Low-dose stevia (Rebaudioside A) consumption perturbs gut microbiota and the mesolimbic dopamine reward system

Nutrients

Volumn 11, Issue 6, 2019, Pages

  Nettleton, Jodi E ^a   Klancic, Teja ^a   Schick, Alana ^b   Choo, Ashley C ^a   Shearer, Jane ^a,b   Borgland, Stephanie L ^c   Chleilat, Faye ^a   Mayengbam, Shyamchand ^a   Reimer, Raylene A ^a,b  

^a UNIVERSITY OF CALGARY   (Canada)

^b UNIVERSITY OF CALGARY   (Canada)

^c UNIVERSITY OF CALGARY   (Canada)

Author keywords

Glucose tolerance; Gut microbiota; Low calorie sweeteners; Mesolimbic reward system; Oligofructose enriched inulin; Rebaudioside A; Stevia

Indexed keywords

ACETIC ACID; BACTERIAL DNA; BUTYRIC ACID; DOPAMINE TRANSPORTER; GENOMIC DNA; GLUCOSE; INSULIN; INULIN; ISOBUTYRIC ACID; ISOVALERIC ACID; PREBIOTIC AGENT; REBAUDIOSIDE A; SHORT CHAIN FATTY ACID; STEVIOSIDE; TYROSINE 3 MONOOXYGENASE; UNCLASSIFIED DRUG; VALERIC ACID; DOPAMINE; FRUCTOSE OLIGOSACCHARIDE; KAURANE DERIVATIVE; N-PENTANOIC ACID; OLIGOSACCHARIDE; VOLATILE FATTY ACID;

ANIMAL EXPERIMENT; ARTICLE; BACTEROIDES THETAIOTAOMICRON; BIFIDOBACTERIACEAE; BIFIDOBACTERIUM; BODY COMPOSITION; BODY WEIGHT GAIN; CECUM; CONTROLLED STUDY; DUAL ENERGY X RAY ABSORPTIOMETRY; DYSBIOSIS; FAT MASS; FECES ANALYSIS; FLUID INTAKE; FOOD INTAKE; GENE EXPRESSION; GLUCOSE METABOLISM; GLUCOSE TOLERANCE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; INSULIN SENSITIVITY; INSULIN TOLERANCE TEST; INTESTINE FLORA; INTESTINE MUCOSA PERMEABILITY; LACTOBACILLUS; LIVER WEIGHT; LOW DRUG DOSE; MALE; MESOLIMBIC DOPAMINERGIC SYSTEM; MRNA EXPRESSION LEVEL; NONHUMAN; NUCLEUS ACCUMBENS; OBESITY; ORAL GLUCOSE TOLERANCE TEST; RAT; STEVIA; ANIMAL; BRAIN; CHEMISTRY; DRUG EFFECT; METABOLISM; RANDOMIZATION; SPRAGUE DAWLEY RAT;

ACETIC ACID; ANIMALS; BRAIN; CECUM; DITERPENES, KAURANE; DOPAMINE; FATTY ACIDS, VOLATILE; GASTROINTESTINAL MICROBIOME; INULIN; MALE; OLIGOSACCHARIDES; PENTANOIC ACIDS; PREBIOTICS; RANDOM ALLOCATION; RATS; RATS, SPRAGUE-DAWLEY;

EID: 85067181618     PISSN: None     EISSN: 20726643     Source Type: Journal    
DOI: 10.3390/nu11061248     Document Type: Article

References (66)

1. WHO. WHO|Obesity and Overweight. Available online: http://www.who.int/mediacentre/factsheets/fs311/en/ (accessed on 5 December 2017).
2. Hill, J.O.; Wyatt, H.R.; Peters, J.C. Energy Balance and Obesity. Circulation 2012, 126, 126–132.
3. Cordain, L.; Eaton, S.B.; Sebastian, A.; Mann, N.; Lindeberg, S.; Watkins, B.A.; O’Keefe, J.H.; Brand-Miller, J. Origins and evolution of the Western diet: Health implications for the 21st century. Am. J. Clin. Nutr. 2005, 81, 341–354.
4. Popkin, B.M.; Adair, L.S.; Ng, S.W. NOW AND THEN: The Global Nutrition Transition: The Pandemic of Obesity in Developing Countries. Nutr. Rev. 2012, 70, 3–21.
5. Liu, R.; Hooker, N.H.; Parasidis, E.; Simons, C.T. A Natural Experiment: Using Immersive Technologies to Study the Impact of ‘All-Natural’ Labeling on Perceived Food Quality, Nutritional Content, and Liking. J. Food Sci. 2017, 82, 825–833.
6. Chambers, E.; Chambers, E.; Castro, M. What Is ‘Natural’? Consumer Responses to Selected Ingredients. Foods 2018, 7, 65.
7. Lemus-Mondaca, R.; Vega-Gálvez, A.; Zura-Bravo, L.; Ah-Hen, K. Stevia rebaudiana Bertoni, source of a high-potency natural sweetener: A comprehensive review on the biochemical, nutritional and functional aspects. Food Chem. 2012, 132, 1121–1132.
8. Nutrition C for FS and A. Food Additives & Ingredients—Additional Information about High-Intensity Sweeteners Permitted for Use in Food in the United States. Available online: http://www.fda.gov/Food/IngredientsPackagingLabeling/FoodAdditivesIngredients/ucm397725.htm (accessed on 11 March 2016).
9. Giuffre, L.; Romaniuk, R.; Ciarlo, E. Stevia, ka’a he’e, wild sweet herb from South America—An overview. Emir. J. Food Agric. 2013, 25, 746–750.
10. Gregersen, S.; Jeppesen, P.B.; Holst, J.J.; Hermansen, K. Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Metab. Clin. Exp. 2004, 53, 73–76.
11. Chen, T.H.; Chen, S.C.; Chan, P.; Chu, Y.L.; Yang, H.Y.; Cheng, J.T. Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia rebaudiana. Planta Med. 2005, 71, 108–113.
12. Stevia Rebaudiana Bertoni: A Natural Alternative for Treating Diseases Associated with Metabolic Syndrome. PubMed-NCBI. Available online: https://www.ncbi.nlm.nih.gov/pubmed/28792778 (accessed on 2 January 2019).
13. Ahmad, U.; Ahmad, R.S. Anti diabetic property of aqueous extract of Stevia rebaudiana Bertoni leaves in Streptozotocin-induced diabetes in albino rats. BMC Complement. Altern. Med. 2018, 18, 179.
14. Health Canada. Consultation on Health Canada’s Proposal to Allow the Use of the Food Additive Steviol Glycosides as a Table-Top Sweetener and as a Sweetener in Certain Food Categories. aem. 2012. Available online: https://www.canada.ca/en/health-canada/services/food-nutrition/public-involvement-partnerships/technical-consultation-proposal-allow-use-food-additive-steviol-glycosides-table-top-sweetener/consultation.html (accessed on 2 January 2019).
15. Feijó, F.d.M.; Ballard, C.R.; Foletto, K.C.; Batista, B.A.M.; Neves, A.M.; Ribeiro, M.F.M.; Bertoluci, M.C. Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels. Appetite 2013, 60, 203–207.
16. Palmnäs, M.S.A.; Cowan, T.E.; Bomhof, M.R.; Su, J.; Reimer, R.A.; Vogel, H.J.; Hittel, D.S.; Shearer, J. Low-Dose Aspartame Consumption Differentially Affects Gut Microbiota-Host Metabolic Interactions in the Diet-Induced Obese Rat. PLoS ONE 2014, 9, e109841.
17. Suez, J.; Korem, T.; Zeevi, D.; Zilberman-Schapira, G.; Thaiss, C.A.; Maza, O.; Israeli, D.; Zmora, N.; Gilad, S.; Weinberger, A., et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 2014, 514, 181–186.
18. Turnbaugh, P.J.; Ley, R.E.; Mahowald, M.A.; Magrini, V.; Mardis, E.R.; Gordon, J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006, 444, 1027–1031.
19. Wang, Q.-P.; Browman, D.; Herzog, H.; Neely, G.G. Non-nutritive sweeteners possess a bacteriostatic effect and alter gut microbiota in mice. PLoS ONE 2018, 13, e0199080.
20. Magnuson, B.A.; Carakostas, M.C.; Moore, N.H.; Poulos, S.P.; Renwick, A.G. Biological fate of low-calorie sweeteners. Nutr. Rev. 2016, 74, 670–689.
21. Gibson, G.R.; Hutkins, R.; Sanders, M.E.; Prescott, S.L.; Reimer, R.A.; Salminen, S.J.; Scott, K.; Stanton, C.; Swanson, K.S.; Cani, P.D., et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol. Hepatol. 2017, 14, 491–502.
22. Paul, H.A.; Collins, K.H.; Nicolucci, A.C.; Urbanski, S.J.; Hart, D.A.; Vogel, H.J.; Reimer, R.A. Maternal prebiotic supplementation reduces fatty liver development in offspring through altered microbial and metabolomic profiles in rats. FASEB J. 2019, 33, 5153–5167.
23. Delzenne, N.M.; Neyrinck, A.M.; Cani, P.D. Gut microbiota and metabolic disorders: How prebiotic can work? Br. J. Nutr. 2013, 109 (Suppl. 2), S81–S85.
24. 16S-metagenomic-library-prep-guide-15044223-b.pdf. Available online: https://support.illumina.com/content/dam/illumina-support/documents/documentation/chemistry_documentation/16s/16s-metagenomic-library-prep-guide-15044223-b.pdf (accessed on 15 April 2019).
25. Callahan, B.J.; McMurdie, P.J.; Rosen, M.J.; Han, A.W.; Johnson, A.J.A.; Holmes, S.P. DADA2: High-resolution sample inference from Illumina amplicon data. Nat. Methods 2016, 13, 581–583.
26. McMurdie, P.J.; Holmes, S. phyloseq: An R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE 2013, 8, e61217.
27. Segata, N.; Izard, J.; Waldron, L.; Gevers, D.; Miropolsky, L.; Garrett, W.S.; Huttenhower, C. Metagenomic biomarker discovery and explanation. Genome Biol. 2011, 12, R60.
28. Miwa, H.; Yamamoto, M. High-performance liquid chromatographic analysis of serum short-chain fatty acids by direct derivatization. J. Chromatogr. 1987, 421, 33–41.
29. Roitman, M.F.; Stuber, G.D.; Phillips, P.E.M.; Wightman, R.M.; Carelli, R.M. Dopamine operates as a subsecond modulator of food seeking. J. Neurosci. 2004, 24, 1265–1271.
30. Anton, S.D.; Martin, C.K.; Han, H.; Coulon, S.; Cefalu, W.T.; Geiselman, P.; Williamson, D.A. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite 2010, 55, 37–43.
31. Rizzo, B.; Zambonin, L.; Angeloni, C.; Leoncini, E.; Dalla Sega, F.V.; Prata, C.; Fiorentini, D.; Hrelia, S. Steviol glycosides modulate glucose transport in different cell types. Oxid. Med. Cell. Longev. 2013, 2013, 348169.
32. Jeppesen, P.B.; Gregersen, S.; Poulsen, C.R.; Hermansen, K. Stevioside acts directly on pancreatic beta cells to secrete insulin: Actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. Metab. Clin. Exp. 2000, 49, 208–214.
33. Jeppesen, P.B.; Gregersen, S.; Alstrup, K.K.; Hermansen, K. Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo: Studies in the diabetic Goto-Kakizaki (GK) rats. Phytomedicine 2002, 9, 9–14.
34. Effect of Stevia Sweetener Consumption as Non-Caloric Sweetening on Body Weight Gain and Biochemical’s Parameters in Overweight Female Rats. ScienceDirect. Available online: https://www.sciencedirect.com/science/article/pii/S0570178315000561 (accessed on 19 March 2019).
35. Urías-Silvas, J.E.; Cani, P.D.; Delmée, E.; Neyrinck, A.; López, M.G.; Delzenne, N.M. Physiological effects of dietary fructans extracted from Agave tequilana Gto. and Dasylirion spp. Br. J. Nutr. 2008, 99, 254–261.
36. Jakobsdottir, G.; Jädert, C.; Holm, L.; Nyman, M.E. Propionic and butyric acids, formed in the caecum of rats fed highly fermentable dietary fibre, are reflected in portal and aortic serum. Br. J. Nutr. 2013, 110, 1565–1572.
37. Parnell, J.A.; Raman, M.; Rioux, K.P.; Reimer, R.A. The potential role of prebiotic fibre for treatment and management of non-alcoholic fatty liver disease and associated obesity and insulin resistance. Liver Int. 2012, 32, 701–711.
38. Meyer, D.; Stasse-Wolthuis, M. The bifidogenic effect of inulin and oligofructose and its consequences for gut health. Eur. J. Clin. Nutr. 2009, 63, 1277–1289.
39. Cani, P.D.; Possemiers, S.; Van de Wiele, T.; Guiot, Y.; Everard, A.; Rottier, O.; Geurts, L.; Naslain, D.; Neyrinck, A.; Lambert, D.M., et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009, 58, 1091–1103.
40. Berthoud, H.-R. Homeostatic and Non-homeostatic Pathways Involved in the Control of Food Intake and Energy Balance. Obesity 2006, 14, 197S–200S.
41. Fulton, S.; Pissios, P.; Manchon, R.P.; Stiles, L.; Frank, L.; Pothos, E.N.; Maratos-Flier, E.; Flier, J.S. Leptin Regulation of the Mesoaccumbens Dopamine Pathway. Neuron 2006, 51, 811–822.
42. Friend, D.M.; Devarakonda, K.; O’Neal, T.J.; Skirzewski, M.; Papazoglou, I.; Kaplan, A.R.; Liow, J.S.; Guo, J.; Rane, S.G.; Rubinstein, M., et al. Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity. Cell Metab. 2017, 25, 312–321.
43. Vaughan, R.A.; Foster, J.D. Mechanisms of dopamine transporter regulation in normal and disease states. Trends Pharmacol. Sci. 2013, 34, 489–496.
44. Jones, K.T.; Woods, C.; Zhen, J.; Antonio, T.; Carr, K.; Reith, M.E.A. Effects of diet and insulin on dopamine transporter activity and expression in rat caudate-putamen, nucleus accumbens, and midbrain. J. Neurochem. 2017, 140, 728–740.
45. Fordahl, S.C.; Jones, S.R. High-Fat-Diet-Induced Deficits in Dopamine Terminal Function Are Reversed by Restoring Insulin Signaling. ACS Chem. Neurosci. 2017, 8, 290–299.
46. Narayanaswami, V.; Thompson, A.; Cassis, L.; Bardo, M.; Dwoskin, L. Diet-induced obesity: Dopamine transporter function, impulsivity and motivation. Int. J. Obes. (Lond.) 2013, 37, 1095–1103.
47. LeBlanc, J.G.; Chain, F.; Martín, R.; Bermúdez-Humarán, L.G.; Courau, S.; Langella, P. Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb. Cell Fact. 2017, 16, 79.
48. Roger, L.C.; Costabile, A.; Holland, D.T.; Hoyles, L.; McCartney, A.L. Examination of faecal Bifidobacterium populations in breast- and formula-fed infants during the first 18 months of life. Microbiology 2010, 156, 3329–3341.
49. Kalliomäki, M.; Collado, M.C.; Salminen, S.; Isolauri, E. Early differences in fecal microbiota composition in children may predict overweight. Am. J. Clin. Nutr. 2008, 87, 534–538.
50. O’Callaghan, A.; van Sinderen, D. Bifidobacteria and Their Role as Members of the Human Gut Microbiota. Front. Microbiol. 2016, 7, 925.
51. Stappenbeck, T.S.; Hooper, L.V.; Gordon, J.I. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc. Natl. Acad. Sci. USA 2002, 99, 15451–15455.
52. Lecomte, V.; Kaakoush, N.O.; Maloney, C.A.; Raipuria, M.; Huinao, K.D.; Mitchell, H.M.; Morris, M.J. Changes in Gut Microbiota in Rats Fed a High Fat Diet Correlate with Obesity-Associated Metabolic Parameters. PLoS ONE 2015, 10, e0126931.
53. Everard, A.; Belzer, C.; Geurts, L.; Ouwerkerk, J.P.; Druart, C.; Bindels, L.B.; Guiot, Y.; Derrien, M.; Muccioli, G.G.; Delzenne, N.M., et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA 2013, 110, 9066–9071.
54. Schug, Z.T.; Peck, B.; Jones, D.T.; Zhang, Q.; Grosskurth, S.; Alam, I.S.; Goodwin, L.M.; Smethurst, E.; Mason, S.; Blyth, K., et al. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell 2015, 27, 57–71.
55. Berg, J.M.; Tymoczko, J.L.; Stryer, L. Cholesterol Is Synthesized from Acetyl Coenzyme A in Three Stages. In Biochemistry, 5th ed.; Published Online First; 2002. Available online: https://www.ncbi.nlm.nih.gov/books/NBK22350/ (accessed on 18 April 2019).
56. Wong, J.M.W.; de Souza, R.; Kendall, C.W.C.; Emam, A.; Jenkins, D.J.A. Colonic health: Fermentation and short chain fatty acids. J. Clin. Gastroenterol. 2006, 40, 235–243.
57. Hong, Y.H.; Nishimura, Y.; Hishikawa, D.; Tsuzuki, H.; Miyahara, H.; Gotoh, C.; Choi, K.C.; Feng, D.D.; Chen, C.; Lee, H.G., et al. Acetate and Propionate Short Chain Fatty Acids Stimulate Adipogenesis via GPCR43. Endocrinology 2005, 146, 5092–5099.
58. Fernandes, J.; Su, W.; Rahat-Rozenbloom, S.; Wolever, T.M.S.; Comelli, E.M. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr. Diabetes 2014, 4, e121.
59. Schwiertz, A.; Taras, D.; Schäfer, K.; Beijer, S.; Bos, N.A.; Donus, C.; Hardt, P.D. Microbiota and SCFA in lean and overweight healthy subjects. Obesity 2010, 18, 190–195.
60. Sasaki, D.; Sasaki, K.; Ikuta, N.; Yasuda, T.; Fukuda, I.; Kondo, A.; Osawa, R. Low amounts of dietary fibre increase in vitro production of short-chain fatty acids without changing human colonic microbiota structure. Sci. Rep. 2018, 8, 435.
61. Pan, X.; Chen, F.; Wu, T.; Tang, H.; Zhao, Z. Prebiotic oligosaccharides change the concentrations of short-chain fatty acids and the microbial population of mouse bowel. J. Zhejiang Univ. Sci. B 2009, 10, 258–263.
62. Sawin, E.A.; De Wolfe, T.J.; Aktas, B.; Stroup, B.M.; Murali, S.G.; Steele, J.L.; Ney, D.M. Glycomacropeptide is a prebiotic that reduces Desulfovibrio bacteria, increases cecal short-chain fatty acids, and is anti-inflammatory in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2015, 309, G590–G601.
63. Genda, T.; Kondo, T.; Hino, S.; Sugiura, S.; Nishimura, N.; Morita, T. The Impact of Fructo-Oligosaccharides on Gut Permeability and Inflammatory Responses in the Cecal Mucosa Quite Differs between Rats Fed Semi-Purified and Non-Purified Diets. J. Nutr. Sci. Vitaminol. 2018, 64, 357–366.
64. Singh, V.; Yeoh, B.S.; Chassaing, B.; Xiao, X.; Saha, P.; Aguilera Olvera, R.; Lapek, J.D.; Zhang, L.; Wang, W.B.; Hao, S., et al. Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer. Cell 2018, 175, 679–694.
65. de la Cuesta-Zuluaga, J.; Mueller, N.T.; Álvarez-Quintero, R.; Velásquez-Mejía, E.P.; Sierra, J.A.; Corrales-Agudelo, V.; Carmona, J.A.; Abad, J.M.; Escobar, J.S. Higher Fecal Short-Chain Fatty Acid Levels Are Associated with Gut Microbiome Dysbiosis, Obesity, Hypertension and Cardiometabolic Disease Risk Factors. Nutrients 2018, 11, 51.
66. Sanna, S.; van Zuydam, N.R.; Mahajan, A.; Kurilshikov, A.; Vila, A.V.; Võsa, U.; Mujagic, Z.; Masclee, A.A.M.; Jonkers, D.M.A.E.; Oosting, M., et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nat. Genet. 2019, 51, 600.