Shifts in gene expression profiles are associated with weak and strong Crassulacean acid metabolism

Statins are the most widely prescribed medications worldwide for the treatment of hypercholesterolemia. They inhibit the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R), an enzyme involved in cholesterol synthesis in higher organisms and in isoprenoid biosynthesis in some bacteria. We hypothesized that statins may influence the microbial community in the gut through either direct inhibition or indirect mechanisms involving alterations to host responses. We therefore examined the impact of rosuvastatin (RSV) on the community structure of the murine gastrointestinal microbiota. RSV was orally administered to mice and the effects on the gut microbiota, host bile acid profiles, and markers of inflammation were analyzed. RSV significantly influenced the microbial community in both the cecum and feces, causing a significant decrease in α-diversity in the cecum and resulting in a reduction of several physiologically relevant bacterial groups. RSV treatment of mice significantly affected bile acid metabolism and impacted expression of inflammatory markers known to influence microbial community structure (including RegIIIγ and Camp) in the gut. This study suggests that a commonly used statin (RSV) leads to an altered gut microbial composition in normal mice with attendant impacts on local gene expression profiles, a finding that should prompt further studies to investigate the implications of statins for gut microbiota stability and health in humans. NEW & NOTEWORTHY This work demonstrates that rosuvastatin administration in mice affects the gastrointestinal microbiota, influences bile acid metabolism, and alters transcription of genes encoding factors involved in gut homeostasis and immunity in the gastrointestinal tract.

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Transcriptional regulation of cholesterol and bile acid metabolism after dietary soyabean meal treatment in Atlantic salmon (Salmo salar L.)

British Journal Of Nutrition ◽

10.1017/s0007114512002024 ◽

2012 ◽

Vol 109 (4) ◽

pp. 593-604 ◽

Cited By ~ 63

Author(s):

Trond M. Kortner ◽

Jinni Gu ◽

Åshild Krogdahl ◽

Anne Marie Bakke

Keyword(s):

Gene Expression ◽

Bile Acid ◽

Atlantic Salmon ◽

Acid Metabolism ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Bile Acid Metabolism ◽

Atp Binding ◽

Hepatic Gene Expression ◽

Soyabean Meal

Inclusion of plant protein sources such as soyabean meal (SBM) in aquafeeds is associated with decreased lipid digestibility, reduced bile acid levels and hypocholesterolaemia. The mechanism for these metabolic abnormalities is unknown. The present study aimed at gaining further insight into how cholesterol and bile acid metabolism is modulated by SBM feeding by quantifying a number of mRNA species corresponding to key proteins involved in cholesterol and bile acid metabolism using quantitative real-time PCR. A 21 d feeding trial with sequential sampling at ten time points following initiation of 20 % SBM exposure was conducted on Atlantic salmon. A histological evaluation confirmed distal intestinal enteritis after 5 d of dietary exposure to the SBM, whereas diminished glycogen/lipid deposition was the only relevant finding observed in the liver. SBM inclusion resulted in reduced body pools of cholesterol and bile acids. Hepatic gene expression profiles revealed up-regulation of genes encoding rate-limiting enzymes in cholesterol (3-hydroxy-3-methyl-glutaryl-CoA reductase; HMGCR) and bile acid (cytochrome P4507A1 (CYP7A1)) biosynthesis, as well as up-regulation of their associated transcription factors (sterol regulatory element binding proteins 1 and 2, liver X receptor, farnesoid X receptor and PPAR isoforms). Hepatic gene expressions of cholesterol (ATP binding cassette G5 (ABCG5)) and bile acid (ATP binding cassette B11 (ABCB11)) transporters were, by and large, not influenced by the SBM, but distal intestinal expression patterns of ABCG5 and apical Na-dependent bile acid transporter indicated impaired cholesterol and bile acid reabsorption. In conclusion, hepatic gene expression profiles indicated that the capacity for cholesterol and bile acid synthesis was up-regulated, whereas the indicated impaired cholesterol and bile acid reabsorption probably occurred as a direct result of distal intestinal inflammation.

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