EFFECTS OF FOOD ADDITIVES ON MICROBIOTA

Abstract

Microbiota is expressed as the community of microorganisms and intestinal microbiota begins to change and develop with birth. Nutrition can affect the microbiota by providing the necessary nutrients for bacteria, changing the microenvironment and modulating the composition and functions of bacteria. Since the early 20th century, important changes have been seen in the diets, especially consumption of processed foods began popular hence consumptions of food additives, added to almost all these foods, have increased. The effects of some dietary components such as carbohydrates, fats, proteins and phytochemicals on microbiota have been evaluated but the effect of food additives on microbiota is still uncertain. Today, although there are upper limits for many food additives, studies suggesting that they may affect health negatively. Therefore, it is important to raise awareness of the society by comprehensively evaluating their effect on microbiota. The aim of this review is to collect the studies, determining the effects of food additives on gut microbiota in 3 groups (as sweeteners, emulsifiers and other additives) and to evaluate them comprehensively with current approaches. 

Keywords

• Food additives
• microbiota
• sweeteners
• emulsifiers

GIDA KATKI MADDELERİNİN MİKROBİYOTA ÜZERİNE ETKİSİ

Abstract

Mikrobiyota, mikroorganizmaların oluşturduğu topluluk olarak ifade edilmektedir ve bağırsak mikrobiyotası doğum ile birlikte değişmeye ve gelişmeye başlamaktadır. Beslenme, bakteriler için gerekli besinleri sağlayarak, mikro çevrelerini değiştirerek ve kompozisyonları ile fonksiyonlarını modüle ederek mikrobiyota üzerine etkiler gösterebilmektedir. 20. yüzyılın başlarından beri insanların diyetlerinde önemli değişiklikler görülmeye başlanmış olup özellikle işlenmiş gıdalara yönelmeleri sonucu tüm bu vb. gıdalara eklenen katkı maddelerinin tüketimleri artış göstermiştir. Karbonhidratlar, yağlar, proteinler ve fitokimyasallar gibi bazı diyet bileşenlerinin mikrobiyota üzerine etkisi değerlendirilmiştir fakat gıda katkı maddelerinin mikrobiyota üzerine etkisi belirsizliğini korumaktadır. Günümüzde birçok gıda katkı maddesi için belirlenmiş üst limitler olsa da sağlığı olumsuz yönde etkileyebileceğini düşündüren çalışmalar mevcuttur. Bu nedenle mikrobiyota üzerine etkisini kapsamlı bir şekilde değerlendirerek toplumu bilinçlendirmek önem arz etmektedir. Bu derlemenin amacı gıda katkı maddelerinin bağırsak mikrobiyotası üzerine etkilerini inceleyen literatürde bulunan çalışmaları 3 grup halinde (tatlandırıcılar, emülsifiyerler ve diğer katkı maddeleri olarak) bir araya toplayıp güncel yaklaşımlar ile kapsamlı bir şekilde değerlendirmektir.

Keywords

• Gıda katkı maddeleri
• mikrobiyota
• yapay tatlandırıcılar
• emülsifiyerler

References

1. Abou-Donia, M.B., El-Masry, E.M., Abdel-Rahman, A.A., McLendon, R.E., Schiffman, S.S. (2008). Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health Sci, 71(21), 1415-1429, doi:10.1080/15287390802328630.
2. Ahmad, S.Y., Friel, J.K., Mackay, D. S. (2020). Effect of sucralose and aspartame on glucose metabolism and gut hormones. Nutr Rev, 0(0), 1-23, doi:10.1093/nutrit/nuz099.
3. Ali, W.A.-G., Mohammed, S.A., Abdullah, E.M., ElDeen, E.M.S. (2019). Aspartame: Basic Information for Toxicologists. Sohog Medical Journal, 23(2), 47-51, doi:10.21608/SMJ.2019.46212.
4. Amin, K. A., Al-Muzafar, H.M., Elsttar, A.H.A. (2016). Effect of sweetener and flavoring agent on oxidative indices, liver and kidney function levels in rats. Indian J Exp Biol, 54, 56-63.
5. Anderson, R., Kirkland, J.J. (1980). The effect of sodium saccharin in the diet on caecal microflora. Food Cosmet Toxicol, 18(4), 353-355, doi: 10.1016/0015-6264(80)90188-1.
6. Anderson, R.L. (1985). Some changes in gastro-intestinal metabolism and in the urine and bladders of rats in response to sodium saccharin ingestion. Food Chem. Toxicol, 23(4-5): 457-463, doi:10.1016/0278-6915(85)90140-1.
7. Ardalan, M. R., Tabibi, H., Attari, V. E., Mahdavi, A. M. (2017). Nephrotoxic Effect of Aspartame as an Artificial Sweetener: a Brief Review. Iran J Kidney Dis, 11(5): 339.
8. Bandyopadhyay, A., Ghoshal, S., Mukherjee, A. (2008). Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-K, and saccharin. Drug Chem Toxıcol, 31(4), 447-457, doi: 10.1080/01480540802390270.

9. Bellisle, F., Drewnowski, A. (2007). Intense sweeteners, energy intake and the control of body weight. Eur J Clin Nutr, 61(6), 691-700, doi: 10.1038/sj.ejcn.1602649.
10. Bian, X., Chi, L., Gao, B., Tu, P., Ru, H., & Lu, K. (2017a). Gut microbiome response to sucralose and its potential role in inducing liver inflammation in mice. Front Physıol, 8, 487, doi: 10.3389/fphys.2017.00487.
11. Bian, X., Chi, L., Gao, B., Tu, P., Ru, H., & Lu, K. (2017b). The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PloS One, 12(6), e0178426, doi: 10.1371/journal.pone.0178426
12. Bian, X., Tu, P., Chi, L., Gao, B., Ru, H., Lu, K. (2017c). Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions. Food Chem Toxicol, 107, 530-539, doi: 10.1016/j.fct.2017.04.045.
13. Biesiekierski, J. R., Jalanka, J., Staudacher, H. M. (2019). Can gut microbiota composition predict response to dietary treatments? Nutrients, 11(5), 1134, doi: 10.3390/nu11051134.
14. Campbell, H.E., Escudier, M.P., Patel, P., Challacombe, S.J., Sanderson, J.D., Lomer, M.C. (2011). Review article: cinnamon‐and benzoate‐free diet as a primary treatment for orofacial granulomatosis. Aliment Pharm Ther, 34(7), 687-701, doi:10.1111/j.1365-2036.2011.04792.x.
15. Cani, P. D., Everard, A. (2016). Talking microbes: when gut bacteria interact with diet and host organs. Mol Nutr Food Res, 60(1), 58-66, doi: 10.1002/mnfr.201500406. Cao, Y., Liu, H., Qin, N., Ren, X., Zhu, B., Xia, X. (2020). Impact of food additives on the composition and function of gut microbiota: A review. Trends Food Sci Tech, 99, 295-310, doi: 10.1016/j.tifs.2020.03.006.
16. Chassaing, B., Koren, O., Goodrich, J.K., Poole, A.C., Srinivasan, S., Ley, R.E., Gewirtz, A.T. (2015). Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature, 519(7541), 92-96, doi: 10.1038/nature14232.
17. Chassaing, B., Van de Wiele, T., De Bodt, J., Marzorati, M., Gewirtz, A.T. (2017). Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut, 66(8), 1414-1427, doi:10.1136/gutjnl-2016-313099.
18. Chi, L., Bian, X., Gao, B., Tu, P., Lai, Y., Ru, H., Lu, K. (2018). Effects of the artificial sweetener neotame on the gut microbiome and fecal metabolites in mice. Molecules, 23(2), 367, doi: 10.3390/molecules23020367.
19. Choudhary, A.K., Pretorius, E. (2017). Revisiting the safety of aspartame. Nutr Rev, 75(9), 718-730, doi: 10.1093/nutrit/nux035.
20. Clemente, J.C., Ursell, L.K., Parfrey, L.W., Knight, R. (2012). The impact of the gut microbiota on human health: an integrative view. Cell, 148(6), 1258-1270, doi:10.1016/j.cell.2012.01.035.
21. Daly, K., Darby, A.C., Hall, N., Nau, A., Bravo, D., Shirazi-Beechey, S.P. (2014). Dietary supplementation with lactose or artificial sweetener enhances swine gut Lactobacillus population abundance. Brit J Nutr, 111(S1), 30-35, doi: 10.1017/S0007114513002274.
22. Del Olmo, A., Calzada, J., Nuñez, M. (2017). Benzoic acid and its derivatives as naturally occurring compounds in foods and as additives: Uses, exposure, and controversy. Crit Rev Food Sci Nutr, 57(14), 3084-3103, doi:10.1080/10408398.2015.1087964.
23. Dhingra, R., Sullivan, L., Jacques, P.F., Wang, T.J., Fox, C.S., Meigs, J.B., D’Agostino, R.B., Gaziona, J.M., Vasan, R.S. (2007). Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation, 116(5), 480-488, doi: 10.1161/CIRCULATIONAHA.107.689935.
24. Diao, H., Zheng, P., Yu, B., He, J., Mao, X., Yu, J., Chen, D. (2015). Effects of benzoic acid and thymol on growth performance and gut characteristics of weaned piglets. Asian Austral J Anim, 28(6), 827-839, doi: 10.5713/ajas.14.0704.
25. Diao, H., Zheng, P., Yu, B., He, J., Mao, X., Yu, J., Chen, D. (2014). Effects of dietary supplementation with benzoic acid on intestinal morphological structure and microflora in weaned piglets. Livest Sci, 167, 249-256, doi: 10.1016/j.livsci.2014.05.029.
26. Eweka, A.O., Eweka, A., Om'iniabohs, F.A. (2010). Histological studies of the effects of monosodium glutamate of the fallopian tubes of adult female Wistar rats. N Am J Med Sci, 2(3), 146–149, doi: 10.4297/najms.2010.3146.
27. Feng, Z.M., Li, T.J., Wu, L., Xiao, D.F., Blachier, F., Yin, Y.L. (2015). Monosodium L-glutamate and dietary fat differently modify the composition of the intestinal microbiota in growing pigs. Obesity facts, 8(2), 87-100, doi: 10.1159/000380889.
28. Fındıklı, Z., Türkoğlu, Ş. (2014). Determination of the effects of some artificial sweeteners on human peripheral lymphocytes using the comet assay. J Toxicol Environ Health Sci, 6(8), 147-153, doi: 10.5897/JTEHS2014.0313.
29. Fitch, C., Keim, K.S. (2012). Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet, 112(5), 739-758, doi: 10.1016/j.jand.2012.03.009
30. Foletto, K.C., Melo Batista, B.A., Neves, A.M., de Matos Feijó, F., Ballard, C.R.,Marques Ribeiro, M.F.,Bertoluci, M.C. (2016). Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats. Appetite, 96, 604-610, doi: 10.1016/j.appet.2015.11.003.
31. Frankenfeld, C.L., Sikaroodi, M., Lamb, E., Shoemaker, S., Gillevet, P.M. (2015). High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States. Ann Epidemiol, 25(10), 736-742, doi: 10.1016/j.annepidem.2015.06.083.
32. Furuhashi, H., Higashiyama, M., Okada, Y., Kurihara, C., Wada, A., Horiuchi, K., Hanawa, Y., Mizoguchi, A., Nishii, S., Inaba, K., Sugihara, N., Watanabe, C., Komoto, S., Tomita, K., Miura, S., Hokari, R. (2020). Dietary emulsifier polysorbate-80-induced small-intestinal vulnerability to indomethacin-induced lesions via dysbiosis. J Gastroen Hepatol, 35(1), 110-117, doi: 10.1111/jgh.14808.
33. Gardana, C., Simonetti, P., Canzi, E., Zanchi, R., Pietta, P. (2003). Metabolism of stevioside and rebaudioside A from Stevia rebaudiana extracts by human microflora. J Agric Food Chem, 51(22), 6618-6622, doi: 10.1021/jf0303619.
34. Gong, T., Wei, Q.W., Mao, D.G., Nagaoka, K., Watanabe, G., Taya, K., Shi, F.X. (2016). Effects of daily exposure to saccharin and sucrose on testicular biologic functions in mice. Biol. Reprod, 95(6), 116, 111-113, doi: 10.1095/biolreprod.116.140889.
35. Grotz, V. L., Pi-Sunyer, X., Porte Jr, D., Roberts, A., Richard Trout, J. (2017). A 12-week randomized clinical trial investigating the potential for sucralose to affect glucose homeostasis. Regul Toxıcol Pharm, 88, 22-33, doi: 10.1016/j.yrtph.2017.05.011.
36. Halas, D., Hansen, C.F., Hampson, D.J., Mullan, B.P., Kim, J.C., Wilson, R.H., Pluske, J.R. (2010). Dietary supplementation with benzoic acid improves apparent ileal digestibility of total nitrogen and increases villous height and caecal microbial diversity in weaner pigs. Anim Feed Sci Tech, 160(3-4), 137-147, doi: 10.1016/j.anifeedsci.2010.07.001.
37. Halmos, E.P., Mack, A., Gibson, P.R. (2019). Review article: emulsifiers in the food supply and implications for gastrointestinal disease. Aliment Pharm Ther, 49(1), 41-50, doi: 10.1111/apt.15045.
38. Hrncirova, L., Hudcovic, T., Sukova, E., Machova, V., Trckova, E., Krejse, J., Hrncir, T. (2019a). Human gut microbes are susceptible to antimicrobial food additives in vitro. Folia Parasitol (Praha), 64(4), 497-508, doi: 10.1007/s12223-018-00674-z. Hrncirova, L., Machova, V., Trckova, E., Krejse, J., Hrncir, T. (2019b). Food Preservatives Induce Proteobacteria Dysbiosis in Human-Microbiota Associated Nod2-Deficient Mice. Microorganisms, 7(10), 383, doi: 10.3390/microorganisms7100383.
39. Husøy, T., Mangschou, B., Fotland, T.Ø., Kolset, S.O., Nøtvik Jakobsen, H., Tømmerberg, I., Bergsten, C., Alexander, J., Frost Andersen, L. (2008). Reducing added sugar intake in Norway by replacing sugar sweetened beverages with beverages containing intense sweeteners–a risk benefit assessment. Food Chem Toxıcol, 46(9), 3099-3105, doi: 10.1016/j.fct.2008.06.013. Iammarino, M., Di Taranto, A., Palermo, C., Muscarella, M. (2011). Survey of benzoic acid in cheeses: contribution to the estimation of an admissible maximum limit. Food Addit Contam B, 4(4), 231-237, doi: 10.1080/19393210.2011.620355.
40. Imamura, F., O’Connor, L., Ye, Z., Mursu, J., Hayashino, Y., Bhupathiraju, S.N., Forouhi, N. G. (2015). Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. Br. Med. J, 351, h3576, doi: 10.1136/bmj.h3576.
41. Irwin, S.V., Fisher, P., Graham, E., Malek, A., & Robidoux, A. (2017). Sulfites inhibit the growth of four species of beneficial gut bacteria at concentrations regarded as safe for food. PloS One, 12(10), e0186629, doi: 10.1371/journal.pone.0186629.
42. Isa, A. S., Muhammad, M.S., Hudu, A.A., Jamba, B.I., Choji, E.S., Isah, H O., Magaji, M.G. (2019). Assessment of cognitive and motor endurance activities in male wistar rats administered carboxymethyl cellulose. Afr. J. Biomed. Res, 22(2), 195-199. John, C. (2016). Aspartame: An Investigation of the Use of Artificial Sweeteners. JHDRP, 9(5), 61.
43. Józefiak, D., Kaczmarek, S., Bochenek, M., Rutkowski, A. (2007). A note on effects of benzoic acid supplementation on the performance and microbiota populations of broiler chickens. J Anim Feed Sci, 16(2), 252-256, doi:10.22358/jafs/66746/2007.
44. Kim, H.L., Ha, A.W., Kim, W.K. (2020). Effect of saccharin on inflammation in 3T3-L1 adipocytes and the related mechanism. Nutr Res Pract, 14(2), 109-116, doi: 10.4162/nrp.2020.14.2.109.
45. Kluge, H., Broz, J., Eder, K. (2006). Effect of benzoic acid on growth performance, nutrient digestibility, nitrogen balance, gastrointestinal microflora and parameters of microbial metabolism in piglets. J Anim Physiol An N, 90(7‐8), 316-324, doi: 10.1111/j.1439-0396.2005.00604.x.
46. Lawrie, C., Renwick, A.G., Sims, J. (1985). The urinary excretion of bacterial amino-acid metabolites by rats fed saccharin in the diet. Food Chem Toxıcol, 23(4-5), 445-450, doi: 10.1016/0278-6915(85)90138-3.
47. Le Roy, C.I., Bowyer, R.C.E., Castillo-Fernandez, J.E., Pallister, T., Menni, C., Steves, C.J., Berry, S.E., Spector, T.D., Bell, J.T. (2019). Dissecting the role of the gut microbiota and diet on visceral fat mass accumulation. Sci. Rep, 9(1), 9758, doi: 10.1038/s41598-019-46193-w.
48. Lindemann, B., Ogiwara, Y., Ninomiya, Y. (2002). The discovery of umami. Chem. Senses, 27(9), 843-844, doi: 10.1093/chemse/27.9.843.
49. Mallett, A.K., Rowland, I.R., Bearne, C.A. (1985). Modification of rat caecal microbial biotransformation activities by dietary saccharin. European PMC, 36(2-3), 253-262, doi: 10.1016/0300-483x(85)90058-7
50. Matysková, R., Maletínská, L., Maixnerová, J., Pirník, Z., Kiss, A., Zelezná, B. (2008). Comparison of the obesity phenotypes related to monosodium glutamate effect on arcuate nucleus and/or the high fat diet feeding in C57BL/6 and NMRI mice. Physiol Res, 57, 727-734.
51. Mayhew, D.A., Comer, C.P., Stargel, W.W. (2003). Food consumption and body weight changes with neotame, a new sweetener with intense taste: Differentiating effects of palatability from toxicity in dietary safety studies. Regul Toxicol Pharm, 38(2), 124-143, doi: 10.1016/s0273-2300(03)00074-6.
52. Naim, M., Zechman, J.M., Brand, J.G., Kare, M.R., Sandovsky, V. (1985). Effects of sodium saccharin on the activity of trypsin, chymotrypsin, and amylase and upon bacteria in small intestinal contents of rats. Proc. Soc. Exp, 178(3), 392-401, doi: 10.3181/00379727-178-42022.
53. Niaz, K., Zaplatic, E., & Spoor, J. (2018). Extensive use of monosodium glutamate: A threat to public health?. EXCLI J, 17, 273–278, doi: 10.17179/excli2018-1092.
54. Ortiz, G.G., Bitzer-Quintero, O.K., Zárate, C.B., Rodríguez-Reynoso, S., Larios-Arceo, F., Velázquez-Brizuela, I.E., Pacheco-Moisés, F., Rosales-Corral, S.A. (2006). Monosodium glutamate-induced damage in liver and kidney: a morphological and biochemical approach. Bıomed Pharmacother, 60(2), 86-91, doi: 10.1016/j.biopha.2005.07.012.
55. Özbek, Y., Yentür, G. (1993). Gıdalarda aspartamın katkı maddesi olarak kullanılması. GIDA, 18(1), 67-71.
56. Özdemir, D., Başer, H., Çakır, B. (2014). Tatlandırıcılar. Türkiye Klinikleri Endokrinoloji Dergisi, 9(2), 60-70.
57. Öztürkcan, S.A., Acar, S. (2017). Yaygın Olarak Kullanılan Antimikrobiyal Gıda Katkı Maddeleri ile İlgili Genel Bir Değerlendirme. İGÜSABDER, 1(1), 1-17.
58. Palmnäs, M.S., Cowan, T.E., Bomhof, M.R., Su, J., Reimer, R.A., Vogel, H.J., Hittel, D.S., Shearer, J. (2014). Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PloS One, 9(10), e109841, doi: 10.1371/journal.pone.0109841
59. Peng, Q., Huo, D., Ma, C., Jiang, S., Wang, L., Zhang, J. (2018). Monosodium glutamate induces limited modulation in gut microbiota. J Funct Foods, 49, 493-500, doi: 10.1016/j.jff.2018.09.015.
60. Pepino, M.Y., Tiemann, C D., Patterson, B.W., Wice, B.M., & Klein, S. (2013). Sucralose affects glycemic and hormonal responses to an oral glucose load. Diabetes Care, 36(9), 2530-2535, doi: 10.2337/dc12-2221.
61. Pepino, M.Y. (2018). The not-so-sweet effects of sucralose on blood sugar control. The American Eur J Clin Nutr, 108(3), 431-432, doi: 10.1093/ajcn/nqy205.
62. Roca-Saavedra, P., Mendez-Vilabrille, V., Miranda, J M., Nebot, C., Cardelle-Cobas, A., Franco, C.M., Cepeda, A. (2018). Food additives, contaminants and other minor components: effects on human gut microbiota—a review. Physiol Biochem, 74(1), 69-83, doi: 10.1007/s13105-017-0564-2
63. Rodriguez-Palacios, A., Harding, A., Menghini, P., Himmelman, C., Retuerto, M., Nickerson, K.P., Lam, M., Croniger, C.M., McLean, M.H., Durum, S.K., Pizarro, T.T., Ghannoum, M.A., Ilic, S., McDonald, C., Cominelli, F. (2018). The artificial sweetener splenda promotes gut proteobacteria, dysbiosis, and myeloperoxidase reactivity in Crohn’s disease–like ileitis. Inflamm Bowel Dis, 24(5), 1005-1020, doi: 10.1093/ibd/izy060.
64. Ruiz-Ojeda, F.J., Plaza-Díaz, J., Sáez-Lara, M.J., Gil, A. (2019). Effects of sweeteners on the gut microbiota: a review of experimental studies and clinical trials. Adv Nutr, 10(suppl_1), S31-S48, doi: 10.1093/advances/nmy037.
65. Saad, R., Rizkallah, M.R., Aziz, R K. (2012). Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes. Gut Pathog, 4(1), 16, doi: 10.1186/1757-4749-4-16.
66. Salminen, S., Salminen, E., Bridges, J., Marks, V. (1986). The effects of sorbitol on the gastrointestinal microflora in rats. Zeitschrift fÜr Ern~ihrungswissenschaff, 25(2), 91-95. Santos, N.C., de Araujo, L.M., De Luca Canto, G., Guerra, E.N.S., Coelho, M.S., Borin, M.F. (2018). Metabolic effects of aspartame in adulthood: A systematic review and meta-analysis of randomized clinical trials. Crit Rev Food Sci Nutr, 58(12), 2068-2081, doi: 10.1080/10408398.2017.1304358.
67. Sanyaolu, A., Marinkovic, A., Gosse, J., Likaj, L., Ayodele, O., Okorie, C., Verner, O. (2019). Artificial sweeteners and their association with Diabetes: A review. Public Health Nutr, 1(4), 1-3.
68. Schoeler, M., Caesar, R. (2019). Dietary lipids, gut microbiota and lipid metabolism. Rev Endocr Metab Dis, 20(4), 461-472, doi: 10.1007/s11154-019-09512-0.
69. Sekirov, I., Russell, S.L., Antunes, L.C., Finlay, B.B. (2010). Gut Microbiota in Health and Disease. Am J Physiol-Cell Ph, 90(3), 859-904, doi: 10.1152/physrev.00045.2009.
70. Serrano, E., Riebl, S. (2019). Non nutritive Are They Safe? Virginia Cooperative Extension, Virginia State University, Virginia, Amerika Birleşik Devletleri, 1 -5.
71. Singh, R.K., Wheildon, N., Ishikawa, S. (2016). Food Additive P-80 Impacts Mouse Gut Microbiota Promoting Intestinal Inflammation, Obesity and Liver Dysfunction. SOJMID, 4(1), 10.15226/sojmid/4/1/00148, doi: 10.15226/sojmid/4/1/00148.
72. Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C.A., Maza, O., Israeli, D., Zmora, N., Gilad, S., Weinberger, A., Kuperman, Y., Harmelin, A., Kolodkin-Gal, I., Shapiro, H., Halpern, Z., Segal, E., Elinav, E. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature, 514(7521), 181-186, doi: 10.1038/nature13793.
73. Suez, J., Korem, T., Zilberman-Schapira, G., Segal, E., Elinav, E. (2015). Non-caloric artificial sweeteners and the microbiome: findings and challenges. Gut Microbes, 6(2), 149-155, doi: 10.1080/19490976.2015.1017700.
74. Swidsinski, A., Ung, V., Sydora, B.C., Loening-Baucke, V., Doerffel, Y., Verstraelen, H., Fedorak, R. N. (2009). Bacterial overgrowth and inflammation of small intestine after carboxymethylcellulose ingestion in genetically susceptible mice. Inflamm Bowel Dis, 15(3), 359-364, doi: 10.1002/ibd.20763.
75. Temizkan, S., Deyneli, O., Yasar, M., Arpa, M., Gunes, M., Yazici, D., Sirikci, O., Haklar, G., Imeryuz, N., Yavuz, D.G. (2015). Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in patients with type 2 diabetes. Eur J Clin Nutr, 69(2), 162-166, doi: 10.1038/ejcn.2014.208.
76. Uebanso, T., Ohnishi, A., Kitayama, R., Yoshimoto, A., Nakahashi, M., Shimohata, T., Mawata, K., Takahashi, A. (2017). Effects of low-dose non-caloric sweetener consumption on gut microbiota in mice. Nutrients, 9(6), 560, doi: 10.3390/nu9060560.
77. Viennois, E., Merlin, D., Gewirtz, A.T., Chassaing, B. (2017). Dietary emulsifier–induced low-grade inflammation promotes colon carcinogenesis. Cancer Res, 77(1), 27-40, doi: 10.1158/0008-5472.CAN-16-1359.
78. Viennois, E., Chassaing, B. (2018). First victim, later aggressor: How the intestinal microbiota drives the pro-inflammatory effects of dietary emulsifiers? Gut microbes, 9(3), 1–4, doi: 10.1080/19490976.2017.1421885.
79. Wang, B., Yao, M., Lv, L., Ling, Z., Li, L. (2017). The human microbiota in health and disease. J Eng, 3(1), 71-82, doi: 10.1016/J.ENG.2017.01.008
80. Wang, Q.P., Browman, D., Herzog, H., Neely, G.G. (2018). Non-nutritive sweeteners possess a bacteriostatic effect and alter gut microbiota in mice. PloS One, 13(7), e0199080, doi: 10.1371/journal.pone.0199080.
81. Zhao, X., Yan, J., Chen, K., Song, L., Sun, B., Wei, X. (2018). Effects of saccharin supplementation on body weight, sweet receptor mRNA expression and appetite signals regulation in post-weanling rats. Peptides, 107, 32-38, doi: 10.1016/j.peptides.2018.07.006.
82. Zmora, N., Suez, J., Elinav, E. (2019). You are what you eat: diet, health and the gut microbiota. Nat Rev Gastro Hepat, 16(1): 35-56, doi: 10.1038/s41575-018-0061-2.