Broccoli consumption attenuates inflammation and modulates gut microbiome composition and gut integrity-related factors in mice fed with a high-fat high-cholesterol diet

  • Gil Zandani The Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel
  • Sarit Anavi-Cohen Peres Academic Center, Rehovot, Israel
  • Noa Sela Department of Plant Pathology and Weed Research, Volcani Center, Rishon LeZion, Israel
  • Abraham Nyska Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Zecharia Madar The Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel;
DOI: https://doi.org/10.29219/fnr.v65.7631
Keywords: broccoli, inflammation, NAFLD, gut microbiome, barrier integrity

Abstract

Background: Nonalcoholic fatty-liver disease (NAFLD) is a global health problem associated with gut dysbiosis and intestinal permeability. Broccoli is a natural source of bioactive phytochemicals, characterized by health-promoting properties.

Objective: This study evaluated the effect of broccoli florets and stalks on liver fat accumulation, inflammation, gut microbiome, and intestinal barrier integrity.

Design: Male C57BL/6J mice (n = 32, 8-week-old) were fed with a high-fat high-cholesterol diet (HFCD) with/without 15% broccoli (florets or stalks) for 7 weeks. Liver damage was evaluated by changes in glucose response and histological and biochemical parameters. Protein and gene expressions related to liver inflammation were examined. The effect of broccoli on microbiota population together with genes related to barrier integrity in the gut was investigated.

Results: Dietary broccoli improved the glycemic response assessed by oral glucose tolerance test (OGTT). Histological evaluation showed no change in hepatic steatosis. Broccoli consumption also attenuated inflammation as revealed by lower inducible nitric oxide synthase (iNOS) and serum amyloid A1 (SAA1) expression levels in broccoli-supplemented groups. Gut microbiota analysis demonstrated elevated Acidifaciens and reduced Mucispirillum schaedleri abundance in the stalks group, whereas Proteobacteria strains abundance was increased in the florets group. Gut integrity remained unchanged.

Conclusion: Broccoli supplementation improves glucose tolerance, attenuates liver inflammation, and alters microbial composition, but does not affect gut integrity. This research provides new evidence on the effects of dietary broccoli under HFCD.

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References


  1. Cotter TG, Rinella M. NAFLD 2020: the state of the disease. Gastroenterology 2020; 158(7): 1851–64. doi: 10.1053/j.gastro.2020.01.052

  2. Moschen AR, Kaser S, Tilg H. Non-alcoholic steatohepatitis: a microbiota-driven disease. Trends Endocrinol Metab 2013; 24(11): 537–45. doi: 10.1016/j.tem.2013.05.009

  3. Grabherr F, Grander C, Effenberger M, Adolph TE, Tilg H. Gut dysfunction and non-alcoholic fatty liver disease. Front Endocrinol 2019; 10(September): 1–9. doi: 10.3389/fendo.2019.00611

  4. Lau JKC, Zhang X, Yu J. Animal models of non-alcoholic fatty liver disease: current perspectives and recent advances. J Pathol 2017; 241(1): 36–44. doi: 10.1002/path.4829

  5. Stefan N, Häring HU, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol 2019; 7(4): 313–24. doi: 10.1016/S2213-8587(18)30154-2

  6. Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat Med 2018; 24(7): 908–22. doi: 10.1038/s41591-018-0104-9

  7. Schwenger KJP, Bolzon CM, Li C, Allard JP. Non-alcoholic fatty liver disease and obesity: the role of the gut bacteria. Eur J Nutr 2019; 58(5): 1771–84. doi: 10.1007/s00394-018-1844-5

  8. Araújo AR, Rosso N, Bedogni G, Tiribelli C, Bellentani S. Global epidemiology of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: what we need in the future. Liver Int 2018; 38(November 2017): 47–51. doi: 10.1111/liv.13643

  9. Raiola A, Errico A, Petruk G, Monti DM, Barone A, Rigano MM. Bioactive compounds in brassicaceae vegetables with a role in the prevention of chronic diseases. Molecules 2018; 23(1): 1–10. doi: 10.3390/molecules23010015

  10. Jeffery EH, Araya M. Physiological effects of broccoli consumption. Phytochem Rev 2009; 8(1): 283–98. doi: 10.1007/s11101-008-9106-4

  11. Sanlier N, Guler SM. The benefits of Brassica vegetables on human health. J. Hum. Health Res 2018; 1(1): 1–13.

  12. Lee SG, Kim JH, Son MJ, Lee EJ, Park WD, Kim JB, et al. Influence of extraction method on quality and functionality of broccoli juice. Prev Nutr Food Sci. 2013; 18(2): 133–8. doi: 10.3746/pnf.2013.18.2.133

  13. Guo Y, Wang L, Chen Y, Yun L, Liu S, Li Y. Stalk length affects the mineral distribution and floret quality of broccoli (Brassica oleracea L. var. italica) heads during storage. Postharvest Biol Technol 2018; 145(May): 166–71. doi: 10.1016/j.postharvbio.2018.07.003

  14. Yagishita Y, Fahey JW, Dinkova-Kostova AT, Kensler TW. Broccoli or sulforaphane: is it the source or dose that matters? Molecules 2019; 24(19): 3593. doi: 10.3390/molecules24193593

  15. Fahey JW, Holtzclaw WD, Wehage SL, Wade KL, Stephenson KK, Talalay P. Sulforaphane bioavailability from glucoraphanin-rich broccoli: control by active endogenous myrosinase. PLoS One 2015; 10(11): 1–13. doi: 10.1371/journal.pone.0140963

  16. Xu X, Dai M, Lao F, Chen F, Hu X, Liu Y, et al. Effect of glucoraphanin from broccoli seeds on lipid levels and gut microbiota in high-fat diet-fed mice. J Funct Foods. 2020;68(17):103858. doi: 10.1016/j.jff.2020.103858

  17. Armah CN, Derdemezis C, Traka MH, Dainty JR, Doleman JF, Saha S, et al. Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: Evidence from randomised controlled trials. Mol Nutr Food Res 2015; 59(5): 918–26. doi: 10.1002/mnfr.201400863

  18. Vanduchova A, Anzenbacher P, Anzenbacherova E. Isothiocyanate from broccoli, sulforaphane, and its properties. J Med Food 2019; 22(2): 121–6. doi: 10.1089/jmf.2018.0024

  19. Jiang X, Liu Y, Ma L, Ji R, Qu Y, Xin Y, et al. Chemopreventive activity of sulforaphane. Drug Des Devel Ther 2018; 12: 2905–13. doi: 10.2147/DDDT.S100534

  20. Schafer KA, Eighmy J, Fikes JD, Halpern WG, Hukkanen RR, Long GG, et al. Use of Severity Grades to Characterize Histopathologic Changes. Toxicol Pathol 2018; 46(3): 256–65. doi: 10.1177/0192623318761348

  21. Folch J, Lees M, Sloane-Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 226: 497–509.

  22. Van Herck MA, Vonghia L, Francque SM. Animal models of nonalcoholic fatty liver disease – a starter’s guide. Nutrients 2017; 9(10): 1–13. doi: 10.3390/nu9101072

  23. Matsuzawa N, Takamura T, Kurita S, Misu H, Ota T, Ando H, et al. Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet. Hepatology 2007; 46(5): 1392–1403. doi: 10.1002/hep.21874

  24. Takahashi Y, Soejima Y, Fukusato T. Animal models of nonalcoholic fatty liver disease/ nonalcoholic steatohepatitis. World J Gastroenterol 2012; 18(19): 2300–8. doi: 10.3748/wjg.v18.i19.2300

  25. Neuman MG, Cohen LB, Nanau RM. Biomarkers in nonalcoholic fatty liver disease. Can J Gastroenterol Hepatol 2014; 28(11): 607–18. doi: 10.1155/2014/757929

  26. Contreras-Zentella ML, Hernández-Muñoz R. Is liver enzyme release really associated with cell necrosis induced by oxidant stress? Oxid Med Cell Longev 2016; 2016: 3529149. doi: 10.1155/2016/3529149

  27. Bajaj JK, Salwan P, Salwan S. Various possible toxicants involved in thyroid dysfunction: a review. J Clin Diagn Res 2016; 10(1): FE01–3. doi: 10.7860/JCDR/2016/15195.7092

  28. McMillan M, Spinks EA, Fenwick GR. Preliminary observations the effect of dietary brussels sprouts on on thyroid function. Hum Toxicol 1986; 5: 15–19. doi: 10.1177/096032718600500104

  29. Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res 2017; 120(4): 713–35. doi: 10.1161/CIRCRESAHA.116.309326

  30. Hwang JH, Lim S Bin. Antioxidant and anti-inflammatory activities of Broccoli florets in LPS-stimulated RAW 264.7 Cells. Prev Nutr Food Sci 2014; 19(2): 89–97. doi: 10.3746/pnf.2014.19.2.089

  31. Ritz SA, Wan J, Diaz-Sanchez D. Sulforaphane-stimulated phase II enzyme induction inhibits cytokine production by airway epithelial cells stimulated with diesel extract. Am J Physiol Lung Cell Mol Physiol 2007; 292(1): 33–9. doi: 10.1152/ajplung.00170.2006

  32. Heiss E, Herhaus C, Klimo K, Bartsch H, Gerhäuser C. Nuclear factor κB is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J Biol Chem 2001; 276(34): 32008–15. doi: 10.1074/jbc.M104794200

  33. Hatziagelaki E, Karageorgopoulos DE, Chounta A, Tsiavou A, Falagas ME, Dimitriadis G. Predictors of impaired glucose regulation in patients with non-alcoholic fatty liver disease. Exp Diabetes Res 2012; 2012: 351974. doi: 10.1155/2012/351974

  34. Axelsson AS, Tubbs E, Mecham B, Chacko S, Nenonen HA, Tang Y, et al. Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. Sci Transl Med 2017; 9(394): 1–13. doi: 10.1126/scitranslmed.aah4477

  35. Goff HD, Repin N, Fabek H, El Khoury D, Gidley MJ. Dietary fibre for glycaemia control: towards a mechanistic understanding. Bioact Carbohydr Diet Fibre 2018; 14(April 2017): 39–53. doi: 10.1016/j.bcdf.2017.07.005

  36. Ruan H, Dong LQ. Adiponectin signaling and function in insulin target tissues. J Mol Cell Biol 2016; 8(2): 101–9. doi: 10.1093/jmcb/mjw014

  37. Savard C, Tartaglione EV, Kuver R, Haigh WG, Farrell GC, Subramanian S, et al. Synergistic interaction of dietary cholesterol and dietary fat in inducing experimental steatohepatitis. Hepatology 2013; 57(1): 81–92. doi: 10.1002/hep.25789

  38. Ding Y, Yanagi K, Cheng C, Alaniz RC, Lee K, Jayaraman A. Interactions between gut microbiota and non-alcoholic liver disease: the role of microbiota-derived metabolites. Pharmacol Res 2019; 141(December 2018): 521–9. doi: 10.1016/j.phrs.2019.01.029

  39. Makki K, Deehan EC, Walter J, Bäckhed F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe 2018; 23(6): 705–15. doi: 10.1016/j.chom.2018.05.012

  40. Wong VWS, Tse CH, Lam TTY, Wong GLH, Chim AML, Chu WCW, et al. Molecular Characterization of the Fecal Microbiota in Patients with Nonalcoholic Steatohepatitis - A Longitudinal Study. PLoS One 2013; 8(4): 1–11. doi: 10.1371/journal.pone.0062885

  41. Sobhonslidsuk A, Chanprasertyothin S, Pongrujikorn T, Kaewduang P, Promson K, Petraksa S, et al. The Association of Gut Microbiota with Nonalcoholic Steatohepatitis in Thais. Biomed Res Int 2018; 2018: 9340316. doi: 10.1155/2018/9340316

  42. Shtriker MG, Peri I, Taieb E, Nyska A, Tirosh O, Madar Z. Galactomannan more than pectin exacerbates liver injury in mice fed with high-fat, high-cholesterol diet. Mol Nutr Food Res 2018; 62(20): 1–9. doi: 10.1002/mnfr.201800331

  43. Assa-Glazer T, Gorelick J, Sela N, Nyska A, Bernstein N, Madar Z. Cannabis extracts affected metabolic syndrome parameters in mice fed high-fat/cholesterol diet. Cannabis Cannabinoid Res 2020; 5(3): 202–14. doi: 10.1089/can.2020.0013

  44. Rizzatti G, Lopetuso LR, Gibiino G, Binda C, Gasbarrini A. Proteobacteria: a common factor in human diseases. Biomed Res Int 2017; 2017: 9351507. doi: 10.1155/2017/9351507

  45. Shin NR, Whon TW, Bae JW. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol 2015; 33(9): 496–503. doi: 10.1016/j.tibtech.2015.06.011

  46. Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GG, Neyrinck AM, et al. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 2011; 60(November): 2775–86. doi: 10.2337/db11-0227

  47. El Aidy S, Derrien M, Aardema R, Hooiveld G, Richards SE, Dane A, et al. Transient inflammatory-like state and microbial dysbiosis are pivotal in establishment of mucosal homeostasis during colonisation of germ-free mice. Benef Microbes 2014; 5(1): 67–77. doi: 10.3920/BM2013.0018

  48. Loy A, Pfann C, Steinberger M, Hanson B, Herp S, Brugiroux S, et al. Gut commensal Bacteroides acidifaciens prevents obesity and improves insulin sensitivity in mice. Mucosal Immunol 2017; 10(1): 104–16. doi: 10.1111/j.1751-8369.2007.00022.x

  49. Yang JY, Lee YS, Kim Y, Lee SH, Ryu S, Fukuda S, et al. Gut commensal Bacteroides acidifaciens prevents obesity and improves insulin sensitivity in mice. Mucosal Immunol 2017; 10(1): 104–16. doi: 10.1038/mi.2016.42

  50. Bernd K, Schnabl B. Is intestinal inflammation linking dysbiosis to gut barrier dysfunction during liver disease?, Expert Rev Gastroenterol Hepatol 2015; 9(8): 1069–76. doi: 10.1586/17474124.2015.1057122

  51. Chelakkot C, Ghim J, Ryu SH. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med 2018; 50(8): 1–9. doi: 10.1038/s12276-018-0126-x

  52. Lee SH. Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases. Intest Res 2015; 13(1): 11. doi: 10.5217/ir.2015.13.1.11

  53. Rakha EA, Boyce RWG, El-rehim DA, Kurien T, Green AR, Paish EC, et al. Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod Pathol 2005; 18(10): 1295–304. doi: 10.1038/modpathol.3800445

  54. Natividad JMM, Hayes CL, Motta JP, Jury J, Galipeau HJ, Philip V, et al. Differential induction of antimicrobial REGIII by the intestinal microbiota and Bifidobacterium breve NCC2950. Appl Environ Microbiol 2013; 79(24): 7745–54. doi: 10.1128/AEM.02470-13

  55. Urban J. Intstinal IgA production and its role in hot-microbe interaction Immunol Rev. 2010; 5(3): 379–90. doi: 10.1111/imr.12189.Intestinal

Published
2021-09-06
How to Cite
Zandani G., Anavi-Cohen S., Sela N., Nyska A., & Madar Z. (2021). Broccoli consumption attenuates inflammation and modulates gut microbiome composition and gut integrity-related factors in mice fed with a high-fat high-cholesterol diet. Food & Nutrition Research, 65. https://doi.org/10.29219/fnr.v65.7631
Issue
Vol 65 (2021)
Section
Original Articles
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