Chronic kidney disease (CKD), which represents a significant global health concern, is characterized by a gradual decline in kidney function, leading to complications such as electrolyte imbalance, cardiovascular disease, and immune dysfunction. Standard CKD management includes dietary modifications, ketoanalogues supplementation, blood pressure and blood glucose control, hydration maintenance, and treatment of the underlying causes. Emerging evidence has indicated a significant role of the gut microbiota in CKD, and that dysbiosis of the gut microbiota contributes to the progression of CKD towards end-stage renal disease. Probiotics and prebiotics have recently garnered attention owing to their potential to enhance gastrointestinal health and well-being by restoring the balance of the gut microbiota. Specific probiotic strains, including Lactobacillus and Bifidobacterium, promote beneficial bacterial growth, suppress harmful bacteria, and exert anti-inflammatory, antihypertensive, and antidiabetic effects. The combination of Streptococcus thermophilus, Lactobacillus acidophilus, Bifidobacterium longum, and Bacillus coagulans has demonstrated potential as a therapeutic formulation for CKD management in various studies, highlighting its promise in treating CKD; however, supporting evidence remains limited, making it crucial to conduct further investigations to determine the specific effects of different probiotic formulations on outcomes in patients with CKD.

• Chronic kidney disease
• Gut microbiota
• Prebiotics
• Lactobacillus
• Bifidobacterium

• adequacy
• creatinine
• fiber
• protein-bound
• toxin
• uraemic
• urea

• Humans
• Gastrointestinal Microbiome/physiology
• Thrombosis/microbiology
• Animals
• Dysbiosis

• Bibliometrics
• Complement system
• Gut-kidney aixs
• IgAN
• Innate immunity

• Humans
• Immunity, Innate
• Bibliometrics
• Glomerulonephritis, IGA/immunology
• Kidney/immunology
• Gastrointestinal Microbiome/immunology
• Animals
• Complement System Proteins/immunology

• 16S rRNA
• Constipation
• Intestinal biomarker
• Maintenance haemodialysis (MHD)
• gut microbiome

• Humans
• Constipation/microbiology
• Gastrointestinal Microbiome
• Renal Dialysis
• Feces/microbiology
• Male
• RNA, Ribosomal, 16S/genetics
• Middle Aged
• Female
• Bacteria/classification
• Bacteria/isolation & purification
• Bacteria/genetics
• Aged
• Adult

• gut microbiota
• gut-brain axis
• metabolites
• prebiotic
• probiotic

• Humans
• Gastrointestinal Microbiome
• COVID-19/microbiology
• Bacteria/pathogenicity
• Bacteria/classification
• Bacteria/genetics
• Dysbiosis/microbiology
• SARS-CoV-2/pathogenicity
• Microbial Interactions

• chronic kidney disease (CKD)
• gut microbiota
• microbiome
• prebiotics
• probiotics
• uremic toxins

• Humans
• Gastrointestinal Microbiome
• Renal Insufficiency, Chronic/microbiology
• Renal Insufficiency, Chronic/metabolism
• Glomerular Filtration Rate
• Probiotics/therapeutic use
• Uremic Toxins/metabolism
• Synbiotics
• Animals
• Oxidative Stress
• Cresols/metabolism
• Dysbiosis/microbiology
• Indican/metabolism

• chronic kidney disease
• dialysis
• end-stage kidney disease
• gut microbiota

• Humans
• Gastrointestinal Microbiome/physiology
• Renal Dialysis/adverse effects
• Dysbiosis/microbiology
• Kidney Failure, Chronic/therapy
• Kidney Failure, Chronic/microbiology
• Renal Insufficiency, Chronic/therapy
• Renal Insufficiency, Chronic/microbiology
• Renal Insufficiency, Chronic/complications
• Probiotics/therapeutic use
• Prebiotics/administration & dosage

• chronic kidney disease
• metabolism
• probiotic
• renal function
• synbiotic

• chronic kidney disease
• gut-dysbiosis
• gut−kidney axis
• host−microbe interactions
• probiotic adjuvant therapy

• Humans
• Dysbiosis
• Kidney
• Renal Insufficiency, Chronic/therapy
• Probiotics/therapeutic use
• Gastrointestinal Microbiome

• Council of Agriculture

• Diabetes
• dietary
• dysbiosis
• nephropathy
• prebiotics
• probiotics
• retinopathy
• synbiotics

• Humans
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/therapy
• Synbiotics/administration & dosage
• Gastrointestinal Microbiome
• Probiotics/therapeutic use
• Dietary Supplements
• Prebiotics
• Insulin Resistance
• Diabetes Complications/prevention & control
• Diabetes Complications/therapy

• Bifidobacterium
• deoxycholic acid
• indoles
• metabolome
• p-cresol
• uremic toxin

• K24 HL150235 NHLBI NIH HHS

• chronic kidney disease
• functional ingredient
• gut microbiota
• gut–kidney axis
• nutraceuticals

• Cardiovascular diseases
• gut microbiota
• lifelong care
• precision medicine

• Humans
• Precision Medicine
• Cardiovascular Diseases/therapy
• Gastrointestinal Microbiome
• Artificial Intelligence
• Dietary Supplements

• Chronic kidney disease
• creatinine
• meta-analysis
• prebiotics
• probiotics
• synbiotics

• Gut-derived uremic toxins
• indoxyl sulfate
• mechanism-based inhibitor
• microbiome-targeted inhibition
• tryptophanase

• Humans
• Mice
• Animals
• Indican/pharmacology
• Indican/metabolism
• Tryptophanase
• Gastrointestinal Microbiome/physiology
• Indoles/pharmacology
• Indoles/metabolism
• Renal Insufficiency, Chronic/drug therapy
• Mammals/metabolism

• R01 GM135218 NIGMS NIH HHS
• R01 GM137286 NIGMS NIH HHS
• T32 GM135095 NIGMS NIH HHS
• T32 DK007750 NIDDK NIH HHS

• chronic kidney disease
• gut microbiota
• interventions
• nutrition
• residual kidney function

• Humans
• Gastrointestinal Microbiome
• Dysbiosis
• Quality of Life
• Fecal Microbiota Transplantation
• Kidney

• Canagliflozin
• Chronic kidney disease
• Gut microbiota

• Rats
• Animals
• Canagliflozin/pharmacology
• Canagliflozin/therapeutic use
• Sodium-Glucose Transporter 2 Inhibitors/pharmacology
• Cardiovascular System
• Glucose
• Fibrosis

• JP22gm1010007 Japanese Agency for Medical Research and Development
• JP22gm1010007 Japanese Agency for Medical Research and Developement

• Diabetic kidney disease
• Gut microbiota
• Host immunity
• Inflammation
• Novel biomarkers

• Cardiovascular Burden
• Chronic Kidney Disease
• Gut-derived Uremic Toxins
• Inflammation
• Microbiome
• Synbiotic

• diet
• gastrointestinal physiology
• gastrointestinal transit
• intestinal microbiology

• Humans
• Gastrointestinal Microbiome
• Microbiota
• Feces
• Diet

• Danmarks Frie Forskningsfond
• Novo Nordisk Fonden

Gut microbiota dysbiosis in patients with chronic kidney disease on haemodialysis (CKD-HD) creates an increase in proteolytic bacteria activity, leading to an increase in the production of uraemic toxins, such as indoxyl sulphate, worsening of constipation symptoms and reducing patients’ quality of life. Improving gut microbiota dysbiosis is expected to improve this condition. This study aimed to evaluate the effect of synbiotics on indoxyl sulphate levels, constipation symptoms, and constipation-related quality of life in haemodialysis patients.

This was a double-blinded randomized controlled clinical trial with a parallel design involving haemodialysis patients. We included chronic haemodialysis patients with gastrointestinal complaints, difficulty defecating, faeces with hard consistency, or a bowel movement frequency of fewer than three times per week. Patients were randomly divided into two groups (synbiotics (Lactobacillus acidophilus and Bifidobacterium longum 5x10⁹ CFU) and placebo) for 60 days of oral intervention. All participants, caregivers, and outcome assessors were blinded to group assignment. The primary outcome was a decrease in indoxyl sulphate toxin levels. Meanwhile, improvement in constipation symptoms (measured using the Patient Assessment of Constipation: Symptoms (PAC-SYM) questionnaire) and improvement in constipation-related quality of life (measured using the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire) were assessed as secondary outcomes.

We included 60 patients (30 intervention; median age of 51.23 (13.57) years, 33.3% male; 30 control; median age of 52.33 (11.29) years, 36.7% male). There was no significant difference in terms of pre- and postintervention indoxyl sulphate toxin levels in the synbiotics group compared to the placebo group (p=0.438). This study found an improvement in constipation symptoms (p = 0.006) and constipation-related quality of life (p=0.001) after synbiotic administration.

Two months of synbiotic supplementation did not lower indoxyl sulphate toxin levels. Nevertheless, it had a major effect in improving constipation and quality of life affected by constipation in patients undergoing chronic haemodialysis.

NCT04527640 (date of first registration: 26/08/2020)

The online version contains supplementary material available at 10.1186/s12882-022-02890-9.

The clinical value of the relationship between gastrointestinal microbiome imbalance and its corresponding interventions with kidney disease is emerging. This study describes the hotspots and evolution of gastrointestinal microbiome and kidney disease research over the past three decades by scientific collaboration networks and finally predicts future trends in the field through bibliometric analysis and visualization studies. CiteSpace was used to explore the original articles from January 1990 to August 2021 to visualize the knowledge network of journals, countries, institutions, authors, references, and keywords in this field. Publications were extracted from Web of Science Core Collection database using the terms “gastrointestinal microbiome” and “kidney disease” (and their synonyms in MeSH). A total of 2145 publications with 93880 references in 102 journals were included in the analyses. The number of studies combining gastrointestinal microbiomes with kidney diseases has increased significantly over the past two decades. The United States is the leading country in the number of documents, and the leading institution is the Cleveland Clinic. The most landmark articles in the field are on chronic renal failure, L-Carnitin, and cardiovascular disease. The pathogenesis of uremia toxin is an emerging trend in gastrointestinal microbiomes and kidney diseases. In addition, probiotic or synbiotic supplements have strong clinical value in adjusting abnormal intestinal symbiotic environments. This study demonstrates a growing understanding of the interaction between gut microbiota and kidney disease over time. Using microbial supplements to improve the living conditions of kidney disease patients is a promising and hot research focus. Based on publications extracted from the database, this study may provide clinicians and researchers with valuable information to identify potential collaborators and partner institutions and better predict their dynamic progression.

• Bibliometrics
• Gastrointestinal Microbiome
• Humans
• Kidney
• Kidney Diseases
• Probiotics
• United States

• National Natural Science Foundation of China

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.

• Diabetes
• Gut microbiota
• Insulin resistance
• Diabetic kidney disease
• Pathogenesis
• Therapeutic targets

• FMT
• chronic kidney disease
• gut microbiota
• metabolic disorders
• probiotics

Metabolic acidosis is one of the most common complications of chronic kidney disease (CKD). It is associated with the progression of CKD, and many other functional impairments. Until recently, only serum bicarbonate levels have been used to evaluate acid-base changes in patients with reduced kidney function. However, recent emerging evidence suggests that nephrologists should reevaluate the clinical approach for diagnosing metabolic acidosis in patients with CKD based on two perspectives; pH and anion gap. Biochemistry and physiology textbooks clearly indicate that blood pH is the most important acid-base parameter for cellular function. Therefore, it is important to determine if the prognostic impact of hypobicarbonatemia varies according to pH level. A recent cohort study of CKD patients showed that venous pH modified the association between a low bicarbonate level and the progression of CKD. Furthermore, acidosis with a high anion gap has recently been recognized as an important prognostic factor, because veverimer, a nonabsorbable hydrochloride-binding polymer, has been shown to improve kidney function and decrease the anion gap. Acidosis with high anion gap frequently develops in later stages of CKD. Therefore, the anion gap is a time-varying factor and renal function (estimated glomerular filtration rate) is a time-dependent confounder for the anion gap and renal outcomes. Recent analyses using marginal structural models showed that acidosis with a high anion gap was associated with a high risk of CKD. Based on these observations, reconsideration of the clinical approach to diagnosing and treating metabolic acidosis in CKD may be warranted.

Uremic toxins are defined as harmful metabolites that accumulate in the human body of patients whose renal function declines, especially chronic kidney disease (CKD) patients. Growing evidence demonstrates the deteriorating effect of uremic toxins on CKD progression and CKD-related complications, and removing uremic toxins in CKD has become the conventional treatment in the clinic. However, studies rarely pay attention to uremic toxin clearance in the early stage of acute kidney injury (AKI) to prevent progression to CKD despite increasing reports demonstrating that uremic toxins are correlated with the severity of injury or mortality. This review highlights the current evidence of uremic toxin accumulation in AKI and the therapeutic value to prevent CKD progression specific to protein-bound uremic toxins (PBUTs).

• acute kidney injury
• indoxyl sulfate
• p-cresyl sulfate
• protein-bound uremic toxins

• Diet-microbe-host interactions
• gut microbiota
• metaorganismal relay biotransformation
• pleiotropic effects of metabolites

Chronic kidney disease (CKD) is a serious non-communicable disease that poses a significant burden on healthcare and society. It is essential to devise new strategies to better treat patients with CKD. Research has illustrated that gut dysbiosis, describing an abnormal intestinal ecology, is closely associated with CKD. In this narrative review, we summarized the evidence of their mutual relationship and discussed the potential treatment options to correct gut dysbiosis in patients with CKD. Gut dysbiosis significantly increases the risk of CKD, especially in the older population. Gut dysbiosis also plays a role in CKD complications, such as hypertension, cardiovascular events, and cognitive dysfunction. The relationship between gut dysbiosis and CKD is bidirectional, and CKD itself can lead to changes in gut microecology. The usual therapies for CKD can also increase the incidence of gut dysbiosis. Meanwhile, probiotics and antibiotics are generally used to correct gut dysbiosis. Further studies are required to elaborate the association between gut dysbiosis and CKD, and more treatment options should be explored to prevent CKD in patients with gut dysbiosis.

• Chronic kidney disease
• antibiotics
• gut dysbiosis
• gut microecology
• hypertension
• prebiotics
• probiotics

• Autism spectrum disorders
• Colonic epithelial cells
• Intestinal microbiota
• Uremic toxins
• p-Cresol

• chronic kidney disease
• complementary and alternative medicine
• conventional medical therapy
• diet control
• dietary supplement
• uremic toxin

• Adult
• Aged
• Aged, 80 and over
• Complementary Therapies/methods
• Diet Therapy/methods
• Dietary Supplements
• Female
• Humans
• Kidney Diseases/drug therapy
• Kidney Diseases/physiopathology
• Kidney Diseases/therapy
• Male
• Middle Aged
• Probiotics/therapeutic use
• Renal Replacement Therapy/methods
• Uremia/chemically induced
• Uremia/therapy
• Uremic Toxins/toxicity

Chronic kidney disease (CKD) is a condition of widespread epidemiology and serious consequences affecting all organs of the organism and associated with significant mortality. The knowledge on CKD is rapidly evolving, especially concerning adults. Recently, more data is also appearing regarding CKD in children. Chronic itch (CI) is a common symptom appearing due to various underlying dermatological and systemic conditions. CI may also appear in association with CKD and is termed chronic kidney disease-associated itch (CKD-aI). CKD-aI is relatively well-described in the literature concerning adults, yet it also affects children. Unfortunately, the data on paediatric CKD-aI is particularly scarce. This narrative review aims to describe various aspects of CKD-aI with an emphasis on children, based on the available data in this population and the data extrapolated from adults. Its pathogenesis is described in details, focusing on the growing role of uraemic toxins (UTs), as well as immune dysfunction, altered opioid transmission, infectious agents, xerosis, neuropathy and dialysis-associated aspects. Moreover, epidemiological and clinical aspects are reviewed based on the few data on CKD-aI in children, whereas treatment recommendations are proposed as well, based on the literature on CKD-aI in adults and own experience in managing CI in children.

• children
• chronic kidney disease
• itch
• uraemic toxins

• antioxidants
• chronic kidney disease
• fecal batches
• microbiota
• prebiotics
• probiotics
• synbiotic

The aim of the present study was to evaluate whether probiotic administration could slow declining renal function. C57BL/6 mice (6–8 weeks of age, male) were fed a diet supplemented with adenine to induce chronic kidney disease (CKD). The experimental groups were additionally supplemented with 10⁹ colony-forming units (CFU)/day (high-dose) and 10⁷ CFU/day (low-dose) probiotics containing Lactobacillus acidophilus (TYCA06), Bifidobacterium longum subspecies infantis (BLI-02), and B. bifidum (VDD088). Renal function and histology were examined. Patients with stage 3–5 CKD and not on dialysis were recruited from July 2017 to January 2019. Two capsules of probiotics containing 2.5 × 10⁹ CFU with the same composition were administered twice daily for 6 months. The decline in the estimated glomerular filtration rate (eGFR) was measured before and after the intervention. In addition, changes in the serum endotoxin and cytokine levels, gastrointestinal symptom scores, and the stool microbiota were measured. Probiotics could attenuate renal fibrosis and improve renal function in CKD mice. Thirty-eight patients completed the 6-month study. The mean baseline eGFR was 30.16 ± 16.52 ml/min/1.73 m². The rate of decline in the eGFR was significantly slower, from −0.54 (−0.18, −0.91) to 0.00 (0.48, −0.36) ml/min/1.73 m²/month (P = 0.001) after 6 months of treatment. The serum levels of TNF-α, IL-6, IL-18, and endotoxin were significantly decreased after probiotic administration. Borborygmus and flatulence scores, as well as stool formation improved significantly. The abundance of B. bifidum and B. breve in the stool microbiota increased significantly. In conclusion, a combination of probiotics might attenuate renal function deterioration in CKD mice and human patients.

• chronic kidney disease
• microbiota
• microorganisms
• probiotics
• renal function

• AGEs
• RAGE
• TMAO
• chronic kidney disease
• dysbiosis
• gut microbiota

• Animals
• Cardiovascular Diseases/physiopathology
• Disease Progression
• Dysbiosis/physiopathology
• Gastrointestinal Microbiome
• Glycation End Products, Advanced/metabolism
• Humans
• Methylamines/metabolism
• Renal Insufficiency, Chronic/physiopathology

• chronic kidney disease
• diabetic kidney disease
• inflammation
• metabolites
• microbiota

• Diabetes Mellitus
• Diabetic Nephropathies
• Disease Progression
• Gastrointestinal Microbiome
• Humans
• Inflammation
• Microbiota
• Renal Insufficiency, Chronic

The retention of uremic toxins and their pathological effects occurs in the advanced phases of chronic kidney disease (CKD), mainly in stage 5, when the implementation of conventional thrice-weekly hemodialysis is the prevalent and life-saving treatment. However, the start of hemodialysis is associated with both an acceleration of the loss of residual kidney function (RKF) and the shift to an increased intake of proteins, which are precursors of uremic toxins. In this phase, hemodialysis treatment is the only way to remove toxins from the body, but it can be largely inefficient in the case of high molecular weight and/or protein-bound molecules. Instead, even very low levels of RKF are crucial for uremic toxins excretion, which in most cases are protein-derived waste products generated by the intestinal microbiota. Protection of RKF can be obtained even in patients with end-stage kidney disease (ESKD) by a gradual and soft shift to kidney replacement therapy (KRT), for example by combining a once-a-week hemodialysis program with a low or very low-protein diet on the extra-dialysis days. This approach could represent a tailored strategy aimed at limiting the retention of both inorganic and organic toxins. In this paper, we discuss the combination of upstream (i.e., reduced production) and downstream (i.e., increased removal) strategies to reduce the concentration of uremic toxins in patients with ESKD during the transition phase from pure conservative management to full hemodialysis treatment.

• CKD
• ESKD
• dietary protein
• infrequent dialysis
• nutrition
• nutritional therapy
• residual kidney function
• uremic toxins

• Biomarkers/blood
• Combined Modality Therapy
• Diet, Protein-Restricted/adverse effects
• Disease Progression
• Humans
• Kidney Failure, Chronic/blood
• Kidney Failure, Chronic/diagnosis
• Kidney Failure, Chronic/physiopathology
• Kidney Failure, Chronic/therapy
• Renal Dialysis/adverse effects
• Toxins, Biological/blood
• Treatment Outcome
• Uremia/blood
• Uremia/diagnosis
• Uremia/physiopathology
• Uremia/therapy

• cardiovascular risk
• chronic kidney disease
• gut microbiota
• uremic toxins

• Animals
• Bacteria/metabolism
• Dietary Supplements
• Disease Progression
• Dysbiosis
• Gastrointestinal Microbiome
• Host-Pathogen Interactions
• Humans
• Intestines/microbiology
• Renal Dialysis
• Renal Insufficiency, Chronic/blood
• Renal Insufficiency, Chronic/diagnosis
• Renal Insufficiency, Chronic/microbiology
• Renal Insufficiency, Chronic/therapy
• Toxins, Biological/blood
• Uremia/blood
• Uremia/diagnosis
• Uremia/microbiology
• Uremia/therapy

• Chronic kidney diseases
• Lactobacillaceae
• Proteobacteria
• adenine
• firmicutes
• gum acacia
• microbiome
• short-chain fatty acids

Despite research into the epidemiological link between exposure to particulate matter (PM) and renal disorder, there is limited information available on the etiological complexity and molecular mechanisms. Among the early responsive tissues to PM exposure, the mucosal barrier of the airway and alimentary tract may be a crucial source of pathologic mediators leading to inflammatory renal diseases, including chronic kidney disease (CKD). Given that harmful responses and products in mucosa exposed to PM may enter the circulation and cause adverse outcomes in the kidney, the aim of the present review was to address the impact of PM exposure on the mucosal barrier and the vicious feedback cycle in the mucosal environment. In addition to the PM-induced alteration of mucosal barrier integrity, the microbial community has a pivotal role in the xenobiotic metabolism and individual susceptibility to PM toxicity. The dysbiosis-induced deleterious metabolites of PM and nutrients are introduced systemically via a disrupted mucosal barrier, contributing to renal injuries and pathologic severity. In contrast, the progress of mucosa-associated renal disease is counteracted by endogenous protective responses in the mucosa. Along with direct elimination of the toxic mediators, modulators of the mucosal microbial community should provide a promising platform for mucosa-based personalized interventions against renal disorders caused by air pollution.

• chronic kidney disease
• microbiota
• mucosal barrier
• mucosal exposure
• particulate matter

• Chronic kidney disease
• Indoxyl sulfate
• Protein-bound uremic toxins
• p-Cresyl sulfate

Chronic kidney disease (CKD) has long been known to cause significant digestive tract pathology. Of note, indoxyl sulfate is a gut microbe-derived uremic toxin that accumulates in CKD patients. Nevertheless, the relationship between gut microbiota, fecal indole content, and blood indoxyl sulfate level remains unknown. In our study, we established an adenine-induced CKD rat model, which recapitulates human CKD-related gut dysbiosis. Synbiotic treatment in CKD rats showed a significant reduction in both the indole-producing bacterium Clostridium and fecal indole amount. Furthermore, gut microbiota diversity was reduced in CKD rats but was restored after synbiotic treatment. Intriguingly, in our end-stage kidney disease (ESKD) patients, the abundance of indole-producing bacteria, Bacteroides, Prevotella, and Clostridium, is similar to that of healthy controls. Consistently, the fecal indole tends to be higher in the ESKD patients, but the difference did not achieve statistical significance. However, the blood level of indoxyl sulfate was significantly higher than that of healthy controls, implicating that under an equivalent indole production rate, the impaired renal excretion contributes to the accumulation of this notorious uremic toxin. On the other hand, we did identify two short-chain fatty acid-producing bacteria, Faecalibacterium and Roseburia, were reduced in ESKD patients as compared to the healthy controls. This may contribute to gut dysbiosis. We also identified that three genera Fusobacterium, Shewanella, and Erwinia, in the ESKD patients but not in the healthy controls. Building up gut symbiosis to treat CKD is a novel concept, but once proved effective, it will provide an additional treatment strategy for CKD patients.

• chronic kidney disease
• dysbiosis
• gut indole
• synbiotics

• Adenine
• Aged
• Animals
• Bacteria/metabolism
• Biodiversity
• Body Weight
• Diet
• Disease Models, Animal
• Dysbiosis/blood
• Dysbiosis/complications
• Feces/microbiology
• Female
• Gastrointestinal Microbiome
• Gastrointestinal Tract/metabolism
• Humans
• Indican/blood
• Indoles/metabolism
• Kidney/pathology
• Male
• Middle Aged
• Rats
• Renal Insufficiency, Chronic/blood
• Renal Insufficiency, Chronic/complications
• Synbiotics
• Time Factors

There is increasing evidence that Chronic Kidney Disease (CKD) can cause intestinal dysfunction, which in turn aggravates the progression of kidney disease. Studies have shown that the immune response of macrophage plays an important role in promoting inflammation in kidney and intestine of CKD. Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) is a widely used traditional medicine for the treatment of CKD in China, however, the underlying mechanism is largely unclear. In this study, we aimed to explore the role of A&P and Bifidobacterium combination treatment in regulation of inflammatory response of macrophage in kidney and intestine of CKD mouse, as well as the potential molecular mechanism. We established a CKD mouse model with 5/6 nephrectomy and a macrophage inflammatory cellular model with LPS and urotoxin in vivo and in vitro. The results showed that A&P combined with Bifidobacterium significantly reduced the expression and secretion of IL-1β, IL-6, TNFα, and MCP-1 in kidney and blood, as well as in inflammatory macrophage. Interestingly, A&P combined with Bifidobacterium strongly improved the intestinal flora and protected the intestinal barrier. Notably, the maintainer of macrophage polarization, Mincle, was activated in kidney and intestine of CKD mouse as well as in urotoxin stimulated macrophage, that was effectively inhibited by the treatment of A&P and Bifidobacterium combination. Overexpression of Mincle by genetic modification can abolish the inhibitory effects of A&P combined with Bifidobacterium on inflammation in urotoxin stimulated RAW264.7 cells. In summary, these findings demonstrated that A&P combined with Bifidobacterium can protect kidney against CKD by down-regulating macrophage inflammatory response in kidney and intestine via suppressing Mincle signaling, which provides a new insight in the treatment of CKD with traditional medicine.

• Astragalus mongholicus Bunge and Panax notoginseng formula
• CKD
• Mincle
• bifidobacterium
• macrophage