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.
Click here to read the full text study.
Posted February 25, 2019.
References:
- Harraan D. Aging: a theory based on free radical and radiation chemistry. 1956.
- Roopchand DE, Carmody RN, Kuhn P, et al. Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet–induced metabolic syndrome. Diabetes. 2015;64(8):2847-2858.
- Anhê FF, Roy D, Pilon G, et al. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut. 2015;64(6):872-883.
- Masumoto S, Terao A, Yamamoto Y, Mukai T, Miura T, Shoji T. Non-absorbable apple procyanidins prevent obesity associated with gut microbial and metabolomic changes. Scientific reports. 2016;6:31208.
- Forslund K, Hildebrand F, Nielsen T, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528(7581):262.
- Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proceedings of the National Academy of Sciences. 2013;110(22):9066-9071.
- Abia R, Fry SC. Degradation and metabolism of 14C‐labelled proanthocyanidins from carob (Ceratonia siliqua) pods in the gastrointestinal tract of the rat. Journal of the Science of Food and Agriculture. 2001;81(12):1156-1165.
- González-Sarrías A, Espín JC, Tomás-Barberán FA. Non-extractable polyphenols produce gut microbiota metabolites that persist in circulation and show anti-inflammatory and free radical-scavenging effects. Trends in Food Science & Technology. 2017;69:281-288.
- Teixeira TF, Collado MC, Ferreira CL, Bressan J, Maria do Carmo GP. Potential mechanisms for the emerging link between obesity and increased intestinal permeability. Nutrition research. 2012;32(9):637-647.
- Kuhn P, Kalariya HM, Poulev A, et al. Grape polyphenols reduce gut-localized reactive oxygen species associated with the development of metabolic syndrome in mice. PloS one. 2018;13(10):e0198716.