scholarly journals The Role of Gut Microbiota and Microbiota-Related Serum Metabolites in the Progression of Diabetic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Zhang ◽  
Yanmei Zhang ◽  
Lu Zeng ◽  
Guowei Chen ◽  
La Zhang ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Diabetic Kidney Disease ◽  
Intestinal Flora ◽  
Clinical Indicators ◽  
Serum Metabolites

Objective: Diabetic kidney disease (DKD) has become the major cause of end-stage renal disease (ESRD) associated with the progression of renal fibrosis. As gut microbiota dysbiosis is closely related to renal damage and fibrosis, we investigated the role of gut microbiota and microbiota-related serum metabolites in DKD progression in this study.Methods: Fecal and serum samples obtained from predialysis DKD patients from January 2017 to December 2019 were detected using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Forty-one predialysis patients were divided into two groups according to their estimated glomerular filtration rate (eGFR): the DKD non-ESRD group (eGFR ≥ 15 ml/min/1.73 m2) (n = 22), and the DKD ESRD group (eGFR < 15 ml/min/1.73 m2) (n = 19). The metabolic pathways related to differential serum metabolites were obtained by the KEGG pathway analysis. Differences between the two groups relative to gut microbiota profiles and serum metabolites were investigated, and associations between gut microbiota and metabolite concentrations were assessed. Correlations between clinical indicators and both microbiota-related metabolites and gut microbiota were calculated by Spearman rank correlation coefficient and visualized by heatmap.Results: Eleven different intestinal floras and 239 different serum metabolites were identified between the two groups. Of 239 serum metabolites, 192 related to the 11 different intestinal flora were mainly enriched in six metabolic pathways, among which, phenylalanine and tryptophan metabolic pathways were most associated with DKD progression. Four microbiota-related metabolites in the phenylalanine metabolic pathway [hippuric acid (HA), L-(−)-3-phenylactic acid, trans-3-hydroxy-cinnamate, and dihydro-3-coumaric acid] and indole-3 acetic acid (IAA) in the tryptophan metabolic pathway positively correlated with DKD progression, whereas L-tryptophan in the tryptophan metabolic pathway had a negative correlation. Intestinal flora g_Abiotrophia and g_norank_f_Peptococcaceae were positively correlated with the increase in renal function indicators and serum metabolite HA. G_Lachnospiraceae_NC2004_Group was negatively correlated with the increase in renal function indicators and serum metabolites [L-(−)-3-phenyllactic acid and IAA].Conclusions: This study highlights the interaction among gut microbiota, serum metabolites, and clinical indicators in predialysis DKD patients, and provides new insights into the role of gut microbiota and microbiota-related serum metabolites that were enriched in the phenylalanine and tryptophan metabolic pathways, which correlated with the progression of DKD.

scholarly journals MO046MICROBIOTA DERIVED SHORT CHAIN FATTY ACIDS, PROPIONATE AND BUTYRATE, CONTRIBUTE TO MODULATE THE INFLAMMATORY RESPONSE IN CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Viviana Corte ◽  
Ana Cristina Andrade ◽  
Paula Diaz-Bulnes ◽  
Nuria Salazar Garzo ◽  
Jose Joaquin Bande ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Fatty Acids ◽  
Renal Function ◽  
Kidney Disease ◽  
Inflammatory Response ◽  
Gut Microbiota ◽  
Immune Cells ◽  
Short Chain Fatty Acids

Abstract Background and Aims Dysbiosis, or changes in the gut microbiota composition, had been related to the developed of several pathologies, such as chronic kidney disease. Until now, multiple studies have focused on the influence of diet on outcomes of patients with CKD. These patients with advanced disease are recommended a restricted intake of vegetable fiber due to the phosphorus and potassium levels, and low proteins to avoid the generation of uremic toxins. It is known that dietary changes lead to alterations in gut microbiota, but also in microbial metabolites production, some of which could be beneficial for the host. A recent and exciting area of research has begun to explore the role of microbiota-derived metabolites in the renal physiology. Short-chain fatty acids (SCFA, acetate, propionate and butyrate) are a type metabolite produced from dietary fiber by gut microbiota that enter in the bloodstream leading to distal effects, such as modulation of the immune cells. SCFAs are essential to maintain the permeability of the intestinal epithelial barrier, the metabolic functions and have potent anti-inflammatory effects. The aim of this study was to identify the SCFAs levels during the progression of CKD and determinate the functional role of these metabolites in the renal inflammation. Method SFCAs (acetate, propionate and butyrate) levels were determined using gas chromatography-mass spectrometry in fecal samples collected from patients with different stages of CKD (n=60) and age-matched healthy control (n=20). Moreover, common bacterial families were determined by quantitative PCR. Additionally, the in-vitro effect of the three SCFAs was evaluated in the human tubular epithelial cell line HK2 using RNA-seq, specific silencing with siRNAs and histone deacetylases (HDAC) inhibitors. To evaluate the effect in immune cells, monocyte and macrophages were treated with LPS and ATP /Nigericin to induce inflammasome activation. Results The SCFAs levels were significantly lower in patients with CKD than in healthy controls, mainly propionate and butyrate. Moreover, these levels progressively decreased with the developed of the disease, showing the patients with stage 5 (CKD5) have the lowest levels that correlates with a lesser abundance of Clostridium IV family. According to the renal function, butyrate levels were positively correlated with the glomerular filtration rate and negatively with the blood urea nitrogen and creatinine levels. Surprisingly, high propionate levels correlate with the most elevated serum calcidiol concentrations. Functionally, propionate and butyrate show a similar pattern in the modulation of inflammatory genes in HK2 cells. Most regulated pathways are associated with Inflammatory response (GO:0006954: IL6, TNF, CCL2, RELB, IRAK2, NFKB1,CCL20) and immune response (GO:0006955: CSF2, CXCL3, CD40, IL7R, LIF). Additionally, both SCFAs regulates the expression of multiple epigenetic enzymes involves in the chromatin remodeling, mainly in histone acetylation. In monocytes/macrophages, propionate and butyrate inhibits the IL1B, CASP, and ASC gene transcription damaging the IL-1β secretion. We determined that the effect of SCFAs in these in-vitro models is mediated by inhibition of HDAC although also change other histone modifications (H3K9me3, H3K27me3) and through the GPR109A receptor. Conclusion Our initial results showed that patients with advanced CKD have low levels of SCFAs, and those were correlated with the renal function. Treatment of human renal and immune cells with propionate and butyrate induces profound changes in the chromatin structure, changing the whole-genome gene expression and modulating key pathways in the renal pathology. Increasing the SCFAs levels in those patients could be a potential therapeutic strategy to slow down the disease progression.

scholarly journals Sustained Drug Treatment Alters the Gut Microbiota in Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Liyan Mei ◽  
Zhihua Yang ◽  
Xiaolin Zhang ◽  
Zehao Liu ◽  
Maojie Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Drug Treatment ◽  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Causative Role ◽  
Clinical Indicators ◽  
Reactive Protein ◽  
Over Time

Several studies have investigated the causative role of the microbiome in the development of rheumatoid arthritis (RA), but changes in the gut microbiome in RA patients during drug treatment have been less well studied. Here, we tracked the longitudinal changes in gut bacteria in 22 RA patients who were randomized into two groups and treated with Huayu-Qiangshen-Tongbi formula (HQT) plus methotrexate (MTX) or leflunomide (LEF) plus MTX. There were differences in the gut microbiome between untreated (at baseline) RA patients and healthy controls, with 37 species being more abundant in the RA patients and 21 species (including Clostridium celatum) being less abundant. Regarding the functional analysis, vitamin K2 biosynthesis was associated with RA-enriched bacteria. Additionally, in RA patients, alterations in gut microbial species appeared to be associated with RA-related clinical indicators through changing various gut microbiome functional pathways. The clinical efficacy of the two treatments was further observed to be similar, but the response trends of RA-related clinical indices in the two treatment groups differed. For example, HQT treatment affected the erythrocyte sedimentation rate (ESR), while LEF treatment affected the C-reactive protein (CRP) level. Further, 11 species and 9 metabolic pathways significantly changed over time in the HQT group (including C. celatum, which increased), while only 4 species and 2 metabolic pathways significantly changed over time in the LEF group. In summary, we studied the alterations in the gut microbiome of RA patients being treated with HQT or LEF. The results provide useful information on the role of the gut microbiota in the pathogenesis of RA, and they also provide potentially effective directions for developing new RA treatments.

scholarly journals Role of lung and gut microbiota on lung cancer pathogenesis

2021 ◽  
Author(s):  
Yue Zhao ◽  
Yuxia Liu ◽  
Shuang Li ◽  
Zhaoyun Peng ◽  
Xiantao Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Cancer Progression ◽  
Gut Microbiome ◽  
Intestinal Flora ◽  
Inflammatory Factors ◽  
Cancer Pathogenesis ◽  
Research Findings ◽  
Relationship Of

Abstract Background Lung cancer is the leading cause of cancer-related deaths worldwide (Ferlay et al., Int J Cancer 136:E359–386, 2015). In addition, lung cancer is associated with the highest mortality among all cancer types (Wu et al., Exp Ther Med 16:3004–3010, 2018). Previous studies report that microbiota play an important role in lung cancer. Notably, changes in lung and gut microbiota, are associated with progression of lung cancer. Several studies report that lung and gut microbiome promote lung cancer initiation and development by modulating metabolic pathways, inhibiting the function of immune cells, and producing pro-inflammatory factors. In addition, some factors such as microbiota dysbiosis, affect production of bacteriotoxins, genotoxicity and virulence effect, therefore, they play a key role in cancer progression. These findings imply that lung and gut microbiome are potential markers and targets for lung cancer. However, the role of microbiota in development and progression of lung cancer has not been fully explored. Purpose The aim of this study was to systemically review recent research findings on relationship of lung and gut microbiota with lung cancer. In addition, we explored gut–lung axis and potential mechanisms of lung and gut microbiota in modulating lung cancer progression. Conclusion Pulmonary and intestinal flora influence the occurrence, development, treatment and prognosis of lung cancer, and will provide novel strategies for prevention, diagnosis, and treatment of lung cancer.

scholarly journals Effect of Pentoxifylline on Renal Function and Urinary Albumin Excretion in Patients with Diabetic Kidney Disease: The PREDIAN Trial

2014 ◽  
Vol 26 (1) ◽  
pp. 220-229 ◽  
Author(s):  
Juan F. Navarro-González ◽  
Carmen Mora-Fernández ◽  
Mercedes Muros de Fuentes ◽  
Jesús Chahin ◽  
María L. Méndez ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Urinary Albumin Excretion ◽  
Urinary Albumin ◽  
Diabetic Kidney ◽  
Albumin Excretion

scholarly journals The Role of Gut Microbiota and Diet on Uremic Retention Solutes Production in the Context of Chronic Kidney Disease

Toxins ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 155 ◽  
Author(s):  
Laetitia Koppe ◽  
Denis Fouque ◽  
Christophe Soulage
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota

scholarly journals Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease

Toxins ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 50
Author(s):  
Satoshi Kumakura ◽  
Emiko Sato ◽  
Akiyo Sekimoto ◽  
Yamato Hashizume ◽  
Shu Yamakage ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Kidney Disease ◽  
Mouse Model ◽  
Metabolic Pathways ◽  
Krebs Cycle ◽  
Inflammatory Reactions ◽  
Progression Of Kidney Disease ◽  
Progression Of Renal Failure

Nicotinamide adenine dinucleotide (NAD+) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney disease (CKD) leads to the accumulation of uremic toxins, which induces chronic inflammation. In this study, the role of NAD+ in kidney disease was investigated through the supplementation of nicotinamide (Nam), a precursor of NAD+, to an adenine-induced CKD mouse model. Nam supplementation reduced kidney inflammation and fibrosis and, therefore, prevented the progression of kidney disease. Notably, Nam supplementation also attenuated the accumulation of glycolysis and Krebs cycle metabolites that occurs in renal failure. These effects were due to increased NAD+ supply, which accelerated NAD+-consuming metabolic pathways. Our study suggests that Nam administration may be a novel therapeutic approach for CKD prevention.

scholarly journals Reduced fecal short-chain fatty acids levels and the relationship with gut microbiota in IgA nephropathy

2021 ◽  
Author(s):  
Lingxiong Chai ◽  
Qun Luo ◽  
Kedan Cai ◽  
Kaiyue Wang ◽  
Binbin Xu
Keyword(s):  
Gut Microbiota ◽  
Iga Nephropathy ◽  
Butyric Acid ◽  
Intestinal Flora ◽  
Short Chain Fatty Acids ◽  
Caproic Acid ◽  
Isobutyric Acid ◽  
Control Group ◽  
Β Diversity

Abstract Background: IgA nephropathy(IgAN)) is the common pathological type of glomerular diseases. The role of gut microbiota in mediating "gut-IgA nephropathy" has not received sufficient attention in the previous studies. The purpose of this study was to investigate the changes of fecal short-chain fatty acids(SCFAs), a metabolite of the intestinal microbiota, in patients with IgAN and its correlation with intestinal flora and clinical indicators, and to further investigate the role of the gut-renal axis in IgAN.Methods: There were 29 patients with IgAN and 29 normal control subjects recruited from January 2018 to May 2018. The fresh feces were collected. The fecal SCFAs were measured by gas chromatography/mass spectrometry and gut microbiota was analysed by16S rDNA sequences, followed by estimation of α- and β-diversity. Correlation analysis was performed using the spearman’s correlation test between SCFAs and gut microbiota. Results:The levels of acetic acid, propionic acid, butyric acid, isobutyric acid and caproic acid in the IgAN patients were significantly reduced compared with control group(P<0.05). Butyric acid(r=-0.336, P=0.010) and isobutyric acid(r=-0.298, P=0.022) were negatively correlated with urea acid; butyric acid(r=-0.316, P=0.016) was negatively correlated with urea nitrogen; caproic acid(r=-0.415,P=0.025) showed negative correlation with 24-h urine protein level.Exemplified by the results of α-diversity and β-diversity, the intestinal flora of IgAN patients was significantly different from that of the control group. Acetic acid was positively associated with c_Clostridia(r=0.357, P=0.008), o_Clostridiales(r=0.357, P=0.008) and g_Eubacterium_coprostanoligenes_group(r=0.283, P=0.036). Butyric acid was positively associated with g_Alistipes (r=0.278, P=0.040). The relative abundance of those were significantly decreased in IgAN group compared to control group.Conclusion: The levels of fecal SCFAs in the IgAN patients were reduced, and correlated with clinical parameters and gut microbiota, which may be involved in the pathogenesis of IgAN, and this finding may provide a new therapeutic approach.

scholarly journals The Immunomodulatory Effect of the Gut Microbiota in Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Mingxuan Chi ◽  
Kuai Ma ◽  
Jing Wang ◽  
Zhaolun Ding ◽  
Yunlong Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Intestinal Flora ◽  
Inflammatory Factors ◽  
Renal Diseases

The human gut microbiota is a complex cluster composed of 100 trillion microorganisms, which holds a symbiotic relationship with the host under normal circumstances. Intestinal flora can facilitate the treatment of human metabolic dysfunctions and interact with the intestinal tract, which could influence intestinal tolerance, immunity, and sensitivity to inflammation. In recent years, significant interests have evolved on the association of intestinal microbiota and kidney diseases within the academic circle. Abnormal changes in intestinal microbiota, known as dysbiosis, can affect the integrity of the intestinal barrier, resulting in the bacterial translocation, production, and accumulation of dysbiotic gut-derived metabolites, such as urea, indoxyl sulfate (IS), and p-cresyl sulfate (PCS). These processes lead to the abnormal activation of immune cells; overproduction of antibodies, immune complexes, and inflammatory factors; and inflammatory cell infiltration that can directly or indirectly cause damage to the renal parenchyma. The aim of this review is to summarize the role of intestinal flora in the development and progression of several renal diseases, such as lupus nephritis, chronic kidney disease, diabetic nephropathy, and renal ischemia-reperfusion injury. Further research on these mechanisms should provide insights into the therapeutic potential of regulating intestinal flora and intervening related molecular targets for the abovementioned nephropathy.

The Potential Role of Catheter-Based Renal Sympathetic Denervation in Chronic and End-Stage Kidney Disease

2016 ◽  
Vol 21 (4) ◽  
pp. 344-352 ◽  
Author(s):  
Yusuke Sata ◽  
Markus P. Schlaich
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Kidney Disease ◽  
End Stage Renal Disease ◽  
Renal Denervation ◽  
Potential Role ◽  
Stage Renal Disease ◽  
End Stage ◽  
Renal Sympathetic

Sympathetic activation is a hallmark of chronic and end-stage renal disease and adversely affects cardiovascular prognosis. Hypertension is present in the vast majority of these patients and plays a key role in the progressive deterioration of renal function and the high rate of cardiovascular events in this patient cohort. Augmentation of renin release, tubular sodium reabsorption, and renal vascular resistance are direct consequences of efferent renal sympathetic nerve stimulation and the major components of neural regulation of renal function. Renal afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control via hypothalamic integration. Renal denervation of the kidney has been shown to reduce blood pressure in many experimental models of hypertension. Targeting the renal nerves directly may therefore be specifically useful in patients with chronic and end-stage renal disease. In this review, we will discuss the potential role of catheter-based renal denervation in patients with impaired kidney function and also reflect on the potential impact on other cardiovascular conditions commonly associated with chronic kidney disease such as heart failure and arrhythmias.

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