The role of the gut microbiota in the onset and progression of heart failure: insights into epigenetic mechanisms and aging

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Nov. 29, 2024

The gut microbiota (GM) plays a critical role in regulating human physiology, with dysbiosis linked to various diseases, including heart failure (HF). HF is complex syndrome significant global health impact, as its incidence doubles each decade of life, and prevalence peaks individuals over 80 years. A bidirectional interaction exists between GM HF, where alterations can worsen the disease's progression. "gut hypothesis HF" suggests that HF-induced changes, such reduced intestinal perfusion altered motility, negatively impact composition, leading increased permeability, release GM-derived metabolites into bloodstream, systemic inflammation. This process creates vicious cycle further deteriorates function. metabolites, trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), secondary bile (BAs), influence gene expression through epigenetic mechanisms, DNA methylation histone modifications. These changes may play crucial mediating effects dysbiotic microbial linking them cardiac contributing progression HF. particularly relevant older individuals, aging itself has been associated both cumulative alterations, intensifying interplay GM, increasing risk elderly. Despite growing body evidence, modifications, remains poorly understood. dynamic nature epigenetics shaped by factors age, diet, lifestyle, presents challenges elucidating precise mechanisms underlying this relationship. Future research should prioritize innovative approaches overcome these limitations. By identifying specific metabolite-induced modifications modulating composition function novel personalized therapeutic strategies for prevention and/or treatment be developed. Moreover, targeted focusing specifically on understanding intricate connections epigenetics, during aging.

Language: Английский

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Gut Microbiota and Osteoarthritis: From Pathogenesis to Novel Therapeutic Opportunities

The American Journal of Chinese Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 24

Published: Jan. 29, 2025

Osteoarthritis (OA) is the most common chronic degenerative joint disease, characterized by cartilage damage, synovial inflammation, subchondral bone sclerosis, marginal loss, and osteophyte development. Clinical manifestations include inflammatory pain, swelling, osteophytes, limitation of motion. The pathogenesis osteoarthritis has not yet been fully uncovered. With ongoing research, however, it gradually determined that OA caused solely mechanical injury or aging, but rather involves low-grade metabolic imbalances, dysfunctional adaptive immunity, alterations in central pain processing centers. main risk factors for obesity, age, gender, genetics, sports injuries. In recent years, extensive research on gut microbiota revealed dysbiosis associated with some OA, may intervene its through both direct indirect mechanisms. Therefore, flora imbalance as a pathogenic factor become hotspot topic potential therapeutic connotations. this paper, we review role describe relationship factors, address candidate markers diagnosis. addition, focus therapies, discuss effects interventions targeting microbiota, well impact bacteria efficacy drugs.

Language: Английский

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Gut microbial metabolites as a convergence point between autoimmunity and solid tumors

Gut Microbes Reports, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: March 12, 2025

Language: Английский

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Significance of FXR agonists in MASLD treatment: a deep dive into lipid alteration by analytical techniques

Published: March 25, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as a global health crisis, affecting over 30% of the population and demanding urgent attention. This redefined condition, previously known non-alcoholic fatty (NAFLD), reflects deeper understanding intricate interplay between metabolic dysfunction health. At heart MASLD lies troubling accumulation triglycerides (TGs) in hepatocytes, which precipitates insulin resistance oxidative stress, ultimately leading to more severe forms like steatohepatitis (MASH). Excitingly, recent research has spotlighted farnesoid X receptor (FXR) groundbreaking therapeutic target. FXR not only regulates lipid metabolism but also combats inflammation resistance, making it potential game-changer fight against MASLD. With one FDA-approved drug, resmetirom, currently available, exploration agonists opens new avenues for innovative treatments that could revolutionize patient care. By harnessing power restore balance integrating advanced strategies lipidomics acid profiling, we stand on brink transforming how approach its associated complications, paving way healthier future. review delves into promising role combating implications related disorders, emphasizing urgency detect manage this burgeoning epidemic.

Language: Английский

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Unraveling the gut microbiota’s role in obesity: key metabolites, microbial species, and therapeutic insights

Journal of Bacteriology, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

ABSTRACT Obesity, characterized by excessive fat accumulation, stems from an imbalance between energy intake and expenditure, with the gut microbiota playing a crucial role. This review highlights how influences metabolic pathways, inflammation, adipose tissue regulation in obesity. Specific bacteria metabolites, such as lipopolysaccharides (LPS) short-chain fatty acids (SCFAs), modulate permeability, harvest, impacting obesity development. Certain bacteria, including Clostridium XIVb , Dorea spp., Enterobacter cloacae Collinsella aerofaciens promote increasing inflammatory response through LPS translocation into bloodstream. Conversely, beneficial like Akkermansia muciniphila Lactobacillus Bifidobacterium spp. enhance barrier integrity, regulate SCFA production, fasting-induced factor, which collectively support health reducing storage inflammation. Metabolites SCFAs (acetate, propionate, butyrate) interact G-protein coupled receptors to lipid metabolism browning of white (WAT), thus enhancing thermogenesis expenditure. However, contributes insulin resistance highlighting dual roles these microbial metabolites both supporting disrupting function. Therapeutic interventions targeting microbiota, promoting WAT activating brown (BAT), hold promise for management. personalized approaches are necessary due individual microbiome variability. Further research is essential translate insights microbiota-based clinical therapies.

Language: Английский

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Cooked Bean (Phaseolus vulgaris L.) Consumption Alters Bile Acid Metabolism in a Mouse Model of Diet-Induced Metabolic Dysfunction: Proof-of-Concept Investigation

Nutrients, Journal Year: 2025, Volume and Issue: 17(11), P. 1827 - 1827

Published: May 28, 2025

Background/Objectives: Metabolic dysregulation underlies a myriad of chronic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity, bile acids emerge as an important mediator in their etiology. Weight control by improving diet quality is the standard care prevention these diseases. Inclusion pulses, such common bean, affordable yet neglected approach to outcomes. Thus, this study evaluated possibility that bean alters acid metabolism health-beneficial manner. Methods: Using biospecimens from several similarly designed studies, cecal content, feces, tissue, plasma samples C57BL/6 mice fed obesogenic lacking (control) or containing cooked were subjected total analysis untargeted metabolomics. RNA-seq, qPCR, Western blot assays tissue complemented analyses. Microbial composition predicted function contents using 16S rRNA gene amplicon shotgun metagenomic sequencing. Results: Bean-fed had increased content excreted more per gram feces. Consistent with effects, synthesis was observed. capacity metabolize markedly altered greater prominence secondary metabolites bean-fed mice, i.e., microbial chenodeoxycholate/lithocholate while hyocholate reduced. Conclusions: In rendering resistant diet-induced MASLD consumption sequesters acids, increasing hepatic enhancing diversity through metabolism. Bean-induced changes have potential improve dyslipidemia.

Language: Английский

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Engineering Regioselectivity of P450 BM3 Enables the Biosynthesis of Murideoxycholic Acid by 6β‐Hydroxylation of Lithocholic Acid

Biotechnology Journal, Journal Year: 2024, Volume and Issue: 19(11)

Published: Nov. 1, 2024

Murideoxycholic acid (MDCA), as a significant secondary bile derived from the metabolism of α/β-muricholic in rodents, is an important component maintaining homeostasis. However, biosynthesis MDCA remains challenging task. Here, we present development cytochrome P450 monooxygenase CYP102A1 (P450 BM3) Bacillus megaterium, employing semi-rational protein engineering technique. Following three rounds mutagenesis, triple variant (T260G/G328A/L82V) has been discovered that proficiently catalyzes 6β-hydroxylation lithocholic (LCA), thereby generating with impressive 8.5-fold increase yield compared to template BM3 mutant. The selectivity also promoted 62.0% 96.3%. This biocatalyst introduces novel approach for LCA. Furthermore, molecular docking and dynamics simulations have employed unravel mechanisms underlying enhanced LCA conversion selectivity.

Language: Английский

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Hormone based therapy and crosstalk beyond hormones

Medical Review, Journal Year: 2024, Volume and Issue: 4(4), P. 257 - 261

Published: July 24, 2024

Language: Английский

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Silicon-Enriched Meat Ameliorates Diabetic Dyslipidemia by Improving Cholesterol, Bile Acid Metabolism and Ileal Barrier Integrity in Rats with Late-Stage Type 2 Diabetes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11405 - 11405

Published: Oct. 23, 2024

Silicon as a functional ingredient of restructured meat (RM) shows antidiabetic and hypocholesterolemic effects in type 2 diabetes mellitus (T2DM) rat model. The present paper investigated the mechanisms involved this cholesterol-lowering effect by studying impact silicon-RM consumption on bile acid (BA) cholesterol metabolism. In addition, main cecal BA short-chain fatty acids derived from microbiota intestinal barrier integrity were also tested. Rats fed an RM high-saturated-fat, high-cholesterol diet (HSFHCD) combined with low dose streptozotocin plus nicotinamide injection (LD group) for 8 wk. period. Silicon-RM was included HSFHCD food (LD-Si group). An early-stage T2DM group high-saturated-fat (ED used reference. decreased pool higher hydrophilic profile lower ability to digest fat damaging effects, increasing occludin levels barrier. ileal uptake hepatic synthesis through CYP7A1 reduced FXR/FGF15 signaling activation. silicon up-regulated FXR LXRα/β, improving transintestinal (TICE), biliary effluxes. inclusion products could be new therapeutic nutritional tool treatment diabetic dyslipidemia.

Language: Английский

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