Interactions of Non-Nutritive Artificial Sweeteners with the Microbiome in Metabolic Syndrome-Immunometabolism-CSCIED科技核心评价数据库-手机版

Interactions of Non-Nutritive Artificial Sweeteners with the Microbiome in Metabolic Syndrome

Interactions of Non-Nutritive Artificial Sweeteners with the Microbiome in Metabolic Syndrome

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DOI	10.20900/immunometab20220012
刊名	Immunometabolism IJ
年，卷(期)	2022, 4(2)
作者	Harrington, Valerie; Lau, Lilian; Crits-Christoph, Alexander; Suez, Jotham,
作者单位	[Harrington, Valerie; Lau, Lilian; Crits-Christoph, Alexander; Suez, Jotham] Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA
摘要	Replacing sugar with non-nutritive artificial sweeteners (NAS) is a popular dietary choice for the prevention and management of metabolic syndrome and its comorbidities. However, evidence in human trials is conflicted regarding the efficacy of this strategy and whether NAS may counterintuitively promote, rather than prevent, metabolic derangements. The heterogeneity in outcomes may stem in part from microbiome variation between human participants and across research animal vivaria, leading to differential interactions of NAS with gut bacteria. An increasing body of evidence indicates that NAS can alter the mammalian gut microbiome composition, function, and metabolome, which can, in turn, influence host metabolic health. While there is evidence for microbiome-mediated metabolic shifts in response to NAS, the mechanisms by which NAS affect the gut microbiome, and how the microbiome subsequently affects host metabolic processes, remain unclear. In this viewpoint, we discuss data from human and animal trials and provide an overview of the current evidence for NAS-mediated microbial and metabolomic changes. We also review potential mechanisms through which NAS may influence the microbiome and delineate the next steps required to inform public health policies.
Abstract	Replacing sugar with non-nutritive artificial sweeteners (NAS) is a popular dietary choice for the prevention and management of metabolic syndrome and its comorbidities. However, evidence in human trials is conflicted regarding the efficacy of this strategy and whether NAS may counterintuitively promote, rather than prevent, metabolic derangements. The heterogeneity in outcomes may stem in part from microbiome variation between human participants and across research animal vivaria, leading to differential interactions of NAS with gut bacteria. An increasing body of evidence indicates that NAS can alter the mammalian gut microbiome composition, function, and metabolome, which can, in turn, influence host metabolic health. While there is evidence for microbiome-mediated metabolic shifts in response to NAS, the mechanisms by which NAS affect the gut microbiome, and how the microbiome subsequently affects host metabolic processes, remain unclear. In this viewpoint, we discuss data from human and animal trials and provide an overview of the current evidence for NAS-mediated microbial and metabolomic changes. We also review potential mechanisms through which NAS may influence the microbiome and delineate the next steps required to inform public health policies.
关键词	microbiome; non-nutritive artificial sweeteners (NAS); metabolic syndrome; obesity; diabetes; metagenomics; metabolomics
KeyWord	microbiome; non-nutritive artificial sweeteners (NAS); metabolic syndrome; obesity; diabetes; metagenomics; metabolomics
基金项目
页码	1-30

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1. Sylvetsky AC, Walter PJ, Martin Garraffo H, Robien K, Rother KI. Widespread sucralose exposure in a randomized clinical trial in healthy young adults. Am J Clin Nutr. 2017;105(4):820-3.
2. Katzmarzyk P, Broyles S, Champagne C, Chaput J-P, Fogelholm M, Hu G, et al. Relationship between Soft Drink Consumption and Obesity in 9–11 Years Old Children in a Multi-National Study. Nutrients. 2016;8(12):770.
3. Dunford EK, Miles DR, Ng SW, Popkin B. Types and Amounts of Nonnutritive Sweeteners Purchased by US Households: A Comparison of 2002 and 2018 Nielsen Homescan Purchases. J Acad Nutr Diet. 2020;120(10):1662-71.e10.
4. Johnson RK, Lichtenstein AH, Anderson CAM, Carson JA, Després JP, Hu FB, et al. Low-Calorie Sweetened Beverages and Cardiometabolic Health: A Science Advisory From the American Heart Association. Circulation. 2018;138(9):e126-40. doi: 10.1161/CIR.0000000000000569
5. NCD Risk Factor Collaboration. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017 Dec 16;390(10113):2627-42.
6. Swithers SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab. 2013 Sep;24(9):431-41. doi: 10.1016/j.tem.2013.05.005
7. Fowler SPG. Low-calorie sweetener use and energy balance: Results from experimental studies in animals, and large-scale prospective studies in humans. Physiol Behav. 2016;164(Pt B):517-23.
8. Fagherazzi G, Gusto G, Affret A, Mancini FR, Dow C, Balkau B, et al. Chronic Consumption of Artificial Sweetener in Packets or Tablets and Type 2 Diabetes Risk: Evidence from the E3N-European Prospective Investigation into Cancer and Nutrition Study. Ann Nutr Metab. 2017;70(1):51-8.
9. Mossavar-Rahmani Y, Kamensky V, Manson JE, Silver B, Rapp SR, Haring B, et al. Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women’s Health Initiative. Stroke. 2019;50(3):555-62. doi: 10.1161/STROKEAHA.118.023100
10. Mathur K, Agrawal RK, Nagpure S, Deshpande D. Effect of artificial sweeteners on insulin resistance among type-2 diabetes mellitus patients. Journal of family medicine and primary care. 2020;9(1):69-71. doi: 10.4103/jfmpc.jfmpc_329_19
11. Sylvetsky AC, Gardner AL, Bauman V, Blau JE, Garraffo HM, Walter PJ, et al. Nonnutritive Sweeteners in Breast Milk. J Toxicol Environ Health A. 2015;78(16):1029-32. doi: 10.1080/15287394.2015.1053646
12. Halasa BC, Sylvetsky AC, Conway EM, Shouppe EL, Walter MF, Walter PJ, et al. Non-Nutritive Sweeteners in Human Amniotic Fluid and Cord Blood: Evidence of Transplacental Fetal Exposure. Am J Perinatol. 2021. doi: 10.1055/s-0041-1735555
13. Azad MB, Sharma AK, de Souza RJ, Dolinsky VW, Becker AB, Mandhane PJ, et al. Association Between Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index. JAMA Pediatr. 2016 Jul 1;170(7):662-70. doi: 10.1001/jamapediatrics.2016.0301
14. Azad MB, Archibald A, Tomczyk MM, Head A, Cheung KG, de Souza RJ, et al. Nonnutritive sweetener consumption during pregnancy, adiposity, and adipocyte differentiation in offspring: evidence from humans, mice, and cells. Int J Obes . 2020 Oct;44(10):2137-48. doi: 10.1038/s41366-020-0575-x
15. Zhu Y, Olsen SF, Mendola P, Halldorsson TI, Rawal S, Hinkle SN, et al. Maternal consumption of artificially sweetened beverages during pregnancy, and offspring growth through 7 years of age: a prospective cohort study. Int J Epidemiol. 2017;46(5):1499-508. doi: 10.1093/ije/dyx095
16. Cai C, Sivak A, Davenport MH. Effects of prenatal artificial sweeteners consumption on birth outcomes: a systematic review and meta-analysis. Public Health Nutr. 2021 Oct;24(15):5024-33. doi: 10.1017/S1368980021000173
17. Gillman MW, Rifas-Shiman SL, Fernandez-Barres S, Kleinman K, Taveras EM, Oken E. Beverage Intake During Pregnancy and Childhood Adiposity. Pediatrics. 2017 Aug;140(2):e20170031. doi: 10.1542/peds.2017-0031
18. Archibald AJ, Dolinsky VW, Azad MB. Early-Life Exposure to Non-Nutritive Sweeteners and the Developmental Origins of Childhood Obesity: Global Evidence from Human and Rodent Studies. Nutrients. 2018;10(2):194. doi: 10.3390/nu10020194
19. Bueno-Hernández N, Esquivel-Velázquez M, Alcántara-Suárez R, Gómez-Arauz AY, Espinosa-Flores AJ, de León-Barrera KL, et al. Chronic sucralose consumption induces elevation of serum insulin in young healthy adults: a randomized, double blind, controlled trial. Nutr J. 2020;19(1):32. doi: 10.1186/s12937-020-00549-5
20. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514(7521):181-6. doi: 10.1038/nature13793
21. Romo-Romo A, Aguilar-Salinas CA, Brito-Córdova GX, Gómez-Díaz RA, Almeda-Valdes P. Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial. Am J Clin Nutr. 2018;108(3):485-91.
22. Dalenberg JR, Patel BP, Denis R, Veldhuizen MG, Nakamura Y, Vinke PC, et al. Short-Term Consumption of Sucralose with, but Not without, Carbohydrate Impairs Neural and Metabolic Sensitivity to Sugar in Humans. Cell Metab. 2020;31(3):493-502.e7.
23. Lertrit A, Srimachai S, Saetung S, Chanprasertyothin S, Chailurkit L-O, Areevut C, et al. Effects of sucralose on insulin and glucagon-like peptide-1 secretion in healthy subjects: a randomized, double-blind, placebo-controlled trial. Nutrition. 2018;55-56:125-30.
24. Thomson P, Santibañez R, Aguirre C, Galgani JE, Garrido D. Short-term impact of sucralose consumption on the metabolic response and gut microbiome of healthy adults. Br J Nutr. 2019;122(8):856-62. doi: 10.1017/S0007114519001570
25. Ahmad SY, Friel J, Mackay D. The Effects of Non-Nutritive Artificial Sweeteners, Aspartame and Sucralose, on the Gut Microbiome in Healthy Adults: Secondary Outcomes of a Randomized Double-Blinded Crossover Clinical Trial. Nutrients. 2020;12(11):6402. doi: 10.3390/nu12113408
26. Ebbeling CB, Feldman HA, Steltz SK, Quinn NL, Robinson LM, Ludwig DS. Effects of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Beverages on Cardiometabolic Risk Factors, Body Composition, and Sweet Taste Preference: A Randomized Controlled Trial. J Am Heart Assoc. 2020;9(15):e015668.
27. Blackburn GL, Kanders BS, Lavin PT, Keller SD, Whatley J. The effect of aspartame as part of a multidisciplinary weight-control program on short- and long-term control of body weight. Am J Clin Nutr. 1997;65(2):409-18. doi: 10.1093/ajcn/65.2.409
28. Katan MB, de Ruyter JC, Kuijper LD, Chow CC, Hall KD, Olthof MR. Impact of Masked Replacement of Sugar-Sweetened with Sugar-Free Beverages on Body Weight Increases with Initial BMI: Secondary Analysis of Data from an 18 Month Double-Blind Trial in Children. PLoS One. 2016;11(7):e0159771. doi: 10.1371/journal.pone.0159771
29. Masic U, Harrold JA, Christiansen P, Cuthbertson DJ, Hardman CA, Robinson E, et al. EffectS of non-nutritive sWeetened beverages on appetITe during aCtive weigHt loss (SWITCH): Protocol for a randomized, controlled trial assessing the effects of non-nutritive sweetened beverages compared to water during a 12-week weight loss period and a follow up weight maintenance period. Contemp Clin Trials. 2017;53:80-8. doi: 10.1016/j.cct.2016.12.012
30. Tate DF, Turner-McGrievy G, Lyons E, Stevens J, Erickson K, Polzien K, et al. Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial. Am J Clin Nutr. 2012;95(3):681-96. doi: 10.3945/ajcn.111.026278
31. Higgins KA, Mattes RD. A randomized controlled trial contrasting the effects of 4 low-calorie sweeteners and sucrose on body weight in adults with overweight or obesity. Am J Clin Nutr. 2019;109(5):1288-301.
32. Azad MB, Abou-Setta AM, Chauhan BF, Rabbani R, Lys J, Copstein L, et al. Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ. 2017;189(28):E929-39.
33. Miller PE, Perez V. Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. Am J Clin Nutr. 2014;100(3):765-77.
34. Toews I, Lohner S, de Gaudry D K, Sommer H, Meerpohl JJ. Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies. BMJ. 2019;364:l156. doi: 10.1136/bmj.k4718
35. Serrano J, Smith KR, Crouch AL, Sharma V, Yi F, Vargova V, et al. High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome. 2021;9(1):11.
36. Kim Y, Keogh JB, Clifton PM. Consumption of a Beverage Containing Aspartame and Acesulfame K for Two Weeks Does Not Adversely Influence Glucose Metabolism in Adult Males and Females: A Randomized Crossover Study. Int J Environ Res Public Health. 2020;17(23):9049. doi: 10.3390/ijerph17239049
37. Weaver CM, Miller JW. Challenges in conducting clinical nutrition research. Nutr Rev. 2017;75(7):491-99.
38. Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, McLendon RE, Schiffman SS. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 2008;71(21):1415-29.
39. Bian X, Chi L, Gao B, Tu P, Ru H, Lu K. The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLoS One. 2017;12(6):e0178426.
40. Bian X, Chi L, Gao B, Tu P, Ru H, Lu K. Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice. Front Physiol. 2017;8:487.
41. Collison KS, Makhoul NJ, Zaidi MZ, Al-Rabiah R, Inglis A, Andres BL, et al. Interactive effects of neonatal exposure to monosodium glutamate and aspartame on glucose homeostasis. Nutr Metab. 2012;9(1):58.
42. Feijó F de M, Ballard CR, Foletto KC, Batista BAM, Neves AM, Ribeiro MFM, et al. Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels. Appetite. 2013;60(1):203-7.
43. Gul SS, Hamilton ARL, Munoz AR, Phupitakphol T, Liu W, Hyoju SK, et al. Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice. Appl Physiol Nutr Metab. 2017;42(1):77-83.
44. Leibowitz A, Bier A, Gilboa M, Peleg E, Barshack I, Grossman E. Saccharin Increases Fasting Blood Glucose but Not Liver Insulin Resistance in Comparison to a High Fructose-Fed Rat Model. Nutrients. 2018;10(3):341. doi: 10.3390/nu10030341
45. Mitsutomi K, Masaki T, Shimasaki T, Gotoh K, Chiba S, Kakuma T, et al. Effects of a nonnutritive sweetener on body adiposity and energy metabolism in mice with diet-induced obesity. Metabolism. 2014;63(1):69-78.
46. Olivier-Van Stichelen S, Rother KI, Hanover JA. Maternal Exposure to Non-nutritive Sweeteners Impacts Progeny’s Metabolism and Microbiome. Front Microbiol. 2019;10:1360.
47. Otero-Losada M, Cao G, Mc Loughlin S, Rodríguez-Granillo G, Ottaviano G, Milei J. Rate of atherosclerosis progression in ApoE−/− mice long after discontinuation of cola beverage drinking. PLoS One. 2014;9(3):e89838. doi: 10.1371/journal.pone.0089838
48. Palmnäs MSA, Cowan TE, Bomhof MR, Su J, Reimer RA, Vogel HJ, et al. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PLoS One. 2014;9(10):e109841.
49. von Poser Toigo E, Huffell AP, Mota CS, Bertolini D, Pettenuzzo LF, Dalmaz C. Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame. Appetite. 2015;87:168-74.
50. Shi Q, Cai L, Jia H, Zhu X, Chen L, Deng S. Low intake of digestible carbohydrates ameliorates duodenal absorption of carbohydrates in mice with glucose metabolism disorders induced by artificial sweeteners. J Sci Food Agric. 2019;99(11):4952-62.
51. Swithers SE, Davidson TL. A role for sweet taste: calorie predictive relations in energy regulation by rats. Behav Neurosci. 2008;122(1):161-73.
52. Uebanso T, Ohnishi A, Kitayama R, Yoshimoto A, Nakahashi M, Shimohata T, et al. Effects of Low-Dose Non-Caloric Sweetener Consumption on Gut Microbiota in Mice. Nutrients. 2017;9(6):560. doi: 10.3390/nu9060560
53. Lin CH, Li HY, Wang SH, Chen YH, Chen YC, Wu HT. Consumption of Non-Nutritive Sweetener, Acesulfame Potassium Exacerbates Atherosclerosis through Dysregulation of Lipid Metabolism in ApoE−/− Mice. Nutrients. 2021;13(11):3984. doi: 10.3390/nu13113984
54. Bailey CJ, Day C, Knapper JM, Turner SL, Flatt PR. Antihyperglycaemic effect of saccharin in diabetic ob/ob mice. Br J Pharmacol. 1997;120(1):74-8.
55. Parlee SD, Simon BR, Scheller EL, Alejandro EU, Learman BS, Krishnan V, et al. Administration of saccharin to neonatal mice influences body composition of adult males and reduces body weight of females. Endocrinology. 2014 Apr;155(4):1313-26. doi: 10.1210/en.2013-1995
56. Risdon S, Meyer G, Marziou A, Riva C, Roustit M, Walther G. Artificial sweeteners impair endothelial vascular reactivity: Preliminary results in rodents. Nutr Metab Cardiovasc Dis. 2020 May 7;30(5):843-6. doi: 10.1016/j.numecd.2020.01.014
57. Tovar AP, Navalta JW, Kruskall LJ, Young JC. The effect of moderate consumption of non-nutritive sweeteners on glucose tolerance and body composition in rats. Appl Physiol Nutr Metab. 2017 Nov;42(11):1225-7. doi: 10.1139/apnm-2017-0120
58. Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol. 2021;19(1):55-71.
59. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576-85.
60. Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015;519(7541):92-6.
61. Berry SE, Valdes AM, Drew DA, Asnicar F, Mazidi M, Wolf J, et al. Human postprandial responses to food and potential for precision nutrition. Nat Med. 2020;26(6):964-73.
62. Korem T, Zeevi D, Zmora N, Weissbrod O, Bar N, Lotan-Pompan M, et al. Bread Affects Clinical Parameters and Induces Gut Microbiome-Associated Personal Glycemic Responses. Cell Metab. 2017;25(6):1243-53.e5.
63. Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vadder F, Arora T, et al. Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella. Cell Metab. 2015;22(6):971-82.
64. Spencer MD, Hamp TJ, Reid RW, Fischer LM, Zeisel SH, Fodor AA. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology. 2011;140(3):976-86.
65. Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger A, et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015;163(5):1079-94.
66. Ananthakrishnan AN, Luo C, Yajnik V, Khalili H, Garber JJ, Stevens BW, et al. Gut Microbiome Function Predicts Response to Anti-integrin Biologic Therapy in Inflammatory Bowel Diseases. Cell Host Microbe. 2017;21(5):603-10.e3.
67. Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103.
68. Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre M-L, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359(6371):104-8.
69. Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91–97.
70. Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S, et al. Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features. Cell. 2018;174(6):1388-405.e21.
71. Walker A, Pfitzner B, Neschen S, Kahle M, Harir M, Lucio M, et al. Distinct signatures of host-microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet. ISME J. 2014;8(12):2380-96.
72. Burberry A, Wells MF, Limone F, Couto A, Smith KS, Keaney J, et al. C9orf72 suppresses systemic and neural inflammation induced by gut bacteria. Nature. 2020;582(7810):89-94.
73. Ericsson AC, Hart ML, Kwan J, Lanoue L, Bower LR, Araiza R, et al. Supplier-origin mouse microbiomes significantly influence locomotor and anxiety-related behavior, body morphology, and metabolism. Commun Biol. 2021;4(1):716.
74. Roberts A, Renwick AG, Sims J, Snodin DJ. Sucralose metabolism and pharmacokinetics in man. Food Chem Toxicol. 2000;38(Suppl 2):S31-41.
75. Matthews HB, Fields M, Fishbein L. Saccharin: distribution and excretion of a limited dose in the rat. J Agric Food Chem. 1973;21(5):916-9.
76. Bian X, Tu P, Chi L, Gao B, Ru H, Lu K. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions. Food Chem Toxicol. 2017;107(Pt B):530-9.
77. Chi L, Bian X, Gao B, Tu P, Lai Y, Ru H, et al. Effects of the Artificial Sweetener Neotame on the Gut Microbiome and Fecal Metabolites in Mice. Molecules. 2018;23(2):367. doi: 10.3390/molecules23020367
78. Nettleton JE, Cho NA, Klancic T, Nicolucci AC, Shearer J, Borgland SL, et al. Maternal low-dose aspartame and stevia consumption with an obesogenic diet alters metabolism, gut microbiota and mesolimbic reward system in rat dams and their offspring. Gut. 2020;69(10):1807-17.
79. Sünderhauf A, Pagel R, Künstner A, Wagner AE, Rupp J, Ibrahim SM, et al. Saccharin Supplementation Inhibits Bacterial Growth and Reduces Experimental Colitis in Mice. Nutrients. 2020;12(4):1122. doi: 10.3390/nu12041122
80. Cheng X, Guo X, Huang F, Lei H, Zhou Q, Song C. Effect of different sweeteners on the oral microbiota and immune system of Sprague Dawley rats. AMB Express. 2021;11(1):8.
81. Anderson RL, Kirkland JJ. The effect of sodium saccharin in the diet on caecal microflora. Food Cosmet Toxicol. 1980;18(4):353-5.
82. Falcon T, Foletto KC, Siebert M, Pinto DE, Andrades M, Bertoluci MC. Metabarcoding reveals that a non-nutritive sweetener and sucrose yield similar gut microbiota patterns in Wistar rats. Genet Mol Biol. 2020;43(1):e20190028.
83. Lyte M, Fodor AA, Chapman CD, Martin GG, Perez-Chanona E, Jobin C, et al. Gut Microbiota and a Selectively Bred Taste Phenotype: A Novel Model of Microbiome-Behavior Relationships. Psychosom Med. 2016;78(5):610-9.
84. Daly K, Darby AC, Hall N, Wilkinson MC, Pongchaikul P, Bravo D, et al. Bacterial sensing underlies artificial sweetener-induced growth of gut Lactobacillus. Environ Microbiol. 2016;18(7):2159-71.
85. Guo M, Liu X, Tan Y, Kang F, Zhu X, Fan X, et al. Sucralose enhances the susceptibility to dextran sulfate sodium (DSS) induced colitis in mice with changes in gut microbiota. Food Funct. 2021;12(19):9380-90.
86. Rodriguez-Palacios A, Harding A, Menghini P, Himmelman C, Retuerto M, Nickerson KP, et al. The Artificial Sweetener Splenda Promotes Gut Proteobacteria, Dysbiosis, and Myeloperoxidase Reactivity in Crohn’s Disease-Like Ileitis. Inflamm Bowel Dis. 2018;24(5):1005-20.
87. Martínez-Carrillo BE, Rosales-Gómez CA, Ramírez-Durán N, Reséndiz-Albor AA, Escoto-Herrera JA, Mondragón-Velásquez T, et al. Effect of Chronic Consumption of Sweeteners on Microbiota and Immunity in the Small Intestine of Young Mice. Int J Food Sci. 2019;2019:9619020.
88. Wang Q-P, Browman D, Herzog H, Neely GG. Non-nutritive sweeteners possess a bacteriostatic effect and alter gut microbiota in mice. PLoS One. 2018;13(7):e0199080.
89. Li J, Zhu S, Lv Z, Dai H, Wang Z, Wei Q, et al. Drinking Water with Saccharin Sodium Alters the Microbiota-Gut-Hypothalamus Axis in Guinea Pig. Animals. 2021;11(7):1875. doi: 10.3390/ani11071875
90. Dai X, Guo Z, Chen D, Li L, Song X, Liu T, et al. Maternal sucralose intake alters gut microbiota of offspring and exacerbates hepatic steatosis in adulthood. Gut Microbes. 2020;11(4):1043-63.
91. Sánchez-Tapia M, Miller AW, Granados-Portillo O, Tovar AR, Torres N. The development of metabolic endotoxemia is dependent on the type of sweetener and the presence of saturated fat in the diet. Gut Microbes. 2020;12(1):1801301.
92. Zhang M, Chen J, Yang M, Qian C, Liu Y, Qi Y, et al. Low Doses of Sucralose Alter Fecal Microbiota in High-Fat Diet-Induced Obese Rats. Front Nutr. 2021;8:1151.
93. Hanawa Y, Higashiyama M, Kurihara C, Tanemoto R, Ito S, Mizoguchi A, et al. Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa. J Gastroenterol Hepatol. 2021;36(11):3140-8.
94. Li X, Liu Y, Wang Y, Li X, Liu X, Guo M, et al. Sucralose Promotes Colitis-Associated Colorectal Cancer Risk in a Murine Model Along With Changes in Microbiota. Front Oncol. 2020;10:710.
95. Dai X, Wang C, Guo Z, Li Y, Liu T, Jin G, et al. Maternal sucralose exposure induces Paneth cell defects and exacerbates gut dysbiosis of progeny mice. Food Funct. 2021;12(24):12634-46.
96. Wang W, Nettleton JE, Gänzle MG, Reimer RA. A metagenomics investigation of intergenerational effects of non-nutritive sweeteners on gut microbiome. Front Nutr. 2021;8:795848.
97. Frankenfeld CL, Sikaroodi M, Lamb E, Shoemaker S, Gillevet PM. 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. 2015;25(10):736-42.e4. doi: 10.1016/j.annepidem.2015.06.083
98. Laforest-Lapointe I, Becker AB, Mandhane PJ, Turvey SE, Moraes TJ, Sears MR, et al. Maternal consumption of artificially sweetened beverages during pregnancy is associated with infant gut microbiota and metabolic modifications and increased infant body mass index. Gut Microbes. 2021;13(1):1-15.
99. Weerasekera MM, Jayarathna TA, Wijesinghe GK, Gunasekara CP, Fernando N, Kottegoda N, et al. The Effect of Nutritive and Non-Nutritive Sweeteners on the Growth, Adhesion, and Biofilm Formation of Candida albicans and Candida tropicalis. Med Princ Pract. 2017;26(6):554-60.
100. Wood SG, John BA, Hawkins DR. The pharmacokinetics and metabolism of sucralose in the dog. Food Chem Toxicol. 2000;38(Suppl 2):S99-106.
101. John BA, Wood SG, Hawkins DR. The pharmacokinetics and metabolism of sucralose in the mouse. Food Chem Toxicol. 2000;38(Suppl 2):S107-10.
102. Sims J, Roberts A, Daniel JW, Renwick AG. The metabolic fate of sucralose in rats. Food Chem Toxicol. 2000;38(Suppl 2):S115-21.
103. Sylvetsky AC, Bauman V, Blau JE, Garraffo HM, Walter PJ, Rother KI. Plasma concentrations of sucralose in children and adults. Toxicol Environ Chem. 2017;99(3):535-42.
104. Bornemann V, Werness SC, Buslinger L, Schiffman SS. Intestinal Metabolism and Bioaccumulation of Sucralose In Adipose Tissue In The Rat. J Toxicol Environ Health A. 2018;81(18):913–923.
105. Renwick AG. The metabolism of intense sweeteners. Xenobiotica. 1986;16(10–11):1057-71.
106. Bekersky I, Poynor WJ, Colburn WA. Pharmacokinetics of saccharin in the rat. Renal clearance in vivo and in the isolated perfused kidney. Drug Metab Dispos. 1980;8(2):64-7.
107. Byard JL, McChesney EW, Golberg L, Coulston F. Excretion and metabolism of saccharin in man. II. Studies with 14C-labelled and unlabelled saccharin. Food Cosmet Toxicol. 1974;12(2):175-84.
108. McChesney EW, Golberg L. The excretion and metabolism of saccharin in man. I. Methods of investigation and preliminary results. Food Cosmet Toxicol. 1973;11(3):403-14.
109. Lethco EJ, Wallace WC. The metabolism of saccharin in animals. Toxicology. 1975;3(3):287-300.
110. Mayer D. Acesulfame-k. Boca Raton (US): CRC Press; 1991.
111. Collings AJ. Metabolism of cyclamate and its conversion to cyclohexylamine. Diabetes Care. 1989;12(1):50-5; discussion 81-2.
112. Drasar BS, Renwick AG, Williams RT. The role of the gut flora in the metabolism of cyclamate. Biochem J. 1972;129(4):881-90.
113. Tesoriero AA, Roxon JJ.
[35S]Cyclamate metabolism: incorporation of 35S into proteins of intestinal bacteria in vitro and production of volatile 35S-containing compounds. Xenobiotica. 1975;5(1):25-31.
114. Ranney RE, Oppermann JA, Muldoon E, McMahon FG. Comparative metabolism of aspartame in experimental animals and humans. J Toxicol Environ Health. 1976;2(2):441-51.
115. Shil A, Olusanya O, Ghufoor Z, Forson B, Marks J, Chichger H. Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. Nutrients. 2020;12(6):1862. doi: 10.3390/nu12061862
116. Turner A, Veysey M, Keely S, Scarlett CJ, Lucock M, Beckett EL. Intense Sweeteners, Taste Receptors and the Gut Microbiome: A Metabolic Health Perspective. Int J Environ Res Public Health. 2020;17(11):4094. doi: 10.3390/ijerph17114094
117. Ubukata K, Nakayama A, Mihara R. Pharmacokinetics and metabolism of N-
[N-
[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-l-phenylalanine 1-methyl ester, monohydrate (advantame) in the rat, dog, and man. Food Chem Toxicol. 2011;49(Suppl 1):S8-29.
118. Deng Y, Wang Y, Xia Y, Zhang AN, Zhao Y, Zhang T. Genomic resolution of bacterial populations in saccharin and cyclamate degradation. Sci Total Environ. 2019;658:357-66.
119. Schleheck D, Cook AM. Saccharin as a sole source of carbon and energy for Sphingomonas xenophaga SKN. Arch Microbiol. 2003;179(3):191-6.
120. Manca de Nadra MC, Anduni GJ, Farías ME. Influence of artificial sweeteners on the kinetic and metabolic behavior of Lactobacillus delbrueckii subsp. bulgaricus. J Food Prot. 2007;70(10):2413-6.
121. Wyss C. Aspartame as a source of essential phenylalanine for the growth of oral anaerobes. FEMS Microbiol Lett. 1993;108(3):255-8. doi: 10.1111/j.1574-6968.1993.tb06111.x
122. Ziesenitz SC, Siebert G. Uptake of saccharin and related intense sweeteners by Streptococcus mutans NCTC 10449. Z Ernahrungswiss. 1988;27(3):155-69.
123. Mahmud R, Shehreen S, Shahriar S, Rahman MS, Akhteruzzaman S, Sajib AA. Non-Caloric Artificial Sweeteners Modulate the Expression of Key Metabolic Genes in the Omnipresent Gut Microbe Escherichia coli. J Mol Microbiol Biotechnol. 2019;29(1-6):43-56.
124. Prashant GM, Patil RB, Nagaraj T, Patel VB. The antimicrobial activity of the three commercially available intense sweeteners against common periodontal pathogens: an in vitro study. J Contemp Dent Pract. 2012;13(6):749-52.
125. Omran A, Ahearn G, Bowers D, Swenson J, Coughlin C. Metabolic Effects of Sucralose on Environmental Bacteria. J Toxicol. 2013;2013:372986. doi: 10.1155/2013/372986
126. Linke HA, Chang CA. Physiological effects of sucrose substitutes and artificial sweeteners on growth pattern and acid production of glucose-grown Streptococcus mutans strains in vitro. Z Naturforsch C. 1976;31(5-6):245-51.
127. Young DA, Bowen WH. The influence of sucralose on bacterial metabolism. J Dent Res. 1990;69(8):1480-4.
128. Rettig S, Tenewitz J, Ahearn G, Coughlin C. Sucralose causes a concentration dependent metabolic inhibition of the gut flora Bacteroides , B. fragilis and B. uniformis not observed in the Firmicutes, E. faecalis and C. sordellii (1118.1). FASEB J. 2014;28(S1):1118.1. doi: 10.1096/fasebj.28.1_supplement.1118.1
129. Harpaz D, Yeo LP, Cecchini F, Koon THP, Kushmaro A, Tok AIY, et al. Measuring Artificial Sweeteners Toxicity Using a Bioluminescent Bacterial Panel. Molecules. 2018;23(10):2454. doi: 10.3390/molecules23102454
130. Naim M, Zechman JM, Brand JG, Kare MR, Sandovsky V. Effects of sodium saccharin on the activity of trypsin, chymotrypsin, and amylase and upon bacteria in small intestinal contents of rats. Proc Soc Exp Biol Med. 1985;178(3):392-401.
131. Pfeffer M, Ziesenitz SC, Siebert G. Acesulfame K, cyclamate and saccharin inhibit the anaerobic fermentation of glucose by intestinal bacteria. Z Ernahrungswiss. 1985;24(4):231-5.
132. Markus V, Share O, Shagan M, Halpern B, Bar T, Kramarsky-Winter E, et al. Inhibitory Effects of Artificial Sweeteners on Bacterial Quorum Sensing. Int J Mol Sci. 2021;22(18):9863. doi: 10.3390/ijms22189863
133. Yu Z, Wang Y, Lu J, Bond PL, Guo J. Nonnutritive sweeteners can promote the dissemination of antibiotic resistance through conjugative gene transfer. ISME J. 2021;15(7):2117-30.
134. Li Z, Gao J, Guo Y, Cui Y, Wang Y, Duan W, et al. Enhancement of antibiotic resistance dissemination by artificial sweetener acesulfame potassium: Insights from cell membrane, enzyme, energy supply and transcriptomics. J Hazard Mater. 2022;422:126942.
135. Shil A, Chichger H. Artificial Sweeteners Negatively Regulate Pathogenic Characteristics of Two Model Gut Bacteria, E. coli and E. f

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Harrington, Valerie; Lau, Lilian; Crits-Christoph, Alexander; Suez, Jotham. Interactions of Non-Nutritive Artificial Sweeteners with the Microbiome in Metabolic Syndrome [J]. Immunometabolism. 2022; 4; (2). 1 - 30.

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