Research Article Details
| Article ID: | A06038 |
| PMID: | 33032263 |
| Source: | J Endocrinol |
| Title: | Lactobacillus pentosus strain S-PT84 improves steatohepatitis by maintaining gut permeability. |
| Abstract: | Intestinal mucosal barrier dysfunction is closely related to the pathogenesis of nonalcoholic steatohepatitis (NASH). Gut immunity has been recently demonstrated to regulate gut barrier function. The Lactobacillus pentosus strain S-PT84 activates helper T cells and natural killer/natural killer T cells. In this study, we examined the effect of S-PT84 on NASH progression induced by high-cholesterol/high-fat diet (CL), focusing on the immune responses involved in gut barrier function. C57BL/6 mice were fed a normal chow or CL diet with or without 1 × 1010 S-PT84 for 22 weeks. S-PT84 administration improved hepatic steatosis by decreasing triglyceride and free fatty acid levels by 34% and 37%, respectively. Furthermore, S-PT84 inhibited the development of hepatic inflammation and fibrosis, suppressed F4/80+ macrophage/Kupffer cell infiltration, and reduced liver hydroxyproline content. Administration of S-PT84 alleviated hyperinsulinemia and enhanced hepatic insulin signalling. Compared with mice fed CL diet, mice fed CL+S-PT84 had 71% more CD11c-CD206+ M2 macrophages, resulting in a significantly decreased M1/M2 macrophage ratio in the liver. Moreover, S-PT84 inhibited the CL diet-mediated increase in intestinal permeability. Additionally, S-PT84 reduced the recruitment of interleukin-17-producing T cells and increased the levels of intestinal tight junction proteins, including zonula occludens-1, occludin, claudin-3, and claudin-7. In conclusion, our findings suggest that S-PT84 attenuates diet-induced insulin resistance and subsequent NASH development by maintaining gut permeability. Thus, S-PT84 represents a feasible approach to prevent the development of NASH. |
| DOI: | 10.1530/JOE-20-0105 |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |