Abstract
Necrotizing enterocolitis (NEC) is severe inflammatory disease that predominantly affects preterm infants and is closely related to shaping the gut microenvironment and immune system. Early-life feeding plays a critical role in the pathophysiology of NEC. Xanthan gum (XG) has viscosity-stabilizing properties and resistance to breast milk amylase. Therefore, XG has therefore been used in the management of dysphagia in infants. However, its safety in the intestines of premature infants remains controversial. This study aims to review current scientific evidence on the use of XG in NEC and to evaluate potential pathophysiological mechanisms from a clinical perspective. Current data suggest that fermentation of XG by the colonic microbiota into short-chain fatty acids may contribute to mucosal injury in the immature gut, although a causal relationship has not been established. Clinical studies show that NEC cases associated with XG-based thickeners have a later onset than classical NEC, with approximately half of cases developing post-discharge. Therefore, regulatory authorities such as the FDA, EFSA, and JECFA have published restrictive guidelines on the use of XG in neonates. In this context, it is crucial that XG-based products be carefully evaluated, especially in at-risk infants, and that the decision to thicken the product be made through a multidisciplinary, individualized approach that considers the infant’s intestinal maturity.
Keywords: food additives, necrotizing enterocolitis, preterm infants, xanthan gum
License
Copyright (c) 2026 The Author(s). This is an open access article distributed under the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.
How to Cite
References
- Whelan K, Bancil AS, Lindsay JO, Chassaing B. Ultra-processed foods and food additives in gut health and disease. Nat Rev Gastroenterol Hepatol. 2024;21(6):406-427. https://doi.org/10.1038/s41575-024-00893-5 DOI: https://doi.org/10.1038/s41575-024-00893-5
- Zhou X, Qiao K, Wu H, Zhang Y. The impact of food additives on the abundance and composition of gut microbiota. Molecules. 2023;28(2):631. https://doi.org/10.3390/molecules28020631 DOI: https://doi.org/10.3390/molecules28020631
- Seto T, Grondin JA, Khan WI. Food additives: emerging detrimental roles on gut health. FASEB J. 2025;39(13):e70810. https://doi.org/10.1096/fj.202500737R DOI: https://doi.org/10.1096/fj.202500737R
- Faizan MA, Khalid I, Yeo A, et al. Necrotising enterocolitis biomarkers: a systematic review. Front Pediatr. 2026;13:1652566. https://doi.org/10.3389/fped.2025.1652566 DOI: https://doi.org/10.3389/fped.2025.1652566
- Liu A, Liang T, Zhang R, et al. Predictive value of biomarkers in neonatal necrotizing enterocolitis. Front Pediatr. 2025;13:1661371. https://doi.org/10.3389/fped.2025.1661371 DOI: https://doi.org/10.3389/fped.2025.1661371
- N Kukaev E, Tokareva AO, Krogh-Jensen OA, Lenyushkina AA, Starodubtseva NL. Gut microbiota and short-chain fatty acids in the pathogenesis of necrotizing enterocolitis in very preterm infants. Acta Naturae. 2025;17(4):38-51. https://doi.org/10.32607/actanaturae.27623 DOI: https://doi.org/10.32607/actanaturae.27623
- Niño DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat Rev Gastroenterol Hepatol. 2016;13(10):590-600. https://doi.org/10.1038/nrgastro.2016.119 DOI: https://doi.org/10.1038/nrgastro.2016.119
- Murphy K, Ross RP, Ryan CA, Dempsey EM, Stanton C. Probiotics, prebiotics, and synbiotics for the prevention of necrotizing enterocolitis. Front Nutr. 2021;8:667188. https://doi.org/10.3389/fnut.2021.667188 DOI: https://doi.org/10.3389/fnut.2021.667188
- Han X, Hou Y, Chen T, et al. The glutamine metabolic switch influences the response of neonatal intestinal macrophages to breast milk. Cell Mol Gastroenterol Hepatol. 2026;20(3):101683. https://doi.org/10.1016/j.jcmgh.2025.101683 DOI: https://doi.org/10.1016/j.jcmgh.2025.101683
- Rizzi M, Manzoni P, Germano C, Quevedo MF, Sainaghi PP. Lactoferrin, a natural protein with multiple functions in health and disease. Nutrients. 2025;17(21):3403. https://doi.org/10.3390/nu17213403 DOI: https://doi.org/10.3390/nu17213403
- Gosa MM, Corkins MR. Necrotizing enterocolitis and the use of thickened liquids for infants with dysphagia. Perspectives on Swallowing and Swallowing Disorders (Dysphagia). 2015;24(2):44-49. https://doi.org/10.1044/sasd24.2.44 DOI: https://doi.org/10.1044/sasd24.2.44
- Beal J, Silverman B, Bellant J, Young TE, Klontz K. Late onset necrotizing enterocolitis in infants following use of a xanthan gum-containing thickening agent. J Pediatr. 2012;161(2):354-6. https://doi.org/10.1016/j.jpeds.2012.03.054 DOI: https://doi.org/10.1016/j.jpeds.2012.03.054
- Abdulezer A, Mooney P, Besner ME, et al. Xanthan- and rice cereal-based thickeners in infants: a multidisciplinary single-center experience. JPGN Rep. 2022;3(2):e190. https://doi.org/10.1097/PG9.0000000000000190 DOI: https://doi.org/10.1097/PG9.0000000000000190
- Henderickx JGE, Zwittink RD, Renes IB, et al. Maturation of the preterm gastrointestinal tract can be defined by host and microbial markers for digestion and barrier defense. Sci Rep. 2021;11(1):12808. https://doi.org/10.1038/s41598-021-92222-y DOI: https://doi.org/10.1038/s41598-021-92222-y
- Neu J. Gastrointestinal development and meeting the nutritional needs of premature infants. Am J Clin Nutr. 2007;85(2):629S-634S. https://doi.org/10.1093/ajcn/85.2.629S DOI: https://doi.org/10.1093/ajcn/85.2.629S
- Halpern MD, Denning PW. The role of intestinal epithelial barrier function in the development of NEC. Tissue Barriers. 2015;3(1-2):e1000707. https://doi.org/10.1080/21688370.2014.1000707 DOI: https://doi.org/10.1080/21688370.2014.1000707
- Ling X, Linglong P, Weixia D, Hong W. Protective effects of bifidobacterium on intestinal barrier function in LPS-induced enterocyte barrier injury of Caco-2 monolayers and in a rat NEC model. PLoS One. 2016;11(8):e0161635. https://doi.org/10.1371/journal.pone.0161635 DOI: https://doi.org/10.1371/journal.pone.0161635
- Unger S, Stintzi A, Shah P, Mack D, O’Connor DL. Gut microbiota of the very-low-birth-weight infant. Pediatr Res. 2015;77(1-2):205-13. https://doi.org/10.1038/pr.2014.162 DOI: https://doi.org/10.1038/pr.2014.162
- Lin J. Too much short chain fatty acids cause neonatal necrotizing enterocolitis. Med Hypotheses. 2004;62(2):291-3. https://doi.org/10.1016/S0306-9877(03)00333-5 DOI: https://doi.org/10.1016/S0306-9877(03)00333-5
- Waligora-Dupriet AJ, Dugay A, Auzeil N, Huerre M, Butel MJ. Evidence for clostridial implication in necrotizing enterocolitis through bacterial fermentation in a gnotobiotic quail model. Pediatr Res. 2005;58(4):629-35. https://doi.org/10.1203/01.PDR.0000180538.13142.84 DOI: https://doi.org/10.1203/01.PDR.0000180538.13142.84
- Waligora-Dupriet AJ, Dugay A, Auzeil N, et al. Short-chain fatty acids and polyamines in the pathogenesis of necrotizing enterocolitis: kinetics aspects in gnotobiotic quails. Anaerobe. 2009;15(4):138-44. https://doi.org/10.1016/j.anaerobe.2009.02.001 DOI: https://doi.org/10.1016/j.anaerobe.2009.02.001
- Yu W, Venkatraman A, Menden HL, Martinez M, Umar S, Sampath V. Short-chain fatty acids ameliorate necrotizing enterocolitis-like intestinal injury through enhancing Notch1-mediated single immunoglobulin interleukin-1-related receptor, toll-interacting protein, and A20 induction. Am J Physiol Gastrointest Liver Physiol. 2023;324(1):G24-G37. https://doi.org/10.1152/ajpgi.00057.2022 DOI: https://doi.org/10.1152/ajpgi.00057.2022
- He Y, Du W, Xiao S, et al. Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells. J Transl Med. 2021;19(1):510. https://doi.org/10.1186/s12967-021-03109-5 DOI: https://doi.org/10.1186/s12967-021-03109-5
- Liu XC, Du TT, Gao X, et al. Gut microbiota and short-chain fatty acids may be new biomarkers for predicting neonatal necrotizing enterocolitis: a pilot study. Front Microbiol. 2022;13:969656. https://doi.org/10.3389/fmicb.2022.969656 DOI: https://doi.org/10.3389/fmicb.2022.969656
- U.S. Food and Drug Administration. Xanthan gum. 21 CFR 172.695. Washington (DC): Office of the Federal Register. Available at: https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-172/subpart-G/section-172.695 (Acceseed on Aug 30, 2026).
- Camesano TA, Wilkinson KJ. Single molecule study of xanthan conformation using atomic force microscopy. Biomacromolecules. 2001;2(4):1184-91. https://doi.org/10.1021/bm015555g DOI: https://doi.org/10.1021/bm015555g
- Zhong L, Oostrom M, Truex MJ, Vermeul VR, Szecsody JE. Rheological behavior of xanthan gum solution related to shear thinning fluid delivery for subsurface remediation. J Hazard Mater. 2013;244-245:160-70. https://doi.org/10.1016/j.jhazmat.2012.11.028 DOI: https://doi.org/10.1016/j.jhazmat.2012.11.028
- Junyaprasert VB, Manwiwattanakul G. Release profile comparison and stability of diltiazem-resin microcapsules in sustained release suspensions. Int J Pharm. 2008;352(1-2):81-91. https://doi.org/10.1016/j.ijpharm.2007.10.018 DOI: https://doi.org/10.1016/j.ijpharm.2007.10.018
- Salyers AA, Vercellotti JR, West SE, Wilkins TD. Fermentation of mucin and plant polysaccharides by strains of Bacteroides from the human colon. Appl Environ Microbiol. 1977;33(2):319-22. https://doi.org/10.1128/aem.33.2.319-322.1977 DOI: https://doi.org/10.1128/aem.33.2.319-322.1977
- Daly J, Tomlin J, Read NW. The effect of feeding xanthan gum on colonic function in man: correlation with in vitro determinants of bacterial breakdown. Br J Nutr. 1993;69(3):897-902. https://doi.org/10.1079/bjn19930089 DOI: https://doi.org/10.1079/BJN19930089
- Berman L, Moss RL. Necrotizing enterocolitis: an update. Semin Fetal Neonatal Med. 2011;16(3):145-50. https://doi.org/10.1016/j.siny.2011.02.002 DOI: https://doi.org/10.1016/j.siny.2011.02.002
- Woods CW, Oliver T, Lewis K, Yang Q. Development of necrotizing enterocolitis in premature infants receiving thickened feeds using SimplyThick®. J Perinatol. 2012;32(2):150-2. https://doi.org/10.1038/jp.2011.105 DOI: https://doi.org/10.1038/jp.2011.105
- Spaargaren E. Clinical characteristics and prevalence of necrotizing enterocolitis among infants with dysphagia using SimplyThick [Master’s thesis]. Boston: Boston University; 2017. Available at: https://hdl.handle.net/2144/23722
- Yoon SN, Yoo B. Rheological behaviors of thickened infant formula prepared with xanthan gum-based food thickeners for dysphagic infants. Dysphagia. 2017;32(3):454-462. https://doi.org/10.1007/s00455-017-9786-2 DOI: https://doi.org/10.1007/s00455-017-9786-2
- Panigrahi P. Probiotics and prebiotics in neonatal necrotizing enterocolitis: New opportunities for translational research. Pathophysiology. 2014;21(1):35-46. https://doi.org/10.1016/j.pathophys.2013.11.016 DOI: https://doi.org/10.1016/j.pathophys.2013.11.016
- Sun X, Zhao C, Hu X, et al. Body weight regulation of a low molecular weight xanthan gum on normal mice via gut microbiota. J Funct Foods. 2022;88:104874. https://doi.org/10.1016/j.jff.2021.104874 DOI: https://doi.org/10.1016/j.jff.2021.104874
- Alsharairi NA. Therapeutic potential of gut microbiota and its metabolite short-chain fatty acids in neonatal necrotizing enterocolitis. Life (Basel). 2023;13(2):561. https://doi.org/10.3390/life13020561 DOI: https://doi.org/10.3390/life13020561
- Lin J, Nafday SM, Chauvin SN, et al. Variable effects of short chain fatty acids and lactic acid in inducing intestinal mucosal injury in newborn rats. J Pediatr Gastroenterol Nutr. 2002;35(4):545-50. https://doi.org/10.1097/00005176-200210000-00016 DOI: https://doi.org/10.1002/j.1536-4801.2002.tb07883.x
- Levrat-Verny MA, Behr S, Mustad V, Rémésy C, Demigné C. Low levels of viscous hydrocolloids lower plasma cholesterol in rats primarily by impairing cholesterol absorption. J Nutr. 2000;130(2):243-8. https://doi.org/10.1093/jn/130.2.243 DOI: https://doi.org/10.1093/jn/130.2.243
- Patel J, Maji B, Moorthy NSHN, Maiti S. Xanthan gum derivatives: review of synthesis, properties and diverse applications. RSC Adv. 2020;10(45):27103-27136. https://doi.org/10.1039/d0ra04366d DOI: https://doi.org/10.1039/D0RA04366D
- Trout DL, Ryan RO, Bickard MC. The amount and distribution of water, dry matter, and sugars in the digestive tract of rats fed xanthan gum. Proc Soc Exp Biol Med. 1983;172(3):340-5. https://doi.org/10.3181/00379727-172-41567 DOI: https://doi.org/10.3181/00379727-172-41567
- Li J, Han G, Ma M, et al. Xanthan gum ameliorates osteoarthritis and mitigates cartilage degradation via regulation of the wnt3a/β-catenin signaling pathway. Med Sci Monit. 2019;25:7488-7498. https://doi.org/10.12659/MSM.916092 DOI: https://doi.org/10.12659/MSM.916092
- Rosen R, Vandenplas Y, Singendonk M, et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2018;66(3):516-554. https://doi.org/10.1097/MPG.0000000000001889 DOI: https://doi.org/10.1097/MPG.0000000000001889
- Liu F, Zhang X, Ling P, et al. Immunomodulatory effects of xanthan gum in LPS-stimulated RAW 264.7 macrophages. Carbohydr Polym. 2017;169:65-74. https://doi.org/10.1016/j.carbpol.2017.04.003 DOI: https://doi.org/10.1016/j.carbpol.2017.04.003
- Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2009;49(4):498-547. https://doi.org/10.1097/MPG.0b013e3181b7f563 DOI: https://doi.org/10.1097/MPG.0b013e3181b7f563
- U.S. Food and Drug Administration. FDA Warns Not to Feed SimplyThick to Premature Infants. 2011. Available at: https://stacks.cdc.gov/view/cdc/25230
- Joint FAO/WHO Expert Committee on Food Additives. Evaluation of certain food additives: eighty-second report of the Joint FAO/WHO Expert Committee on Food Additives. WHO Technical Report Series, No. 1000. Geneva: World Health Organization; 2016. Available at: https://www.who.int/publications/i/item/9789241210003
- EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS); Mortensen A, Aguilar F, et al. Re-evaluation of xanthan gum (E 415) as a food additive. EFSA J. 2017;15(7):e04909. https://doi.org/10.2903/j.efsa.2017.4909 DOI: https://doi.org/10.2903/j.efsa.2017.4909
- EFSA Panel on Food Additives and Flavourings (FAF); Younes M, Aquilina G, et al. Re-evaluation of xanthan gum (E 415) as a food additive in foods for infants below 16 weeks of age and follow-up of its re-evaluation as a food additive for uses in foods for all population groups. EFSA J. 2023;21(5):e07951. https://doi.org/10.2903/j.efsa.2023.7951 DOI: https://doi.org/10.2903/j.efsa.2023.7951
