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Black raspberry extract can lower serum LDL cholesterol via modulation of gut microbial composition and serum bile acid profile in rats fed trimethylamine-N-oxide with a high-fat diet.

ABSTRACT: Blood trimethylamine-N-oxide (TMAO) has been associated with cardiovascular disease. Black raspberry (Rubus occidentalis, BR) has been regarded to be beneficial for cardiovascular health. This study aimed to investigate how BR extract affects serum lipid profile, gut microbial composition, metabolites in rats fed TMAO with a high-fat diet. Dietary TMAO increased serum LDL cholesterol, while BR extract decreased its level. α-Diversity of gut microbiota was not changed; however, in the rats fed TMAO, Macellibacteroides and Mucispirillum were enriched, while Ruminococcaceae was reduced. The BR supplementation could restore Macellibacteroides, Clostridium, and Ruminococcaceae. The BR supplementation increased cecal hippuric acid and serum farnesoid X receptor-antagonistic bile acids, including ursodeoxycholic acid (UDCA), tauro-α-muricholic acid, and tauro-UDCA. The BR supplementation tended to upregulate Cyp7a1 and Abcg5 expressions while downregulating Srebf2 and Hmgcr expressions. BR extract affects the gut bacterial community and microbial metabolites, lowering serum LDL cholesterol in rats with elevated serum TMAO.

Supplementary information

The online version contains supplementary material available at 10.1007/s10068-022-01079-y.

SUBMITTER: Lim T

PROVIDER: S-EPMC9300784 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Black raspberry extract can lower serum LDL cholesterol via modulation of gut microbial composition and serum bile acid profile in rats fed trimethylamine-N-oxide with a high-fat diet.

Lim Taehwan T Lee Kiuk K Kim Ryun Hee RH Cha Kwang Hyun KH Koo Song Yi SY Moon Eun Chae EC Hwang Keum Taek KT

Food science and biotechnology 20220410 8

Blood trimethylamine-N-oxide (TMAO) has been associated with cardiovascular disease. Black raspberry (<i>Rubus occidentalis</i>, BR) has been regarded to be beneficial for cardiovascular health. This study aimed to investigate how BR extract affects serum lipid profile, gut microbial composition, metabolites in rats fed TMAO with a high-fat diet. Dietary TMAO increased serum LDL cholesterol, while BR extract decreased its level. α-Diversity of gut microbiota was not changed; however, in the rats ...[more]

PMID: 35873380

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Project description:Sinapine derived from cruciferous plants could be converted into trimethylamine by intestinal microbiota. Its metabolite, trimethylamine N-oxide (TMAO), is closely linked to increased risk of cardiovascular disease and fat deposition in mammals. Hens fed with rapeseed meal (RSM) suffered from fatty liver hemorrhage syndrome (FLHS). This study was conducted to investigate whether RSM-induced fatty liver is due to TMAO via altering microbiota composition and diversity. At 33 weeks of age, 600 laying hens were randomly divided into 5 treatment groups, namely control and 14% RSM treatment groups (DY5, with 16.2% erucic acid [EA] and 74.66% glucosinolate [Gl] contents; MB1, with 3.50% EA and 43.23% Gl contents; DY6, with 6.7% EA and 22.67% Gl contents; XH3, with 44.60% EA and 132.83% Gl contents) for 8 weeks. Results revealed that 3 hens died due to liver hemorrhage after ingesting 14% RSM diet. The 14% RSM decreased serum low-density lipoprotein cholesterol (LDL-C) content (P < 0.01) while tended to increase serum TMAO content compared to the control group (P = 0.08). The 14% RSM diet increased red oil O optical density (P < 0.01), and increased total cholesterol (TC) and LDL-C content in the liver (P < 0.01, and P < 0.01, respectively). The 14% RSM decreased liver total bile acid (TBA) content compared to the control (P < 0.01). The DY6 had a higher TBA content in the liver than the XH3 (P < 0.01). The 14% RSM decreased mRNA abundance of liver X receptors alpha (LXR-α, P = 0.01), and increased mRNA abundance of sterol response element binding protein 2 (SREBP-2, P = 0.04). Results revealed that the in-feed RSM could alter richness and diversity of cecal microbiota compared to the control (P < 0.05). Liver TC content and serum TMAO showed a negative relationship with Proteobacteria and Actinobacteria (P = 0.04). In conclusion, 14% RSM increased liver TC and induced high liver score of FLHS, which was possibly associated with the altered cecal microbiota composition, increased serum TMAO levels and LXR-α and SREBP-2 expressions.

Project description:BackgroundPhenylketonuria (PKU; OMIM#261600) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in high phenylalanine (Phe) in blood and brain. If not treated early this results in intellectual disability, behavioral and psychiatric problems, microcephaly, motor deficits, eczematous rash, autism, seizures, and developmental problems. There is a controversial discussion of whether patients with PKU have an additional risk for atherosclerosis due to interference of Phe with cholesterol synthesis and LDL-cholesterol regulation. Since cholesterol also plays a role in membrane structure and myelination, better insight into the clinical significance of the impact of Phe on lipoprotein metabolism is desirable. In 22 treated PKU patients (mean age 38.7 years) and 14 healthy controls (mean age 35.2 years), we investigated plasma with NMR spectroscopy and quantified 105 lipoprotein parameters (including lipoprotein subclasses) and 24 low molecular weight parameters. Analysis was performed on a 600 MHz Bruker AVANCE IVDr spectrometer as previously described.ResultsConcurrent plasma Phe in PKU patients showed a wide range with a mean of 899 μmol/L (50-1318 μmol/L). Total cholesterol and LDL-cholesterol were significantly lower in PKU patients versus controls: 179.4 versus 200.9 mg/dL (p < 0.02) and 79.5 versus 104.1 mg/dL (p < 0.0038), respectively. PKU patients also had lower levels of 22 LDL subclasses with the greatest differences in LDL2 Apo-B, LDL2 Particle Number, LDL2-phospholipids, and LDL2-cholesterol (p < 0.0001). There was a slight negative correlation of total cholesterol and LDL-cholesterol with concurrent Phe level. VLDL5-free cholesterol, VLDL5-cholesterol, VLDL5-phospholipids, and VLDL4-free cholesterol showed a significant (p < 0.05) negative correlation with concurrent Phe level. There was no difference in HDL and their subclasses between PKU patients and controls. Tyrosine, glutamine, and creatinine were significantly lower in PKU patients compared to controls, while citric and glutamic acids were significantly higher.ConclusionsUsing NMR spectroscopy, a unique lipoprotein profile in PKU patients can be demonstrated which mimics a non-atherogenic profile as seen in patients treated by statins.

Dataset Information

Black raspberry extract can lower serum LDL cholesterol via modulation of gut microbial composition and serum bile acid profile in rats fed trimethylamine-N-oxide with a high-fat diet.

Supplementary information

Publications

Black raspberry extract can lower serum LDL cholesterol via modulation of gut microbial composition and serum bile acid profile in rats fed trimethylamine-N-oxide with a high-fat diet.

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