Maternal consumption of artificially sweetened beverages during pregnancy is associated with infant gut microbiota and metabolic modifications and increased infant body mass index

References

• Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity among adults and youth: United States, 2015-2016. NCHS Data Brief. 2017;1–15.
   Google Scholar
• Daniels SR, Arnett DK, Eckel RH, Gidding SS, Hayman LL, Kumanyika S, Robinson TN, Scott BJ, St. Jeor S, Williams CL, et al. Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment. Circulation. 2005;111:1999–2012. doi:10.1161/01.CIR.0000161369.71722.10.
   Google Scholar
• Azad MB, Sharma AK, de Souza RJ, Dolinsky VW, Becker AB, Mandhane PJ, Turvey SE, Subbarao P, Lefebvre DL, Sears MR, et al. Association Between Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index. JAMA Pediatr. 2016;170:662–670. doi:10.1001/jamapediatrics.2016.0301.
   Google Scholar
• 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). doi:10.3390/nu10020194
   Google Scholar
• Cox LM, Blaser MJ. Pathways in microbe-induced obesity. Cell Metab. 2013;17:883–894.
   Google Scholar
• Vatanen T, Franzosa EA, Schwager R, Tripathi S, Arthur TD, Vehik K, Lernmark Å, Hagopian WA, Rewers MJ, She J-X, et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature. 2018;562:589–594. doi:10.1038/s41586-018-0620-2.
   Google Scholar
• Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–214. doi:10.1038/nature11234.
   Google Scholar
• Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486:222–227. doi:10.1038/nature11053.
   Google Scholar
• Backhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, Li Y, Xia Y, Xie H, Zhong H, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015;17:852. doi:10.1016/j.chom.2015.05.012.
   Google Scholar
• Stewart CJ, Ajami NJ, O’Brien JL, Hutchinson DS, Smith DP, Wong MC, Ross MC, Lloyd RE, Doddapaneni H, Metcalf GA, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;562:583–588. doi:10.1038/s41586-018-0617-x.
   Google Scholar
• Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T, Rupp S, Uchimura Y, Li H, Steinert A, Heikenwalder M, Hapfelmeier S, Sauer U, et al. The maternal microbiota drives early postnatal innate immune development. Science. 2016;351:1296–1302. doi:10.1126/science.aad2571.
   Google Scholar
• Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr. 2012;96:544–551. doi:10.3945/ajcn.112.037382.
   Google Scholar
• Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107:11971–11975.
   Google Scholar
• Yassour M, Vatanen T, Siljander H, Hämäläinen A-M, Härkönen T, Ryhänen SJ, Franzosa EA, Vlamakis H, Huttenhower C, Gevers D, et al. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci Transl Med. 2016;8:343ra81. doi:10.1126/scitranslmed.aad0917.
   Google Scholar
• Madan JC, Hoen AG, Lundgren SN, Farzan SF, Cottingham KL, Morrison HG, Sogin ML, Li H, Moore JH, Karagas MR, et al. Association of cesarean delivery and formula supplementation with the intestinal microbiome of 6-week-old infants. JAMA Pediatr. 2016;170:212–219. doi:10.1001/jamapediatrics.2015.3732.
   Google Scholar
• Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5:e177. doi:10.1371/journal.pbio.0050177.
   Google Scholar
• Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, Mazmanian SK. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science. 2011;332:974–977. doi:10.1126/science.1206095.
   Google Scholar
• Pannaraj PS, Li F, Cerini C, Bender JM, Yang S, Rollie A, Adisetiyo H, Zabih S, Lincez PJ, Bittinger K, et al. Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatr. 2017;171:647–654. doi:10.1001/jamapediatrics.2017.0378.
   Google Scholar
• Zeissig S, Blumberg RS. Life at the beginning: perturbation of the microbiota by antibiotics in early life and its role in health and disease. Nat Immunol. 2014;15:307–310. doi:10.1038/ni.2847.
   Google Scholar
• Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9:313–323. doi:10.1038/nri2515.
   Google Scholar
• 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;87:168–174. doi:10.1016/j.appet.2014.12.213.
   Google Scholar
• Collison KS, Makhoul NJ, Zaidi MZ, Saleh SM, Andres B, Inglis A, Al-Rabiah R, Al-Mohanna FA. Gender dimorphism in aspartame-induced impairment of spatial cognition and insulin sensitivity. PLoS One. 2012;7:e31570. doi:10.1371/journal.pone.0031570.
   Google Scholar
• Zhang G-H, Chen M-L, Liu -S-S, Zhan Y-H, Quan Y, Qin Y-M, Deng S-P. Effects of mother’s dietary exposure to acesulfame-K in pregnancy or lactation on the adult offspring’s sweet preference. Chem Senses. 2011;36:763–770. doi:10.1093/chemse/bjr050.
   Google Scholar
• Stichelen O-V, Rother KI, Hanover JA. Maternal exposure to non-nutritive sweeteners impacts progeny’s metabolism and microbiome. Front Microbiol. 2019;10:1360. doi:10.3389/fmicb.2019.01360.
   Google Scholar
• Palatnik A, Moosreiner A, Olivier-Van Stichelen S. Consumption of non-nutritive sweeteners during pregnancy. Am J Obstet Gynecol. 2020;223:211–218. doi:10.1016/j.ajog.2020.03.034.
   Google Scholar
• Suez J, Korem T, Zilberman-Schapira G, Segal E, Elinav E. Non-caloric artificial sweeteners and the microbiome: findings and challenges. Gut Microbes. 2015;6:149–155. doi:10.1080/19490976.2015.1017700.
   Google Scholar
• Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, 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. doi:10.1038/nature13793.
   Google Scholar
• Holmes I, Harris K, Quince C, Gilbert JA. Dirichlet multinomial mixtures: generative models for microbial metagenomics. PLoS One. 2012;7:e30126. doi:10.1371/journal.pone.0030126.
   Google Scholar
• Chong J, Xia J. Using metaboanalyst 4.0 for metabolomics data analysis, interpretation, and integration with other omics data. Methods Mol Biol. 2020;2104:337–360.
   Google Scholar
• 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:e0178426. doi:10.1371/journal.pone.0178426.
   Google Scholar
• 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. doi:10.3389/fphys.2017.00487.
   Google Scholar
• Pereira TJ, Moyce BL, Kereliuk SM, Dolinsky VW. Influence of maternal overnutrition and gestational diabetes on the programming of metabolic health outcomes in the offspring: experimental evidence. Biochem Cell Biol. 2015;93:438–451. doi:10.1139/bcb-2014-0141.
   Google Scholar
• Symonds ME, Sebert SP, Hyatt MA, Budge H. Nutritional programming of the metabolic syndrome. Nat Rev Endocrinol. 2009;5:604–610. doi:10.1038/nrendo.2009.195.
   Google Scholar
• Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol. 2014;5:427.
   Google Scholar
• Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Nat Acad Sci. 2010;107:11971–11975.
   Google Scholar
• Sprockett D, Fukami T, Relman DA. Role of priority effects in the early-life assembly of the gut microbiota. Nat Rev Gastroenterol Hepatol. 2018;15:197–205. doi:10.1038/nrgastro.2017.173.
   Google Scholar
• Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis. 2015;26:26191.
   Google Scholar
• Chi L, Bian X, Gao B, Tu P, Lai Y, Ru H, Lu K.  Effects of the artificial sweetener neotame on the gut microbiome and fecal metabolites in mice. Molecules. 2018;23(2):367. doi:10.3390/molecules23020367.
   Google Scholar
• Tofalo R, Cocchi S, Suzzi G. Polyamines and gut microbiota. Front Nutr. 2019;6:16. doi:10.3389/fnut.2019.00016.
   Google Scholar
• Igarashi K, Kashiwagi K. Modulation of cellular function by polyamines. Int J Biochem Cell Biol. 2010;42:39–51. doi:10.1016/j.biocel.2009.07.009.
   Google Scholar
• Noack J, Dongowski G, Hartmann L, Blaut M. The human gut bacteria Bacteroides thetaiotaomicron and Fusobacterium varium produce putrescine and spermidine in cecum of pectin-fed gnotobiotic rats. J Nutr. 2000;130:1225–1231. doi:10.1093/jn/130.5.1225.
   Google Scholar
• Ramos-Molina B, Queipo-Ortuno MI, Lambertos A, Tinahones FJ, Peñafiel R.  Dietary and gut microbiota polyamines in obesity- and age-related diseases. Front Nutr. 2019;6:24.
   Google Scholar
• Connors J, Dawe N, Van Limbergen J. The role of succinate in the regulation of intestinal inflammation. Nutrients. 2018;11(1):25. doi:10.3390/nu11010025
   Google Scholar
• Serena C, Ceperuelo-Mallafre V, Keiran N, Queipo-Ortuño MI, Bernal R, Gomez-Huelgas R, Urpi-Sarda M, Sabater M, Pérez-Brocal V, Andrés-Lacueva C, et al. Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota. Isme J. 2018;12:1642–1657.
   Google Scholar
• Nettleton JE, Cho NA, Klancic T, Nicolucci AC, Shearer J, Borgland SL, Johnston LA, Ramay HR, Noye Tuplin E, Chleilat F, 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;69:1807–1817. doi:10.1136/gutjnl-2018-317505.
   Google Scholar
• Rother KI, Sylvetsky AC, Walter PJ, Garraffo HM, Fields DA. Pharmacokinetics of sucralose and acesulfame-potassium in breast milk following ingestion of diet soda. J Pediatr Gastroenterol Nutr. 2018;66:466–470. doi:10.1097/MPG.0000000000001817.
   Google Scholar
• Sylvetsky AC, Gardner AL, Bauman V, Blau JE, Garraffo HM, Walter PJ, Rother KI. Nonnutritive sweeteners in breast milk. J Toxicol Environ Health A. 2015;78:1029–1032. doi:10.1080/15287394.2015.1053646.
   Google Scholar
• Lloyd-Price J, Mahurkar A, Rahnavard G, Crabtree J, Orvis J, Hall AB, Brady A, Creasy HH, McCracken C, Giglio MG, et al. Strains, functions and dynamics in the expanded human microbiome project. Nature. 2017;550:61–66. doi:10.1038/nature23889.
   Google Scholar
• Costea PI, Coelho LP, Sunagawa S, Munch R, Huerta‐Cepas J, Forslund K, Hildebrand F, Kushugulova A, Zeller G, Bork P, et al. Subspecies in the global human gut microbiome. Mol Syst Biol. 2017;13:960. doi:10.15252/msb.20177589.
   Google Scholar
• Subbarao P, Anand SS, Becker AB, Befus AD, Brauer M, Brook JR, Denburg JA, HayGlass KT, Kobor MS, Kollmann TR, et al. The Canadian healthy infant longitudinal development (CHILD) study: examining developmental origins of allergy and asthma. Thorax. 2015;70:998–1000. doi:10.1136/thoraxjnl-2015-207246.
   Google Scholar
• Takaro TK, Scott JA, Allen RW, Anand SS, Becker AB, Befus AD, Brauer M, Duncan J, Lefebvre DL, Lou W, et al. The Canadian healthy infant longitudinal development (CHILD) birth cohort study: assessment of environmental exposures. J Expo Sci Environ Epidemiol. 2015;25:580–592. doi:10.1038/jes.2015.7.
   Google Scholar
• Group WHOMGRS. WHO child growth standards based on length/height, weight and age. Acta Paediatr Suppl 2006;450:76–85.
   Google Scholar
• Kozich JJ, Westcott SL, Baxter NT, Highlander SK, Schloss PD. Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform. Appl Environ Microbiol. 2013;79:5112–5120. doi:10.1128/AEM.01043-13.
   Google Scholar
• Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13:581–583. doi:10.1038/nmeth.3869.
   Google Scholar
• Foroutan A, Guo AC, Vazquez-Fresno R, Lipfert M, Zhang L, Zheng J, Badran H, Budinski Z, Mandal R, Ametaj BN, et al. Chemical composition of commercial cow’s milk. J Agric Food Chem. 2019;67:4897–4914. doi:10.1021/acs.jafc.9b00204.
   Google Scholar
• Foroutan A, Fitzsimmons C, Mandal R, Piri-Moghadam H, Zheng J, Guo A, Li C, Guan LL, Wishart DS. The bovine metabolome. Metabolites. 2020;10(6):233. doi:10.3390/metabo10060233.
   Google Scholar
• Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S, Fadrosh D, Panzer AR, LaMere B, Rackaityte E, Lukacs NW, et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med. 2016;22:1187–1191. doi:10.1038/nm.4176.
   Google Scholar
• Ding T, Schloss PD. Dynamics and associations of microbial community types across the human body. Nature. 2014;509:357–360. doi:10.1038/nature13178.
   Google Scholar
• McFall-Ngai M, Hadfield MG, Bosch TC, Carey HV, Domazet-Lošo T, Douglas AE, Dubilier N, Eberl G, Fukami T, Gilbert SF, et al. Animals in a bacterial world, a new imperative for the life sciences. Proc Natl Acad Sci U S A. 2013;110:3229–3236. doi:10.1073/pnas.1218525110.
   Google Scholar
• McMurdie PJ, Holmes S. Waste not, want not: why rarefying microbiome data is inadmissible. PLoS Comput Biol. 2014;10:e1003531.
   Google Scholar
• Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol. 2010;11:R106. doi:10.1186/gb-2010-11-10-r106.
   Google Scholar
• Oksanen J, Blanchet FG, Kindt R, Legendre P, Minchin PR, O’hara RB, Simpson GL, Solymos P, Stevens MH, Wagner H, Oksanen MJ. Package ‘vegan’. Community ecology package, version 2 (9). The R foundation for statistical computing. (https://www. r-project. org). 2013.
   Google Scholar