Ditte Olsen, Lützhøft and Tim, Sinioja and Berit Ø., Christoffersen and Jakobsen, Rasmus Riemer and Dawei, Geng and Hajar Fauzan, Ahmad and Ellen Marie, Straarup and Karen-Margrethe, Pedersen and Kot, Witold and Henrik Duelund, Pedersen and Susanna, Cirera and Tuulia, Hyötyläinen and Dennis Sandris, Nielsen and Axel Kornerup, Hansen (2022) Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model. BMC Microbiology, 22 (287). pp. 1-14. ISSN 14712180. (Published)
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Abstract
Background: Gut microbiota dysbiosis is associated with the development of non‑alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short‑chain fatty acid production. The aim of this study was to describe the impact of a choline‑deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH. Results: Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short‑chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids. Conclusions: Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.
| Item Type: | Article |
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| Additional Information: | Indexed by Scopus |
| Uncontrolled Keywords: | Bile acids; colon microbiota; Hyperglucagonemia; Imidazole propionate; pH; SCFA |
| Subjects: | H Social Sciences > HD Industries. Land use. Labor Q Science > Q Science (General) |
| Faculty/Division: | Faculty of Industrial Sciences And Technology |
| Depositing User: | Dr. Hajar Fauzan Ahmad |
| Date Deposited: | 27 Jul 2023 02:54 |
| Last Modified: | 27 Jul 2023 02:54 |
| URI: | http://umpir.ump.edu.my/id/eprint/38074 |
| Download Statistic: | View Download Statistics |
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