Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Animal models

Resveratrol-induced gut microbiota reduces obesity in high-fat diet-fed mice

International Journal of Obesity volume 44, pages 213–225 (2020)Cite this article

Subjects

Abstract

Objective

Resveratrol (RSV) is a natural polyphenol with putative anti-obesity effects; however, its mechanisms of action remain unclear due to its low bioavailability. Microbial functions in the physiology result from the microbiota–host coevolution has profoundly affected host metabolism. Here, we sought to determine how beneficial microbiome caused by RSV interventions affects antiobesity.

Methods

C57BL/6J mice were fed either standard diet (SD) or RSV (300 mg/kg/day) diet for 16 weeks. The composition of the gut microbiota was assessed by analyzing 16S rRNA gene sequences. Then, transplant the RSV-microbiota to high-fat diet (HFD)-fed mice (HFD-RSVT) to explore the function of microbiota. Body weight and food intake were monitored. Markers of lipid metabolism, inflammation, gut microbiota compostion, and intestinal barrier were determined.

Results

Mice treated with RSV shows a remarkable alteration in microbiota composition compared with that of SD-fed mice and is characterized by an enrichment of Bacteroides, Lachnospiraceae_NK4A136_group, Blautia, Lachnoclostridium, Parabacteroides, and Ruminiclostridium_9, collectively referred to as RSV-microbiota. We further explored whether RSV-microbiota has anti-obesity functions. Transplantation of the RSV-microbiota to high-fat diet (HFD)-fed mice (HFD-RSVT) was sufficient to decrease their weight gain and increase their insulin sensitivity. Moreover, RSV-microbiota was able to modulate lipid metabolism, stimulate the development of beige adipocytes in WAT, reduce inflammation and improve intestinal barrier function.

Conclusions

Our study demonstrates that RSV-induced microbiota plays a key role in controlling obesity development and brings new insights to a potential therapy based on host–microbe interactions.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Organization WH. World Health Organization obesity and overweight fact sheet; 2016.

  2. David LA, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559.

    CAS  PubMed  Google Scholar 

  3. Carmody RN, et al. Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe. 2015;17:72–84.

    CAS  PubMed  Google Scholar 

  4. Yatsunenko T, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Zhang C, et al. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J. 2010;4:232.

    CAS  PubMed  Google Scholar 

  6. Scarpellini E, et al. Gut microbiota and obesity. Intern Emerg Med. 2010;5:53–56.

    Google Scholar 

  7. Le Chatelier E, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541.

    PubMed  Google Scholar 

  8. Ley RE, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA. 2005;102:11070–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Turnbaugh PJ, Bäckhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3:213–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci USA. 2007;104:979–84.

    PubMed  PubMed Central  Google Scholar 

  11. Shin N-R, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63:727–35.

    PubMed  Google Scholar 

  12. Price NL, et al. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab. 2012;15:675–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Mattison JA, et al. Resveratrol prevents high fat/sucrose diet-induced central arterial wall inflammation and stiffening in nonhuman primates. Cell Metab. 2014;20:183–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Timmers S, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011;14:612–22.

    CAS  PubMed  Google Scholar 

  15. Jimenez-Gomez Y, et al. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet. Cell Metab. 2013;18:533–45.

    CAS  PubMed  Google Scholar 

  16. Qiao Y, et al. Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat-induced obesity. Food Funct. 2014;5:1241–9.

    CAS  PubMed  Google Scholar 

  17. Walle T. Bioavailability of resveratrol. Ann N Y Acad Sci. 2011;1215:9–15.

    CAS  PubMed  Google Scholar 

  18. Walle T, Hsieh F, DeLegge MH, Oatis JE, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004;32:1377–82.

    CAS  PubMed  Google Scholar 

  19. Francioso A, Mastromarino P, Masci A, d’Erme M, Mosca L. Chemistry, stability and bioavailability of resveratrol. Med Chem. 2014;10:237–45.

    PubMed  Google Scholar 

  20. Sung MM, et al. Improved glucose homeostasis in obese mice treated with resveratrol is associated with alterations in the gut microbiome. Diabetes. 2017;66:418–25.

    PubMed  Google Scholar 

  21. Etxeberria U, et al. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats. J Nutr Biochem. 2015;26:651–60.

    CAS  PubMed  Google Scholar 

  22. Li X, Guo J, Ji K, Zhang P. Bamboo shoot fiber prevents obesity in mice by modulating the gut microbiota. Sci Rep. 2016;6:32953.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Anhê FF, 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;64:872–83.

    PubMed  Google Scholar 

  24. Xu P, et al. Melatonin prevents obesity through modulation of gut microbiota in mice. J Pineal Res. 2017;62:e12399.

    Google Scholar 

  25. Wang S, et al. Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1. Int J Obes. 2015;39:967.

    CAS  Google Scholar 

  26. Qiang L, et al. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ. Cell. 2012;150:620–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Xiao S, et al. A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome. FEMS Microbiol Ecol. 2014;87:357–67.

    CAS  PubMed  Google Scholar 

  28. Guo X, et al. Rutin and its combination with inulin attenuates gut dysbiosis, the inflammatory status and endoplasmic reticulum stress in Paneth cell of obese mice induced by high-fat diet. Front Microbiol. 2018;9:2651.

    PubMed  PubMed Central  Google Scholar 

  29. Kim K-A, Gu W, Lee I-A, Joh E-H, Kim D-H. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS ONE 2012;7:e47713.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Togo A, Valero R, Delerce J, Raoult D, Million M. “Anaerotruncus massiliensis,” a new species identified from human stool from an obese patient after bariatric surgery. New Microbes New Infect. 2016;14:56–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Golubeva AV, et al. Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood. Psychoneuroendocrinology. 2015;60:58–74.

    PubMed  Google Scholar 

  32. Cho I, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012;488:621.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Million M, et al. New insights in gut microbiota and mucosal immunity of the small intestine. Hum Microbiome J. 2018;7:23–32.

    Google Scholar 

  34. Hooper LV, et al. Molecular analysis of commensal host–microbial relationships in the intestine. Science. 2001;291:881–4.

    CAS  PubMed  Google Scholar 

  35. Desai MS, et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016;167:1339–53. e1321.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Fan P, Liu P, Song P, Chen X, Ma X. Moderate dietary protein restriction alters the composition of gut microbiota and improves ileal barrier function in adult pig model. Sci Rep. 2017;7:43412.

    PubMed  PubMed Central  Google Scholar 

  37. Cani PD, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet–induced obesity and diabetes in mice. Diabetes. 2008;57:1470–81.

    CAS  PubMed  Google Scholar 

  38. Volynets V, et al. Intestinal barrier function and the gut microbiome are differentially affected in mice fed a western-style diet or drinking water supplemented with fructose-3. J Nutr. 2017;147:770–80.

    CAS  PubMed  Google Scholar 

  39. Bae M-J, et al. Baicalein induces CD4+ Foxp3+T cells and enhances intestinal barrier function in a mouse model of food allergy. Sci Rep. 2016;6:32225.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Neish AS. Mucosal immunity and the microbiome. Ann Am Thorac Soc. 2014;11(Suppl. 1):S28–S32.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Monk JM, et al. Chickpea-supplemented diet alters the gut microbiome and enhances gut barrier integrity in c57bl/6 male mice. J Funct Foods. 2017;38:663–74.

    CAS  Google Scholar 

  42. Krimi RB, et al. Resistin-like molecule β regulates intestinal mucous secretion and curtails TNBS-induced colitis in mice. Inflamm Bowel Dis. 2008;14:931–41.

    PubMed  Google Scholar 

  43. Vaishnava S, et al. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science. 2011;334:255–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Chavan S, et al. Reduced glutathione: importance of specimen collection. Indian J Clin Biochem. 2005;20:150.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Drew JE, et al. Salicylic acid modulates oxidative stress and glutathione peroxidase activity in the rat colon. Biochem Pharmacol. 2005;70:888–93.

    CAS  PubMed  Google Scholar 

  46. Winer DA, Luck H, Tsai S, Winer S. The intestinal immune system in obesity and insulin resistance. Cell Metab. 2016;23:413–26.

    CAS  PubMed  Google Scholar 

  47. Schneeberger M, et al. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci Rep. 2015;5:16643.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Lagouge M, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell. 2006;127:1109–22.

    CAS  PubMed  Google Scholar 

  49. Park S-J, et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 2012;148:421–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Chang C-J, et al. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun. 2015;6:7489.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Singh DP, et al. Isomalto-oligosaccharides, a prebiotic, functionally augment green tea effects against high fat diet-induced metabolic alterations via preventing gut dysbacteriosis in mice. Pharmacol Res. 2017;123:103–13.

    CAS  PubMed  Google Scholar 

  52. Zhang X, et al. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Sci Rep. 2015;5:14405.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Zhang J, et al. Intestinal microbiota are involved in the immunomodulatory activities of longan polysaccharide. Mol Nutr Food Res. 2017;61:1700466.

    Google Scholar 

  54. Reeves AE, Koenigsknecht MJ, Bergin IL, Young VB. Suppression of Clostridium difficile in the gastrointestinal tracts of germfree mice inoculated with a murine isolate from the family Lachnospiraceae. Infect Immun. 2012;80:3786–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Kang C, et al. Gut microbiota mediates the protective effects of dietary capsaicin against chronic low-grade inflammation and associated obesity induced by high-fat diet. mBio. 2017;8:e00470–00417.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Menni C, et al. Gut microbial diversity is associated with lower arterial stiffness in women. Eur Heart J. 2018;39:2390–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Neyrinck AM, et al. Rhubarb extract prevents hepatic inflammation induced by acute alcohol intake, an effect related to the modulation of the gut microbiota. Mol Nutr Food Res. 2017;61:1500899.

    Google Scholar 

  58. Meehan CJ, Beiko RG. A phylogenomic view of ecological specialization in the Lachnospiraceae, a family of digestive tract-associated bacteria. Genome Biol Evol. 2014;6:703–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Chevalier C, et al. Gut microbiota orchestrates energy homeostasis during cold. Cell. 2015;163:1360–74.

    CAS  PubMed  Google Scholar 

  60. Suez J, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514:181.

    CAS  PubMed  Google Scholar 

  61. Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013;108:500.

    PubMed  Google Scholar 

  62. Zhang F, Luo W, Shi Y, Fan Z, Ji G. Should we standardize the 1,700-year-old fecal microbiota transplantation? Am J Gastroenterol. 2012;107:1755.

    PubMed  Google Scholar 

  63. Vrieze A, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913–6. e917

    CAS  PubMed  Google Scholar 

  64. Kootte RS, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab. 2017;26:611–9. e616

    CAS  PubMed  Google Scholar 

  65. Bäckhed F, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA. 2004;101:15718–23.

    PubMed  PubMed Central  Google Scholar 

  66. Caesar R, Tremaroli V, Kovatcheva-Datchary P, Cani PD, Bäckhed F. Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab. 2015;22:658–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Ling K-H, Wan MLY, El-Nezami H, Wang M. Protective capacity of resveratrol, a natural polyphenolic compound, against deoxynivalenol-induced intestinal barrier dysfunction and bacterial translocation. Chem Res Toxicol. 2016;29:823–33.

    CAS  PubMed  Google Scholar 

  68. Xu J, et al. Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula. ISME J. 2015;9:552–62.

    PubMed  Google Scholar 

  69. Gulhane M, et al. High fat diets induce colonic epithelial cell stress and inflammation that is reversed by IL-22. Sci Rep. 2016;6:28990.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Bergstrom KS, Xia L. Mucin-type O-glycans and their roles in intestinal homeostasis. Glycobiology. 2013;23:1026–37.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Bing Zhou and Runze Shang for technical assistance and manuscript editing. This work was supported by Beijing Municipal Science and Technology Project Fund [grant number D161100005416001].

Author information

Authors and Affiliations

  1. College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture; Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, 100083, Beijing, China

    Pan Wang, Daotong Li, Weixin Ke, Dong Liang, Xiaosong Hu & Fang Chen

Authors
  1. Pan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daotong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weixin Ke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dong Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaosong Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fang Chen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, P., Li, D., Ke, W. et al. Resveratrol-induced gut microbiota reduces obesity in high-fat diet-fed mice. Int J Obes 44, 213–225 (2020). https://doi.org/10.1038/s41366-019-0332-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-019-0332-1

This article is cited by

Search

Advanced search

Quick links