Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(15), С. 5214 - 5214

Опубликована: Июль 23, 2020

Gut microbiota dysregulation plays a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) through its metabolites. Therefore, restoration gut and supplementation with commensal bacterial metabolites can be therapeutic benefit against disease. In this review, we summarize roles various NAFLD their implications. The is feature NAFLD, signatures are associated severity altered Disturbance bile acid metabolism leads to underactivation receptors FXR TGR5, causal for decreased energy expenditure, increased lipogenesis, synthesis macrophage activity. Decreased production butyrate results intestinal inflammation, permeability, endotoxemia systemic inflammation. Dysregulation amino acids choline also contributes lipid accumulation chronic inflammatory status. some patients, overproduction ethanol produced by bacteria responsible hepatic Many approaches including probiotics, prebiotics, synbiotics, faecal microbiome transplantation fasting-mimicking diet have been applied restore improvement NAFLD.

Язык: Английский

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The Gut Microbiota at the Service of Immunometabolism

Cell Metabolism, Год журнала: 2020, Номер 32(4), С. 514 - 523

Опубликована: Сен. 17, 2020

Язык: Английский

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Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Авг. 13, 2022

Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form NAFL, can be progressive and more susceptible to developing cirrhosis hepatocellular carcinoma. Currently, lifestyle interventions are most essential effective strategies for preventing controlling NAFL without development fibrosis. While there still limited appropriate drugs specifically treat NAFL/NASH, growing progress is being seen in elucidating pathogenesis identifying therapeutic targets. In this review, we discussed recent developments etiology prospective targets, as well pharmacological candidates pre/clinical trials patents, with a focus on diabetes, hepatic lipid metabolism, inflammation, Importantly, evidence elucidates that disruption gut-liver axis microbe-derived metabolites drive NAFL/NASH. Extracellular vesicles (EVs) act signaling mediator, resulting accumulation, macrophage stellate cell activation, further promoting inflammation fibrosis progression during Targeting gut microbiota or EVs may serve new treatment Finally, other mechanisms, such therapy genetic approaches, also have enormous potential. Incorporating different mechanisms personalized medicine improve efficacy better benefit patients

Язык: Английский

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The Protective Role of Butyrate against Obesity and Obesity-Related Diseases

Molecules, Год журнала: 2021, Номер 26(3), С. 682 - 682

Опубликована: Янв. 28, 2021

Worldwide obesity is a public health concern that has reached pandemic levels. Obesity the major predisposing factor to comorbidities, including type 2 diabetes, cardiovascular diseases, dyslipidemia, and non-alcoholic fatty liver disease. The common forms of are multifactorial derive from complex interplay environmental changes individual genetic predisposition. Increasing evidence suggest pivotal role played by alterations gut microbiota (GM) could represent causative link between factors onset obesity. beneficial effects GM mainly mediated secretion various metabolites. Short-chain acids (SCFAs) acetate, propionate butyrate small organic metabolites produced fermentation dietary fibers resistant starch with vast in energy metabolism, intestinal homeostasis immune responses regulation. An aberrant production SCFAs emerged metabolic diseases. Among SCFAs, because it might have potential alleviating related comorbidities. Here we reviewed preclinical clinical data contribute explain this context, highlighting its crucial diet-GM-host axis.

Язык: Английский

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Gut Microbiota-Derived Components and Metabolites in the Progression of Non-Alcoholic Fatty Liver Disease (NAFLD)

Nutrients, Год журнала: 2019, Номер 11(8), С. 1712 - 1712

Опубликована: Июль 25, 2019

Human gut microbiota has been increasingly recognized as a pivotal determinant of non-alcoholic fatty liver disease (NAFLD). Apart from the changes in composition microbiota, components and metabolites derived intestinal have emerged key factors modulating pathological process NAFLD. Compelling evidences revealed that generates variety bioactive substances interact with host cells through portal vein. These include bacteria such lipopolysaccharides, peptidoglycan, DNA, extracellular vesicles, well ranging short-chain acids, indole its derivatives, trimethylamine, secondary bile to carotenoids phenolic compounds. The mechanisms underlying hepatic responses associated regulation glycolipid metabolism, immune signaling response, redox homeostasis. Illuminating interplay between unique produced microbiome will provide novel therapeutical target for current review highlights recent advances on by which ingredients modulate development progression

Язык: Английский

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The Key Role of Mitochondrial Function in Health and Disease

Antioxidants, Год журнала: 2023, Номер 12(4), С. 782 - 782

Опубликована: Март 23, 2023

The role of mitochondrial function in health and disease has become increasingly recognized, particularly the last two decades. Mitochondrial dysfunction as well disruptions cellular bioenergetics have been shown to be ubiquitous some most prevalent diseases our society, such type 2 diabetes, cardiovascular disease, metabolic syndrome, cancer, Alzheimer’s disease. However, etiology pathogenesis multiple yet elucidated, making it one significant medical challenges history. rapid advances knowledge metabolism coupled with novel understanding at molecular genetic levels show tremendous promise day elucidate mysteries this ancient organelle order treat therapeutically when needed. DNA mutations, infections, aging, a lack physical activity identified major players diseases. This review examines complexities function, whose incorporation into eukaryotic cells for energy purposes was key survival creation new species. Among these complexities, tightly intertwined derived from combustion alimentary substrates oxygen are necessary homeostasis, including production reactive discusses different etiological mechanisms by which mitochondria could dysregulated, determining fate tissues organs being protagonist many non–communicable Finally, is canonical evolutionary characteristic humans that remains embedded genes. normalization modern society led perception exercise an “intervention”. modus vivendi engrained genes sedentary real intervention collateral effect societies. It known leads and, hence, probably becomes factor affecting Since only stimulus we know can improve maintain emphasis on promotion should imperative prevent populations chronic where involved, individualized prescription crucial “metabolic rehabilitation” patients. From lessons learned elite athletes (the perfect human machines), possible translate apply concepts betterment

Язык: Английский

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Akkermansia muciniphila Ameliorates Acetaminophen-Induced Liver Injury by Regulating Gut Microbial Composition and Metabolism

Microbiology Spectrum, Год журнала: 2022, Номер 10(1)

Опубликована: Фев. 2, 2022

Our work revealed that A. muciniphila attenuated APAP-induced liver injury by alleviating oxidative stress and inflammation in the liver, its hepatoprotective effect was accompanied activation of PI3K/Akt pathway mediated regulation composition metabolic function intestinal microbiota. This finding suggested microbial community is a non-negligible impact on drug metabolism probiotic administration could be potential therapy for drug-induced injury.

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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The Role of Gut–Liver Axis in Gut Microbiome Dysbiosis Associated NAFLD and NAFLD-HCC

Biomedicines, Год журнала: 2022, Номер 10(3), С. 524 - 524

Опубликована: Фев. 23, 2022

Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most prevalent chronic diseases worldwide due to rapidly rising prevalence obesity and metabolic syndrome. As a hepatic manifestation disease, NAFLD begins with fat accumulation progresses inflammation, termed non-alcoholic steatohepatitis (NASH), fibrosis/cirrhosis, finally leading NAFLD-related hepatocellular carcinoma (NAFLD-HCC). Accumulating evidence showed that gut microbiome plays vital role in initiation progression through gut–liver axis. The axis mutual communication between comprising portal circulation, bile duct, systematic circulation. dysbiosis contributes development by dysregulating axis, increased intestinal permeability unrestrained transfer microbial metabolites into liver. In this review, we systematically summarized up-to-date information metabolomic changes along stages steatosis, NASH, fibrosis, NAFLD-HCC. components functions its association were then discussed. addition, highlighted current knowledge microbiome-based treatment strategies targeting for preventing associated HCC.

Язык: Английский

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Butyrate to combat obesity and obesity‐associated metabolic disorders: Current status and future implications for therapeutic use

Obesity Reviews, Год журнала: 2022, Номер 23(10)

Опубликована: Июль 20, 2022

Summary Evidence is increasing that disturbances in the gut microbiome may play a significant role etiology of obesity and type 2 diabetes. The short chain fatty acid butyrate, major end product bacterial fermentation indigestible carbohydrates, reputed to have anti‐inflammatory properties positive effects on body weight control insulin sensitivity. However, whether butyrate has therapeutic potential for treatment prevention obesity‐related complications remains be elucidated. Overall, animal studies strongly indicate administered via various routes (e.g., orally) positively affects adipose tissue metabolism functioning, energy substrate metabolism, systemic tissue‐specific inflammation, sensitivity control. A limited number human demonstrated interindividual differences clinical effectiveness suggesting outcomes depend metabolic, microbial, lifestyle‐related characteristics target population. Hence, despite abundant evidence from data, support data urgently required implementation evidence‐based oral gut‐derived interventions. To increase efficacy butyrate‐focused interventions, future research should investigate which factors impact including baseline microbial activity functionality, thereby optimizing targeted‐interventions identifying individuals merit most such

Язык: Английский

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