Addition of grapes to both a standard and a high-fat Western pattern diet modifies hepatic and urinary metabolite profiles in the mouse

Beyoğlu, Diren; Park, Eun-Jung; Quiñones-Lombraña, Adolfo; Dave, Asim; Parande, Falguni; Pezzuto, John M.; Idle, Jeffrey R.

doi:10.1039/d2fo00961g

Cited by 10 publications

(11 citation statements)

References 46 publications

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“…In fact, we have confirmed alterations in hepatic and urinary metabolite patterns based on gas chromatography-mass spectrometry-based metabolomics. The grape diet was found to reprogram gut microbiota metabolism, attenuate the hepatic oxidative stress of a high-fat diet, and increase the efficiency of glucose utilization by the liver for energy production [77].…”

Section: Discussionmentioning

confidence: 99%

Consumption of Grapes Modulates Gene Expression, Reduces Non-Alcoholic Fatty Liver Disease, and Extends Longevity in Female C57BL/6J Mice Provided with a High-Fat Western-Pattern Diet

Dave

Park

Kumar

et al. 2022

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A key objective of this study was to explore the potential of dietary grape consumption to modulate adverse effects caused by a high-fat (western-pattern) diet. Female C57BL/6J mice were purchased at six-weeks-of-age and placed on a standard (semi-synthetic) diet (STD). At 11 weeks-of-age, the mice were continued on the STD or placed on the STD supplemented with 5% standardized grape powder (STD5GP), a high-fat diet (HFD), or an HFD supplemented with 5% standardized grape powder (HFD5GP). After being provided with the respective diets for 13 additional weeks, the mice were euthanized, and liver was collected for biomarker analysis, determination of genetic expression (RNA-Seq), and histopathological examination. All four dietary groups demonstrated unique genetic expression patterns. Using pathway analysis tools (GO, KEGG and Reactome), relative to the STD group, differentially expressed genes of the STD5GP group were significantly enriched in RNA, mitochondria, and protein translation related pathways, as well as drug metabolism, glutathione, detoxification, and oxidative stress associated pathways. The expression of Gstp1 was confirmed to be upregulated by about five-fold (RT-qPCR), and, based on RNA-Seq data, the expression of additional genes associated with the reduction of oxidative stress and detoxification (Gpx4 and 8, Gss, Gpx7, Sod1) were enhanced by dietary grape supplementation. Cluster analysis of genetic expression patterns revealed the greatest divergence between the HFD5GP and HFD groups. In the HFD5GP group, relative to the HFD group, 14 genes responsible for the metabolism, transportation, hydrolysis, and sequestration of fatty acids were upregulated. Conversely, genes responsible for lipid content and cholesterol synthesis (Plin4, Acaa1b, Slc27a1) were downregulated. The two top classifications emerging as enriched in the HFD5GP group vs. the HFD group (KEGG pathway analysis) were Alzheimer’s disease and nonalcoholic fatty liver disease (NAFLD), both of which have been reported in the literature to bear a causal relationship. In the current study, nonalcoholic steatohepatitis was indicated by histological observations that revealed archetype markers of fatty liver induced by the HFD. The adverse response was diminished by grape intervention. In addition to these studies, life-long survival was assessed with C57BL/6J mice. C57BL/6J mice were received at four-weeks-of-age and placed on the STD. At 14-weeks-of-age, the mice were divided into two groups (100 per group) and provided with the HFD or the HFD5GP. Relative to the HFD group, the survival time of the HFD5GP group was enhanced (log-rank test, p = 0.036). The respective hazard ratios were 0.715 (HFD5GP) and 1.397 (HFD). Greater body weight positively correlated with longevity; the highest body weight of the HFD5GP group was attained later in life than the HFD group (p = 0.141). These results suggest the potential of dietary grapes to modulate hepatic gene expression, prevent oxidative damage, induce fatty acid metabolism, ameliorate NAFLD, and increase longevity when co-administered with a high-fat diet.

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Section: Discussionmentioning

confidence: 99%

Consumption of Grapes Modulates Gene Expression, Reduces Non-Alcoholic Fatty Liver Disease, and Extends Longevity in Female C57BL/6J Mice Provided with a High-Fat Western-Pattern Diet

Dave

Park

Kumar

et al. 2022

Foods

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“…As described previously [ 17 , 18 ], quality control (QC) samples were prepared by pooling 50 μL aliquots of all the plasma samples, and every sample was divided into 200 μL aliquots and stored in Eppendorf tubes. All samples were analyzed in duplicate and together with the QC samples.…”

Section: Methodsmentioning

confidence: 99%

Short-Term Grape Consumption Diminishes UV-Induced Skin Erythema

et al. 2022

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Over three million Americans are affected by skin cancer each year, largely as a result of exposure to sunlight. The purpose of this study was to determine the potential of grape consumption to modulate UV-induced skin erythema. With 29 human volunteers, we report that nine demonstrated greater resistance to UV irradiation of the skin after consuming the equivalent of three servings of grapes per day for two weeks. We further explored any potential relationship to the gut–skin axis. Alpha- and beta-diversity of the gut microbiome were not altered, but grape consumption modulated microbiota abundance, enzyme levels, and KEGG pathways. Striking differences in the microbiome and metabolome were discerned when comparing the nine individuals showing greater UV resistance with the 20 non-responders. Notably, three urinary metabolites, 2′-deoxyribonic acid, 3-hydroxyphenyl acetic and scyllo-inositol, were depressed in the UV-resistant group. A ROC curve revealed a 71.8% probability that measurement of urinary 2′-deoxyribonic acid identifies a UV skin non-responder. 2′-Deoxyribonic acid is cleaved from the DNA backbone by reactive oxygen species. Three of the nine subjects acquiring UV resistance following grape consumption showed a durable response, and these three demonstrated unique microbiomic and metabolomic profiles. Variable UV skin sensitivity was likely due to glutathione S-transferase polymorphisms. We conclude that a segment of the population is capable of demonstrating greater resistance to a dermal response elicited by UV irradiation as a result of grape consumption. It is uncertain if modulation of the gut-skin axis leads to enhanced UV resistance, but there is correlation. More broadly, it is reasonable to expect that these mechanisms relate to other health outcomes anticipated to result from grape consumption.

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“…With mice given a high-fat diet supplemented with enriched grape powder, the abundance of genes that regulate microbial production of butyrate were selectively increased 11 . In our murine work, urinary excretion of the gut microbiota metabolites 4-hydroxyphenylacetic acid, 5-hydroxyindole, glyceric acid, gluconic acid and myo -inositol was attenuated when grape was added to a standard diet, and the gut microbiota metabolites gluconic acid, scyllo -inositol, mannitol, xylitol, 5-hydroxyindole and 2′-deoxyribonic acid were increased in urine when grape was added to a high-fat diet 12 – 14 . Further, in a two-phase human intervention study (4-week standardization phase and a 4-week grape intervention phase), Yang et al observed an increase in the alpha-diversity index of the gut microbiome (Shannon index), as well as a decrease in total cholesterol and total bile acid 15 .…”

Section: Introductionmentioning

confidence: 63%

Influence of grape consumption on the human microbiome

Dave

Beyoğlu

Park

et al. 2023

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Over the years, a substantial body of information has accumulated suggesting dietary consumption of grapes may have a positive influence on human health. Here, we investigate the potential of grapes to modulate the human microbiome. Microbiome composition as well as urinary and plasma metabolites were sequentially assessed in 29 healthy free-living male (age 24–55 years) and female subjects (age 29–53 years) following two-weeks of a restricted diet (Day 15), two-weeks of a restricted diet with grape consumption (equivalent to three servings per day) (Day 30), and four-weeks of restricted diet without grape consumption (Day 60). Based on alpha-diversity indices, grape consumption did not alter the overall composition of the microbial community, other than with the female subset based on the Chao index. Similarly, based on beta-diversity analyses, the diversity of species was not significantly altered at the three time points of the study. However, following 2 weeks of grape consumption, taxonomic abundance was altered (e.g., decreased Holdemania spp. and increased Streptococcus thermophiles), as were various enzyme levels and KEGG pathways. Further, taxonomic, enzyme and pathway shifts were observed 30 days following the termination of grape consumption, some of which returned to baseline and some of which suggest a delayed effect of grape consumption. Metabolomic analyses supported the functional significance of these alterations wherein, for example, 2′-deoxyribonic acid, glutaconic acid, and 3-hydroxyphenylacetic acid were elevated following grape consumption and returned to baseline following the washout period. Inter-individual variation was observed and exemplified by analysis of a subgroup of the study population showing unique patterns of taxonomic distribution over the study period. The biological ramifications of these dynamics remain to be defined. However, while it seems clear that grape consumption does not perturb the eubiotic state of the microbiome with normal, healthy human subjects, it is likely that shifts in the intricate interactive networks that result from grape consumption have physiological significance of relevance to grape action.

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Addition of grapes to both a standard and a high-fat Western pattern diet modifies hepatic and urinary metabolite profiles in the mouse

Abstract: The benefits of fruit and vegetable dietary consumption are largely defined in epidemiological terms. Relatively little is known about the discrete effects on metabolic pathways elicited by individual dietary fruits...

Cited by 10 publications

References 46 publications

Consumption of Grapes Modulates Gene Expression, Reduces Non-Alcoholic Fatty Liver Disease, and Extends Longevity in Female C57BL/6J Mice Provided with a High-Fat Western-Pattern Diet

Consumption of Grapes Modulates Gene Expression, Reduces Non-Alcoholic Fatty Liver Disease, and Extends Longevity in Female C57BL/6J Mice Provided with a High-Fat Western-Pattern Diet

Short-Term Grape Consumption Diminishes UV-Induced Skin Erythema

Influence of grape consumption on the human microbiome

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