Objective To investigate the effects of different doses of quercetin on gut microbiota in mice treated with antibiotics, and explore effective dose of quercetin. Methods Sixty male Kunming mice were randomly divided into control group (C), model group (M, 0 mg/kg quercetin), low dose quercetin group (LQ, 200 mg/kg), moderate dose quercetin group (MQ, 400 mg/kg), and high dose quercetin group (HQ, 600 mg/kg). The gut microbial disorder was induced by gavage of an antibiotic cocktail. The C and M groups were fed the AIN-93G diet, and LQ, MQ, HQ groups were fed the AIN-93G diets with different doses of quercetin for 10 days. At the end of experiment, the fecal, small intestinal tissue, blood samples were collected. 16SrDNA high-throughput sequencing, gas chromatography, hematoxylin-eosin staining and ELISA methods were used to analyze gut microbial structure, short chain fatty acids, intestinal tissue and gut permeability, respectively. Results Compared with the C group at phylum level, 7 days antibiotic cocktail treatment decreased gut microbial diversity, except Proteobacteria, Firmicutes, and Bacteroidetes, which indicate gut microbial disrupted model were successfully established. Compared with the M group, LQ, MQ, HQ groups decreased Firmicutes/Bacteroides ratio by 32.8%、66.3%、62.9%, respectively. At the genus level, the inhibitory rates of different doses of quercetin on Escherichia Shigella and Klebsiella were all up to 99%. The increased bacteria genus Lactococcus and Desulfovibrio in the LQ group were positively related with butyric acid content (correlation coefficients were 0.74 and 0.78, respectively, P<0.001). The fecal butyric acid content in the LQ group((0.27±0.12) mmol/kg) was significantly higher than in the M group ((0.04±0.02) mmol/kg, P<0.05)). In addition, the recovery of intestinal mucosa and villi became more pronounced with the increase of quercetin dosage. The content of diamine oxidase in serum decreased by 29.25%, 37.90%, and 41.49%, respectively. Conclusion Lower quercetin dose was beneficial for butyric acid producing bacteria growth, while moderate and high quercetin doses were effective in inhibiting conditional pathogenic bacteria, and stabilizing intestinal micro-environment.
Key words
qurcetin /
gut microbiota /
short chain fatty acid /
bioavailability
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References
[1] 郭长江, 徐静, 韦京豫, 等. 我国常见蔬菜类黄酮物质的含量[J]. 营养学报, 2009, 31:185–190.
[2] 郭长江, 徐静, 韦京豫, 等. 我国常见水果类黄酮物质的含量[J]. 营养学报, 2008, 30:130–135.
[3] Patel RV, Mistry BM, Shinde SK, et al. Therapeutic potential of quercetin as a cardiovascular agent[J].Eur J Med Chem, 2018, 53:155889–155904.
[4] Dabeek WM, Marra MV.Dietary quercetin and kaempferol: bioavailability and potential cardiovascular-related bioactivity in humans[J]. Nutrients, 2019, 11:2288–2307.
[5] Reyes-farias M, Carrasco-pozo C. The anti-cancer effect of quercetin: molecular implications in cancer metabolism[J]. Int J Mol Sci, 2019, 20:3177–3196.
[6] Xu D, Hu MJ, Wang YQ, et al. Antioxidant activities of quercetin and its complexes for medicinal application[J]. Molecules, 2019, 24:1123–1138.
[7] Crespy V, Morand C, Manach C, et al. Part of quercetin absorbed in the small intestine is conjugated and further secreted in the intestinal lumen[J]. Am J Physiol, 1999, 277: G120–G126.
[8] Hirai I, Okuno M, Katsuma R, et al. Characterisation of anti-Staphylococcus aureus activity of quercetin[J]. Int J Food Sci Tech, 2010, 45:1250–1254.
[9] Serra A, Macia A, Romero MP, et al. Metabolic pathways of the colonic metabolism of flavonoids (flavonols, flavones and flavanones) and phenolic acids[J]. Food Chem, 2012, 130:383–393.
[10] Walle T, Walle UK, Halushka PV.Carbon dioxide is the major metabolite of quercetin in humans[J] J. Nutr, 2001, 131:2648–2652.
[11] Lee YK, Mazmanian SK.Has the microbiota played a critical role in the evolution of the adaptive immune system[J]. Science, 2010, 330:1768–1773.
[12] Zhao L, Shen J.Whole-body systems approaches for gut microbiota-targeted, preventive health care[J]. J Biotechnol, 2010, 149:183–190.
[13] Heijtz RD, Wang S, Anuar F, et al. Normal gut microbiota modulates brain development and behavior[J]. PNAS, 2011, 108:3047–3052.
[14] Mayer EA, Savidge T, Shulman RJ.Brain-gut microbiome interactions and functional bowel disorders[J]. Gas-troenterology,2014, 146:1500–1512.
[15] Reves PG, Nielsen FH, Fahey GC.AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet[J]. J Nutr, 1993, 123:1939–1951.
[16] Wallace AJ, Eady SL, Hunter DC, et al. No difference in fecal levels of bacteria or short chain fatty acids in humans when consuming fruit juice beverages containing fruit fiber, fruit polyphenols, and their combination[J].Nutr Res, 2014, 35:23–34.
[17] Ijssennagger N, Belzer C, Hooiveld GJ, et al. Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon[J]. PNAS, 2015, 112:10038–10043.
[18] Clements SJ, Carding SR, et al. Diet, the intestinal microbiota, and immune health in aging[J]. Crit Rev Food Sci, 2016, 58:651-661.
[19] Gill HS, Rutherfurd KJ, Cross ML, et al. Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019[J]. Am J Clin Nutr, 2001,74:833-839.
[20] Shin NR, Whon TW, Bae JW.Proteobacteria: microbial signature of dysbiosis in gut microbiota[J].Trends Biotechnol, 2015, 33: 496–503.
[21] 郑有坤, 刘凯, 熊子君, 等. 药用植物内生放线菌多样性及天然活性物质研究进展[J]. 中草药, 2014, 45: 2089–2099.
[22] Binda C, Lopetuso LR, Rizzatti G, et al. Actinobacteria: a relevant minority for the maintenance of gut homeostasis[J]. Digest Liver Dis, 2018, 50:421–428.
[23] 罗君, 付伟杰, 杨二军, 等. 槲皮素对杂交石斑鱼生长性能、抗氧化能力和肠道菌群的影响[J].广东海洋大学学报, 2022, 42:13–22.
[24] Dong Y, Lei J, Zhang B.Effects of dietary quercetin on the antioxidative status and cecal microbiota in broiler chickens fed with oxidized oil[J]. Poultry Sci, 2020, 99:4892–4903.
[25] 梅华迪, 李袁飞, 田琦, 等. 槲皮素对断奶仔猪生长性能、营养物质表观消化率、血清生化指标、粪便微生物及其代谢产物的影响[J]. 动物营养学报, 2022, 34:2884–2895.
[26] 陈樱萌, 胡满江, 曾钰鹏, 等. 槲皮素对肠道菌群的调节作用研究[J]. 食品研究与开发, 2020, 41:6–15.
[27] Etxeberria U, Arias N, Boque N, et al. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats[J].J Nutr Biochm, 2015, 26:651–660.
[28] Nie J, Zhang L, Zhao G, et al. Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites[J]. J Appl Microbiol, 2019, 127:1824–1834.
[29] Shin HS, Yoo JH, Min TS, et al. The effects of quercetin on physiological characteristics and oxidative stress resistance in olive flounder, Paralichthys olivaceus[J]. Asian Austral J Anim, 2010, 23 : 588–597.
[30] 牛鹏飞, 王延召, 曾庆敏, 等.肠黏膜屏障功能及损伤机制研究进展[J] .中华临床医师杂志,2020,14:735–739.
[31] 梅华迪, 李袁飞, 马现永, 等. 槲皮素对动物肠道黏膜屏障功能的影响及其调控机制[J]. 动物营养学报, 2022, 34:5475–5488.
