The Role of the Gut Microbiota in the Pathogenesis of Diabetes

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(1), P. 480 - 480

Published: Jan. 1, 2022

Diabetes mellitus is a significant clinical and therapeutic problem because it can lead to serious long-term complications. Its pathogenesis not fully understood, but there are indications that dysbiosis play role in the development of diabetes, or appears during course disease. Changes microbiota composition observed both type 1 diabetes (T1D) 2 (T2D) patients. These modifications associated with pro-inflammation, increased intestinal permeability, endotoxemia, impaired β-cell function insulin resistance. This review summarizes gut healthy individuals changes bacterial be T1D T2D. It also presents new developments therapy based on influencing as promising method alter diabetes. Moreover, highlights lacking data suggests future directions needed prove causal relationship between

Language: Английский

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Moutan Cortex polysaccharide ameliorates diabetic kidney disease via modulating gut microbiota dynamically in rats

International Journal of Biological Macromolecules, Journal Year: 2022, Volume and Issue: 206, P. 849 - 860

Published: March 17, 2022

Language: Английский

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New insights into the role of immunity and inflammation in diabetic kidney disease in the omics era

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 29, 2024

Diabetic kidney disease (DKD) is becoming the leading cause of chronic disease, especially in industrialized world. Despite mounting evidence has demonstrated that immunity and inflammation are highly involved pathogenesis progression DKD, underlying mechanisms remain incompletely understood. Substantial molecules, signaling pathways, cell types participate DKD inflammation, by integrating into a complex regulatory network. Most studies have focused on individual components, without presenting their importance global or system-based processes, which largely hinders clinical translation. Besides, conventional technologies failed to monitor different behaviors resident renal cells immune cells, making it difficult understand contributions DKD. Recently, advancement omics including genomics, epigenomics, transcriptomics, proteomics, metabolomics revolutionized biomedical research, allows an unbiased analysis changes DNA, RNA, proteins, metabolites settings, even at single-cell spatial resolutions. They help us identify critical regulators processes provide overview heterogeneity This review aims summarize application multiple field emphasize latest interplay revealed these technologies, will new insights role lead development novel therapeutic approaches diagnostic biomarkers.

Language: Английский

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Lipid metabolism disorder in diabetic kidney disease

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: April 29, 2024

Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, droplets, and bile acids (BAs). Altered metabolism serves as crucial pathogenic mechanism DKD, potentially intertwined cellular ferroptosis, lipophagy, reprogramming, immune modulation gut microbiota (thus impacting the liver-kidney axis). elucidation these mechanisms opens new potential therapeutic pathways for management. This research explores link between disruptions onset.

Language: Английский

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

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Nov. 24, 2021

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

Language: Английский

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Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associatied with increasing effect on the gut microbiota in db/db mice

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 26, 2023

Background The intestinal microbiota disorder gradually aggravates during the progression of diabetes. Dapagliflozin (DAPA) can improve diabetes and diabetic kidney disease(DKD). However, whether gut plays a role in protection DAPA for DKD remains unclear. Methods To investigate effects on composition disease progression, our study, we performed 16S rRNA gene sequencing fecal samples from db/m mice (control group), db/db (DKD model those treated with (treat group) at three timepoints 14weeks\18weeks\22weeks. Results We found that remarkably prevented weight loss lowered fasting blood glucose eventually delaying DKD. Intriguingly, study strongly suggested there is aggravated dysbacteriosis increased bile acid development More importantly, comparisons relative abundance phylum level partial least squares-discriminant analysis (PLS-DA) plots roughly reflected effect modulating flora time. Specifically, dominant Firmicutes Bacteroidetes was not meaningfully changed among groups 14 weeks as previous studies described. Interestingly, they were altered treat group compared to more protracted intervention 18 22 weeks. Furthermore, decrease Lactobacillus increase norank_f:Muribaculaceae could account differences observed between Conclusion firstly protective may be related dynamic improvement over time, possibly associated impact pool its antioxidation effect.

Language: Английский

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Phenylsulfate-induced oxidative stress and mitochondrial dysfunction in podocytes are ameliorated by Astragaloside IV activation of the SIRT1/PGC1α /Nrf1 signaling pathway

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117008 - 117008

Published: June 19, 2024

Astragaloside IV (AS-IV) exhibits diverse biological activities. Despite this, the detailed molecular mechanisms by which AS-IV ameliorates diabetic nephropathy (DN) and shields podocytes from oxidative stress (OS) mitochondrial dysfunction remain poorly understood. In this study, we used biochemical assays, histopathological analysis, Doppler ultrasound, transmission electron microscopy，flow cytometry, fluorescence staining, Western blotting other methods. was administered to db/db mice for in vivo experimentation. Our findings indicated that treatment significantly reduced diabetes-associated markers, proteinuria, kidney damage. It also diminished ROS levels kidney, enhanced expression of endogenous antioxidant enzymes, improved health. Phenyl sulfate (PS), a protein-bound uremic solute enteric origin, has been closely linked with DN represents promising avenue further research. vitro, PS exposure induced OS podocytes, increasing while decreasing enzyme activity (Catalase, Heme Oxygenase-1, Superoxide Dismutase, Glutathione Peroxidase). inhibitors (N-acetyl-L-cysteine, NAC) as positive control group can reduce restore enzymes protein levels. Additionally, markers associated biosynthesis function (SIRT1, PGC1α, Nrf1, TFAM). These adverse effects were partially reversed treatment. However, co-treatment SIRT1 inhibitor EX527 failed these indicators. Overall, our study demonstrates effectively attenuates mitigates PS-induced via SIRT1/PGC1α/Nrf1 pathway.

Language: Английский

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Exercise in Diabetic Nephropathy: Protective Effects and Molecular Mechanism

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3605 - 3605

Published: March 23, 2024

Diabetic nephropathy (DN) is a serious complication of diabetes, and its progression influenced by factors like oxidative stress, inflammation, cell death, fibrosis. Compared to drug treatment, exercise offers cost-effective low-risk approach slowing down DN progression. Through multiple ways mechanisms, helps control blood sugar pressure reduce serum creatinine albuminuria, thereby alleviating kidney damage. This review explores the beneficial effects on improvement highlights potential mechanisms for ameliorating DN. In-depth understanding role mechanism in improving would pave way formulating safe effective programs treatment prevention

Language: Английский

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Molecular mechanisms of gut microbiota in diabetic nephropathy

Diabetes Research and Clinical Practice, Journal Year: 2024, Volume and Issue: 213, P. 111726 - 111726

Published: June 4, 2024

Language: Английский

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Reno-protective Effects of Empagliflozin in High Fat Diet Induced Obesity-Related Glomerulopathy by Regulation of Gut-Kidney Axis

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 327(4), P. C994 - C1011

Published: Aug. 26, 2024

The increasing prevalence of obesity-related glomerulopathy (ORG) poses a significant threat to public health. Sodium-glucose cotransporter-2 (SGLT2) inhibitors effectively reduce body weight and total fat mass in individuals with obesity halt the progression ORG. However, underlying mechanisms their reno-protective effects ORG remain unclear. We established high-fat diet-induced model using C57BL/6J mice, which were divided into three groups: normal chow diet (NCD group), (HFD) mice treated placebo (ORG HFD empagliflozin (EMPA group). conducted 16S ribosomal RNA gene sequencing feces analyzed metabolites from kidney, feces, liver, serum samples. showed increased urinary albumin creatinine ratio, cholesterol, triglyceride levels, glomerular diameter compared NCD (all P < 0.05). EMPA treatment significantly alleviated these parameters Multitissue metabolomics analysis revealed lipid metabolic reprogramming was altered by treatment. MetOrigin close association between EMPA-related pathways gut microbiota alterations, characterized reduced abundances Firmicutes Desulfovibrio abundance Akkermansia homeostasis especially metabolism, disrupted closely associated contributing improved kidney function morphology regulating metabolism through gut-kidney axis, highlighting novel therapeutic approach for NEW & NOTEWORTHY Our study uncovered that (EMPA) potentially protects renal axis. EMPA's are glycerophospholipid pantothenate/CoA synthesis pathways. modulation appears be pivotal suppressing glycerol 3-phosphate CoA synthesis. insights microbiota-host interactions offer

Language: Английский

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