Gut microbiota: a novel target for exercise-mediated regulation of NLRP3 inflammasome activation

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) is a key pattern recognition in the innate immune system. Its overactivation leads to production of pro-inflammatory cytokines, such as IL-1β and IL-18, which contribute development progression various diseases. In recent years, evidence has shown that gut microbiota plays an important role regulating activation NLRP3 inflammasome. Variations function composition can directly or indirectly influence inflammasome by influencing bacterial components metabolites. Additionally, exercise been effectively reduce while promoting beneficial changes microbiota. This suggests may play mediating effects on regulation. review explores impact activation, examines mechanisms through mediates anti-inflammatory exercise, providing new avenues for research.

Language: Английский

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Dynamic Changes in Gut Microbiota-Derived Metabolite Trimethylamine-N-Oxide and Risk of Type 2 Diabetes Mellitus: Potential for Dietary Changes in Diabetes Prevention

Nutrients, Journal Year: 2024, Volume and Issue: 16(11), P. 1711 - 1711

Published: May 30, 2024

Background: A gut-microbial metabolite, trimethylamine N-oxide (TMAO), has been associated with type 2 diabetes mellitus (T2DM). Few previous prospective studies have addressed associations between the changes in TMAO and T2DM incidence. Methods: Data were derived from a longitudinal cohort conducted 2019 to 2021 rural areas of Fuxin County, Liaoning Province, China, 1515 diabetes-free participants aged above 35 years included. The concentrations serum its precursors measured at two time points, namely 2021. (ΔTMAO) separately tested logistic regression model. For further examination, odds ratios (ORs) for calculated according combination levels ΔTMAO levels. Results: During median follow-up 1.85 years, 81 incident cases (5.35%) identified. Baseline exhibited nonlinear relationship, first decreasing then increasing, only highest quartile was it risk T2DM. OR 3.35 (95%CI: 1.55–7.26, p = 0.002), compared lowest quartile. As precursors, choline level Q3 Q4 3.37 1.41–8.05, 0.006) 4.72 1.47–15.13, 0.009), respectively. When considering both baseline over time, sustained high demonstrated significantly increased T2DM, multivariable-adjusted 8.68 1.97, 38.34). Conclusion: Both initial long-term collectively occurrence subsequent events. Interventions aimed normalizing levels, such as adopting healthy dietary pattern, may be particularly beneficial prevention.

Language: Английский

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Targeting Gut microbiota as a therapeutic target in T2DM: a review of Multi-target interactions of probiotics, prebiotics, postbiotics, and synbiotics with the Intestinal Barrier

Pharmacological Research, Journal Year: 2024, Volume and Issue: 210, P. 107483 - 107483

Published: Nov. 8, 2024

The global epidemic of type 2 diabetes mellitus (T2DM) imposes a substantial burden on public health and healthcare expenditures, thereby driving the pursuit cost-effective preventive therapeutic strategies. Emerging evidence suggests potential association between dysbiosis gut microbiota its metabolites with T2DM, indicating that targeted interventions aimed at modulating may represent promising approach for management T2DM. In this review, we concentrated multifaceted interactions intestinal barrier in context We systematically summarized imbalance beneficial constitute viable Meanwhile, mechanisms by which interventions, such as probiotics, prebiotics, postbiotics, synbiotics, synergistically improve insulin resistance T2DM are summarized. These include restoration structure, upregulation epithelial cell proliferation differentiation, enhancement tight junction protein expression, promotion mucin secretion goblet cells, immunosuppressive functions regulatory T cells (Treg) M2 macrophages. Collectively, these actions contribute to amelioration body's metabolic inflammatory status. Our objective is furnish supports clinical application postbiotics

Language: Английский

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Nano-engineered probiotic treats atherosclerosis via inhibiting intestinal microbiota-TMA-TMAO axis

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Considerable numbers of patient are suffering from atherosclerosis without typical risk factors, which can cause severe cardiovascular complication but is lack practical treatment. Thereinto, trimethylamine N-oxide (TMAO), originated enteric microorganism, emerges as an unconventional and crucial factor causing atherosclerosis. Here we demonstrate a strategy to inhibit TMAO through intestinal microbiota-trimethylamine (TMA)-TMAO axis for atherosclerotic The therapy performed by oral-treated nano-engineered probiotic PDMF@LGG, where the Lacticaseibacillus rhamnosus GG (LGG) armed with polydopamine coating conjugated PMF nanoparticles based on ROS-responsive polymeric prodrug fluoromethylcholine (FMC). PDMF@LGG durably colonize canal due sticky protection against ROS-induced injury. ROS trigger delivery FMC nanoparticles, TMA production in microorganisms. Meanwhile, LGG strengthen tight junctions epithelium reduce entering blood. in vivo study suggests that reduces plasma suppresses progression. Furthermore, microbiomics metabolomics show also regulates gut microbial composition various metabolites, assisting therapeutic outcome. Together, offers potential candidate caused broadens range treatable

Language: Английский

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Exploring the Cardiovascular Benefits of Extra Virgin Olive Oil: Insights into Mechanisms and Therapeutic Potential

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 284 - 284

Published: Feb. 14, 2025

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, driven by complex interactions among genetic, environmental, and lifestyle factors, with diet playing a pivotal role. Extra Virgin Olive Oil (EVOO), cornerstone Mediterranean (MedDiet), is plant-based fat that has garnered attention for its robust cardiovascular benefits, which attributed to unique composition monounsaturated fatty acids (MUFAs), particularly oleic acid (OA); bioactive polyphenols, such as Hydroxytyrosol (HT) oleocanthal. These compounds collectively exert antioxidant, anti-inflammatory, vasodilatory, lipid-modulating effects. Numerous clinical preclinical studies have demonstrated EVOO's properties reduce major modifiable risk including hypertension, dyslipidemia, obesity, type 2 diabetes. EVOO also promotes endothelial function increasing nitric oxide (NO) bioavailability, thus favoring vasodilation, lowering blood pressure (BP), supporting vascular integrity. Furthermore, it modulates biomarkers health, C-reactive protein, low-density lipoprotein (LDL) cholesterol, NT-proBNP, aligning improved hemostatic balance reduced arterial vulnerability. Emerging evidence highlights interaction gut microbiota, further augmenting cardioprotective This review synthesizes current evidence, elucidating multifaceted mechanisms action therapeutic potential. Future directions emphasize need advanced extraction techniques, nutraceutical formulations, personalized dietary recommendations maximize health benefits. represents valuable addition strategies aimed at reducing global burden diseases.

Language: Английский

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Trimethylamine N-oxide (TMAO) treatment triggers premature ovarian insufficiency (POI) via the activation of mitochondrial pathway apoptosis in granulosa cells

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Premature ovarian insufficiency (POI) is characterized by follicular development failure or dysplasia, therefore causing the lack of normal function before 40 years age. Trimethylamine N-oxide (TMAO) a metabolite high choline diet rich in red meat and directly associated with gut microbiota. Correlation TMAO level female fertility decline has been shown; however, its mechanism largely unknown. To unveil which affects reproductive function, we established TMAO-treated mouse model exhibited pathological manifestations POI including increased follicle-stimulating hormone luteinizing levels, decreased estradiol anti-Müllerian reduced growing mature follicles, atretic fertility. Meanwhile, these mice showed an apoptosis ratio damaged mitochondrial granulosa cells, nursing supporting cells for oocyte development. Moreover, treatment significantly elevated oxidative stress antioxidative capacity whereas antioxidants N-acetylcysteine alleviated such detriment. Mechanism investigation demonstrated that up-regulated phosphatase tensin homolog expression levels thereby inhibiting phosphorylation AKT subsequently BCL-2-associated X protein, key molecule mitochondria pathway, leading to cell apoptosis. Our findings documented TMAO-induced POI, may provide potential target curing clinically.

Language: Английский

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Gut microbiota and its metabolites regulate insulin resistance: traditional Chinese medicine insights for T2DM

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: March 19, 2025

The gut microbiota is closely associated with the onset and development of type 2 diabetes mellitus (T2DM), characterized by insulin resistance (IR) chronic low-grade inflammation. However, despite widespread use first-line antidiabetic drugs, IR in its complications continue to rise. metabolic products may promote T2DM exacerbating IR. Therefore, regulating has become a promising therapeutic strategy, particular attention given probiotics, prebiotics, synbiotics, fecal transplantation. This review first examines relationship between T2DM, summarizing research progress microbiota-based therapies modulating We then delve into how microbiota-related contribute Finally, we summarize findings on role traditional Chinese medicine improve In conclusion, play crucial pathophysiological process IR, offering new insights potential strategies for T2DM.

Language: Английский

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IL-6 Affects Liver Metabolic Abnormalities Caused by Silicon Exposure by Regulating the PKC/YY1 Signaling Pathway

Genes, Journal Year: 2025, Volume and Issue: 16(4), P. 456 - 456

Published: April 16, 2025

Background: This study aims to investigate the impact of coal dust (silicon dioxide) exposure on dyslipidemia and its underlying mechanisms, with a focus association between hepatic metabolic disorders. Methods: Clinical data were collected from 5433 mine workers compare incidence dust-exposed group non-exposed group. A mouse model silicon dioxide was established observe fat accumulation pathological changes. Liver tissue sequencing performed screen for key differential genes. In vitro cell experiments utilized identify molecular mechanisms hepatocyte abnormalities induced by exposure. Results: revealed that 69.2% miners in developed dyslipidemia, which higher than 30.7% Animal showed led deposition damage, degree injury positively correlated time. identified significant upregulation FMO3 (flavin monooxygenase 3) gene liver following exposure, accompanied enhanced inflammatory responses. Mechanistic studies demonstrated activates Kupffer cells secrete IL-6 (interleukin-6), induces high expression hepatocytes through PKC/YY1 signaling pathway, thereby disrupting lipid metabolism. Conclusions: Silicon can promote activating release via ultimately leading disorders

Language: Английский

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Gut Microbiota Metabolites and Chronic Diseases: Interactions, Mechanisms, and Therapeutic Strategies

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3752 - 3752

Published: April 16, 2025

The gut microbiota, shaped by factors such as diet, lifestyle, and genetics, plays a pivotal role in regulating host metabolism, immune function, overall health. diversity balance of the microbiota are closely linked to onset progression various chronic diseases. A growing body evidence has demonstrated that alterations composition, metabolites significantly associated with cardiovascular diseases, including hypertension, atherosclerosis, heart failure; metabolic disorders obesity, type 2 diabetes, dysfunction-associated steatotic liver disease; gastrointestinal conditions like inflammatory bowel disease colorectal cancer. Despite substantial advances microbiome research, challenges remain fully elucidating causal relationships between disease, well translating these insights into clinical applications. This review aims investigate regulatory pathways via which affects health, disease. Additionally, it highlights emerging strategies for prevention treatment conditions, focusing on microbiota-targeted therapies personalized dietary interventions promising approaches improving health outcomes.

Language: Английский

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Probiotics: A potential strategy for improving diabetes mellitus complicated with cognitive impairment

Microbiological Research, Journal Year: 2024, Volume and Issue: 290, P. 127960 - 127960

Published: Nov. 1, 2024

Language: Английский

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