Grape expectations: Dietary grapes promote subtle shifts in human microbiome with potential health implications

By Dr. Priyom Bose, Ph.D.May 16 2023Reviewed by Benedette Cuffari, M.Sc.

Several studies have indicated that diet plays a crucial role in maintaining and altering the gut microbiome. In fact, the amount of fat, protein, phytoestrogens, polyphenols, and carbohydrates consumed by an individual influences microbial diversity. Gut microbial population and abundance affect the levels of metabolites, such as acetate, butyrate, and propionate, which affect physiological functions. 

A recent Scientific Reports study investigates how grapes influence the human microbiome.

Study: Influence of grape consumption on the human microbiome. Image Credit: Andrew Hagan / Shutterstock.com

Background

In the United States alone, six million tons of grapes are produced every year. Several studies have indicated that grape consumption manifests an array of responses associated with inflammation, gastrointestinal health, urinary bladder function, vision, atherosclerosis, and arteriosclerosis. Furthermore, mouse models have revealed that dietary grapes have pronounced effects on gene expression that influences several diseases in the liver or brain. 

Over 1,600 phytochemical compounds have been identified in grapes which, alone or in combination with other compounds, affect different physiological processes. The most common chemical constituent of a grape is resveratrol, which has been studied extensively.

One previous study has shown that human intestinal microbiota treated with total grape seed led to a change in short-chain fatty acids (SCFAs) profile and relevant microbial populations. Mice subjected to a high-fat diet along with grape powder exhibited an increase in microbial populations that synthesize butyrate. 

When the grape powder was added to a standard murine diet, urinary excretion of the gut microbiota metabolites 5-hydroxyindole, gluconic acid, glyceric acid, myo-inositol and 4-hydroxyphenylacetic acid were attenuated. In contrast, an increase in certain metabolites such as scyllo-inositol, xylitol, 5-hydroxyindole, gluconic acid, 2′-deoxyribonic acid, and mannitol was observed.

In humans, grape consumption can lead to an increase in the alpha-diversity index of the gut microbiome. Reduced total bile acid and cholesterol levels has also been correlated with grape consumption. 

About the study

A total of forty healthy, free-living human participants were recruited in this trial which was conducted for two months. All participants were subjected to two-weeks of a restricted diet (Day 15), two-weeks of a restricted diet supplemented with the equivalent of three servings of grapes per day (Day 30), and a one-month washout period (Day 60).

Subsequently, plasma, urine, and fecal samples were collected from each participant. Out of the forty participants initially recruited for the study, only twenty-nine individuals completed the trial.

Study findings

Alpha-diversity reflects the richness and relative abundance of microbial population in the gut. In the current study, no alterations in alpha diversity were observed among male participants between 24 and 44 years of age. However, female participants between 29 and 39 years of age exhibited a difference in alpha diversity on Day 60 as compared to Day 15.

Principal component analyses (PCA) and principal coordinate analyses (PCoA) were used to analyze beta diversity. Based on cluster analysis, no significant differences in beta diversity were observed in the study period, irrespective of gender-based subgroup analysis.

Common microbial species found on Day 15, 30, and 60 were Faecalibacterium prausnitzi,i Eubacterium rectale, Prevotella copri, Alistipes finegoldii, Fusicatenibacter saccharivorans,  Bacteroides vulgatus, Alistipes putredinis, Bacteroides stercoris, Parabacteroides merdae, Bacteroides uniformis, Bifidobacterium adolescentis, Bacteroides coprocola, and Collinsella aerofaciens.

Microbial taxonomic analyses revealed significant microbial alterations at each time point. On Day 30, an increased level of Streptococcus thermophiles was observed.

Previous studies have revealed that this bacterium produces lactic acid in the gut and is considered a probiotic. In addition, a decrease in Holdemania spp. was observed. A similar microbial profile was recorded in those under a vegetarian diet. 

At Day 30, an increase in the abundance of Holdemania was noted; however, no change in Streptococcus thermophiles occurred. At Day 60, a significant increase in the level of organisms associated with the production of metabolites was observed. These findings indicate a delayed gut microbial response to grape consumption, as no microbial alterations were found on Day 15.

Grape consumption manifested changes in certain enzyme levels. For example, an increase in catechol 2,3-dioxygenase level was observed, which causes metabolic detoxification. In addition, a decrease in the(3S)-malyl-CoA thioesterase was observed, which influences the glyoxylate cycle of microorganisms.

As compared to day 15, a significant increase in error-prone DNA polymerase was observed on Days 30 and 60. These findings indicate a delayed effect of grape consumption on enzyme levels.

As compared to Day 15, elevated levels of cysteine peptidases and decreased levels of ABC transporters and Narl family were observed on Day 30. Additionally, as compared to Day 30, an increase in oxidoreductases, ABC Transporters, and Nonribosomal peptide synthetase (NRPS) was reported on Day 60.

Conclusions

The current study revealed that grape consumption does not alter the eubiotic state of the microbiome that prevails in healthy participants. Nevertheless, grape consumption alters the taxonomic composition of the microbiome, KEGG pathways, enzyme levels, and metabolic profile. In the future, more research is needed to understand whether these changes have broader health benefits.