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Global, distinctive and personal changes in molecular and microbial profiles induced by specific fibers in humans (Targeted)

ABSTRACT: Dietary fibers act through the microbiome and improve cardiovascular health, metabolic disorders and cancer prevention. To understand health benefits of dietary fiber supplementation we investigated two popular purified fibers, arabinoxylan (AX) and long-chain inulin (LCI), and a mixture of five fibers. We present multi-omic signatures of metabolomics, lipidomics, proteomics, metagenomics, a cytokine panel and clinical measurements on healthy and insulin resistant participants. Each fiber is associated with fiber-dependent biochemical and microbial responses. AX consumption associates with a significant reduction in LDL and an increase in bile acids, contributing to its observed cholesterol reduction. LCI is associated with an increase in Bifidobacterium. However, at the highest LCI dose there is increased inflammation and elevation in the liver enzyme alanine aminotransferase. This study yields insights into the effects of fiber supplementation, it provides insights into mechanisms behind fiber induced cholesterol reduction, and it shows effects of individual, purified fibers on the microbiome.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

SUBMITTER: Samuel Lancaster

PROVIDER: ST002180 | MetabolomicsWorkbench | Fri Mar 18 00:00:00 GMT 2022

REPOSITORIES: MetabolomicsWorkbench

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Global, distinctive and personal changes in molecular and microbial profiles induced by specific fibers in humans (Untargeted)

Project description:Dietary fibers act through the microbiome and improve cardiovascular health, metabolic disorders and cancer prevention. To understand health benefits of dietary fiber supplementation we investigated two popular purified fibers, arabinoxylan (AX) and long-chain inulin (LCI), and a mixture of five fibers. We present multi-omic signatures of metabolomics, lipidomics, proteomics, metagenomics, a cytokine panel and clinical measurements on healthy and insulin resistant participants. Each fiber is associated with fiber-dependent biochemical and microbial responses. AX consumption associates with a significant reduction in LDL and an increase in bile acids, contributing to its observed cholesterol reduction. LCI is associated with an increase in Bifidobacterium. However, at the highest LCI dose there is increased inflammation and elevation in the liver enzyme alanine aminotransferase. This study yields insights into the effects of fiber supplementation, it provides insights into mechanisms behind fiber induced cholesterol reduction, and it shows effects of individual, purified fibers on the microbiome.

2022-05-06 | ST002112 | MetabolomicsWorkbench

Dietary cholesterol supplementation to a plant-based diet for Atlantic salmon

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2013-10-31 | E-GEOD-51887 | biostudies-arrayexpress

Comparison of the effects of five dietary fibers on mucosal transcriptional profiles, and luminal microbiota composition and SCFA concentrations in murine colon

Project description:Consumption of diets rich in fibers has been associated with several beneficial effects on gastrointestinal health. However, detailed studies on the molecular effects of fibers in colon are limited. In this study we investigated and compared the influence of five different fibers on the mucosal transcriptome, and luminal microbiota and SCFA concentrations in murine colon. Mice were fed diets enriched with fibers that differed in carbohydrate composition, namely inulin (IN), oligofructose (FOS), arabinoxylan (AX), guar gum (GG), resistant starch (RS) or a control diet (corn starch) for 10 days. Gene expression profiling revealed the regulation of specific, but also overlapping sets of epithelial genes by each fiber, which on a functional level were mainly linked to cell cycle and various metabolic pathways including fatty acid oxidation, tricarboxylic acid cycle, and electron transport chain. In addition, the transcription factor PPAR was predicted to be a prominent upstream regulator of these processes. Microbiota profiles were distinct per dietary fiber, but the fibers IN, FOS, AX and GG induced a common change in microbial groups. All dietary fibers, except resistant starch, increased SCFA concentrations but to a different extent. Multivariate data integration revealed strong correlations between the expression of genes involved in energy metabolism and the relative abundance of bacteria belonging to the group of Clostridium cluster XIVa, that are known butyrate producers. These findings illustrate the potential of multivariate data analysis to unravel simple relationships in complex systems. Keywords: Expression profiling by array Mice received a control diet, or a diet supplemented with 10% dietary fibers for 10 days. After an overnight fast colon was removed, epithelial cells were scraped off, and subjected to gene expression profiling.

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Project description:Skeletal muscle is highly developed after birth, consisting of glycolytic fast- and oxidative slow-twitch fibers; however, the mechanisms of fiber type-specific differentiation are poorly understood. Here, we found an unexpected role for mitochondrial fission in the differentiation of fast-twitch oxidative fibers. Depletion of the mitochondrial fission factor dynamin-related protein 1 (Drp1) in mouse skeletal muscle and cultured myotubes resulted in the specific reduction of fast-twitch muscle fibers independently of respiratory function. Altered mitochondrial fission caused the activation of the Akt/mammalian target of rapamycin (mTOR) pathway via the mitochondrial accumulation of mTOR complex 2 (mTORC2), and rapamycin administration rescued the reduction of fast-twitch fibers in vivo and in vitro. Under Akt/mTOR activation, the mitochondria-related cytokine growth differentiation factor-15 was upregulated, which repressed fast-twitch fiber differentiation. Our findings reveal a novel role for mitochondrial dynamics in the activation of mTORC2 on mitochondria, resulting in the differentiation of muscle fibers.

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2008-10-20 | E-GEOD-9711 | biostudies-arrayexpress

Dietary supplementation to a plant-based diet for Atlantic salmon

Project description:The study evaluated effects of dietary cholesterol (CH), taurocholate (TC), choline (CN) and taurine (TA) in Atlantic salmon fed a plant based diet for 77 days. The additives did not affect growth or organ weights of Atlantic salmon, but promoted induction of cholesterol and plant sterol efflux in the intestine, whereas sterol uptake was suppressed. Microarray analyses in the liver indicated decreased cholesterol biosynthesis and enhanced conversion to bile acids. The marked effect of cholesterol on bile acid synthesis suggests that dietary cholesterol can be used to stimulate bile acid synthesis in fish. The study clearly demonstrated how Atlantic salmon adjusted metabolic functions in response to the dietary load of cholesterol, and has expanded our understanding of sterol metabolism and turnover that adds to the knowledge of these processes in fish. Feed supplementation with choline improved lipid absorption and suppressed abnormal accumulation of fat in the gut.

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Comparison of the effects of five dietary fibers on mucosal transcriptional profiles, and luminal microbiota composition and SCFA concentrations in murine colon

2015-05-26 | GSE59494 | GEO

Dietary folate depletion and repletion in C57BL/6J mice, ApoE knockout mice, and choline supplemented C57BL/6J mice

Project description:Defects in homocysteine and folate metabolism are associated with increased risks for neural tube and congenital heart defects, cardiovascular disease and stroke, cancers, and neurodegeneration. In many but not all cases, dietary supplementation with folate significantly reduces the severity and incidence of these conditions. Common polymorphisms modulate these metabolic pathways and disease risks, but do not fully account for the particular birth defects and adult diseases that occur in at-risk individuals. To test whether other pathways contribute to disease pathogenesis, we analyzed global and pathway-specific changes in gene expression and levels of selected metabolites after depletion and repletion of dietary folate in two genetically distinct inbred strains of mice. Compared to the C57BL/6J strain, A/J showed greater homeostatic response to folate perturbation by retaining a higher serum folate level and minimizing global gene expression changes. Remarkably, folate perturbation led to systematic strain-specific differences only in the expression profile of the cholesterol biosynthesis pathway and translated to changes in levels of serum and liver total cholesterol. By genetically increasing serum and liver total cholesterol levels in APOE deficient mice, we modestly but significantly improved folate retention during folate depletion, suggesting an interplay between homocysteine and folate metabolism and cholesterol metabolism. Absence of measurable changes in global methylation patterns or amelioration of effects with supplementation with an alternative methyl donor suggest that dietary folate perturbations do not act through large-scale or general changes in methylation. These results suggest that homeostatic responses in cholesterol metabolism contribute to the beneficial effects of dietary folate supplementation. Keywords: time course, stress response, diet, genetic, homeostasis

2008-08-27 | GSE9243 | GEO

Dietary folate depletion and repletion in A/J and C57BL/6J mice

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