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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. Access through your institution Buy or

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NUCIFERINE MODULATES THE GUT MICROBIOTA AND PREVENTS OBESITY IN HIGH-FAT DIET-FED RATS Article Open access 01 December 2020 RUTIN ALLEVIATES COLON LESIONS AND REGULATES GUT MICROBIOTA IN

DIABETIC MICE Article Open access 25 March 2023 POLYUNSATURATED FATTY ACIDS-RICH DIETARY LIPID PREVENTS HIGH FAT DIET-INDUCED OBESITY IN MICE Article Open access 05 April 2023 REFERENCES *

Organization WH. World Health Organization obesity and overweight fact sheet; 2016. * David LA, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559.

CAS  PubMed  Google Scholar  * 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  *

Yatsunenko T, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222. CAS  PubMed  PubMed Central  Google Scholar  * 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  * Scarpellini E, et al. Gut microbiota and

obesity. Intern Emerg Med. 2010;5:53–56. Google Scholar  * Le Chatelier E, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541. PubMed  Google

Scholar  * Ley RE, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA. 2005;102:11070–5. CAS  PubMed  PubMed Central  Google Scholar  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * Walle T. Bioavailability of

resveratrol. Ann N Y Acad Sci. 2011;1215:9–15. CAS  PubMed  Google Scholar  * 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  * 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  * 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  * 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  * 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  * 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  * Xu P, et al. Melatonin

prevents obesity through modulation of gut microbiota in mice. J Pineal Res. 2017;62:e12399. Google Scholar  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * Hooper LV, et al. Molecular analysis of commensal host–microbial relationships in the intestine. Science. 2001;291:881–4. CAS 

PubMed  Google Scholar  * 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  * 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  * 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  * 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  * 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  * Neish AS. Mucosal

immunity and the microbiome. Ann Am Thorac Soc. 2014;11(Suppl. 1):S28–S32. CAS  PubMed  PubMed Central  Google Scholar  * 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  * 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  * 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  * Chavan S, et al. Reduced glutathione: importance of specimen

collection. Indian J Clin Biochem. 2005;20:150. CAS  PubMed  PubMed Central  Google Scholar  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * Zhang J, et al. Intestinal microbiota are involved in the immunomodulatory activities of longan polysaccharide. Mol Nutr Food Res. 2017;61:1700466. Google Scholar

  * 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  * 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  * 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  * 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  * 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  * Chevalier C, et al. Gut microbiota orchestrates energy homeostasis during cold. Cell. 2015;163:1360–74. CAS  PubMed  Google Scholar  * Suez J, et al. Artificial sweeteners induce

glucose intolerance by altering the gut microbiota. Nature. 2014;514:181. CAS  PubMed  Google Scholar  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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  * 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 * 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 * Pan Wang View author publications You can also search for this author inPubMed Google Scholar * Daotong Li View author publications You can also search

for this author inPubMed Google Scholar * Weixin Ke View author publications You can also search for this author inPubMed Google Scholar * Dong Liang View author publications You can also

search for this author inPubMed Google Scholar * Xiaosong Hu View author publications You can also search for this author inPubMed Google Scholar * Fang Chen View author publications You can

also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Fang Chen. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict

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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: 24

September 2018 * Revised: 10 January 2019 * Accepted: 16 January 2019 * Published: 04 February 2019 * Issue Date: January 2020 * DOI: https://doi.org/10.1038/s41366-019-0332-1 SHARE THIS

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