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- Lützhøft, Ditte Olsen, et al.
(författare)
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Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model
- 2022
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Ingår i: BMC Microbiology. - : BioMed Central (BMC). - 1471-2180. ; 22:1
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Madsen, Marie Terese Barlebo, et al.
(författare)
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Effects of Wholegrain Compared to Refined Grain Intake on Cardiometabolic Risk Markers, Gut Microbiota, and Gastrointestinal Symptoms in Children: A Randomized Crossover Trial
- 2024
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Ingår i: The American journal of clinical nutrition. - 0002-9165 .- 1938-3207. ; 119:1, s. 18-28
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Tidskriftsartikel (refereegranskat)abstract
- Background: Wholegrain intake is associated with lower risk of cardiometabolic diseases in adults, potentially via changes in the gut microbiota. Although cardiometabolic prevention should start early, we lack evidence on the effects in children. Objectives: This study investigated the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL) cholesterol and plasma insulin (coprimary outcomes), other cardiometabolic markers, body composition, gut microbiota composition and metabolites, and gastrointestinal symptoms in children with high body mass index (BMI). Methods: In a randomized crossover trial, 55 healthy Danish 8- to 13-y-olds received wholegrain oats and rye (“WG”) or refined grain (“RG”) products ad libitum for 8 wk in random order. At 0, 8, and 16 wk, we measured anthropometry, body composition by dual-energy absorptiometry, and blood pressure. Fasting blood and fecal samples were collected for analysis of blood lipids, glucose homeostasis markers, gut microbiota, and short-chain fatty acids. Gut symptoms and stool characteristics were determined by questionnaires. Diet was assessed by 4-d dietary records and compliance by plasma alkylresorcinols (ARs). Results: Fifty-two children (95%) with a BMI z-score of 1.5 ± 0.6 (mean ± standard deviation) completed the study. They consumed 108 ± 38 and 3 ± 2 g/d wholegrain in the WG and RG period, which was verified by a profound difference in ARs (P < 0.001). Compared with RG, WG reduced LDL cholesterol by 0.14 (95% confidence interval: −0.24, −0.04) mmol/L (P = 0.009) and reduced total:high-density lipoprotein cholesterol (P < 0.001) and triacylglycerol (P = 0.048) without altering body composition or other cardiometabolic markers. WG also modulated the abundance of specific bacterial taxa, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. Conclusion: High intake of wholegrain oats and rye reduced LDL cholesterol and triacylglycerol, modulated bacterial taxa, and increased beneficial metabolites in children. This supports recommendations of exchanging refined grain with wholegrain oats and rye among children. This trial was registered at clinicaltrials.gov as NCT04430465.
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