Grape Polyphenols Reduce Intestinal Reactive Oxygen Species in Mice with Metabolic Syndrome

by | Feb 25, 2019 | 2018, Antioxidants, Fruits and Vegetables, Metabolic Syndrome, Obesity, Polyphenols

Written by Angeline A. De Leon, Staff Writer. Supplementation with poorly bioavailable grape polyphenol extract significantly increased free radical scavenging activity of the altered gut microbiome in metabolically compromised obese high fat diet-fed mice.

More than 60 years ago was when scientists first found evidence to suggest that dietary antioxidants, such as those found in fruits, vegetables, coffee, and tea, possessed the ability to protect against chronic non-communicable diseases (e.g., metabolic syndrome, type 2 diabetes) 1. More recent findings suggest that dietary polyphenols from fruits like blueberries, apples, and grapes can alter gut microbiota by reducing intestinal inflammation (acting as scavengers of reactive oxygen species, ROS), improving oral glucose tolerance, and enhancing the gut barrier as well as metabolism 2-4. Polyphenols from grape, cranberry, and apple have also been shown to increase intestinal abundance of a beneficial gut bacterium, Akkermansia muciniphila, which is associated with improved glucose homeostasis and anti-diabetic and anti-obesity properties 5,6. Despite the documented health benefits of antioxidant flavonoids, however, studies have found the majority of polyphenols in grapes and berries to have relatively low systemic absorption 7, although evidence suggests that the small amount of partially metabolizable polyphenols may be responsible for the powerful improvements observed in gut health 8. An imbalance in gut flora, involving a shortage of beneficial bacteria (free radical scavengers) and an overgrowth of pathogenic microbes (increasing ROS), and increased intestinal permeability (leaky gut syndrome), may increase the risk for conditions such as metabolic syndrome, obesity, and chronic intestinal inflammation 9. In a 2018 study 10 conducted by investigators at Rutgers University, researchers imaged ROS in a live rodent model and examined the effects of grape polyphenols and other dietary antioxidants on gut ROS content in healthy and metabolically, compromised HFD-fed mice.

A set of 25 diet-induced obese (HFD) mice and a set of 25 control (low-fat diet, LFD) mice (both sets male and purchased at 13 weeks old) were each randomly divided into five groups: a control group receiving a vehicle solution (water) orally by gavage; a group receiving grape polyphenol extract (GPE, total polyphenol dose of 32 mg/kg, equivalent to a dose of 14.3-43.1 mg/kg for a 70 kg individual); a group receiving proanthocyanidins (PAC, 32 mg/kg); a group receiving beta-carotene (32 mg/kg, poor bioavailability similar to GPE); or a group receiving a mixture of L-ascorbic acid, D-α-tocopherol succinate, and α-lipoic acid (ATL, each 32 mg/kg, relatively more bioavailable). Both sets of mice were also maintained on their respective HF or LF diets for 10 weeks. Feces were collected hourly for the first 12 hours following feeding and at 24 hours following feeding and then analyzed for antioxidant and total polyphenol content. Using a novel non-invasive method, researchers also visualized intestinal ROS in animals using orally administered ROS-sensitive dye (indocyanine green dye).

Fecal samples collected following GPE treatment showed a large increase in antioxidant activity, which was evident at 4 h (in mice allowed ad libitum access to food after treatment). Fecal samples pooled over a 24 h period showed that about 40% of administered GPE antioxidant activity was recovered in feces, confirming poor bioavailability of GPE. Based on analysis of ROS-associated near-infrared fluorescence imaging (NIRF) data, HFD mice exhibited significantly higher accumulation levels of intestinal ROS, compared to LFD mice (4.1 times greater ROS-associated NIRF using rotational imaging, p < 0.0001). Finally, compared to HFD control mice, mice gavaged with GPE, PAC, and beta-carotene showed significant reduction in intestinal ROS (2.7-fold decrease for GPE, p < 0.01; 1.9-fold decrease for PAC and beta-carotene, p < 0.05 for both), while the ATL mixture was not associated with any significant changes in ROS.

Results of the study confirm the association of obesity and a high-fat diet with higher intestinal ROS content. Consumption of dietary antioxidants, even if relatively poor in bioavailability (GPE, PAC, beta-carotene), can reduce ROS in the gut of metabolically compromised mice, potentially restoring a more favorable microbial environment. Investigators, therefore, suggest that grapes and other dietary sources of polyphenols may be utilized to protect against metabolic syndrome, obesity, and diabetes. A potential weakness of the study may be the failure to measure other compositional markers of intestinal health, such as the presence of beneficial anaerobic species (A. Muciniphila), which could further confirm improvement in gut function. Future studies are needed to compare the clinical efficacy of grape polyphenols and other polyphenol sources to prebiotics and probiotics in protecting metabolic health.

Source: Kuhn P, Kalariya HM, Poulev A, Ribnicky DM, Jaja-Chimedza A, Roopchand DE, et al. (2018) Grape polyphenols reduce gut-localized reactive oxygen species associated with the development of metabolic syndrome in mice. PLoS ONE 13(10): e0198716. https://doi.org/10.1371/journal. pone.0198716

Copyright: © 2018 Kuhn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Posted February 25, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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