Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis

Gut Microbes, Journal Year: 2021, Volume and Issue: 13(1)

Published: Jan. 1, 2021

The gut bacterium

Language: Английский

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Endoplasmic reticulum stress in liver diseases

Hepatology, Journal Year: 2022, Volume and Issue: 77(2), P. 619 - 639

Published: May 7, 2022

The endoplasmic reticulum (ER) is an intracellular organelle that fosters the correct folding of linear polypeptides and proteins, a process tightly governed by ER‐resident enzymes chaperones. Failure to shape proper 3‐dimensional architecture proteins culminates in accumulation misfolded or unfolded within ER, disturbs ER homeostasis, leads canonically defined stress. Recent studies have elucidated cellular perturbations, such as lipotoxicity, can also lead In response stress, protein (UPR) activated reestablish homeostasis (“adaptive UPR”), or, conversely, provoke cell death when stress overwhelmed sustained (“maladaptive UPR”). It well documented contributes onset progression multiple hepatic pathologies including NAFLD, alcohol‐associated liver disease, viral hepatitis, ischemia, drug toxicity, cancers. Here, we review key dealing with emerging role UPR pathophysiology diseases from cellular, murine, human models. Specifically, will summarize current available knowledge on pharmacological non‐pharmacological interventions may be used target maladaptive for treatment nonmalignant diseases.

Language: Английский

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Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Cells, Journal Year: 2019, Volume and Issue: 8(12), P. 1471 - 1471

Published: Nov. 20, 2019

Tauroursodeoxycholic acid (TUDCA) is a naturally occurring hydrophilic bile that has been used for centuries in Chinese medicine. Chemically, TUDCA taurine conjugate of ursodeoxycholic (UDCA), which contemporary pharmacology approved by Food and Drug Administration (FDA) treatment primary biliary cholangitis. Interestingly, numerous recent studies demonstrate mechanisms functioning extend beyond hepatobiliary disorders. Thus, demonstrated to display potential therapeutic benefits various models many diseases such as diabetes, obesity, neurodegenerative diseases, mostly due its cytoprotective effect. The underlying this activity have mainly attributed alleviation endoplasmic reticulum (ER) stress stabilization the unfolded protein response (UPR), contributed naming chemical chaperone. Apart from that, also found reduce oxidative stress, suppress apoptosis, decrease inflammation in-vitro in-vivo diseases. latest research suggests can play role an epigenetic modulator act agent certain types cancer. Nevertheless, despite massive amount evidence demonstrating positive effects pre-clinical studies, there are limitations restraining wide use patients. Here, molecular cellular modes action described opportunities discussed.

Language: Английский

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Gut microbiota modulation in patients with non-alcoholic fatty liver disease: Effects of current treatments and future strategies

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 16, 2023

Non-alcoholic fatty liver disease (NAFLD) is frequently associated with metabolic disorders, being highly prevalent in obese and diabetic patients. Many concomitant factors that promote systemic inflammation are involved NAFLD pathogenesis, a growing body of evidence highlighting the key role gut microbiota. Indeed, gut-liver axis has strong impact promotion progression wide spectrum its manifestations, claiming efforts to find effective strategies for microbiota modulation. Diet among most powerful tools; Western diet negatively affects intestinal permeability composition function, selecting pathobionts, whereas Mediterranean fosters health-promoting bacteria, favorable on lipid glucose metabolism inflammation. Antibiotics probiotics have been used improve features, mixed results. More interestingly, medications treat NAFLD-associated comorbidities may also modulate Drugs treatment type 2 diabetes mellitus (T2DM), such as metformin, glucagon-like peptide-1 (GLP-1) agonists, sodium-glucose cotransporter (SGLT) inhibitors, not only regulation homeostasis, but reduction fat content inflammation, they shift towards healthy phenotype. Even bariatric surgery significantly changes microbiota, mostly due modification gastrointestinal anatomy, parallel improvement histological features NAFLD. Other options promising effects reprogramming axis, fecal microbial transplantation (FMT) next-generation deserve further investigation future inclusion therapeutic armamentarium

Language: Английский

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Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases

Cells, Journal Year: 2023, Volume and Issue: 12(14), P. 1888 - 1888

Published: July 19, 2023

The intestinal barrier is a precisely regulated semi-permeable physiological structure that absorbs nutrients and protects the internal environment from infiltration of pathological molecules microorganisms. Bile acids are small synthesized cholesterol in liver, secreted into duodenum, transformed to secondary or tertiary bile by gut microbiota. interact with acid receptors (BARs) microbiota, which plays key role maintaining homeostasis barrier. In this review, we summarize discuss recent studies on disorder associated dysfunction related diseases. We focus roles acids, BARs, microbiota triggering dysfunction. Insights for future prevention treatment diseases provided.

Language: Английский

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Tea Polyphenol Epigallocatechin Gallate Protects Against Nonalcoholic Fatty Liver Disease and Associated Endotoxemia in Rats via Modulating Gut Microbiota Dysbiosis and Alleviating Intestinal Barrier Dysfunction and Related Inflammation

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: April 12, 2024

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation and inflammation. Epigallocatechin gallate (EGCG) has been proven to be effective against NAFLD, but its hepatoprotective mechanisms based on the "gut microbiota-barrier-liver axis" are still not fully understood. Herein, results demonstrated that EGCG effectively ameliorated NAFLD phenotypes metabolic disorders in rats fed a high-fat diet (HFD), inhibited intestinal barrier dysfunction inflammation, which also supported experiment of Caco-2 cells. Moreover, could restore gut microbiota diversity composition, particularly promoting beneficial microbes, including short-chain acids (SCFAs) producers, such as Lactobacillus, suppressing Gram-negative bacteria, Desulfovibrio. The microbial modulation raised SCFA levels, decreased lipopolysaccharide TLR4/NF-κB pathway, strengthened function via Nrf2 pathway activation, thereby alleviating steatosis Spearman's correlation analysis showed 24 key OTUs, negatively or positively associated with disorders, were reshaped EGCG. Our suggested combinative improvement dysbiosis, dysfunction, inflammation might potential therapeutic target for NAFLD.

Language: Английский

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Pharmacological Applications of Bile Acids and Their Derivatives in the Treatment of Metabolic Syndrome

Frontiers in Pharmacology, Journal Year: 2018, Volume and Issue: 9

Published: Dec. 3, 2018

Apart from well-known functions of bile acids in digestion and solubilization lipophilic nutrients drugs the small intestine, emerging evidence past two decades identified role as signaling, endocrine molecules that regulate glucose, lipid, energy metabolism through complex intertwined pathways are largely mediated by activation nuclear receptor farnesoid X (FXR) cell surface G protein-coupled 1, TGR5 (also known GPBAR1). Interactions with gut microbiota result altered composition circulating intestinal pool, modified signaling pathways, further extending complexity biological these steroid derivatives. Thus, have become attractive targets for treatment various metabolic diseases syndrome opening new potential avenue their treatment. In addition, there is a significant effort to unveil some specific properties relevant intrinsic potency selectivity particular receptors design novel modulators improved pharmacokinetic pharmacodynamic profiles. This resulted synthesis few semi-synthetic derivatives such 6α-ethyl-chenodeoxycholic acid (obeticholic acid, OCA), norursodeoxycholic (norUDCA), 12-monoketocholic (12-MKC) proven positive effect hepato-biliary disorders. review presents an overview current knowledge related implications lipid metabolism, well application future perspectives.

Language: Английский

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Interactions between gut microbiota and non-alcoholic liver disease: The role of microbiota-derived metabolites

Pharmacological Research, Journal Year: 2019, Volume and Issue: 141, P. 521 - 529

Published: Jan. 17, 2019

Language: Английский

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The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress–Driven Mucus Depletion and Exacerbates Intestinal Inflammation

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2018, Volume and Issue: 7(2), P. 457 - 473

Published: Sept. 11, 2018

Food additives, such as emulsifiers, stabilizers, or bulking agents, are present in the Western diet and their consumption is increasing. However, little known about potential effects on intestinal homeostasis. In this study we examined effect of some these food additives gut inflammation.Mice were given drinking water containing maltodextrin (MDX), propylene glycol, animal gelatin, then challenged with dextran sulfate sodium indomethacin. parallel, mice fed a MDX-enriched endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA). Transcriptomic analysis, real-time polymerase chain reaction, mucin-2 expression, phosphorylated p38 mitogen-activated protein (MAP) kinase quantification, H&E staining was performed colonic tissues. Mucosa-associated microbiota composition characterized by 16S ribosomal RNA sequencing. For vitro experiments, murine crypts human mucus-secreting HT29-methotrexate treated cell line stimulated MDX presence absence TUDCA MAP inhibitor.Diets enriched MDX, but not glycol exacerbated inflammation both models. Analysis mechanisms underlying detrimental showed up-regulation inositol requiring 1β, sensor ER stress, goblet cells, reduction expression no significant change mucosa-associated microbiota. Stimulation cells induced 1β via kinase-dependent mechanism. Treatment prevented depletion attenuated colitis MDX-fed mice.MDX increases epithelial downstream reducing mucus production enhancing susceptibility.

Language: Английский

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Bile Acids and Microbiota: Multifaceted and Versatile Regulators of the Liver–Gut Axis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(3), P. 1397 - 1397

Published: Jan. 30, 2021

After their synthesis from cholesterol in hepatic tissues, bile acids (BAs) are secreted into the intestinal lumen. Most BAs subsequently re-absorbed terminal ileum and transported back for recycling to liver. Some of them, however, reach colon change physicochemical properties upon modification by gut bacteria, vice versa, also shape composition function microbiota. This mutual interplay both microbiota regulates many physiological processes, including lipid, carbohydrate energy metabolism host. Emerging evidence implies an important role this enterohepatic BA circuit shaping mucosal colonization resistance as well local distant immune responses, tissue physiology carcinogenesis. Subsequently, disrupted interactions bacteria associated with disorders diverse Clostridioides difficile or Salmonella Typhimurium infection, inflammatory bowel disease, type 1 diabetes, asthma, metabolic syndrome, obesity, Parkinson’s schizophrenia epilepsy. As we cannot address all these interesting underlying pathophysiologic mechanisms here, summarize current knowledge about physiologic pathogenic site using a few selected examples liver diseases.

Language: Английский

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