Fare ve Ratlarda Yapay Tatlandırıcıların Bağırsak Mikrobiyotası Üzerine Etkisi: Randomize Kontrollü Çalışmaların Sistematik Derlemesi

Yıl 2022, , 99 - 110, 30.06.2022

Emre Duman , Alev Keser , Selen Yılmaz Işıkhan

https://doi.org/10.17827/aktd.1039222

Öz

Yapay tatlandırıcıların bağırsak mikrobiyotası üzerine etkisini inceleyen fare ve ratlarda yapılmış randomize kontrollü çalışmaların sistematik olarak incelenmesidir. PRISMA bildirgesi rehber alınarak PubMed, Web of Science, EBSCOHost ve Google Akademik olmak üzere 4 veri tabanı kullanılmış, 1 Ocak 2000-31 Aralık 2020 tarihleri arasında yayınlanan tüm rat ve fareler ile ilgili randomize kontrollü çalışmaları belirlemek için sistematik bir tarama yapılmıştır. Yapay tatlandırıcı olarak advantam, asesülfam-K, aspartam, neotam, sakkarin, siklamat ve sükraloz kullanılan çalışmalar dahil edilmiştir. İlk tarama sonucunda fare ve ratlar üzerinde yapılan toplam 901 çalışma elde edilmiştir. Çalışmanın amacına ve dahil etme kriterlerine uygun 11 randomize kontrollü çalışma sistematik derlemeye dahil edilmiştir. Çalışmalardan iki tanesi ratlar üzerinde, dokuz tanesi ise fareler üzerinde gerçekleştirilmiştir. Dahil edilme kriterlerini karşılayan advantam ve siklamat ile yapılmış çalışmaya literatürde rastlanmamıştır. Örneklem sayısının az olması nedeniyle meta-analiz yapılamamıştır. Fare ve ratlarda yapay tatlandırıcıların bağırsak mikrobiyotası üzerine etkisi olmakla birlikte etkisine yönelik net bir kanıt ortaya konulamamıştır. Bağırsak mikrobiyomundaki değişikliklerin insan sağlığını nasıl etkilediğinin araştırılması önemlidir ve bu nedenle yapay tatlandırıcı tüketiminin mikrobiyota üzerindeki etkisini değerlendiren randomize kontrollü klinik çalışmaların sayısının artması önemli bir gerekliliktir.

Anahtar Kelimeler

Mikrobiyota, sistematik derleme, yapay tatlandırıcılar.

Effect of Artificial Sweeteners on Gut Microbiota in Mice and Rats: A Systematic Review of Randomized Controlled Studies

Öz

It is a systematically examine of randomized controlled studies in mice and rats examining effects of artificial sweeteners on gut microbiota. Based on the PRISMA declaration, 4 databases were used, namely PubMed, Web of Science, EBSCOHost and Google Scholar, and a systematic search was conducted to identify randomized controlled studies on all rats and mice published between January 1, 2000-December 31, 2020. Studies using advantam, acesulfame-K, aspartame, neotame, saccharine, cyclamate, and sucralose as artificial sweeteners are included. As a result of first screening, a total of 901 studies on mice and rats were obtained. Eleven randomized controlled trials that met the study objective and inclusion criteria were included in systematic review. Two of studies were carried out on rats and nine of them were performed on mice. No study with advantam and cyclamate meeting the inclusion criteria was found in literature. Due to small sample size, meta-analysis could not be performed. Although artificial sweeteners have an effect on intestinal microbiota in mice and rats, no clear evidence for its effect has been demonstrated. It is important to investigate how changes in gut microbiome affect human health, and therefore it is essential to increase number of randomized controlled clinical trials evaluating effect of artificial sweetener consumption on the microbiota.

Anahtar Kelimeler

Microbiota, systematic review, artificial sweeteners

Kaynakça

• Koenig, JE, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R, et al. Succession of microbial conortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4578-85.
• Rajilic-Stojanovic M, De Vos WM. The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol Rev. 2014;38:996-1047.
• Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635-8.
• Bokulich NA, Blaser MJ. A bitter aftertaste: unintended effects of artificial sweeteners on the gut microbiome. Cell Metab. 2014;20:701-3.
• Kinross JM, Roon ACV, Holmes E, Darzi A, Nicholson JK. The human gut microbiome: implications for future health care. Curr Gastroenterology Rep. 2008;10(4):396-403.
• David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559-63.
• Spencer M, Gupta A, Dam LV, Shannon C, Menees S, Chey WD. Artificial Sweeteners: A Systematic Review and Primer for Gastroenterologists. J Neurogastroenterol Motil. 2016;22(2):168-80.
• Shankar P, Ahuja S, Sriram K. Non-nutritive sweeteners: review and update. Nutrition. 2013;29(11–12):1293-9.
• Moher D, Liberati A, Tetzlaff J, Altman DG, The Prisma Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.
• Checklist for Systematic Reviews and Research Syntheses. Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI). Available from: https://joannabriggs.org/sites/default/files/2020-08/Checklist_for_Systematic_Reviews_and_Research_Syntheses.pdf .Accessed: 21 December 21 2020
• 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.
• 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.
• Palmnäs MS, 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.
• Suez J, Korem T, Zeevi D, Zilberman-Schapıra G, Thaiss CA, Maza O, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514(7521):181-6.
• 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.
• 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;107:530-9.
• Becker SL, Chiang E, Plantinga A, Carey HV, Suen G, Swoap SJ. Effect of stevia on the gut microbiota and glucose tolerance in a murine model of diet-induced obesity. FEMS Microbiol Ecol. 2020;96(6):fiaa079.
• 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.
• 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.
• Rodriguez-Palacıos 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.
• 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.
• Kabeerdoss J, Sankaran V, Pugazhendhi S, Ramakrishna BS. Clostridium leptum group bacteria abundance and diversity in the fecal microbiota of patients with inflammatory bowel disease: a case–control study in India. BMC Gastroenterol. 2013;13(1):1-8.
• Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Human gut microbes associated with obesity. Nature. 2006;444:1022.
• Koliada A, Syzenko G, Moseiko V, Budovska L, Puchkov K, Perederiy V, et al. Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiol. 2017;17:120.
• Riva A, Borgo F, Lassandro C, Verduci E, Morace G, Borghi E, et al. Pediatric obesity is associated with an altered gut microbiota and discordant shifts in Firmicutes populations. Environ Microbiol. 2017;19:95-105.
• Duncan SH, Lobley G, Holtrop G, Ince J, Johnstone A, Louis P, et al. Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes. 2008;32:1720-4.
• Zhang H, Dibaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A. 2009;106:2365-70.
• Jumpertz R, Le DS, Turnbaugh PJ, Trinidad C, Bogardus C, Gordon JI, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr. 2011;94:58–65.
• Fernández J, Redondo-Blanco S, Gutiérrez-Del-Río I, Miguélez EM, Villar CJ, Lombó F. Colon microbiota fermentation of dietary prebiotics towards short-chain fatty acids and their roles as anti-inflammatory and antitumour agents: A review. J Funct Foods. 2016;25:511-22.
• Ng SC, Lam EF, Lam TT, Chan Y, Law W, Tse PC, et al. Effect of probiotic bacteria on the intestinal microbiota in irritable bowel syndrome. J Gastroenterol Hepatol. 2013;28(10):1624-31.