlights various methods that may lead to developing the standard and reproducible protocol for FMT.
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Affiliation(s)
- Suresh C Bokoliya
- Department of Medicine, University of Connecticut (UConn) Health, Farmington, CT, United States
| | - Yair Dorsett
- Department of Medicine, University of Connecticut (UConn) Health, Farmington, CT, United States
| | - Hunter Panier
- Department of Medicine, University of Connecticut (UConn) Health, Farmington, CT, United States
| | - Yanjiao Zhou
- Department of Medicine, University of Connecticut (UConn) Health, Farmington, CT, United States
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46
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Taguchi K, Fukami K, Elias BC, Brooks CR. Dysbiosis-Related Advanced Glycation Endproducts and Trimethylamine N-Oxide in Chronic Kidney Disease. Toxins (Basel) 2021; 13:361. [PMID: 34069405 PMCID: PMC8158751 DOI: 10.3390/toxins13050361] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/17/2021] [Accepted: 05/17/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) is a public health concern that affects approximately 10% of the global population. CKD is associated with poor outcomes due to high frequencies of comorbidities such as heart failure and cardiovascular disease. Uremic toxins are compounds that are usually filtered and excreted by the kidneys. With the decline of renal function, uremic toxins are accumulated in the systemic circulation and tissues, which hastens the progression of CKD and concomitant comorbidities. Gut microbial dysbiosis, defined as an imbalance of the gut microbial community, is one of the comorbidities of CKD. Meanwhile, gut dysbiosis plays a pathological role in accelerating CKD progression through the production of further uremic toxins in the gastrointestinal tracts. Therefore, the gut-kidney axis has been attracting attention in recent years as a potential therapeutic target for stopping CKD. Trimethylamine N-oxide (TMAO) generated by gut microbiota is linked to the progression of cardiovascular disease and CKD. Also, advanced glycation endproducts (AGEs) not only promote CKD but also cause gut dysbiosis with disruption of the intestinal barrier. This review summarizes the underlying mechanism for how gut microbial dysbiosis promotes kidney injury and highlights the wide-ranging interventions to counter dysbiosis for CKD patients from the view of uremic toxins such as TMAO and AGEs.
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Affiliation(s)
- Kensei Taguchi
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA; (B.C.E.); (C.R.B.)
| | - Kei Fukami
- Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan;
| | - Bertha C. Elias
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA; (B.C.E.); (C.R.B.)
| | - Craig R. Brooks
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA; (B.C.E.); (C.R.B.)
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Mosterd CM, Kanbay M, van den Born BJH, van Raalte DH, Rampanelli E. Intestinal microbiota and diabetic kidney diseases: the Role of microbiota and derived metabolites inmodulation of renal inflammation and disease progression. Best Pract Res Clin Endocrinol Metab 2021; 35:101484. [PMID: 33546983 DOI: 10.1016/j.beem.2021.101484] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Diabetic kidney disease (DKD) represents a growing public health burden and is the leading cause of end-stage kidney diseases. In recent years, host-gut microbiota interactions have emerged as an integral part for host homeostasis. In the context of nephropathies, mounting evidence supports a bidirectional microbiota-kidney crosstalk, which becomes particularly manifest during progressive kidney dysfunction. Indeed, in chronic kidney disease (CKD), the "healthy" microbiota structure is disrupted and intestinal microbes produce large quantities of uremic solutes responsible for renal damage; on the other hand, the uremic state, fueled by reduced renal clearance, causes shifts in microbial metabolism and composition, hence creating a vicious cycle in which dysbiosis and renal dysfunction are progressively worsened. In this review, we will summarize the evidence from clinical/experimental studies concerning the occurrence of gut dysbiosis in diabetic and non-diabetic CKD, discuss the functional consequences of dysbiosis for CKD progression and debate putative therapeutic interventions targeting the intestinal microbiome.
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Affiliation(s)
- C M Mosterd
- Department of Internal and Vascular Medicine, Amsterdam UMC, Location VUmc, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
| | - M Kanbay
- Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey
| | - B J H van den Born
- Department of Nephrology and Vascular Medicine, Amsterdam UMC, Location AMC, the Netherlands
| | - D H van Raalte
- Diabetes Center, Department of Internal Medicine, Amsterdam UMC, Location VUmc, Diabetes Center, Amsterdam, the Netherlands
| | - E Rampanelli
- Department of Experimental Vascular Medicine, Amsterdam UMC, Location AMC, Amsterdam Cardiovascular Sciences, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands.
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