Dietary Additives and Supplements Revisited: the Fewer, the Safer for Gut and Liver Health

  • Rachel M. Golonka
  • Beng San Yeoh
  • Matam Vijay-KumarEmail author
Microbiome (A Patterson, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Microbiome


Purpose of Review

The supplementation of dietary additives into processed foods has exponentially increased in the past few decades. Similarly, the incidence rates of various diseases, including metabolic syndrome, gut dysbiosis, and hepatocarcinogenesis, have been elevating. Current research reveals that there is a positive association between food additives and these pathophysiological diseases. This review highlights the research published within the past 5 years that elucidate and update the effects of dietary supplements on liver and intestinal health.

Recent Findings

Some of the key findings include: enterocyte dysfunction of fructose clearance causes non-alcoholic fatty liver disease (NAFLD); non-caloric sweeteners are hepatotoxic; dietary emulsifiers instigate gut dysbiosis and hepatocarcinogenesis; and certain prebiotics can induce cholestatic hepatocellular carcinoma (HCC) in gut dysbiotic mice. Overall, multiple reports suggest that the administration of purified, dietary supplements could cause functional damage to both the liver and gut.


The extraction of bioactive components from natural resources was considered a brilliant method to modulate human health. However, current research highlights that such purified components may negatively affect individuals with microbiotal dysbiosis, resulting in a deeper break of the symbiotic relationship between the host and gut microbiota, which can lead to repercussions on gut and liver health. Therefore, ingestion of these dietary additives should not go without some caution!


Gut microbiome Hepatocellular carcinoma High fructose corn syrup Artificial sweeteners Emulsifiers Probiotics and prebiotics 


Compliance with Ethical Standards

Conflict of Interest

The authors have no conflicts of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).


  1. 1.
    Hrncirova L, Hudcovic T, Sukova E, Machova V, Trckova E, Krejsek J, et al. Human gut microbes are susceptible to antimicrobial food additives in vitro. Folia Microbiol (Praha); 2019;32:99–103.Google Scholar
  2. 2.
    Administration USFaD. CFR - Code of Federal Regulations Title 21, Sec. 184.1866 High fructose corn syrup 2018 [Available from: Accessed 5 Apr 2019.
  3. 3.
    Administration USFaD. Additional information about high-intensity sweeteners permitted for use in food in the United States 2018 [Available from: Accessed 5 Apr 2019.
  4. 4.
    Administration USFaD. CFR - Code of Federal Regulations Title 21, Sec. 182.1745 sodium carboxymethylcellulose 2018 [Available from: Accessed 5 Apr 2019.
  5. 5.
    Administration USFaD. CFR - code of federal regulations title 21, Sec. 172.840 polysorbate 80. 2018 [Available from: Accessed 5 Apr 2019
  6. 6.
    Administration USFaD. CFR - code of federal regulations title 21, Sec. 184.1400 lecithin 2018 [Available from: Accessed 5 Apr 2019.
  7. 7.
    Administration USFaD. Microorganisms & microbial-derived ingredients used in food (partial list) 2018 [Available from: Accessed 7 Apr 2019.
  8. 8.
    Kumar H, Salminen S, Verhagen H, Rowland I, Heimbach J, Banares S, et al. Novel probiotics and prebiotics: road to the market. Curr Opin Biotechnol. 2015;32:99–103.CrossRefPubMedGoogle Scholar
  9. 9.
    Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823–36.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Jiang JW, Chen XH, Ren Z, Zheng SS. Gut microbial dysbiosis associates hepatocellular carcinoma via the gut-liver axis. Hepatobiliary Pancreat Dis Int. 2019;18(1):19–27.CrossRefPubMedGoogle Scholar
  11. 11.
    Roderburg C, Luedde T. The role of the gut microbiome in the development and progression of liver cirrhosis and hepatocellular carcinoma. Gut Microbes. 2014;5(4):441–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Tao X, Wang N, Qin W. Gut microbiota and hepatocellular carcinoma. Gastrointest Tumors. 2015;2(1):33–40.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Asgharpour A, Cazanave SC, Pacana T, Seneshaw M, Vincent R, Banini BA, et al. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer. J Hepatol. 2016;65(3):579–88.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Hara E. Relationship between obesity, gut microbiome and hepatocellular carcinoma development. Dig Dis. 2015;33(3):346–50.CrossRefPubMedGoogle Scholar
  15. 15.
    Newens KJ, Walton J. A review of sugar consumption from nationally representative dietary surveys across the world. J Hum Nutr Diet. 2016;29(2):225–40.CrossRefPubMedGoogle Scholar
  16. 16.
    White JS, Hobbs LJ, Fernandez S. Fructose content and composition of commercial HFCS-sweetened carbonated beverages. Int J Obes. 2015;39(1):176–82.CrossRefGoogle Scholar
  17. 17.
    Jensen T, Abdelmalek MF, Sullivan S, Nadeau KJ, Green M, Roncal C, et al. Fructose and sugar: a major mediator of non-alcoholic fatty liver disease. J Hepatol. 2018;68(5):1063–75.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Pereira RM, Botezelli JD, da Cruz Rodrigues KC, Mekary RA, Cintra DE, Pauli JR, et al. Fructose consumption in the development of obesity and the effects of different protocols of physical exercise on the hepatic metabolism. Nutrients. 2017;9(4):405.Google Scholar
  19. 19.
    Komnenov D, Levanovich PE, Rossi NF. Hypertension associated with fructose and high salt: renal and sympathetic mechanisms. Nutrients. 2019;11(3):569.Google Scholar
  20. 20.
    Hsu CN, Lin YJ, Hou CY, Tain YL. maternal administration of probiotic or prebiotic prevents male adult rat offspring against developmental programming of hypertension induced by high fructose consumption in pregnancy and lactation. Nutrients. 2018;10(9):1229.Google Scholar
  21. 21.
    Astbury S, Song A, Zhou M, Nielsen B, Hoedl A, Willing BP, et al. High fructose intake during pregnancy in rats influences the maternal microbiome and gut development in the offspring. Front Genet. 2018;9:203.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Volynets V, Louis S, Pretz D, Lang L, Ostaff MJ, Wehkamp J, et al. Intestinal barrier function and the gut microbiome are differentially affected in mice fed a Western-style diet or drinking water supplemented with fructose. J Nutr. 2017;147(5):770–80.CrossRefPubMedGoogle Scholar
  23. 23.
    Ozawa T, Maehara N, Kai T, Arai S, Miyazaki T. Dietary fructose-induced hepatocellular carcinoma development manifested in mice lacking apoptosis inhibitor of macrophage (AIM). Genes Cells. 2016;21(12):1320–32.CrossRefPubMedGoogle Scholar
  24. 24.
    Dowman JK, Hopkins LJ, Reynolds GM, Nikolaou N, Armstrong MJ, Shaw JC, et al. Development of hepatocellular carcinoma in a murine model of nonalcoholic steatohepatitis induced by use of a high-fat/fructose diet and sedentary lifestyle. Am J Pathol. 2014;184(5):1550–61.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Schwarz JM, Noworolski SM, Erkin-Cakmak A, Korn NJ, Wen MJ, Tai VW, et al. Effects of dietary fructose restriction on liver fat, de novo lipogenesis, and insulin kinetics in children with obesity. Gastroenterology. 2017;153(3):743–52.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ibarra-Reynoso LDR, Lopez-Lemus HL, Garay-Sevilla ME, Malacara JM. Effect of restriction of foods with high fructose corn syrup content on metabolic indices and fatty liver in obese children. Obes Facts. 2017;10(4):332–40.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lustig RH, Mulligan K, Noworolski SM, Tai VW, Wen MJ, Erkin-Cakmak A, et al. Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome. Obesity (Silver Spring). 2016;24(2):453–60.CrossRefGoogle Scholar
  28. 28.
    Kanwal F, Kramer JR, Mapakshi S, Natarajan Y, Chayanupatkul M, Richardson PA, et al. Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease. Gastroenterology. 2018;155(6):1828–37 e2.CrossRefPubMedGoogle Scholar
  29. 29.
    Goncalves MD, Lu C, Tutnauer J, Hartman TE, Hwang S-K, Murphy CJ, et al. High-fructose corn syrup enhances intestinal tumor growth in mice. Science. 2019;363(6433):1345–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Herman MA, Samuel VT. The sweet path to metabolic demise: fructose and lipid synthesis. Trends Endocrinol Metab. 2016;27(10):719–30.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Jang C, Hui S, Lu W, Cowan AJ, Morscher RJ, Lee G, et al. The small intestine converts dietary fructose into glucose and organic acids. Cell Metab. 2018;27(2):351–61 e3.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Softic S, Cohen DE, Kahn CR. Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease. Dig Dis Sci. 2016;61(5):1282–93.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Poolsri WA, Phokrai P, Suwankulanan S, Phakdeeto N, Phunsomboon P, Pekthong D, et al. Combination of mitochondrial and plasma membrane citrate transporter inhibitors inhibits de novo lipogenesis pathway and triggers apoptosis in hepatocellular carcinoma cells. Biomed Res Int. 2018;2018:3683026.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Mock K, Lateef S, Benedito VA, Tou JC. High-fructose corn syrup-55 consumption alters hepatic lipid metabolism and promotes triglyceride accumulation. J Nutr Biochem. 2017;39:32–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Bawden SJ, Stephenson MC, Ciampi E, Hunter K, Marciani L, Macdonald IA, et al. Investigating the effects of an oral fructose challenge on hepatic ATP reserves in healthy volunteers: a (31)P MRS study. Clin Nutr. 2016;35(3):645–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Sullivan JS, Le MT, Pan Z, Rivard C, Love-Osborne K, Robbins K, et al. Oral fructose absorption in obese children with non-alcoholic fatty liver disease. Pediatr Obes. 2015;10(3):188–95.CrossRefPubMedGoogle Scholar
  37. 37.
    Mosca A, Nobili V, De Vito R, Crudele A, Scorletti E, Villani A, et al. Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents. J Hepatol. 2017;66(5):1031–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Kaneko C, Ogura J, Sasaki S, Okamoto K, Kobayashi M, Kuwayama K, et al. Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation. Biochim Biophys Acta Gen Subj. 2017;1861(3):559–66.CrossRefPubMedGoogle Scholar
  39. 39.
    Softic S, Gupta MK, Wang GX, Fujisaka S, O'Neill BT, Rao TN, et al. Divergent effects of glucose and fructose on hepatic lipogenesis and insulin signaling. J Clin Invest. 2017;127(11):4059–74.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Nakatsu Y, Seno Y, Kushiyama A, Sakoda H, Fujishiro M, Katasako A, et al. The xanthine oxidase inhibitor febuxostat suppresses development of nonalcoholic steatohepatitis in a rodent model. Am J Physiol Gastrointest Liver Physiol. 2015;309(1):G42–51.CrossRefPubMedGoogle Scholar
  41. 41.
    Goffredo M, Mass K, Parks EJ, Wagner DA, McClure EA, Graf J, et al. Role of gut microbiota and short chain fatty acids in modulating energy harvest and fat partitioning in youth. J Clin Endocrinol Metab. 2016;101(11):4367–76.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Toop CR, Muhlhausler BS, O'Dea K, Gentili S. Impact of perinatal exposure to sucrose or high fructose corn syrup (HFCS-55) on adiposity and hepatic lipid composition in rat offspring. J Physiol. 2017;595(13):4379–98.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Yuruk AA, Nergiz-Unal R. Maternal dietary free or bound fructose diversely influence developmental programming of lipogenesis. Lipids Health Dis. 2017;16(1):226.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Sellmann C, Priebs J, Landmann M, Degen C, Engstler AJ, Jin CJ, et al. Diets rich in fructose, fat or fructose and fat alter intestinal barrier function and lead to the development of nonalcoholic fatty liver disease over time. J Nutr Biochem. 2015;26(11):1183–92.CrossRefPubMedGoogle Scholar
  45. 45.
    Jin R, Willment A, Patel SS, Sun X, Song M, Mannery YO, et al. Fructose induced endotoxemia in pediatric nonalcoholic fatty liver disease. Int J Hepatol. 2014;2014:560620.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Seki K, Kitade M, Nishimura N, Kaji K, Asada K, Namisaki T, et al. Oral administration of fructose exacerbates liver fibrosis and hepatocarcinogenesis via increased intestinal permeability in a rat steatohepatitis model. Oncotarget. 2018;9(47):28638–51.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Jegatheesan P, Beutheu S, Freese K, Waligora-Dupriet AJ, Nubret E, Butel MJ, et al. Preventive effects of citrulline on Western diet-induced non-alcoholic fatty liver disease in rats. Br J Nutr. 2016;116(2):191–203.CrossRefPubMedGoogle Scholar
  48. 48.
    Jegatheesan P, Beutheu S, Ventura G, Sarfati G, Nubret E, Kapel N, et al. Effect of specific amino acids on hepatic lipid metabolism in fructose-induced non-alcoholic fatty liver disease. Clin Nutr. 2016;35(1):175–82.CrossRefPubMedGoogle Scholar
  49. 49.
    Wang H, Mei L, Deng Y, Liu Y, Wei X, Liu M, et al. Lactobacillus brevis DM9218 ameliorates fructose-induced hyperuricemia through inosine degradation and manipulation of intestinal dysbiosis. Nutrition. 2018;62:63–73.CrossRefPubMedGoogle Scholar
  50. 50.
    Aldamiz-Echevarria L, de Las Heras J, Couce ML, Alcalde C, Vitoria I, Bueno M, et al. Non-alcoholic fatty liver in hereditary fructose intolerance. Clin Nutr. 2019.Google Scholar
  51. 51.
    Lee AA, Owyang C. Sugars, sweet taste receptors, and brain responses. Nutrients. 2017;9(7):653.Google Scholar
  52. 52.
    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(2):149–55.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Andrejic BM, Mijatovic VM, Samojlik IN, Horvat OJ, Calasan JD, Dolai MA. The influence of chronic intake of saccharin on rat hepatic and pancreatic function and morphology: gender differences. Bosn J Basic Med Sci. 2013;13(2):94–9.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Amin KA, AlMuzafar HM. Alterations in lipid profile, oxidative stress and hepatic function in rat fed with saccharin and methyl-salicylates. Int J Clin Exp Med. 2015;8(4):6133–44.PubMedPubMedCentralGoogle Scholar
  55. 55.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Mansourian M, Mahnam K, Rajabi HR, Roushani M, Doustimotlagh AH. Exploring the binding mechanism of saccharin and sodium saccharin to promoter of human p53 gene by theoretical and experimental methods. J Biomol Struct Dyn. 2019:1–17:457.Google Scholar
  57. 57.
    Dhar D, Antonucci L, Nakagawa H, Kim JY, Glitzner E, Caruso S, et al. Liver cancer initiation requires p53 inhibition by CD44-enhanced growth factor signaling. Cancer Cell. 2018;33(6):1061–77 e6.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Alkafafy Mel S, Ibrahim ZS, Ahmed MM, El-Shazly SA. Impact of aspartame and saccharin on the rat liver: biochemical, molecular, and histological approach. Int J Immunopathol Pharmacol. 2015;28(2):247–55.CrossRefGoogle Scholar
  59. 59.
    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.CrossRefPubMedGoogle Scholar
  60. 60.
    Haighton L, Roberts A, Jonaitis T, Lynch B. Evaluation of aspartame cancer epidemiology studies based on quality appraisal criteria. Regul Toxicol Pharmacol. 2019;103:352–62.CrossRefPubMedGoogle Scholar
  61. 61.
    FDA 101: Dietary supplements: US Food and Drug Administration; 2017 [updated 11/06/2017. Available from: Accessed 26 Mar 2019.
  62. 62.
    Lebda MA, Tohamy HG, El-Sayed YS. Long-term soft drink and aspartame intake induces hepatic damage via dysregulation of adipocytokines and alteration of the lipid profile and antioxidant status. Nutr Res. 2017;41:47–55.CrossRefPubMedGoogle Scholar
  63. 63.
    Finamor I, Perez S, Bressan CA, Brenner CE, Rius-Perez S, Brittes PC, et al. Chronic aspartame intake causes changes in the trans-sulphuration pathway, glutathione depletion and liver damage in mice. Redox Biol. 2017;11:701–7.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Adaramoye OA, Akanni OO. Effects of long-term administration of aspartame on biochemical indices, lipid profile and redox status of cellular system of male rats. J Basic Clin Physiol Pharmacol. 2016;27(1):29–37.CrossRefPubMedGoogle Scholar
  65. 65.
    Qu D, Jiang M, Huang D, Zhang H, Feng L, Chen Y, et al. Synergistic effects of the enhancements to mitochondrial ROS, p53 activation and apoptosis generated by aspartame and potassium sorbate in HepG2 cells. Molecules. 2019;24(3):457.Google Scholar
  66. 66.
    Ashok I, Sheeladevi R. Oxidant stress evoked damage in rat hepatocyte leading to triggered nitric oxide synthase (NOS) levels on long term consumption of aspartame. J Food Drug Anal. 2015;23(4):679–91.CrossRefPubMedGoogle Scholar
  67. 67.
    Palmnas 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.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Martinson JNV, Pinkham NV, Peters GW, Cho H, Heng J, Rauch M, et al. Rethinking gut microbiome residency and the Enterobacteriaceae in healthy human adults. ISME J. 2019.Google Scholar
  69. 69.
    Zhu W, Winter MG, Byndloss MX, Spiga L, Duerkop BA, Hughes ER, et al. Precision editing of the gut microbiota ameliorates colitis. Nature. 2018;553(7687):208–11.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Sanduzzi Zamparelli M, Rocco A, Compare D, Nardone G. The gut microbiota: a new potential driving force in liver cirrhosis and hepatocellular carcinoma. United European Gastroenterol J. 2017;5(7):944–53.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Kakiyama G, Pandak WM, Gillevet PM, Hylemon PB, Heuman DM, Daita K, et al. Modulation of the fecal bile acid profile by gut microbiota in cirrhosis. J Hepatol. 2013;58(5):949–55.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Ponziani FR, Bhoori S, Castelli C, Putignani L, Rivoltini L, Del Chierico F, et al. Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease. Hepatology. 2019;69(1):107–20.CrossRefPubMedGoogle Scholar
  73. 73.
    Chassaing B, Gewirtz AT. Not so splendid for the gut microbiota. Inflamm Bowel Dis. 2018;24(5):1055–6.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    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.Google Scholar
  76. 76.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Dhurandhar D, Bharihoke V, Kalra S. A histological assessment of effects of sucralose on liver of albino rats. Morphologie. 2018;102(338):197–204.CrossRefPubMedGoogle Scholar
  78. 78.
    Liu CW, Chi L, Tu P, Xue J, Ru H, Lu K. Quantitative proteomics reveals systematic dysregulations of liver protein metabolism in sucralose-treated mice. J Proteome. 2019;196:1–10.CrossRefGoogle Scholar
  79. 79.
    Magnuson BA, Roberts A, Nestmann ER. Critical review of the current literature on the safety of sucralose. Food Chem Toxicol. 2017;106(Pt A):324–55.CrossRefPubMedGoogle Scholar
  80. 80.
    Berry C, Brusick D, Cohen SM, Hardisty JF, Grotz VL, Williams GM. Sucralose non-carcinogenicity: a review of the scientific and regulatory rationale. Nutr Cancer. 2016;68(8):1247–61.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    M S, M P, E T, L F, F M, M L, et al. Sucralose administered in feed, beginning prenatally through lifespan, induces hematopoietic neoplasias in male swiss mice. Int J Occup Environ Health. 2016;22(1):7–17.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Qin X. The effect of Splenda on gut microbiota of humans could be much more detrimental than in animals and deserves more extensive research. Inflamm Bowel Dis. 2019;25(2):e7.CrossRefPubMedGoogle Scholar
  83. 83.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    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.Google Scholar
  85. 85.
    Xie G, Wang X, Liu P, Wei R, Chen W, Rajani C, et al. Distinctly altered gut microbiota in the progression of liver disease. Oncotarget. 2016;7(15):19355–66.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Drasar BS, Renwick AG, Williams RT. The conversion of cyclamate into cyclohexylamine by gut bacteria. Biochem J. 1971;123(4):26P–7P.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Halmos EP, Mack A, Gibson PR. Review article: emulsifiers in the food supply and implications for gastrointestinal disease. Aliment Pharmacol Ther. 2019;49(1):41–50.CrossRefPubMedGoogle Scholar
  88. 88.
    Chassaing B, Van de Wiele T, De Bodt J, Marzorati M, Gewirtz AT. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut. 2017;66(8):1414–27.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Holder MK, Peters NV, Whylings J, Fields CT, Gewirtz AT, Chassaing B, et al. Dietary emulsifiers consumption alters anxiety-like and social-related behaviors in mice in a sex-dependent manner. Sci Rep. 2019;9(1):172.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Singh RK, Wheildon N, Ishikawa S. Food additive P-80 impacts mouse gut microbiota promoting intestinal inflammation, obesity and liver dysfunction. SOJ Microbiol Infect Dis. 2016;4(1).Google Scholar
  92. 92.
    Lock JY, Carlson TL, Wang C-M, Chen A, Carrier RL. Acute exposure to commonly ingested emulsifiers alters intestinal mucus structure and transport properties. Sci Rep. 2018;8(1):10008.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Janeiro MH, Ramirez MJ, Milagro FI, Martinez JA, Solas M. Implication of trimethylamine N-oxide (TMAO) in disease: potential biomarker or new therapeutic target. Nutrients. 2018;10(10):1398.Google Scholar
  94. 94.
    Hoyles L, Jimenez-Pranteda ML, Chilloux J, Brial F, Myridakis A, Aranias T, et al. Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota. Microbiome. 2018;6(1):73.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Chen YM, Liu Y, Zhou RF, Chen XL, Wang C, Tan XY, et al. Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults. Sci Rep. 2016;6:19076.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Liu ZY, Tan XY, Li QJ, Liao GC, Fang AP, Zhang DM, et al. Trimethylamine N-oxide, a gut microbiota-dependent metabolite of choline, is positively associated with the risk of primary liver cancer: a case-control study. Nutr Metab (Lond). 2018;15:81.CrossRefGoogle Scholar
  97. 97.
    Cox IJ, Aliev AE, Crossey MM, Dawood M, Al-Mahtab M, Akbar SM, et al. Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: a biomarker corroboration study. World J Gastroenterol. 2016;22(16):4191–200.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Nejrup RG, Licht TR, Hellgren LI. Fatty acid composition and phospholipid types used in infant formulas modifies the establishment of human gut bacteria in germ-free mice. Sci Rep. 2017;7(1):3975.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Bajaj JS, Heuman DM, Hylemon PB, Sanyal AJ, White MB, Monteith P, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol. 2014;60(5):940–7.CrossRefPubMedGoogle Scholar
  100. 100.
    Zhou RF, Chen XL, Zhou ZG, Zhang YJ, Lan QY, Liao GC, et al. Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study. Sci Rep. 2017;7(1):679.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Butler LM, Arning E, Wang R, Bottiglieri T, Govindarajan S, Gao YT, et al. Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma. Cancer Epidemiol Biomark Prev. 2013;22(10):1884–93.CrossRefGoogle Scholar
  102. 102.
    Newman AC, Maddocks ODK. One-carbon metabolism in cancer. Br J Cancer. 2017;116(12):1499–504.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Elbassuoni EA, Ragy MM, Ahmed SM. Evidence of the protective effect of l-arginine and vitamin D against monosodium glutamate-induced liver and kidney dysfunction in rats. Biomed Pharmacother. 2018;108:799–808.CrossRefPubMedGoogle Scholar
  104. 104.
    Coelho CFF, Franca LM, Nascimento JR, Dos Santos AM, Azevedo-Santos APS, Nascimento FRF, et al. Early onset and progression of non-alcoholic fatty liver disease in young monosodium l-glutamate-induced obese mice. J Dev Orig Health Dis. 2018;10(2):188–195.Google Scholar
  105. 105.
    Nakanishi Y, Tsuneyama K, Fujimoto M, Salunga TL, Nomoto K, An JL, et al. Monosodium glutamate (MSG): a villain and promoter of liver inflammation and dysplasia. J Autoimmun. 2008;30(1–2):42–50.CrossRefPubMedGoogle Scholar
  106. 106.
    Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506–14.CrossRefPubMedGoogle Scholar
  107. 107.
    Pandey KR, Naik SR, Vakil BV. Probiotics, prebiotics and synbiotics- a review. J Food Sci Technol. 2015;52(12):7577–87.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Meng X, Li S, Li Y, Gan RY, Li HB. Gut microbiota's relationship with liver disease and role in hepatoprotection by dietary natural products and probiotics. Nutrients. 2018;10(10):1457.Google Scholar
  109. 109.
    Dimidi E, Christodoulides S, Scott SM, Whelan K. Mechanisms of action of probiotics and the gastrointestinal microbiota on gut motility and constipation. Adv Nutr. 2017;8(3):484–94.CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Bartolomaeus H, Balogh A, Yakoub M, Homann S, Marko L, Hoges S, et al. Short-chain fatty acid propionate protects from hypertensive cardiovascular damage. Circulation. 2019;139(11):1407–21.CrossRefPubMedGoogle Scholar
  111. 111.
    Chandrasekharan B, Saeedi BJ, Alam A, Houser M, Srinivasan S, Tansey M, et al. Interactions between commensal bacteria and enteric neurons, via FPR1 induction of ROS, increase gastrointestinal motility in mice. Gastroenterology. 2019.Google Scholar
  112. 112.
    Yadav R, Singh PK, Puniya AK, Shukla P. Catalytic interactions and molecular docking of bile salt hydrolase (BSH) from L. plantarum RYPR1 and its prebiotic utilization. Front Microbiol. 2016;7:2116.PubMedGoogle Scholar
  113. 113.
    Huang L, Duan C, Zhao Y, Gao L, Niu C, Xu J, et al. Reduction of aflatoxin B1 toxicity by Lactobacillus plantarum C88: a potential probiotic strain isolated from Chinese traditional fermented food “tofu”. PLoS One. 2017;12(1):e0170109.CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Ritze Y, Bardos G, Claus A, Ehrmann V, Bergheim I, Schwiertz A, et al. Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice. PLoS One. 2014;9(1):e80169.CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Endo H, Niioka M, Kobayashi N, Tanaka M, Watanabe T. Butyrate-producing probiotics reduce nonalcoholic fatty liver disease progression in rats: new insight into the probiotics for the gut-liver axis. PLoS One. 2013;8(5):e63388.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Xin J, Zeng D, Wang H, Ni X, Yi D, Pan K, et al. Preventing non-alcoholic fatty liver disease through Lactobacillus johnsonii BS15 by attenuating inflammation and mitochondrial injury and improving gut environment in obese mice. Appl Microbiol Biotechnol. 2014;98(15):6817–29.CrossRefPubMedGoogle Scholar
  117. 117.
    Scaldaferri F, Gerardi V, Mangiola F, Lopetuso LR, Pizzoferrato M, Petito V, et al. Role and mechanisms of action of Escherichia coli Nissle 1917 in the maintenance of remission in ulcerative colitis patients: an update. World J Gastroenterol. 2016;22(24):5505–11.CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Crook N, Ferreiro A, Gasparrini AJ, Pesesky MW, Gibson MK, Wang B, et al. Adaptive strategies of the candidate probiotic E. coli Nissle in the mammalian gut. Cell Host Microbe. 2019.Google Scholar
  119. 119.
    Xue L, He J, Gao N, Lu X, Li M, Wu X, et al. Probiotics may delay the progression of nonalcoholic fatty liver disease by restoring the gut microbiota structure and improving intestinal endotoxemia. Sci Rep. 2017;7:45176.CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Nabavi S, Rafraf M, Somi MH, Homayouni-Rad A, Asghari-Jafarabadi M. Effects of probiotic yogurt consumption on metabolic factors in individuals with nonalcoholic fatty liver disease. J Dairy Sci. 2014;97(12):7386–93.CrossRefPubMedGoogle Scholar
  121. 121.
    Famouri F, Shariat Z, Hashemipour M, Keikha M, Kelishadi R. Effects of probiotics on nonalcoholic fatty liver disease in obese children and adolescents. J Pediatr Gastroenterol Nutr. 2017;64(3):413–7.CrossRefPubMedGoogle Scholar
  122. 122.
    Li J, Sung CY, Lee N, Ni Y, Pihlajamaki J, Panagiotou G, et al. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc Natl Acad Sci U S A. 2016;113(9):E1306–15.CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Wan MLY, El-Nezami H. Targeting gut microbiota in hepatocellular carcinoma: probiotics as a novel therapy. Hepatobiliary Surg Nutr. 2018;7(1):11–20.CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    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.CrossRefPubMedGoogle Scholar
  125. 125.
    Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S, et al. Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell. 2018;174(6):1406–23 e16.CrossRefPubMedGoogle Scholar
  126. 126.
    Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, 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(8):491–502.CrossRefPubMedGoogle Scholar
  127. 127.
    Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, et al. Prebiotics: definition, types, sources, mechanisms, and clinical applications. Foods. 2019;8(3):92.Google Scholar
  128. 128.
    Choque Delgado GT, Tamashiro W. Role of prebiotics in regulation of microbiota and prevention of obesity. Food Res Int. 2018;113:183–8.CrossRefPubMedGoogle Scholar
  129. 129.
    Mensink MA, Frijlink HW, van der Voort Maarschalk K, Hinrichs WL. Inulin, a flexible oligosaccharide I: review of its physicochemical characteristics. Carbohydr Polym. 2015;130:405–19.CrossRefPubMedGoogle Scholar
  130. 130.
    Administration USFaD. GRAS notices 2002 [Available from: Accessed 4 Apr 2019.
  131. 131.
    Zou J, Chassaing B, Singh V, Pellizzon M, Ricci M, Fythe MD, et al. Fiber-mediated nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health. Cell Host Microbe. 2018;23(1):41–53 e4.CrossRefPubMedGoogle Scholar
  132. 132.
    Pham VT, Seifert N, Richard N, Raederstorff D, Steinert R, Prudence K, et al. The effects of fermentation products of prebiotic fibres on gut barrier and immune functions in vitro. PeerJ. 2018;6:e5288.CrossRefPubMedPubMedCentralGoogle Scholar
  133. 133.
    Wang X, Gibson GR, Costabile A, Sailer M, Theis S, Rastall RA. Prebiotic supplementation of in vitro faecal fermentations inhibits proteolysis by gut bacteria and host diet shapes gut bacterial metabolism and response to intervention. Appl Environ Microbiol. 2019;85(9):e02749–18.Google Scholar
  134. 134.
    Baxter NT, Schmidt AW, Venkataraman A, Kim KS, Waldron C, Schmidt TM. Dynamics of human gut microbiota and short-chain fatty acids in response to dietary interventions with three fermentable fibers. MBio. 2019;10(1):e02566–18.Google Scholar
  135. 135.
    Vandeputte D, Falony G, Vieira-Silva S, Wang J, Sailer M, Theis S, et al. Prebiotic inulin-type fructans induce specific changes in the human gut microbiota. Gut. 2017;66(11):1968–74.CrossRefPubMedPubMedCentralGoogle Scholar
  136. 136.
    Yang X, He F, Zhang Y, Xue J, Li K, Zhang X, et al. Inulin ameliorates alcoholic liver disease via suppressing LPS-TLR4-Mpsi Axis and modulating gut microbiota in mice. Alcohol Clin Exp Res. 2019;43(3):411–24.CrossRefPubMedGoogle Scholar
  137. 137.
    Chassaing B, Gewirtz AT. Identification of inner mucus-associated bacteria by laser capture microdissection. Cell Mol Gastroenterol Hepatol. 2019;7(1):157–60.CrossRefPubMedGoogle Scholar
  138. 138.
    Healey G, Murphy R, Butts C, Brough L, Whelan K, Coad J. Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic: a randomised, double-blind, placebo-controlled, cross-over, human intervention study. Br J Nutr. 2018;119(2):176–89.CrossRefPubMedGoogle Scholar
  139. 139.
    Li K, Zhang L, Xue J, Yang X, Dong X, Sha L, et al. Dietary inulin alleviates diverse stages of type 2 diabetes mellitus via anti-inflammation and modulating gut microbiota in db/db mice. Food Funct. 2019;10(4):1915–1927.Google Scholar
  140. 140.
    Shang HM, Zhou HZ, Yang JY, Li R, Song H, Wu HX. In vitro and in vivo antioxidant activities of inulin. PLoS One. 2018;13(2):e0192273.CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Kalantari H, Asadmasjedi N, Abyaz MR, Mahdavinia M, Mohammadtaghvaei N. Protective effect of inulin on methotrexate-induced liver toxicity in mice. Biomed Pharmacother. 2019;110:943–50.CrossRefPubMedGoogle Scholar
  142. 142.
    Correa-Ferreira ML, Verdan MH, Dos Reis Livero FA, Galuppo LF, Telles JE, Alves Stefanello ME, et al. Inulin-type fructan and infusion of Artemisia vulgaris protect the liver against carbon tetrachloride-induced liver injury. Phytomedicine. 2017;24:68–76.CrossRefPubMedGoogle Scholar
  143. 143.
    Liu J, Lu JF, Wen XY, Kan J, Jin CH. Antioxidant and protective effect of inulin and catechin grafted inulin against CCl4-induced liver injury. Int J Biol Macromol. 2015;72:1479–84.CrossRefPubMedGoogle Scholar
  144. 144.
    Javadi L, Khoshbaten M, Safaiyan A, Ghavami M, Abbasi MM, Gargari BP. Pro- and prebiotic effects on oxidative stress and inflammatory markers in non-alcoholic fatty liver disease. Asia Pac J Clin Nutr. 2018;27(5):1031–9.PubMedGoogle Scholar
  145. 145.
    Singh V, Yeoh BS, Chassaing B, Xiao X, Saha P, Aguilera Olvera R, et al. Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer. Cell. 2018;175(3):679–94 e22.CrossRefPubMedGoogle Scholar
  146. 146.
    Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013;499(7456):97–101.CrossRefPubMedGoogle Scholar
  147. 147.
    Lam KL, Ko KC, Li X, Ke X, Cheng WY, Chen T, et al. In vitro infant faecal fermentation of low viscosity barley beta-glucan and its acid hydrolyzed derivatives: evaluation of their potential as novel prebiotics. Molecules. 2019;24(5):828.Google Scholar
  148. 148.
    Wang Y, Harding SV, Thandapilly SJ, Tosh SM, Jones PJH, Ames NP. Barley beta-glucan reduces blood cholesterol levels via interrupting bile acid metabolism. Br J Nutr. 2017;118(10):822–9.CrossRefPubMedGoogle Scholar
  149. 149.
    Thandapilly SJ, Ndou SP, Wang Y, Nyachoti CM, Ames NP. Barley beta-glucan increases fecal bile acid excretion and short chain fatty acid levels in mildly hypercholesterolemic individuals. Food Funct. 2018;9(6):3092–6.CrossRefPubMedGoogle Scholar
  150. 150.
    Wang YJ, Zhan R, Sontag-Strohm T, Maina NH. The protective role of phytate in the oxidative degradation of cereal beta-glucans. Carbohydr Polym. 2017;169:220–6.CrossRefPubMedGoogle Scholar
  151. 151.
    Jayachandran M, Chen J, Chung SSM, Xu B. A critical review on the impacts of beta-glucans on gut microbiota and human health. J Nutr Biochem. 2018;61:101–10.CrossRefPubMedGoogle Scholar
  152. 152.
    Mikkelsen MS, Jensen MG, Nielsen TS. Barley beta-glucans varying in molecular mass and oligomer structure affect cecal fermentation and microbial composition but not blood lipid profiles in hypercholesterolemic rats. Food Funct. 2017;8(12):4723–32.CrossRefPubMedGoogle Scholar
  153. 153.
    Gudi R, Perez N, Johnson BM, Sofi MH, Brown R, Quan S, et al. Complex dietary polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes. Immunology. 2019;157(1):70–85.Google Scholar
  154. 154.
    Sun SS, Wang K, Ma K, Bao L, Liu HW. An insoluble polysaccharide from the sclerotium of Poria cocos improves hyperglycemia, hyperlipidemia and hepatic steatosis in ob/ob mice via modulation of gut microbiota. Chin J Nat Med. 2019;17(1):3–14.PubMedGoogle Scholar
  155. 155.
    Teixeira C, Prykhodko O, Alminger M, Fak Hallenius F, Nyman M. Barley products of different Ffiber composition selectively change microbiota composition in rats. Mol Nutr Food Res. 2018;62(19):e1701023.CrossRefPubMedGoogle Scholar
  156. 156.
    Luo Y, Zhang L, Li H, Smidt H, Wright AG, Zhang K, et al. Different types of dietary fibers trigger specific alterations in composition and predicted functions of colonic bacterial communities in BALB/c mice. Front Microbiol. 2017;8:966.CrossRefPubMedPubMedCentralGoogle Scholar
  157. 157.
    De Angelis M, Montemurno E, Vannini L, Cosola C, Cavallo N, Gozzi G, et al. Effect of whole-grain barley on the human fecal microbiota and metabolome. Appl Environ Microbiol. 2015;81(22):7945–56.CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Vetvicka V, Garcia-Mina JM, Proctor M, Yvin JC. Humic acid and glucan: protection against liver injury induced by carbon tetrachloride. J Med Food. 2015;18(5):572–7.CrossRefPubMedGoogle Scholar
  159. 159.
    Nakashima A, Sugimoto R, Suzuki K, Shirakata Y, Hashiguchi T, Yoshida C, et al. Anti-fibrotic activity of Euglena gracilis and paramylon in a mouse model of non-alcoholic steatohepatitis. Food Sci Nutr. 2019;7(1):139–47.CrossRefPubMedGoogle Scholar
  160. 160.
    Suchecka D, Harasym J, Wilczak J, Gromadzka-Ostrowska J. Hepato- and gastro- protective activity of purified oat 1-3, 1-4-beta-d-glucans of different molecular weight. Int J Biol Macromol. 2016;91:1177–85.CrossRefPubMedGoogle Scholar
  161. 161.
    Siddiqui S, Ahmad R, Khan MA, Upadhyay S, Husain I, Srivastava AN. Cytostatic and anti-tumor potential of Ajwa date pulp against human hepatocellular carcinoma HepG2 cells. Sci Rep. 2019;9(1):245.CrossRefPubMedPubMedCentralGoogle Scholar
  162. 162.
    Elsonbaty SM, Zahran WE, Moawed FS. Gamma-irradiated beta-glucan modulates signaling molecular targets of hepatocellular carcinoma in rats. Tumour Biol. 2017;39(8):1010428317708703.CrossRefPubMedGoogle Scholar
  163. 163.
    Zou S, Duan B, Xu X. Inhibition of tumor growth by beta-glucans through promoting CD4(+) T cell immunomodulation and neutrophil-killing in mice. Carbohydr Polym. 2019;213:370–81.CrossRefPubMedGoogle Scholar
  164. 164.
    Sundar Raj A Allwyn, Jayabalan R and Ranganathan T. V. A Review on pectin: chemistry due to general properties of pectin and its pharmaceutical uses: Open Access Scientific Reports; 2012 [Available from: Accessed 4 Apr 2019.
  165. 165.
    Milani C, Duranti S, Bottacini F, Casey E, Turroni F, Mahony J, et al. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev. 2017;81(4):e00036–17.Google Scholar
  166. 166.
    Morel FB, Oozeer R, Piloquet H, Moyon T, Pagniez A, Knol J, et al. Preweaning modulation of intestinal microbiota by oligosaccharides or amoxicillin can contribute to programming of adult microbiota in rats. Nutrition. 2015;31(3):515–22.CrossRefPubMedGoogle Scholar
  167. 167.
    Sierra C, Bernal MJ, Blasco J, Martinez R, Dalmau J, Ortuno I, et al. Prebiotic effect during the first year of life in healthy infants fed formula containing GOS as the only prebiotic: a multicentre, randomised, double-blind and placebo-controlled trial. Eur J Nutr. 2015;54(1):89–99.CrossRefPubMedGoogle Scholar
  168. 168.
    Mao B, Li D, Zhao J, Liu X, Gu Z, Chen YQ, et al. Metagenomic insights into the effects of fructo-oligosaccharides (FOS) on the composition of fecal microbiota in mice. J Agric Food Chem. 2015;63(3):856–63.CrossRefPubMedGoogle Scholar
  169. 169.
    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 (Tokyo). 2018;64(5):357–66.CrossRefGoogle Scholar
  170. 170.
    Ferreira-Lazarte A, Kachrimanidou V, Villamiel M, Rastall RA, Moreno FJ. In vitro fermentation properties of pectins and enzymatic-modified pectins obtained from different renewable bioresources. Carbohydr Polym. 2018;199:482–91.CrossRefPubMedGoogle Scholar
  171. 171.
    Jiang T, Gao X, Wu C, Tian F, Lei Q, Bi J, et al. Apple-derived pectin modulates gut microbiota, improves gut barrier function, and attenuates metabolic Endotoxemia in rats with diet-induced obesity. Nutrients. 2016;8(3):126.CrossRefPubMedPubMedCentralGoogle Scholar
  172. 172.
    Yang J, Ding C, Dai X, Lv T, Xie T, Zhang T, et al. Soluble dietary fiber ameliorates radiation-induced intestinal epithelial-to-mesenchymal transition and fibrosis. JPEN J Parenter Enteral Nutr. 2017;41(8):1399–410.CrossRefPubMedGoogle Scholar
  173. 173.
    Abu-Elsaad NM, Elkashef WF. Modified citrus pectin stops progression of liver fibrosis by inhibiting galectin-3 and inducing apoptosis of stellate cells. Can J Physiol Pharmacol. 2016;94(5):554–62.CrossRefPubMedGoogle Scholar
  174. 174.
    Borges Haubert NJ, Marchini JS, Carvalho Cunha SF, Suen VM, Padovan GJ, Jordao AAJ, et al. Choline and fructooligosaccharide: non-alcoholic fatty liver disease, cardiac fat deposition, and oxidative stress markers. Nutr Metab Insights. 2015;8:1–6.PubMedPubMedCentralGoogle Scholar
  175. 175.
    Chappuis E, Morel-Depeisse F, Bariohay B, Roux J. Alpha-galacto-oligosaccharides at low dose improve liver steatosis in a high-fat diet mouse model. Molecules. 2017;22(10):1725.Google Scholar
  176. 176.
    Ferrere G, Wrzosek L, Cailleux F, Turpin W, Puchois V, Spatz M, et al. Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury in mice. J Hepatol. 2017;66(4):806–15.CrossRefPubMedGoogle Scholar
  177. 177.
    Li W, Zhang K, Yang H. Pectin alleviates high fat (lard) diet-induced nonalcoholic fatty liver disease in mice: possible role of short-chain fatty acids and gut microbiota regulated by pectin. J Agric Food Chem. 2018;66(30):8015–25.CrossRefPubMedGoogle Scholar
  178. 178.
    Matsumoto K, Ichimura M, Tsuneyama K, Moritoki Y, Tsunashima H, Omagari K, et al. Fructo-oligosaccharides and intestinal barrier function in a methionine-choline-deficient mouse model of nonalcoholic steatohepatitis. PLoS One. 2017;12(6):e0175406.CrossRefPubMedPubMedCentralGoogle Scholar
  179. 179.
    Shtriker MG, Peri I, Taieb E, Nyska A, Tirosh O, Madar Z. Galactomannan more than pectin exacerbates liver injury in mice fed with high-fat, high-cholesterol diet. Mol Nutr Food Res. 2018;62(20):e1800331.CrossRefPubMedGoogle Scholar
  180. 180.
    Ke X, Walker A, Haange SB, Lagkouvardos I, Liu Y, Schmitt-Kopplin P, et al. Synbiotic-driven improvement of metabolic disturbances is associated with changes in the gut microbiome in diet-induced obese mice. Mol Metab. 2019;22:96–109.CrossRefPubMedPubMedCentralGoogle Scholar
  181. 181.
    Abrahamse-Berkeveld M, Alles M, Franke-Beckmann E, Helm K, Knecht R, Kollges R, et al. Infant formula containing galacto-and fructo-oligosaccharides and Bifidobacterium breve M-16V supports adequate growth and tolerance in healthy infants in a randomised, controlled, double-blind, prospective, multicentre study. J Nutr Sci. 2016;5:e42.CrossRefPubMedPubMedCentralGoogle Scholar
  182. 182.
    Hibberd AA, Yde CC, Ziegler ML, Honore AH, Saarinen MT, Lahtinen S, et al. Probiotic or symbiotic alters the gut microbiota and metabolism in a randomised controlled trial of weight management in overweight adults. Benefic Microbes. 2019;10(2):121–35.CrossRefGoogle Scholar
  183. 183.
    Rajkumar H, Kumar M, Das N, Kumar SN, Challa HR, Nagpal R. Effect of probiotic Lactobacillus salivarius UBL S22 and prebiotic Fructo-oligosaccharide on serum lipids, inflammatory markers, insulin sensitivity, and gut Bacteria in healthy young volunteers: a randomized controlled single-blind pilot study. J Cardiovasc Pharmacol Ther. 2015;20(3):289–98.CrossRefPubMedGoogle Scholar
  184. 184.
    Asemi Z, Aarabi MH, Hajijafari M, Alizadeh SA, Razzaghi R, Mazoochi M, et al. Effects of synbiotic food consumption on serum minerals, liver enzymes, and blood pressure in patients with type 2 diabetes: a double-blind randomized cross-over controlled clinical trial. Int J Prev Med. 2017;8:43.CrossRefPubMedPubMedCentralGoogle Scholar
  185. 185.
    Malaguarnera M, Vacante M, Antic T, Giordano M, Chisari G, Acquaviva R, et al. Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis. Dig Dis Sci. 2012;57(2):545–53.CrossRefPubMedGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Physiology & PharmacologyUniversity of Toledo College of Medicine and Life SciencesToledoUSA
  2. 2.Graduate Program in Immunology & Infectious DiseasePennsylvania State UniversityUniversity ParkUSA
  3. 3.Department of Medical Microbiology & ImmunologyUniversity of Toledo College of Medicine and Life SciencesToledoUSA

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