Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review

Internal and Emergency Medicine, Год журнала: 2023, Номер 19(2), С. 275 - 293

Опубликована: Июль 28, 2023

Abstract The intestine is the largest interface between internal body and external environment. intestinal barrier a dynamic system influenced by composition of microbiome activity intercellular connections, regulated hormones, dietary components, inflammatory mediators, enteric nervous (ENS). Over years, it has become increasingly evident that maintaining stable crucial to prevent various potentially harmful substances pathogens from entering Disruption referred as 'leaky gut' or leaky gut wall syndrome seems be characterized release bacterial metabolites endotoxins, such lipopolysaccharide (LPS), into circulation. This condition, mainly caused infections, oxidative stress, high-fat diet, exposure alcohol chronic allergens, dysbiosis, appear highly connected with development and/or progression several metabolic autoimmune systemic diseases, including obesity, non-alcoholic fatty liver disease (NAFLD), neurodegeneration, cardiovascular disease, bowel type 1 diabetes mellitus (T1D). In this review, starting description mechanisms enable homeostasis analyzing relationship complex ecosystem pathological conditions, we explore role in driving inflammation, also shedding light on current future therapeutic interventions.

Язык: Английский

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Gut dysbiosis in nonalcoholic fatty liver disease: pathogenesis, diagnosis, and therapeutic implications

Frontiers in Cellular and Infection Microbiology, Год журнала: 2022, Номер 12

Опубликована: Ноя. 8, 2022

The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing recently and has become one the most common clinical diseases. Since pathogenesis NAFLD not been completely elucidated, few effective therapeutic drugs are available. As “second genome” human body, gut microbiota plays an important role in digestion, absorption metabolism food drugs. Gut can act as driver to advance occurrence development NAFLD, accelerate its progression cirrhosis hepatocellular carcinoma. Growing evidence demonstrated that metabolites directly affect intestinal morphology immune response, resulting abnormal activation inflammation endotoxemia; dysbiosis also causes dysfunction gut-liver axis via alteration bile acid pathway. Because composition diversity disease-specific expression characteristics, holds strong promise novel biomarkers targets for NAFLD. Intervening microbiota, such antibiotic/probiotic treatment fecal transplantation, a strategy preventing treating In this article, we have reviewed emerging functions association bacterial components different stages discussed potential implications diagnosis therapy.

Язык: Английский

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Milk-derived extracellular vesicles protect intestinal barrier integrity in the gut-liver axis

Science Advances, Год журнала: 2023, Номер 9(15)

Опубликована: Апрель 12, 2023

Milk-derived extracellular vesicles (mEVs) have been proposed as a potential nanomedicine for intestinal disorders; however, their impact on barrier integrity in gut inflammation and associated metabolic diseases has not explored yet. Here, mEVs derived from bovine human breast milk exert similar protective effects epithelial tight junction functionality vitro, survive harsh gastrointestinal conditions ex vivo, reach the colon vivo. Oral administration of restores at multiple levels, including mucus, epithelial, immune barriers, prevents endotoxin translocation into liver chemical-induced experimental colitis diet-induced nonalcoholic steatohepatitis (NASH), thereby alleviating disorders, inflammation, NASH. treatment gut-liver axis-associated via protection integrity.

Язык: Английский

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Non-alcoholic fatty liver disease: pathophysiological concepts and treatment options

Cardiovascular Research, Год журнала: 2023, Номер 119(9), С. 1787 - 1798

Опубликована: Июнь 26, 2023

Abstract The prevalence of non-alcoholic fatty liver disease (NAFLD) is continually increasing due to the global obesity epidemic. NAFLD comprises a systemic metabolic accompanied frequently by insulin resistance and hepatic inflammation. Whereas simple steatosis most common manifestation, more progressive course characterized fibrosis inflammation (i.e. steatohepatitis) present in 10–20% affected individuals. furthermore progresses substantial number patients towards cirrhosis hepatocellular carcinoma. this now affects almost 25% world’s population mainly observed type 2 diabetes, also lean Pathophysiology involves lipotoxicity, immune disturbances resistance, gut dysbiosis, commonly defining disorder prototypic disorder. Not surprisingly many have other manifestations, indeed cardiovascular disease, chronic kidney extrahepatic malignancies are all contributing substantially patient outcome. Weight loss lifestyle change reflect cornerstone treatment, several medical treatment options currently under investigation. promising strategies include glucagon-like peptide 1 receptor antagonists, sodium–glucose transporter inhibitors, Fibroblast Growth Factor analogues, Farnesoid X agonists, peroxisome proliferator–activated agonists. Here, we review epidemiology, pathophysiology, therapeutic for NAFLD.

Язык: Английский

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Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Май 4, 2023

Abstract Alcoholism is a widespread and damaging behaviour of people throughout the world. Long-term alcohol consumption has resulted in alcoholic liver disease (ALD) being leading cause chronic disease. Many metabolic enzymes, including dehydrogenases such as ADH, CYP2E1, CATacetaldehyde ALDHsand nonoxidative metabolizing enzymes SULT, UGT, FAEES, are involved metabolism ethanol, main component beverages. Ethanol changes functional or expression profiles various regulatory factors, kinases, transcription microRNAs. Therefore, underlying mechanisms ALD complex, involving inflammation, mitochondrial damage, endoplasmic reticulum stress, nitrification, oxidative stress. Moreover, recent evidence demonstrated that gut-liver axis plays critical role pathogenesis. For example, ethanol damages intestinal barrier, resulting release endotoxins alterations flora content bile acid metabolism. However, therapies show low effectiveness. this review summarizes pathways highly influential pathogenic factors pathology with aim new therapeutic insights.

Язык: Английский

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Inflammation and resolution in obesity

Nature Reviews Endocrinology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 24, 2024

Язык: Английский

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Therapeutic targeting of obesity-induced neuroinflammation and neurodegeneration

Frontiers in Endocrinology, Год журнала: 2025, Номер 15

Опубликована: Янв. 17, 2025

Obesity is a major modifiable risk factor leading to neuroinflammation and neurodegeneration. Excessive fat storage in obesity promotes the progressive infiltration of immune cells into adipose tissue, resulting release pro-inflammatory factors such as cytokines adipokines. These inflammatory mediators circulate through bloodstream, propagating inflammation both periphery central nervous system. Gut dysbiosis, which results leaky intestinal barrier, exacerbates plays significant role linking pathogenesis neurodegeneration gut-brain/gut-brain-liver axis. Inflammatory states within brain can lead insulin resistance, mitochondrial dysfunction, autolysosomal increased oxidative stress. disruptions impair normal neuronal function subsequently cognitive decline motor deficits, similar pathologies observed neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, Parkinson's disease. Understanding underlying disease mechanisms crucial for developing therapeutic strategies address defects these metabolic pathways. In this review, we summarize provide insights different strategies, methods alter gut lifestyle changes, dietary supplementation, well pharmacological agents derived from natural sources, that target obesity-induced

Язык: Английский

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Oxidative Stress, Gut Microbiota, and Extracellular Vesicles: Interconnected Pathways and Therapeutic Potentials

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3148 - 3148

Опубликована: Март 28, 2025

Oxidative stress (OS) and gut microbiota are crucial factors influencing human health, each playing a significant role in the development progression of chronic diseases. This review provides comprehensive analysis complex interplay between these two factors, focusing on how an imbalance reactive oxygen species (ROS) antioxidants leads to OS, disrupting cellular homeostasis contributing range conditions, including metabolic disorders, cardiovascular diseases, neurological cancer. The microbiota, diverse community microorganisms residing gastrointestinal tract, is essential for regulating immune responses, pathways, overall health. Dysbiosis, composition, closely associated with inflammation, dysfunction, various highlights influences influenced by complicating pathophysiology many conditions. Furthermore, emerging evidence has identified extracellular vesicles (EVs) as critical facilitators crosstalk OS microbiota. EVs also play signaling host tissues, modulating processes. function holds promise targeted therapies aimed at restoring microbial balance mitigating OS. Personalized therapeutic approaches, probiotics, antioxidants, fecal transplantation-based strategies, can be used address OS-related diseases improve health outcomes. Nonetheless, further research needed study molecular mechanisms underlying interactions potential innovative interventions offer novel strategies managing enhancing

Язык: Английский

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Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Cells, Год журнала: 2021, Номер 10(12), С. 3306 - 3306

Опубликована: Ноя. 25, 2021

Non-alcoholic fatty liver disease (NAFLD) is a global clinical problem. The MD2-TLR4 pathway exacerbates NAFLD progression by promoting inflammation. Long-term exercise considered to improve but the underlying mechanism still unclear. In this study, we examined protective effect and molecular of on high-fat diet (HFD)-induced injury. an HFD-induced mouse model, training significantly decreased hepatic steatosis fibrosis. Interestingly, blocked binding downstream inflammatory response. Irisin myokine that highly expressed in response exerts anti-inflammatory effects. We found circulating irisin levels muscle expression were increased exercised mice, suggesting could mediate NAFLD. vitro studies showed improved lipid metabolism, fibrosis, inflammation palmitic acid (PA)-stimulated AML12 cells. Moreover, assay results disturbed complex formation directly with MD2 not TLR4, interfered recognition stimuli such as PA lipopolysaccharide MD2. Our study provides novel evidence exercise-induced inhibits via competitive Thus, be potential therapy for

Язык: Английский

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Gut Barrier Dysfunction and Bacterial Lipopolysaccharides in Colorectal Cancer

Journal of Gastrointestinal Surgery, Год журнала: 2023, Номер 27(7), С. 1466 - 1472

Опубликована: Март 27, 2023

Inflammation is known to be an essential driver of various types cancer. An increasing number studies have suggested that the occurrence and development colorectal cancer (CRC) are linked inflammatory microenvironment intestine. This assumption further supported by fact patients with bowel disease (IBD) more likely develop CRC. Multiple in mice humans shown preoperative systemic response predictive recurrence after potentially curative resection. Lipopolysaccharides (LPS) membrane surface markers gram-negative bacteria, which induce gut barrier dysfunction inflammation might significantly involved A selective literature search was conducted Medline PubMed, using terms "Colorectal Cancer", "Gut Barrier", "Lipopolysaccharides", "Inflammation". Disruption intestinal homeostasis, including dysfunction, increased LPS levels a critical factor for chronic inflammation. can activate diverse nuclear factor-κB (NF-κB) pathway via Toll-like receptors 4 (TLR4) promote response, aggravates encourages CRC development. intact prevents antigens bacteria from crossing endothelial layer entering circulation. In contrast, damaged triggers responses increases susceptibility Thus, targeting promising novel therapeutic approach additional treatment Gut dysfuction bacterial seem play important role pathogenesis progression therefore require investigation.

Язык: Английский

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