Research Article Details
| Article ID: | A04874 |
| PMID: | 33471632 |
| Source: | Am J Physiol Gastrointest Liver Physiol |
| Title: | Bacterial and eukaryotic extracellular vesicles and nonalcoholic fatty liver disease: new players in the gut-liver axis? |
| Abstract: | The liver and intestine communicate in a bidirectional way through the biliary tract, portal vein, and other components of the gut-liver axis. The gut microbiota is one of the major contributors to the production of several proteins and bile acids. Imbalance in the gut bacterial community, called dysbiosis, participates in the development and progression of several chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD). NAFLD is currently considered the main chronic liver disease worldwide. Dysbiosis contributes to NAFLD development and progression, notably by a greater translocation of pathogen-associated molecular patterns (PAMPs) in the blood. Lipopolysaccharide (LPS) is a PAMP that activates Toll-like receptor 4 (TLR4), induces liver inflammation, and participates in the development of fibrogenesis. LPS can be transported by bacterial extracellular vesicles (EVs). EVs are spherical structures produced by eukaryotic and prokaryotic cells that transfer information to distant cells and may represent new players in NAFLD development and progression. The present review summarizes the role of eukaryotic EVs, either circulating or tissue-derived, in NAFLD features, such as liver inflammation, angiogenesis, and fibrosis. Circulating EV levels are dynamic and correlate with disease stage and severity. However, scarce information is available concerning the involvement of bacterial EVs in liver disease. The present review highlights a potential role of bacterial EVs in insulin resistance and liver inflammation, although the mechanism involved has not been elucidated. In addition, because of their distinct signatures, eukaryotic and prokaryotic EVs may also represent a promising NAFLD diagnostic tool as a "liquid biopsy" in the future. |
| DOI: | 10.1152/ajpgi.00362.2020 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S06 | Regulating intestinal flora | intestine gut microbiota; gut microbiota | farnesoid X receptor (FXR); fibroblast growth factor-19 (FGF19) | Probiotics; Prebiotics; Rifaximin; Yaq-001; Cilofexor; EDP-305; EYP001a; INT-767 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |