Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway

Gut Microbes, Год журнала: 2024, Номер 16(1)

Опубликована: Май 10, 2024

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific and underlying mechanism involved CKD-VC. identified increased abundance Prevotella copri (P. copri) feces CKD rats (induced by using 5/6 nephrectomy followed a high calcium phosphate diet) with aortic via amplicon sequencing 16S rRNA genes. In patients CKD, we further confirmed positive correlation between P. scores. Moreover, oral administration live aggravated CKD-related VC osteogenic differentiation smooth muscle cells vivo, accompanied intestinal destruction, enhanced expression Toll-like receptor-4 (TLR4), elevated lipopolysaccharide (LPS) levels. vitro ex vivo experiments consistently demonstrated copri-derived LPS (Pc-LPS) accelerated phosphate-induced VSMC differentiation. Mechanistically, Pc-LPS bound TLR4, then activated nuclear factor κB (NF-κB) nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome signals during VC. Inhibition NF-κB reduced NLRP3 attenuated Pc-LPS-induced calcification. Our study clarifies novel VC, mechanisms involving inflammation-regulating metabolites including Pc-LPS, activation NF-κB/NLRP3 signaling pathway. These findings highlight its-derived as potential therapeutic targets for CKD.

Язык: Английский

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Relationship between gut microbiota and vascular calcification in hemodialysis patients

Renal Failure, Год журнала: 2023, Номер 45(1)

Опубликована: Янв. 12, 2023

Vascular calcification (VC) is an independent risk factor for cardiovascular mortality in end-stage renal disease (ESRD) patients. The pathogenesis of VC complicated and unclear. Uremic toxins produced by gut microbiota can promote VC. This study aims to identify the differences between different groups main bacteria associated with hemodialysis (HD) patients attempt open up new preventive therapeutic approaches define probable mechanism HD future.A total 73 maintenance were enrolled this cross-sectional study. According abdominal aortic (AAC) scores, participants divided into high AAC score group low group. High-throughput sequencing was performed results evaluated alpha diversity, beta species correlation, model predictive analyses.The prevalence 54.79% (40/73) majority phyla two same, including Firmicutes, Actinobacteriota, Proteobacteria, Bacteroidota. microbial diversity had a decreasing trend (p = 0.050), abundance significantly lower 0.044) than that scores showed increased Proteobacteria decreased abundances Bacteroidota Synergistota at phylum level; Escherichia-Shigella, Ruminococcus_gnavus_group, Lactobacillus; Ruminococcus Lachnospiraceae_NK4A136_group genus level (p<0.05). Escherichia-Shigella Ruminococcus_gnavus_group positively correlated VC, Ruminococcus, Adlercreutzia, Alistipes, norank_f__Ruminococcaceae negatively greatest influence on patients, followed Butyricimonas.Our provide clinical evidence there difference lipopolysaccharide (LPS)-producing bacterium, short-chain fatty acid (SCFA)-producing second strongest underlying worth studying. These findings hint target.

Язык: Английский

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Biomimetic Grapefruit-Derived Extracellular Vesicles for Safe and Targeted Delivery of Sodium Thiosulfate against Vascular Calcification

ACS Nano, Год журнала: 2023, Номер 17(24), С. 24773 - 24789

Опубликована: Дек. 6, 2023

As the prevalence of vascular calcification (VC), a strong contributor to cardiovascular morbidity and mortality, continues increase, need for pharmacologic therapies becomes urgent. Sodium thiosulfate (STS) is clinically approved drug therapy against VC; however, its efficacy hampered by poor bioavailability severe adverse effects. Plant-derived extracellular vesicles have provided options VC treatment since they can be used as biomimetic carriers with higher biosafety targeting abilities than artificial carriers. Inspired natural grapefruit-derived (EVs), we fabricated nanocarrier comprising EVs loaded STS further modified hydroxyapatite crystal binding peptide (ESTP) VC-targeted delivery STS. In vitro, ESTP nanodrug exhibited excellent cellular uptake capacity calcified smooth muscle cells (VSMCs) subsequently inhibited VSMCs calcification. mice model, showed preferentially highest accumulation in arteries compared other groups. Mechanistically, significantly prevented via driving M2 macrophage polarization, reducing inflammation, suppressing bone-vascular axis demonstrated inhibiting osteogenic phenotype trans-differentiation while enhancing bone quality. addition, did not induce hemolysis or cause any damage organs. These results suggest that prove promising agent without concern systemic toxicity.

Язык: Английский

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Biomimetic wrinkled prebiotic microspheres with enhanced intestinal retention for hyperphosphatemia and vascular calcification

Science Advances, Год журнала: 2025, Номер 11(3)

Опубликована: Янв. 17, 2025

It is urgent for patients with chronic kidney disease (CKD) to develop a robust and facile therapy effective control of serum phosphate reasonable regulation gut microbiota, which are aiming prevent cardiovascular calcification reduce complications. Here, bioinspired by intestinal microstructures, we developed biomimetic wrinkled prebiotic-containing microspheres enhanced retention absorption reducing hyperphosphatemia vascular CKD model rats. The resultant CSM@5 exhibited favorable binding capacity in vitro could effectively concentration phosphorous vivo. Through increasing the beneficial bacteria decreasing harmful tract, these prebiotic can modulate microbiota then ameliorate notably. This feasible approach may offer potential strategy treatment prevention its

Язык: Английский

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Vascular Calcification and the Gut and Blood Microbiome in Chronic Kidney Disease Patients on Peritoneal Dialysis: A Pilot Study

Biomolecules, Год журнала: 2022, Номер 12(7), С. 867 - 867

Опубликована: Июнь 21, 2022

Vascular calcification (VC) is a frequent condition in chronic kidney disease (CKD) and well-established risk factor for the development of cardiovascular (CVD). Gut dysbiosis may contribute to CVD inflammation CKD patients. Nonetheless, role gut blood microbiomes CKD-associated VC remains unknown. Therefore, this pilot study aimed explore link between patients on peritoneal dialysis (CKD-PD). Our results showed relative changes specific taxa CKD-PD with without VC, namely Coprobacter, Coprococcus 3, Lactobacillus, Eubacterium eligens group gut, Cutibacterium, Pajaroellobacter, Devosia, Hyphomicrobium, Pelomonas blood. An association all-cause mortality was also observed, higher corroborate Devosia genus Although we did not find differences uremic toxins, intestinal translocation markers, inflammatory parameters among soluble CD14 (sCD14), nonspecific marker monocyte activation, positively correlated severity. group, circulating sCD14 should be further explored as biomarkers CVD, CKD.

Язык: Английский

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An Overview of Chronic Kidney Disease Pathophysiology: The Impact of Gut Dysbiosis and Oral Disease

Biomedicines, Год журнала: 2023, Номер 11(11), С. 3033 - 3033

Опубликована: Ноя. 12, 2023

Chronic kidney disease (CKD) is a severe condition and significant public health issue worldwide, carrying the burden of an increased risk cardiovascular events mortality. The traditional factors that promote onset progression CKD are cardiometabolic like hypertension diabetes, but non-traditional contributors escalating. Moreover, gut dysbiosis, inflammation, impaired immune response emerging as crucial mechanisms in pathology. microbiome exert reciprocal influence commonly referred to "the gut-kidney axis" through induction metabolic, immunological, endocrine alterations. Periodontal diseases strictly involved axis for their impact on microbiota composition metabolic immunological alterations occurring reciprocally affecting both conditions. This review aims provide overview dynamic biological interconnections between oral status, gut, renal pathophysiology, spotlighting oral-gut-kidney raising whether periodontal can be modifiers CKD. By doing so, we try offer new insights into therapeutic strategies may enhance clinical trajectory patients, ultimately advancing our quest improved patient outcomes well-being.

Язык: Английский

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Interplay between gut microbiota, bone health and vascular calcification in chronic kidney disease

European Journal of Clinical Investigation, Год журнала: 2021, Номер 51(9)

Опубликована: Май 5, 2021

Abstract Deregulations in gut microbiota may play a role vascular and bone disease chronic kidney (CKD). As glomerular filtration rate declines, the colon becomes more important as site of excretion urea uric acid, an increased bacterial proteolytic fermentation alters microbial balance. A diet with limited amounts fibre, well certain medications (eg phosphate binders, iron supplementation, antibiotics) further contribute to changes composition among CKD patients. At same time, both calcification are common patients advanced disease. This narrative review describes emerging evidence on dysbiosis, calcification, demineralization their interrelationship termed ‘gut‐bone‐vascular axis’ progressive CKD. The diet, metabolites (ie indoxyl sulphate, p‐cresyl trimethylamine N‐oxide (TMAO) short‐chain fatty acids (SCFA)), vitamin K deficiency, inflammatory cytokines impact health discussed. framework open up novel preventive therapeutic approaches targeting microbiome attempt improve cardiovascular

Язык: Английский

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Chronic kidney disease mineral bone disorder in childhood and young adulthood: a ‘growing’ understanding

Pediatric Nephrology, Год журнала: 2023, Номер 39(3), С. 723 - 739

Опубликована: Авг. 25, 2023

Abstract Chronic kidney disease (CKD) mineral and bone disorder (MBD) comprises a triad of biochemical abnormalities (of calcium, phosphate, parathyroid hormone vitamin D), (turnover, mineralization growth) extra-skeletal calcification. Mineral dysregulation leads to demineralization causing pain an increased fracture risk compared healthy peers. Vascular calcification, with hydroxyapatite deposition in the vessel wall, is part CKD-MBD spectrum and, turn, vascular stiffness, left ventricular hypertrophy very high cardiovascular mortality risk. While growing requires excess calcium can deposit vessels, such that intake calcium- containing medications dialysate need be carefully regulated. Normal physiological continues into third decade life, many years beyond rapid growth childhood adolescence, implying skeletal requirements are much higher younger people elderly. Much research link between (de)mineralization calcification CKD has been performed older adults these data must not extrapolated children or adults. In this article, we explore changes turnover young adults, pathophysiology potential Graphical abstract

Язык: Английский

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Bibliometric Analysis of the Relationship between Gut Microbiota and Chronic Kidney Disease from 2001–2022

Integrative Medicine in Nephrology and Andrology, Год журнала: 2024, Номер 11(1)

Опубликована: Янв. 30, 2024

ABSTRACT Background: The gut microbiota is closely associated with chronic kidney disease (CKD) development and prognosis. However, a comprehensive understanding of publication trends research focuses within this domain remains limited. This study aimed to elucidate the relationship between CKD through bibliometric analysis. Methods: Literature published 2001 2022 on was obtained from Web Science Core Collection database. Bibliometric analysis tools such as VOSviewer CiteSpace were used analyze in area. Results: We extracted 758 articles for further China ranked first 240 documents, followed by USA 211. regarding citation frequency 11,380 citations, while second. University California Irvine Kidney International emerged leading institution journal, respectively, former document production citations. Although featured fewer documents than other journals, it exhibited highest count. keywords representing interests mainly included: (1) influences CKD, (2) application probiotics treatment (3) potential mechanism CKD. Conclusion: Our indicates significant advancements association It also provides overview trends, hotspots, frontiers, which may provide guidelines future research.

Язык: Английский

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Osteoporosis and vascular calcifications

Endocrine Connections, Год журнала: 2023, Номер 12(11)

Опубликована: Сен. 12, 2023

In post-menopausal women, aged individuals, and patients with diabetes mellitus or chronic renal disease, bone mineral density (BMD) decreases while the vasculature accumulates arterial calcifications (ACs). AC can be found in tunica intima and/or media. Prospective studies have shown that initially low BMD presence of fragility fractures at follow-up a significantly increased risk for coronary cerebrovascular events overall cardiovascular mortality. Similarly, presenting abdominal aorta (an easily quantifiable marker vascular pathology) show significant decrease (and an increase fragility) bones irrigated by branches aorta, such as hip lumbar spine. induction is ectopic tissue biomineralization process promoted osteogenic transdifferentiation smooth muscle cells well local systemic secreted factors. many cases, same regulatory molecules modulate metabolism but reverse. Investigation animal vitro models has identified several potential mechanisms this reciprocal bone-vascular regulation, vitamin K D sufficiency, advanced glycation end-products-RAGE interaction, osteoprotegerin/RANKL/RANK, Fetuin A, oestrogen deficiency phytooestrogen supplementation, microbiota its relation to diet, among others. Complete elucidation these mechanisms, their clinical validation via controlled studies, will provide basis pharmacological intervention could simultaneously promote health.

Язык: Английский

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