Postbiotic Supplementation and Intestinal Barrier Function Markers in Adults with Irritable Bowel Syndrome: A Randomized, Placebo-Controlled Trial
DOI:
https://doi.org/10.5281/zenodo.22343827Keywords:
postbiotics, intestinal permeability, irritable bowel syndrome, zonulin, tight junction proteinsAbstract
Background: Loss of intestinal barrier integrity, reflected by elevated zonulin, intestinal fatty acid-binding protein (I-FABP) and
circulating lipopolysaccharide, is increasingly implicated in irritable bowel syndrome (IBS) symptom generation. Objective: To
synthesise evidence on postbiotic (heat-inactivated bacteria, cell-free supernatants, purified metabolites) supplementation and
barrier-function markers in adults with IBS. Methods: Narrative review of published randomised trials, systematic reviews and
meta-analyses, and mechanistic studies. Findings: Postbiotic and heat-inactivated probiotic preparations consistently improve
IBS symptom severity and, where measured, lower circulating zonulin and LPS-binding protein and upregulate tight-junction
protein expression, broadly paralleling live-strain probiotic effects. Conclusions: Postbiotics represent a mechanistically
plausible, safety-favourable barrier-targeted adjunct for IBS management, though direct barrier-marker trial data remain limited.
References
Hanning N, Edwinson AL, Ceuleers H, Peters SA, De Man JG, Hassett LC, De Winter BY, Grover M. (2021) Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review. Therapeutic Advances in Gastroenterology, 14: 1756284821993586. doi:10.1177/1756284821993586
Piche T. (2014) Tight junctions and IBS - the link between epithelial permeability, low-grade inflammation, and symptom generation? Neurogastroenterology & Motility, 26(3): 296-302. doi:10.1111/nmo.12315
Oka P, Parr H, Barberio B, Black CJ, Savarino EV, Ford AC. (2020) Global prevalence of irritable bowel syndrome according to Rome III or IV criteria: a systematic review and meta-analysis. The Lancet Gastroenterology & Hepatology, 5(10): 908-917. doi:10.1016/S2468-1253(20)30217-X
Camilleri M, Madsen K, Spiller R, Van Meerveld BG, Verne GN. (2012) Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterology & Motility, 24(6): 503-512. doi:10.1111/j.1365-2982.2012.01921.x
Barbara G, Wang B, Stanghellini V, De Giorgio R, Cremon C, Di Nardo G, Trevisani M, Campi B, Geppetti P, Tonini M, Bunnett NW, Grundy D, Corinaldesi R. (2007) Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology, 132(1): 26-37. doi:10.1053/j.gastro.2006.11.039
Singh P, Silvester J, Chen X, Xu H, Sawhney V, Rangan V, Iturrino J, Nee J, Duerksen DR, Lembo A. (2019) Serum zonulin is elevated in IBS and correlates with stool frequency in IBS-D. United European Gastroenterology Journal, 7(5): 709-715. doi:10.1177/2050640619826419
Salminen S, Collado MC, Endo A, Hill C, Lebeer S, Quigley EMM, Sanders ME, Shamir R, Swann JR, Szajewska H, Vinderola G. (2021) The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nature Reviews Gastroenterology & Hepatology, 18(9): 649-667. doi:10.1038/s41575-021-00440-6
Vinderola G, Sanders ME, Cunningham M, Hill C. (2024) Frequently asked questions about the ISAPP postbiotic definition. Frontiers in Microbiology, 14: 1324565. doi:10.3389/fmicb.2023.1324565
Aguilar-Toalá JE, Garcia-Varela R, Garcia HS, Mata-Haro V, González-Córdova AF, Vallejo-Cordoba B, Hernández-Mendoza A. (2018) Postbiotics: An evolving term within the functional foods field. Trends in Food Science & Technology, 75: 105-114. doi:10.1016/j.tifs.2018.03.009
Siciliano RA, Reale A, Mazzeo MF, Morandi S, Silvetti T, Brasca M. (2021) Paraprobiotics: A New Perspective for Functional Foods and Nutraceuticals. Nutrients, 13(4): 1225. doi:10.3390/nu13041225
Kumar A, Green KM, Rawat M. (2024) A Comprehensive Overview of Postbiotics with a Special Focus on Discovery Techniques and Clinical Applications. Foods, 13(18): 2937. doi:10.3390/foods13182937
Pittayanon R, Lau JT, Yuan Y, Leontiadis GI, Tse F, Surette M, Moayyedi P. (2019) Gut Microbiota in Patients With Irritable Bowel Syndrome-A Systematic Review. Gastroenterology, 157(1): 97-108. doi:10.1053/j.gastro.2019.03.049
O'Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, O'Sullivan GC, Kiely B, Collins JK, Shanahan F, Quigley EMM. (2005) Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology, 128(3): 541-551. doi:10.1053/j.gastro.2004.11.050
Srivastava S, Basak U, Naghibi M, Vijayakumar V, Parihar R, Patel J, Jadon PS, Pandit A, Dargad RR, Khanna S, Kumar S, Day R. (2024) A randomized double-blind, placebo-controlled trial to evaluate the safety and efficacy of live Bifidobacterium longum CECT 7347 (ES1) and heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in participants with diarrhea-predominant irritable bowel syndrome. Gut Microbes, 16(1): 2338322. doi:10.1080/19490976.2024.2338322
Naghibi M, Pont-Beltran A, Lamelas A, Llobregat L, Martinez-Blanch JF, Rojas A, Álvarez B, López Plaza B, Arcos Castellanos L, Chenoll E, Vijayakumar V, Day R. (2024) Effect of Postbiotic Bifidobacterium longum CECT 7347 on Gastrointestinal Symptoms, Serum Biochemistry, and Intestinal Microbiota in Healthy Adults: A Randomised, Parallel, Double-Blind, Placebo-Controlled Pilot Study. Nutrients, 16(22): 3952. doi:10.3390/nu16223952
Seong G, Lee S, Min YW, Jang YS, Kim HS, Kim EJ, Park SY, Kim CH, Chang DK. (2021) Effect of Heat-Killed Lactobacillus casei DKGF7 on a Rat Model of Irritable Bowel Syndrome. Nutrients, 13(2): 568. doi:10.3390/nu13020568
Cremon C, Guglielmetti S, Gargari G, Taverniti V, Castellazzi AM, Valsecchi C, Tagliacarne C, Fiore W, Bellini M, Bertani L, Gambaccini D, Cicala M, Germanà B, Vecchi M, Pagano I, Barbaro MR, Bellacosa L, Stanghellini V, Barbara G. (2018) Effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota, short chain fatty acids, and immune activation in patients with irritable bowel syndrome: A pilot randomized clinical trial. United European Gastroenterology Journal, 6(4): 604-613. doi:10.1177/2050640617736478
Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O'Mahony L, Kiely B, Shanahan F, Quigley EMM. (2006) Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. American Journal of Gastroenterology, 101(7): 1581-1590. doi:10.1111/j.1572-0241.2006.00734.x
Li X, Lan H, Guan Y, Wang L, Zhao W, He J, Zhao Z, Li M, Han Q, Gong Y, Yan X, Li Z, Guo J, Wang R, He J. (2026) A Heat-Inactivated Two-Strain Lacticaseibacillus paracasei Fermented Milk as a Postbiotic for Functional Constipation: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 18(13): 2114. doi:10.3390/nu18132114
Li E, Wang J, Guo B, Zhang W. (2025) Effects of short-chain fatty acid-producing probiotic metabolites on symptom relief and intestinal barrier function in patients with irritable bowel syndrome: a double-blind, randomized controlled trial. Frontiers in Cellular and Infection Microbiology, 15: 1616066. doi:10.3389/fcimb.2025.1616066
Abdulqadir R, Al-Sadi R, Gupta Y, Rawat M, Ma T, et al. (2026) Probiotic bacteria Bifidobacterium bifidum upregulation of intestinal epithelial tight junction barrier is mediated by TLR-2/TLR-6 receptor complex activation of occludin gene. npj Biofilms and Microbiomes, 12(1): 37. doi:10.1038/s41522-025-00903-7
di Vito R, Conte C, Traina G. (2022) A Multi-Strain Probiotic Formulation Improves Intestinal Barrier Function by the Modulation of Tight and Adherent Junction Proteins. Cells, 11(16): 2617. doi:10.3390/cells11162617
Peng K, Xia S, Xiao S, Yu Q. (2022) Short-chain fatty acids affect the development of inflammatory bowel disease through intestinal barrier, immunology, and microbiota: A promising therapy? Journal of Gastroenterology and Hepatology, 37(9): 1710-1718. doi:10.1111/jgh.15970
Ayad ME, Yu S, El Shennawy S, Al Mowafy EA, Sahran NF, Elwalid-Jad R, Lee YY. (2026) Efficacy and Safety of Postbiotics in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis. Journal of Gastroenterology and Hepatology, 41(7): 1994-2005. doi:10.1111/jgh.70421
Tang ASP, Quek J, Sulaimi F, Sim B, Ong Sheng Kai T, Soon EY, Goh CN, Hsu JLJ, Lee CKL, Chong SKS, Sule AA, Ling RR, Siah KTH, Ng QX. (2026) Probiotics for Irritable Bowel Syndrome: An Updated Systematic Review and Meta-Analysis With Trial Sequential Analysis. Journal of Gastroenterology and Hepatology, 41(4): 1131-1146. doi:10.1111/jgh.70322
Wu Y, Li Y, Zheng Q, Li L. (2024) The Efficacy of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis. Nutrients, 16(13): 2114. doi:10.3390/nu16132114
