The rheumatoid arthritis gut microbial biobank reveals core microbial species that associate and effect on host inflammation and autoimmune responses DOI Creative Commons
Haojie Huang, Chang Liu,

Xin‐Wei Sun

et al.

iMeta, Journal Year: 2024, Volume and Issue: 3(5)

Published: Oct. 1, 2024

Abstract Gut microbiota dysbiosis has been implicated in rheumatoid arthritis (RA) and influences disease progression. Although molecular culture‐independent studies revealed RA patients harbored a core microbiome had characteristic bacterial species, the lack of cultured strains limited investigations on their functions. This study aimed to establish an RA‐originated gut microbial biobank (RAGMB) that covers further correlates validates species clinically used diagnostic inflammation immune indices. We obtained 3200 isolates from fecal samples 20 with seven improved 11 traditional cultivation methods. These were phylogenetically identified selected for RAGMB. The RAGMB 601 represented 280 (including 43 novel species) phyla. covered 93.2% at level medium‐ high‐abundant (relative abundances ≥0.2%) microbes, included four rare phylum Synergistota . was defined composed species. Among these, Mediterraneibacter tenuis Eubacterium rectale two statistically significantly correlated indices such as erythrocyte sedimentation rate (ESR) IL‐10. Thus, M. E. experimental validation using DSS‐treated not mice model. Results demonstrated both exacerbated host inflammatory responses, including shortened colon length increased spleen weight, decreased IL‐10 IL‐17A levels plasma. Overall, we established RAGMB, microbiome, effected responses. work provides diverse resources future etiology potential new targets biomedical practices.

Language: Английский

Different types of bile acids exhibit opposite regulatory effects on lipid metabolism in finishing pigs through bile acid receptors DOI Creative Commons
Yaolian Hu, Ni Sang, Aimin Wu

et al.

Animal nutrition, Journal Year: 2025, Volume and Issue: 21, P. 25 - 36

Published: Jan. 1, 2025

Language: Английский

Citations

0
A gut pathobiont regulates circulating glycine and host metabolism in a twin study comparing vegan and omnivorous diets DOI Creative Commons
Matthew M. Carter, Xianfeng Zeng, Catherine Ward

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

Summary Metabolic diseases including type 2 diabetes and obesity pose a significant global health burden. Plant-based diets, vegan are linked to favorable metabolic outcomes, yet the underlying mechanisms remain unclear. In randomized trial involving 21 pairs of identical twins, we investigated effects omnivorous diets on host metabolome, immune system, gut microbiome. Vegan induced shifts in serum stool metabolomes, cytokine profiles, microbial composition. Despite lower dietary glycine intake, diet subjects exhibited elevated levels reduced abundance pathobiont Bilophila wadsworthia . Functional studies demonstrated that B. metabolizes via reductase pathway modulates availability. Removing from complex microbiota mice improved markers. These findings reveal previously underappreciated mechanism by which regulates status microbiota.

Language: Английский

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Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases DOI Creative Commons
Marilena Durazzo, Arianna Ferro, Victor Navarro‐Tableros

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 121 - 121

Published: Jan. 14, 2025

Chronic hepatobiliary damage progressively leads to fibrosis, which may evolve into cirrhosis and/or hepatocellular carcinoma. The fight against the increasing incidence of liver-related morbidity and mortality is challenged by a lack clinically validated early-stage biomarkers limited availability effective anti-fibrotic therapies. Current research focused on uncovering pathogenetic mechanisms that drive liver fibrosis. Drugs targeting molecular pathways involved in chronic diseases, such as inflammation, hepatic stellate cell activation proliferation, extracellular matrix production, are being developed. Etiology-specific treatments, those for hepatitis B C viruses, already clinical use, efforts develop new, targeted therapies other diseases ongoing. In this review, we highlight major changes occurring patients affected metabolic dysfunction-associated steatotic disease, viral (Delta virus), autoimmune (autoimmune hepatitis, primary biliary cholangitis, sclerosing cholangitis). Further, describe how knowledge linked current well ongoing preclinical novel strategies, including nucleic acid-, mesenchymal stromal/stem cell-, vesicle-based options. Much development obviously still missing, but plethora promising potential treatment strategies holds promise future reversal increase group patients.

Language: Английский

Citations

0
Extracellular vesicles from immortalised human amniotic epithelial cells reduce hepatic fibrosis in mice with Steatohepatitis and Hepatocellular Carcinoma DOI Creative Commons

Mihiri Goonetilleke,

Jeanne Correia,

Yuan Chen

et al.

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

Published: Jan. 28, 2025

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic steatohepatitis (MASH) and cirrhosis hepatocellular carcinoma (HCC) describe progressive stages of that occurs secondary to inflammation driven by abnormal hepatic lipid accumulation. Treatment addresses the pathophysiology underlies MASH/HCC progression is currently lacking. Human amniotic epithelial cell derived EVs (hAEC-EVs) demonstrate anti-inflammatory, anti-fibrotic reparative properties. Methods We aimed investigate therapeutic efficacy immortalised hAEC-EVs (ihAEC-EVs) in a murine model MASH HCC characterize both protein miRNA cargo explain mechanisms. was induced mice following ‘western diet’ carbon tetrachloride (CCl4) exposure for 12 weeks or 24 respectively. 10µg ihAEC (treatment) 10mg/kg obeticholic acid (treatment benchmark) administered via oral gavage. Serum collected parameter analysis livers were histological molecular analysis. Results Oral administration ihAEC-derived extracellular vesicles (EVs) significantly reduced fibrosis reducing stellate cells macrophages. These findings are supported reveals presence EV modulates pathways linked inflammation, fibrosis, LPC response. Conclusions indicate ihAEC-EVs promising cell-free therapy treatment MASLD MASH, having significant impact on possibilities patient's suffering from chronic disease. Further, this study allowed us deduce validate involved identify candidate proteins miRNAs focus future mechanism action experiments.

Language: Английский

Citations

0
A Gut Pathobiont Regulates Circulating Glycine and Host Metabolism in a Twin Study Comparing Vegan and Omnivorous Diets DOI
Matthew M. Carter, Xianfeng Zeng, Catherine Ward

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Epigenetics in metabolic dysfunction and steatohepatitis DOI
Yanru Zhang,

Ruike Ding,

Liangshuo Hu

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111684 - 111684

Published: Feb. 1, 2025

Language: Английский

Citations

0
EHBP1 suppresses liver fibrosis in metabolic dysfunction-associated steatohepatitis DOI
Fanglin Ma, Miriam Longo, Marica Meroni

et al.

Cell Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

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Traditional Mongolian Medicine Qiqirigan-8 alleviates non-alcoholic fatty liver disease via restoring gut microbiota and metabolism DOI Creative Commons
Yang Dandan,

Wuyunsiqin,

YanNiu

et al.

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

Published: Feb. 27, 2025

Mongolian Medicine Qiqirigan-8 (MMQ-8) is a traditional medicine formula used to treat fatty liver disease. However, the material basis and in vivo metabolic process of therapeutic effect MMQ-8 on non-alcoholic disease (NAFLD) remain unclear. The chemical composition was determined using Ultra-high-performance liquid chromatography-quadrupole Exactive Mass spectrometry analysis (UHPLC-QE-MS). C57BL/6J mice were fed choline-deficient diet for 12 weeks induce NAFLD model. Hematoxylin Eosin (H&E)-staining, combined with serum biochemical indexes, observe appearance characterize pathological changes functions liver. HE staining Alcian Blue-Phosphoric Acid Schiff (AB-PAS) colon, along ZO-1 immunofluorescence expression colon reveal disruption intestinal epithelial mucosal barrier NAFLD. tight junction genes analyzed by qRT-PCR protective against disruption. Fecal metagenomics non-targeted metabolomics effects gut microbiota metabolism Finally, we emphasize interaction between metabolites through Spearman correlation coefficient analysis. contains 17 active ingredients, which can reduce hepatic steatosis lobular inflammation NAFLD, have injury. reduced infiltration inflammatory cells epithelium model while restoring number goblet cells. significantly enhanced protein as well mRNA both Occludin. results showed that Bacillota/Bacteroidota ratio mice. Increased abundance beneficial bacteria such Porphyromonadaceae, Prevotella, Bacteroidota. suppressed dysfunctional bacteria, Bacillota, Acetatifactor, Erysipelotrichaceae. Furthermore, studies revealed intervention regulated related glutathione metabolism, butyric acid sphingolipid glycerophospholipid compared group. These pathways play key roles According Spearman's analysis, up-regulation Bacteroidota after negatively correlated LPC levels pathways, positively PC levels. In contrast, relationship Bacillota down-regulated intervention, opposite. addition, fumaric acid, 2-oxoglutaric adenosine, L-glutathione levels, those Acetatifactor all above metabolites. Thus, microbial ecosystem are tightly intertwined this process. summary, these findings indicate has synergistic anti-NAFLD its multi-component, multi-target, microbiota-modulating multi pathway characteristics. host's regulation specific involvement multiple may be one important mechanisms exerts It worth noting closely

Language: Английский

Citations

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Obesity alters testicular gene expression in mice, monkeys and humans DOI Creative Commons
Wenyu Shao, Weijie Li, Xi Yuan

et al.

Zygote, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 7

Published: March 21, 2025

Abstract Obesity, a global health issue, is associated with numerous diseases and has been shown to affect male reproductive by inducing endocrine hormonal changes, chronic inflammation, oxidative stress epigenetic alterations in cells. This study investigates the impact of obesity on testicular gene expression across mice, monkeys humans, identifying 730 conserved testis-specific genes. High-fat diet-induced upregulates GNG5, INHA, MSH5, SLC30A8 SLC7A4 testes, suggesting their potential as regulatory targets damage obesity. Single-cell analysis reveals species-conserved patterns Sertoli cells SPG It also confirmed that were significantly upregulated testes spontaneously obese mice. The findings highlight these genes obesity-related dysfunction, providing insights into impairments caused

Language: Английский

Citations

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Tripeptide DT-109 (Gly-Gly-Leu) attenuates atherosclerosis and vascular calcification in nonhuman primates DOI Creative Commons

Linying Jia,

Pengxiang Qu, Yang Zhao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: April 7, 2025

Abstract Advanced atherosclerotic lesions and vascular calcification substantially increase the risk of cardiovascular events. However, effective strategies for preventing or treating advanced atherosclerosis are currently lacking. This study investigated efficacy DT-109 (Gly-Gly-Leu) in attenuating nonhuman primates, exploring its broader therapeutic potential. In this study, twenty male cynomolgus monkeys were administered a cholesterol-rich diet ad libitum 10 months. Then, animals treated either orally with (150 mg/kg/day) vehicle (H 2 O) 5 months while continuing on same diet. Plasma lipid levels measured monthly at end experiment, pathological examinations aortas coronary arteries RNA sequencing performed. To explore possible molecular mechanisms, effects smooth muscle cells (SMCs) examined vitro. We found that administration significantly suppressed lesion formation both aorta arteries. Pathological revealed treatment reduced lesional macrophage content calcification. analysis showed downregulated pro-inflammatory factors NLRP3 , AIM2 CASP1 oxidative stress NCF2 NCF4 osteogenic RUNX2 COL1A1 MMP2 MMP9 simultaneously upregulating expression SMCs contraction markers ACTA2 CNN1 TAGLN . Furthermore, inhibited SMC inflammasome activation These results demonstrate effectively suppresses findings, conjunction insights from our previous studies, position as novel multifaceted agent diseases.

Language: Английский

Citations

0