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

Frontiers in Microbiology, Год журнала: 2025, Номер 15

Опубликована: Янв. 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.

Язык: Английский

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Chaihuang Qingfu Pills Protect Against Acute Pancreatitis—Associated Acute Lung Injury Through MMP9-NLRP3-Pyroptosis Pathway

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 2317 - 2338

Опубликована: Фев. 1, 2025

Severe acute pancreatitis associated with lung injury (SAP-ALI) is a critical condition high mortality rate. Investigating the pathogenesis of SAP-ALI and developing effective treatments are urgently needed. Chaihuang Qingfu Pills (CHQF), traditional Chinese medicine modified from Qingyi Decoction, has been approved for treating (AP). However, its role in underlying mechanisms remain unclear. 92 AP patients were enrolled to observe protective effect CHQF on AP-ALI. L-arginine was used establish animal model. UHPLC-MS/MS identify components absorbed into serum. Transcriptomics analysis, network pharmacology, proteomics approaches explore molecular mechanism. In vivo vitro experiments conducted validate relevant findings. Clinical data indicated reduced incidence ALI 58.33% 36.36% patients. Animal demonstrated that decreased mortality, attenuated organ damage, inhibited systemic inflammation pathological SAP mice. Differential expression analysis weighted gene co-expression (WGCNA) identified 146 SAP-related differentially expressed genes (DEGs) GSE194331 dataset. acquired 26 blood 271 therapeutic targets. Integrated obtained 52 core targets SAP. Proteomic 216 proteins treatment SAP-ALI. Joint found MMP9 NLRP3 only common Both confirmed levels pyroptosis alveolar macrophages (AMs) under conditions. Moreover, inhibitor suppressed AMs pyroptosis. exerted by inhibiting macrophage through MMP9-NLRP3 pathway, providing novel strategy

Язык: Английский

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Causal link between gut microbiota and four types of pancreatitis: a genetic association and bidirectional Mendelian randomization study

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 23, 2023

Background A number of recent observational studies have indicated a correlation between the constitution gut microbiota and incidence pancreatitis. Notwithstanding, are unreliable for inferring causality because their susceptibility to confounding, bias, reverse causality, causal relationship specific pancreatitis is still unclear. Therefore, our study aimed investigate four types Methods An investigative undertaking encompassing genome-wide association (GWAS) comprising 18,340 participants was undertaken with aim discerning genetic instrumental variables that exhibit associations microbiota, The aggregated statistical data pertaining acute (AP), alcohol-induced AP (AAP), chronic (CP), CP (ACP) were acquired from FinnGen Consortium. two-sample bidirectional Mendelian randomization (MR) approach utilized. Utilizing Inverse-Variance Weighted (IVW) technique as cornerstone primary analysis. Bonferroni analysis used correct multiple testing, In addition, sensitivity methodologies, MR-Egger intercept test, Cochran’s Q MR polymorphism residual outlier (MR-PRESSO) leave-one-out performed evaluate robustness findings. Results total 28 intestinal microflora ascertained significant diverse outcomes Among them, Class Melainabacteria (OR = 1.801, 95% CI: 1.288–2.519, p 0.008) has strong ACP after Bonferroni-corrected in order assess potential causation effects, we exposure variable scrutinized its impact on outcome variable, this revealed 30 distinct microflora. implementation test lack substantial heterogeneity among various single nucleotide polymorphisms (SNP). Conclusion Our first systematic provides evidence taxa may be causally associated disease. This discovery contribute biomarkers conducive preliminary, non-invasive identification Pancreatitis. Additionally, it could present viable targets therapeutic interventions disease’s treatment.

Язык: Английский

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Preventive Effect of the Total Polyphenols from Nymphaea candida on Sepsis-Induced Acute Lung Injury in Mice via Gut Microbiota and NLRP3, TLR-4/NF-κB Pathway

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4276 - 4276

Опубликована: Апрель 12, 2024

This study aimed to investigate the preventive effects of total polyphenols from Nymphaea candida (NCTP) on LPS-induced septic acute lung injury (ALI) in mice and its mechanisms. NCTP could significantly ameliorate tissue pathological as well wet/dry ratio MPO activities (p < 0.05). decrease blood leukocyte, neutrophil, monocyte, basophil, eosinophil amounts LPS contents ALI compared with model group 0.05), improving lymphocyte Moreover, group, TNF-α, IL-6, IL-1β levels 0.05) downregulate protein expression TLR4, MyD88, TRAF6, IKKβ, IκB-α, p-IκB-α, NF-κB p65, p-NF-κB NLRP3, ASC, Caspase1 tissues Furthermore, inhibit ileum histopathological injuries, restoring tight junctions by increasing ZO-1 occludin. Simultaneously, reverse gut microbiota disorder, restore diversity microbiota, increase relative abundance Clostridiales Lachnospiraceae, enhance content SCFAs (acetic acid, propionic butyric acid) feces. These results suggested that has ALI, mechanism is related regulation SCFA metabolism, TLR-4/NF-κB NLRP3 pathways.

Язык: Английский

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Targeting the AMPK/Nrf2 Pathway: A Novel Therapeutic Approach for Acute Lung Injury

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 4683 - 4700

Опубликована: Июль 1, 2024

ALI(acute lung injury) is a severe respiratory dysfunction caused by various intrapulmonary and extrapulmonary factors. It primarily characterized oxidative stress affects the integrity of pulmonary barrier. In cases, ALI can progress to ARDS(acute distress syndrome), condition that poses serious threat lives affected patients. To date, etiological mechanisms underlying remain elusive, available therapeutic options are quite limited. AMPK(AMP-activated protein kinase), an essential serine/threonine kinase, performs pivotal function in regulation cellular energy levels regulatory mechanisms, including detection redox signals mitigating stress. Meanwhile, Nrf2(nuclear factor erythroid 2-related 2), critical transcription factor, alleviates inflammation responses interacting with multiple signaling pathways contributing modulation enzymes associated programmed cell death. Indeed, AMPK induces dissociation Nrf2 from Keap1(kelch-like ECH-associated protein-1) facilitates its translocation into nucleus trigger downstream antioxidant genes, ultimately suppressing expression inflammatory cells lungs. Given their roles, hold promise as novel treatment targets for ALI. This study aimed summarise current status research on AMPK/Nrf2 pathway ALI, encompassing recently reported natural compounds drugs activate alleviate injury, provide theoretical reference early intervention injury future protection.

Язык: Английский

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Causal Relationship between Gut Microbiota, Plasma Metabolites, and Acute Pancreatitis: An Exploratory Mendelian Randomization Study

Опубликована: Янв. 1, 2025

Background: Emerging evidence suggests a significant correlation between pancreatitis and gut microbiota, yet the causal relationship underlying mechanism remain largely undetermined. Given that microbiota plays crucial role in regulating circulating metabolites, we aimed to elucidate how these interactions impact risk of acute (AP).Methods: Using two-sample Mendelian randomization (MR) analysis, investigated links among plasma AP. Enrichment analysis was performed determine primary metabolite classes metabolic pathways associated with AP risk.Findings: The MR revealed 18 microbial taxa 59 metabolites effects on Furthermore, mediation identified seven as potential intermediaries pathway from AP, emphasizing critical carbohydrate metabolism via polyol fructolysis, well lipid homeostasis, disease's pathogenesis.Interpretation: Our systematic study provided comprehensive characterization causally novel mediating microbiota's effect risk. These findings provide new insights into microbiome-related signatures influencing suggest targets for future research intervention.Funding: This supported by Shandong Provincial Natural Science Foundation (Grant/Award Number: ZR2019PH070) Taishan Scholars Program Province China tsqn202306374).Declaration Interest: authors declare no competing interests.Ethical Approval: Ethical approval informed consent participants were acquired each cohort enrolled original GWAS studies, accordance their local regulations institute requirements. All this study, based summary-level data publicly available databases, require further ethical permit.

Язык: Английский

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Cordyceps militaris solid medium extract alleviates lipopolysaccharide-induced acute lung injury via regulating gut microbiota and metabolism

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 20, 2025

Acute lung injury (ALI) is a common respiratory disease, Cordycepin has been reported to reduce ALI, which an effective component in Cordyceps militaris solid medium extract (CMME). Therefore, we aimed explore the alleviating effect and mechanism of CMME on ALI. This study evaluated lipopolysaccharide (LPS)-induced ALI mice by analyzing intestinal flora metabolomics its potential mechanism. We assessed pulmonary changes, inflammation, oxidative stress, macrophage neutrophil activation levels, then analyzed gut microbiota through 16S rRNA profile UPLC-QTOF/MS. The results showed that treatment improved injury, reduced inflammatory factors stress decreased recruitment. revealed significantly increased richness diversity abundance Bacteroides compared with Mod group significantly. Metabolic analysis indicated reversed levels differential metabolites may ameliorate purine metabolism, nucleotide bile acid (BA) did reverse changes BA mice, were associated flora. improve regulating correcting metabolic disorders, providing new insights into action.

Язык: Английский

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Urolithin a attenuates rheumatoid arthritis by inhibiting inflammation and pyroptosis in fibroblasts via the AMPK/ NF-κB signaling pathway

International Immunopharmacology, Год журнала: 2025, Номер 155, С. 114604 - 114604

Опубликована: Апрель 10, 2025

Язык: Английский

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Intestinal Mucosal Immune Barrier: A Powerful Firewall Against Severe Acute Pancreatitis-Associated Acute Lung Injury via the Gut-Lung Axis

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 2173 - 2193

Опубликована: Апрель 1, 2024

The pathogenesis of severe acute pancreatitis-associated lung injury (SAP-ALI), which is the leading cause mortality among hospitalized patients in intensive care unit, remains incompletely elucidated.The intestinal mucosal immune barrier a crucial component epithelial barrier, and its aberrant activation contributes to induction sustained pro-inflammatory responses, paradoxical intercellular communication, bacterial translocation.In this review, we firstly provide comprehensive overview composition pivotal roles SAP-ALI.Secondly, mechanisms crosstalk with gut microbiota, called gut-lung axis, effect on SAP-ALI were summarized.Finally, number drugs that could enhance exhibit potential anti-SAP-ALI activities presented, including probiotics, glutamine, enteral nutrition, traditional Chinese medicine (TCM).The aim offer theoretical framework based perspective protect against SAP-ALI.

Язык: Английский

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Pueraria Extract Ameliorates Alcoholic Liver Disease via the Liver–Gut–Brain Axis: Focus on Restoring the Intestinal Barrier and Inhibiting Alcohol Metabolism

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Окт. 24, 2024

Alcoholic liver disease (ALD) is one of the causes hepatocellular carcinoma, accompanied by intestinal leakage and microbial changes. Pueraria has protective effects on injury. The aim this study was to investigate mechanism pueraria in treatment ALD. UPLC-Q/TOF-MS used analyze composition extract (PUE). Acute chronic ALD models were established evaluate antialcoholic hepatoprotective PUE. As a result, PUE reduced serum levels ALT, AST, TC, TG inflammatory factors alleviated inflammation drunk state. decreased gene expression ADH1 level acetaldehyde (ACH) inhibit generation ACH from ethanol metabolism, increased ALDH2 accelerate decomposition ACH, thereby barrier damage. Meanwhile, 16 S rDNA revealed that altered microbiota composition, amount

Язык: Английский

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