Research Article Details
| Article ID: | A00248 |
| PMID: | 35166723 |
| Source: | Clin Transl Gastroenterol |
| Title: | Relationship between hepatic gene expression, intestinal microbiota and inferred functional metagenomic analysis in NAFLD. |
| Abstract: | INTRODUCTION: We previously reported a lower fecal abundance of Ruminococcus spp., Faecalibacterium prausnitzii, and Coprococcus spp. in non-alcoholic fatty liver disease (NAFLD). Here we assess the associations between hepatic gene expression, the specific taxa, and bacterial pathways. METHODS: The relationships between hepatic genes that were differentially expressed in NAFLD patients vs healthy controls (HC), and the abundance of these specific taxa were studied. Inferred functional metagenomic analysis using Piphillin was also performed to investigate associations with bacterial pathways. RESULTS: Fifteen NAFLD and 6 HC participated. Of 728 hepatic genes examined, 176 correlated with the abundance of Ruminococcus spp., 138 with F. prausnitzii, and 92 with Coprococcus spp. For Ruminococcus spp., genes were enriched in Gene Ontology (GO) terms related to apoptotic process, response to external and cytokine stimuli, and regulation of signaling. Several genes related to the KEGG pathway insulin resistance were correlated with F. prausnitzii. The hepatic genes associated with F. prausnitzii were enriched in GO terms related to cellular response to different stimuli, apoptotic process, and regulation of metabolic pathways. For Coprococcus spp., only the GO term response to external stimulus was enriched. There was a distinct pattern of associations between hepatic genes and bacterial taxa in NAFLD versus HC. For bacterial pathways, 65 and 18 hepatic genes correlated with bacterial metabolic functions in NAFLD and HC, respectively. DISCUSSION: Hepatic gene expression related to insulin resistance, inflammation, external stimuli, and apoptosis correlated with bacterial taxa. NAFLD patients showed a higher presence of bacterial pathways associated with lipid metabolism. |
| DOI: | 10.14309/ctg.0000000000000466 |
| 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 |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| 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 |