Ulcerative colitis (UC) is presently considered a multifactorial pathology, which may lead to persistent inflammatory action of the gastrointestinal tract (GIT) because of an improperly managed immunological reactivity to the intestinal microbiota found in the GIT. The immune response to common commensal microbes plays an essential role in intestinal inflammation related to UC synbiotics, and it is an important element in the optimal therapy of UC. Therefore, synbiotics, i.e., a mixture of prebiotics and probiotics, may help control the diseased state. Synbiotics alleviate the inflammation of the colon by lowering the reactive oxygen species (ROS) and improving the level of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Prebiotic supplementation is not a common practice at the moment, despite numerous research findings proving that the benefits of both probiotics and prebiotics encourage their continued existence and positioning in the GIT, with positive effects on human health by managing the inflammatory response. However, the fact that there have been fewer studies on the treatment of UC with different probiotics coupled with selected prebiotics, i.e., synbiotics, and the outcomes of these studies have been very favorable. This evidence-based study explores the possible role of ROS, SOD, and synbiotics in managing the UC. The proposed review also focuses on the role of alteration of gut microbiota, antioxidant defense in the gastrointestinal tract, and the management of UC. Thus, the current article emphasizes oxidative stress signaling in the GI tract, oxidative stress-based pathomechanisms in UC patients, and UC therapies inhibiting oxidative stress' effects.

Amity Institute of Pharmacy Amity University Madhya Pradesh Gwalior India

Department of Applied Physics Aalto University Espoo Finland

Department of Biomedical Science Faculty of Science Universiti Tunku Abdul Rahman Kampar Malaysia

Department of Biotechnology Graphic Era Deemed to be University Dehradun India

Department of Biotechnology Sharda School of Engineering and Technology Sharda University Greater Noida India

Department of Life Science and Bioinformatics Assam University Silchar India

Department of Life Sciences Sharda School of Basic Sciences and Research Sharda University Greater Noida India

Department of Medical Lab Sciences Prince Sattam Bin Abdulaziz University Al Kharj Saudi Arabia

Department of P G Studies and Research in Chemistry and Pharmacy Rani Durgavati University Jabalpur India

Department of Pharmaceutics Guru Ramdas Institute of Science and Technology Jabalpur India

Department of Pharmaceutics Pandaveswar School of Pharmacy Pandaveswar West Bengal India

Faculty of Health and Life Sciences INTI International University Nilai Malaysia

Health Centre Assam University Silchar India

Laboratory of Animal Immunology and Biotechnology Department of Animal Morphology Physiology and Genetics Faculty of AgriSciences Mendel University in Brno Brno Czechia

See more in PubMed

Adams SM, Close ED, Shreenath AP. Ulcerative colitis: rapid evidence review. Am Fam Physician. (2022) 105:406–11. PMID: PubMed

Zou J, Liu C, Jiang S, Qian D, Duan J. Cross talk between gut microbiota and intestinal mucosal immunity in the development of ulcerative colitis. Infect Immun. (2021) 89:e0001421. doi: 10.1128/IAI.00014-21, PMID: PubMed DOI PMC

Ratajczak W, Rył A, Mizerski A, Walczakiewicz K, Sipak O, Laszczyńska M. Immunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs). Acta Biochim Pol. (2019) 66:1–2. doi: 10.18388/abp.2018_2648, PMID: PubMed DOI

Le Berre C, Ananthakrishnan AN, Danese S, Singh S, Peyrin-Biroulet L. Ulcerative colitis and Crohn’s disease have similar burden and goals for treatment. Clin Gastroenterol Hepatol. (2020) 18:14–23. doi: 10.1016/j.cgh.2019.07.005, PMID: PubMed DOI

Jeruc J. Histomorphological Diagnosis of ulcerative colitis and associated conditions In: Ulcerative colitis–Etiology, Diagnosis, Diet, Special Populations, and The Role Of Interventional Endoscopy. ed. Pal P. (IntechOpen). (2022).

Noviello D, Mager R, Roda G, Borroni RG, Fiorino G, Vetrano S. The IL23-IL17 immune Axis in the treatment of ulcerative colitis: successes, defeats, and ongoing challenges. Front Immunol. (2021) 12:611256. doi: 10.3389/fimmu.2021.611256, PMID: PubMed DOI PMC

Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet (London, England). (2012) 380:1606–19. doi: 10.1016/S0140-6736(12)60150-0 PubMed DOI

Ahmed J, Reddy BS, Mølbak L, Leser TD, MacFie J. Impact of probiotics on colonic microflora in patients with colitis: a prospective double blind randomised crossover study. Int J Surg. (2013) 11:1131–6. doi: 10.1016/j.ijsu.2013.08.019, PMID: PubMed DOI

Hansen J, Gulati A, Sartor RB. The role of mucosal immunity and host genetics in defining intestinal commensal bacteria. Curr Opin Gastroenterol. (2010) 26:564–71. doi: 10.1097/MOG.0b013e32833f1195, PMID: PubMed DOI PMC

Andoh A, Imaeda H, Aomatsu T, Inatomi O, Bamba S, Sasaki M, et al. Comparison of the fecal microbiota profiles between ulcerative colitis and Crohn’s disease using terminal restriction fragment length polymorphism analysis. J Gastroenterol. (2011) 46:479–86. doi: 10.1007/s00535-010-0368-4, PMID: PubMed DOI

Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. (2007) 104:13780–5. doi: 10.1073/pnas.0706625104, PMID: PubMed DOI PMC

Santana PT, Rosas SLB, Ribeiro BE, Marinho Y, de Souza HSP. Dysbiosis in inflammatory bowel disease: pathogenic role and potential therapeutic targets. Int J Mol Sci. (2022) 23:3464. doi: 10.3390/ijms23073464, PMID: PubMed DOI PMC

Udayakumar S, Rasika DMD, Priyashantha H, Vidanarachchi JK, Ranadheera CS. Probiotics and beneficial microorganisms in biopreservation of plant-based foods and beverages. Appl Sci. (2022) 12:11737. doi: 10.3390/app122211737 DOI

Bhatt A, Kothari D, Kothari C, Kothari R. Probiotic: An uprising human health concept. Prebiotics and Probiotics-From Food to Health. ed. Robles EF. Intech (2022) 1–20.

Li X, Wang Q, Hu X, Liu W. Current status of probiotics as supplements in the prevention and treatment of infectious diseases. Front Cell Infect Microbiol. (2022) 12:789063. doi: 10.3389/fcimb.2022.789063, PMID: PubMed DOI PMC

Cunningham M, Vinderola G, Charalampopoulos D, Lebeer S, Ellen SM, Grimaldi R. Applying probiotics and prebiotics in new delivery formats – is the clinical evidence transferable? Trends Food Sci Technol. (2021) 112:495–506. doi: 10.1016/j.tifs.2021.04.009 DOI

Hizay A, Keles Celik N, Department of Anatomy, Akdeniz University Faculty of Medicine, Antalya, Turkey. Acar N, Department of Histology and Embryology, Akdeniz University Faculty of Medicine, Antalya, Turkey. Comak Gocer EM, et al. Probiotics in experimental ulcerative colitis: mast cell density and neuronal hypertrophy. Turk J Gastroenterol. (2022) 33:822–30. doi: 10.5152/tjg.2022.21550, PMID: PubMed DOI PMC

Wu Y, Jha R, Li A, Liu H, Zhang Z, Zhang C, et al. Probiotics ( PubMed DOI PMC

Zhao H, du Y, Liu L, du Y, Cui K, Yu P, et al. Oral nanozyme-engineered probiotics for the treatment of ulcerative colitis. J Mater Chem B. (2022) 10:4002–11. doi: 10.1039/d2tb00300g, PMID: PubMed DOI

Štofilová J, Kvaková M, Kamlárová A, Hijová E, Bertková I, Guľašová Z. Probiotic-based intervention in the treatment of ulcerative colitis: conventional and new approaches. Biomedicine. (2022) 10:2236. doi: 10.3390/biomedicines10092236, PMID: PubMed DOI PMC

Liu Y, Wang J, Wu C. Modulation of gut microbiota and immune system by probiotics, pre-biotics, and post-biotics. Front Nutr. (2022) 8:634897. doi: 10.3389/fnut.2021.634897, PMID: PubMed DOI PMC

Rufino MN, da Costa AL, Jorge EN, Paiano VF, Camparoto ML, Keller R, et al. Synbiotics improve clinical indicators of ulcerative colitis: systematic review with meta-analysis. Nutr Rev. (2022) 80:157–64. doi: 10.1093/nutrit/nuab017, PMID: PubMed DOI

Martyniak A, Medyńska-Przęczek A, Wędrychowicz A, Skoczeń S, Tomasik PJ. Prebiotics, probiotics, Synbiotics, Paraprobiotics and Postbiotic compounds in IBD. Biomol Ther. (2021) 11:1903. doi: 10.3390/biom11121903, PMID: PubMed DOI PMC

Bhattacharya S. Probiotics and herbals as a boom in treatment of ulcerative colitis. Asian J Pharmaceutics (AJP). (2020) 14:301–7. doi: 10.22377/ajp.v14i2.3627 DOI

Zhang Z, Zhang H, Chen T, Shi L, Wang D, Tang D. Regulatory role of short-chain fatty acids in inflammatory bowel disease. Cell Commun Signal. (2022) 20:64. doi: 10.1186/s12964-022-00869-5, PMID: PubMed DOI PMC

Deleu S, Machiels K, Raes J, Verbeke K, Vermeire S. Short chain fatty acids and its producing organisms: An overlooked therapy for IBD? EBioMedicine. (2021) 66:103293. doi: 10.1016/j.ebiom.2021.103293, PMID: PubMed DOI PMC

Biswas V, Praveen A, Marisetti AL, Sharma A, Kumar V, Sahu SK, et al. A mechanistic overview on impact of dietary Fibres on gut microbiota and its association with Colon Cancer. Dietetics. (2022) 1:182–202. doi: 10.3390/dietetics1030017 DOI

Taku K, Britta S, Chen WS, Ferrante M, Shen B, Bernstein CN, et al. Ulcerative colitis (primer). Nat Rev Dis Primers. (2020) 6:74. doi: 10.1038/s41572-020-0205-x PubMed DOI

Shen ZH, Zhu CX, Quan YS, Yang ZY, Wu S, Luo WW, et al. Relationship between intestinal microbiota and ulcerative colitis: mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J Gastroenterol. (2018) 24:5–14. doi: 10.3748/wjg.v24.i1.5, PMID: PubMed DOI PMC

Chen DL, Dai YC, Zheng L, Chen YL, Zhang YL, Tang ZP. Features of the gut microbiota in ulcerative colitis patients with depression: a pilot study. Medicine (Baltimore). (2021) 100:e24845. doi: 10.1097/MD.0000000000024845, PMID: PubMed DOI PMC

Hu Y, Chen Z, Xu C, Kan S, Chen D. Disturbances of the gut microbiota and microbiota-derived metabolites in inflammatory bowel disease. Nutrients. (2022) 14:5140. doi: 10.3390/nu14235140, PMID: PubMed DOI PMC

Zhang Y, Si X, Yang L, Wang H, Sun Y, Liu N. Association between intestinal microbiota and inflammatory bowel disease. Animal Model Exp Med. (2022) 5:311–22. doi: 10.1002/ame2.12255, PMID: PubMed DOI PMC

Xu P, Lv T, Dong S, Cui Z, Luo X, Jia B, et al. Association between intestinal microbiome and inflammatory bowel disease: insights from bibliometric analysis. Comput Struct Biotechnol J. (2022) 20:1716–25. doi: 10.1016/j.csbj.2022.04.006, PMID: PubMed DOI PMC

Martemucci G, Costagliola C, Mariano M, D’andrea L, Napolitano P, D’Alessandro AG. Free radical properties, source and targets. Antioxidant Consumption and Health Oxygen. (2022) 2:48–78. doi: 10.3390/oxygen2020006 DOI

Juan CA, Pérez de la Lastra JM, Plou FJ, Pérez-Lebeña E. The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int J Mol Sci. (2021) 22:4642. doi: 10.3390/ijms22094642, PMID: PubMed DOI PMC

Nakase H, Sato N, Mizuno N, Ikawa Y. The influence of cytokines on the complex pathology of ulcerative colitis. Autoimmun Rev. (2022) 21:103017. doi: 10.1016/j.autrev.2021.103017, PMID: PubMed DOI

Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. (2020) 21:363–83. doi: 10.1038/s41580-020-0230-3, PMID: PubMed DOI

Checa J, Aran JM. Reactive oxygen species: drivers of physiological and pathological processes. J Inflamm Res. (2020) 13:1057–73. doi: 10.2147/JIR.S275595 PubMed DOI PMC

Sharifi-Rad M, Anil Kumar NV, Zucca P, Varoni EM, Dini L, Panzarini E, et al. Lifestyle, oxidative stress, and antioxidants: Back and forth in the pathophysiology of chronic diseases. Front Physiol. (2020) 11:694. doi: 10.3389/fphys.2020.00694, PMID: PubMed DOI PMC

Parada Venegas D, de la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases [published correction appears in front Immunol. 2019 Jun 28;10:1486]. Front Immunol. (2019) 10:277. doi: 10.3389/fimmu.2019.00277, PMID: PubMed DOI PMC

Wiertsema SP, van Bergenhenegouwen J, Garssen J, Knippels LMJ. The interplay between the gut microbiome and the immune system in the context of infectious diseases throughout life and the role of nutrition in optimizing treatment strategies. Nutrients. (2021) 13:886. doi: 10.3390/nu13030886, PMID: PubMed DOI PMC

Alshehri D, Saadah O, Mosli M, Edris S, Alhindi R, Bahieldin A. Dysbiosis of gut microbiota in inflammatory bowel disease: current therapies and potential for microbiota-modulating therapeutic approaches. Bosn J Basic Med Sci. (2021) 21:270–83. doi: 10.17305/bjbms.2020.5016, PMID: PubMed DOI PMC

Martins SG, Zilhão R, Thorsteinsdóttir S, Carlos AR. Linking oxidative stress and DNA damage to changes in the expression of extracellular matrix components. Front Genet. (2021) 12:673002. doi: 10.3389/fgene.2021.673002, PMID: PubMed DOI PMC

Lu Q, Yang MF, Liang YJ, Xu J, Xu HM, Nie YQ, et al. Immunology of inflammatory bowel disease: molecular mechanisms and therapeutics. J Inflamm Res. (2022) 15:1825–44. doi: 10.2147/JIR.S353038, PMID: PubMed DOI PMC

Arosa L, Camba-Gómez M, Conde-Aranda J. Neutrophils in intestinal inflammation: what we know and what we could expect for the near future. Gastrointest Disord. (2022) 4:263–76. doi: 10.3390/gidisord4040025 DOI

Osmakov DI, Kalinovskii AP, Belozerova OA, Andreev YA, Kozlov SA. Lignans as pharmacological agents in disorders related to oxidative stress and inflammation: chemical synthesis approaches and biological activities. Int J Mol Sci. (2022) 23:6031. doi: 10.3390/ijms23116031, PMID: PubMed DOI PMC

Prescott JA, Mitchell JP, Cook SJ. Inhibitory feedback control of NF-κB signalling in health and disease. Biochem J. (2021) 478:2619–64. doi: 10.1042/BCJ20210139, PMID: PubMed DOI PMC

Gargallo-Puyuelo CJ, Laredo V, Gomollón F. Thiopurines in inflammatory bowel disease. How to optimize Thiopurines in the biologic era? Front Med (Lausanne). (2021) 8:681907. doi: 10.3389/fmed.2021.681907, PMID: PubMed DOI PMC

Masnadi Shirazi K, Sotoudeh S, Masnadi Shirazi A, Moaddab SY, Nourpanah Z, Nikniaz Z. Effect of N-acetylcysteine on remission maintenance in patients with ulcerative colitis: a randomized, double-blind controlled clinical trial. Clin Res Hepatol Gastroenterol. (2021) 45:101532. doi: 10.1016/j.clinre.2020.08.010, PMID: PubMed DOI

Bjørndal B, Grimstad T, Cacabelos D, Nylund K, Aasprong OG, Omdal R, et al. Tetradecylthioacetic acid attenuates inflammation and has antioxidative potential during experimental colitis in rats. Dig Dis Sci. (2013) 58:97–106. doi: 10.1007/s10620-012-2321-2, PMID: PubMed DOI

Campregher C, Luciani MG, Biesenbach P, Evstatiev R, Lyakhovich A, Gasche C. The position of the amino group on the benzene ring is critical for mesalamine’s improvement of replication fidelity. Inflamm Bowel Dis. (2010) 16:576–82. doi: 10.1002/ibd.21112, PMID: PubMed DOI

Bruscoli S, Febo M, Riccardi C, Migliorati G. Glucocorticoid therapy in inflammatory bowel disease: mechanisms and clinical practice. Front Immunol. (2021) 12:691480. doi: 10.3389/fimmu.2021.691480, PMID: PubMed DOI PMC

Olsen T, Cui G, Goll R, Husebekk A, Florholmen J. Infliximab therapy decreases the levels of TNF-α and IFN-γ mRNA in the colonic mucosa of ulcerative colitis. Scand J Gastroenterol. (2009) 44:727–35. doi: 10.1080/00365520902803507, PMID: PubMed DOI

Feuerstein JD, Isaacs KL, Schneider Y, Siddique SM, Falck-Ytter Y, Singh S, et al. AGA clinical practice guidelines on the Management of Moderate to severe ulcerative colitis. Gastroenterology. (2020) 158:1450–61. doi: 10.1053/j.gastro.2020.01.006, PMID: PubMed DOI PMC

Leonel AJ, Teixeira LG, Oliveira RP, Santiago AF, Batista NV, Ferreira TR, et al. Antioxidative and immunomodulatory effects of tributyrin supplementation on experimental colitis. Br J Nutr. (2013) 109:1396–407. doi: 10.1017/S000711451200342X, PMID: PubMed DOI

Ota S, Sakuraba H. Uptake and advanced therapy of butyrate in inflammatory bowel disease. Immuno. (2022) 2:692–702. doi: 10.3390/immuno2040042 DOI

Hernández-Delgado NC, Torres-Maravilla E, Mayorga-Reyes L, Martín R, Langella P, Pérez-Pastén-Borja R, et al. Antioxidant and anti-inflammatory properties of probiotic candidate strains isolated during fermentation of Agave ( PubMed DOI PMC

Oniszczuk A, Oniszczuk T, Gancarz M, Szymańska J. Role of gut microbiota, probiotics and prebiotics in the cardiovascular diseases. Molecules. (2021) 26:1172. doi: 10.3390/molecules26041172, PMID: PubMed DOI PMC

Milner E, Stevens B, An M, Lam V, Ainsworth M, Dihle P, et al. Utilizing probiotics for the prevention and treatment of gastrointestinal diseases. Front Microbiol. (2021) 12:689958. doi: 10.3389/fmicb.2021.689958, PMID: PubMed DOI PMC

Huang X, Ai F, Ji C, Tu P, Gao Y, Wu Y, et al. A rapid screening method of candidate probiotics for inflammatory bowel diseases and the anti-inflammatory effect of the selected strain PubMed DOI PMC

Singh A, Negi D, Kaur S, Bhattachary S, Singh G. Fundamentals of Nanocarriers and probiotics in the treatment of cervical Cancer. Curr Nanomed (Formerly: Recent Patents on Nanomedicine). (2020) 10:342–57. doi: 10.2174/2468187310999201105143429 DOI

Singh A, Mandal UK, Narang RK. Development of cellulose acetate phthalate coated pectin microparticles loaded with mesalamine and Saccharomyces boulardii intended for specific colonic drug delivery. J Adv Sci Res. (2021) 12:225–35.

Singh A, Mandal UK, Narang RK. Development and characterization of enteric coated pectin pellets containing mesalamine and Saccharomyces boulardii for specific inflamed colon: in vitro and in vivo evaluation. J Drug Deliv Sci Technol. (2021) 62:102393. doi: 10.1016/j.jddst.2021.102393 DOI

Cristofori F, Dargenio VN, Dargenio C, Miniello VL, Barone M, Francavilla R. Anti-inflammatory and immunomodulatory effects of probiotics in gut inflammation: a door to the body. Front Immunol. (2021) 12:578386. doi: 10.3389/fimmu.2021.578386, PMID: PubMed DOI PMC

Hiraishi K, Zhao F, Kurahara L-H, Li X, Yamashita T, Hashimoto T, et al. Lactulose modulates the structure of gut microbiota and alleviates colitis-associated tumorigenesis. Nutrients. (2022) 14:649. doi: 10.3390/nu14030649, PMID: PubMed DOI PMC

Williams CJ, Torquati L, Li Z, Lea RA, Croci I, Keating E, et al. Oligofructose-enriched inulin intake, gut microbiome characteristics, and the V̇O2 peak response to high-intensity interval training in healthy inactive adults. J Nutr. (2022) 152:680–9. doi: 10.1093/jn/nxab426, PMID: PubMed DOI

Valcheva R., Armstrong H., Kovic O., Bording-Jorgensen M., Veniamin S., Pérez-Muñoz M. E., et al. Double blind placebo-controlled trial for the prevention of ulcerative colitis relapses by β-fructan prebiotics: Efficacy and metabolomic analysis. DOI

Valcheva R, Koleva P, Martínez I, Walter J, Gänzle MG, Dieleman LA. Inulin-type fructans improve active ulcerative colitis associated with microbiota changes and increased short-chain fatty acids levels. Gut Microbes. (2019) 10:334–57. doi: 10.1080/19490976.2018.1526583, PMID: PubMed DOI PMC

Derwa Y, Gracie DJ, Hamlin PJ, Ford AC. Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease. Aliment Pharmacol Ther. (2017) 46:389–400. doi: 10.1111/apt.14203, PMID: PubMed DOI

Méndez I, Audivert S, Farran-Codina A, Espadaler J. The efficacy of probiotics, prebiotic inulin-type fructans, and synbiotics in human ulcerative colitis: a systematic review and meta-analysis. Nutrients. (2019) 11:293. doi: 10.3390/nu11020293 PubMed DOI PMC

Shuang Yan S, Yan BY, Yang B, Ross RP, Ross RP, Stanton C, et al. DOI

Yao S, Zhao Z, Wang W, Liu X. PubMed DOI PMC

Aviello G, Knaus UG. R.O.S. in gastrointestinal inflammation: rescue or sabotage? Br J Pharmacol. (2017) 174:1704–18. doi: 10.1111/bph.13428, PMID: PubMed DOI PMC

Wan Y, Yang L, Jiang S, Qian D, Duan J. Excessive apoptosis in ulcerative colitis: crosstalk between apoptosis, ROS, ER stress, and intestinal homeostasis. Inflamm Bowel Dis. (2022) 28:639–48. doi: 10.1093/ibd/izab277, PMID: PubMed DOI

Tan C, Fan H, Ding J, Han C, Guan Y, Zhu F, et al. ROS-responsive nanoparticles for oral delivery of luteolin and targeted therapy of ulcerative colitis by regulating pathological microenvironment. Mater Today Bio. (2022) 14:100246. doi: 10.1016/j.mtbio.2022.100246, PMID: PubMed DOI PMC

Yang X, Mao Z, Huang Y, Yan H, Yan Q, Hong J, et al. Reductively modified albumin attenuates DSS-induced mouse colitis through rebalancing systemic redox state. Redox Biol. (2021) 41:101881. doi: 10.1016/j.redox.2021.101881, PMID: PubMed DOI PMC

Nguyen TT, Trinh NT, Tran HN, Tran HT, le PQ, Ngo DN, et al. Improving silymarin oral bioavailability using silica-installed redox nanoparticle to suppress inflammatory bowel disease. J Control Release. (2021) 331:515–24. doi: 10.1016/j.jconrel.2020.10.042, PMID: PubMed DOI

Plichta DR, Graham DB, Subramanian S, Xavier RJ. Therapeutic opportunities in inflammatory bowel disease: mechanistic dissection of host-microbiome relationships. Cells. (2019) 178:1041–56. doi: 10.1016/j.cell.2019.07.045, PMID: PubMed DOI PMC

Hirano T, Nakase H. The multifaceted effects of gut microbiota on the immune system of the intestinal mucosa. Immuno. (2021) 1:583–94. doi: 10.3390/immuno1040041 DOI

de Vos WM, Tilg H, van Hul M, Cani PD. Gut microbiome and health: mechanistic insights. Gut. (2022) 71:1020–32. doi: 10.1136/gutjnl-2021-326789, PMID: PubMed DOI PMC

Carstens A, Dicksved J, Nelson R, Lindqvist M, Andreasson A, Bohr J, et al. The gut microbiota in collagenous colitis shares characteristics with inflammatory bowel disease-associated Dysbiosis. Clin Transl Gastroenterol. (2019) 10:e00065. doi: 10.14309/ctg.0000000000000065, PMID: PubMed DOI PMC

Nakanishi Y, Sato T, Ohteki T. Commensal gram-positive bacteria initiates colitis by inducing monocyte/macrophage mobilization. Mucosal Immunol. (2015) 8:152–60. doi: 10.1038/mi.2014.53, PMID: PubMed DOI

Qiao YQ, Cai CW, Ran ZH. Therapeutic modulation of gut microbiota in inflammatory bowel disease: more questions to be answered. J Dig Dis. (2016) 17:800–10. doi: 10.1111/1751-2980.12422, PMID: PubMed DOI

Broekaert WF, Courtin CM, Verbeke K, Van De WT, Verstraete W, Delcour JA. Prebiotic and other health-related effects of cereal-derived arabinoxylans, arabinoxylan-oligosaccharides, and xylooligosaccharides. Crit Rev Food Sci Nutr. (2011) 51:178–94. doi: 10.1080/10408390903044768, PMID: PubMed DOI

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) 14:491–502. doi: 10.1038/nrgastro.2017.75, PMID: PubMed DOI

Simon E, Călinoiu LF, Mitrea L, Vodnar DC. Probiotics, prebiotics, and Synbiotics: implications and beneficial effects against irritable bowel syndrome. Nutrients. (2021) 13:2112. doi: 10.3390/nu13062112, PMID: PubMed DOI PMC

Sheng K, He S, Sun M, Zhang G, Kong X, Wang J, et al. Synbiotic supplementation containing Bifidobacterium infantis and xylooligosaccharides alleviates dextran sulfate sodium-induced ulcerative colitis. Food Funct. (2020) 11:3964–74. doi: 10.1039/d0fo00518e, PMID: PubMed DOI

Li Z, Li Z, Zhu L, Dai N, Sun G, Peng L, et al. Effects of Xylo-oligosaccharide on the gut microbiota of patients with ulcerative colitis in clinical remission. Front Nutr. (2021) 8:778542. doi: 10.3389/fnut.2021.778542, PMID: PubMed DOI PMC

Le B, Ngoc APT, Yang SH. Synbiotic fermented soymilk with PubMed DOI

Kleniewska P, Pawliczak R. Assessment of human 4-hydroxynonenal, 8-isoprostane concentrations and glutathione reductase activity after synbiotics administration. Adv Med Sci. (2018) 63:301–5. doi: 10.1016/j.advms.2018.04.003, PMID: PubMed DOI

Finamore A, Roselli M, Donini L, Brasili E, Rami R, Carnevali P, et al. Supplementation with PubMed DOI

Furrie E, Macfarlane S, Kennedy A, Cummings JH, Walsh SV, O’neil DA. Synbiotic therapy ( PubMed DOI PMC

Fujimori S, Gudis K, Mitsui K, Seo T, Yonezawa M, Tanaka S, et al. A randomized controlled trial on the efficacy of synbiotic versus probiotic or prebiotic treatment to improve the quality of life in patients with ulcerative colitis. Nutrition. (2009) 25:520–5. doi: 10.1016/j.nut.2008.11.017 PubMed DOI

Federico A, Tuccillo C, Grossi E, Abbiati R, Garbagna N, Romano M, et al. The effect of a new symbiotic formulation on plasma levels and peripheral blood mononuclear cell expression of some proinflammatory cytokines in patients with ulcerative colitis: a pilot study. Eur Rev Med Pharmacol Sci. (2009) 13:285–93. PMID: PubMed

Ishikawa H, Matsumoto S, Ohashi Y, Imaoka A, Setoyama H, Umesaki Y, et al. Beneficial effects of probiotic bifidobacterium and galacto-oligosaccharide in patients with ulcerative colitis: a randomized controlled study. Digestion. (2011) 84:128–33. doi: 10.1159/000322977, PMID: PubMed DOI

Ahmed J, Reddy BS, Mølbak L, Leser TD, MacFie J. Impact of probiotics on colonic microflora in patients with colitis: a prospective double blind randomised crossover study. Int J Surg. (2013) 11:1131–6. doi: 10.1016/j.ijsu.2013.08.019 PubMed DOI

Altun HK, Yıldız EA, Akın M. Effects of synbiotic therapy in mild-to-moderately active ulcerative colitis: a randomized placebo-controlled study. Turk J Gastroenterol. (2019) 30:313–20. doi: 10.5152/tjg.2019.18356, PMID: PubMed DOI PMC

Malathi K, Nandini R, Dhanasekar K, Shilpa B. A randomized open label study to evaluate the efficacy and tolerability of synbiotic in the treatment of ulcerative colitis. J Hepatol Gastroint Dis. (2019) 10:398. doi: 10.35248/2475-3181.19.5.165 DOI