Targeting Gut Microbiota Dysbiosis in Inflammatory Bowel Disease: a Systematic Review of Current Evidence

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2025 Mar 5

PMID 40041456

Authors

Asmaa Farah

Pradipta Paul

Anfal Sher Khan

Aparajita Sarkar

Saad Laws

Ali Chaari

Affiliations

Soon will be listed here.

Abstract

Introduction: The dysbiosis of the gut microbiota has been identified as a central factor in the pathogenesis of inflammatory bowel disease (IBD), a chronic condition characterized by frequent recurrence and various adverse effects of traditional therapies. While treatments targeting the gut microbiota show promise, their efficacy in IBD management still requires extensive evaluation. Our systematic review analyzes recent studies to elucidate the advancements and challenges in treating IBD using microbial-based therapies.

Methods: Through a comprehensive systematic review spanning key scientific databases-PubMed, Embase, Cochrane, Web of Science, Scopus, and Google Scholar-we scrutinized the impact of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on individuals with IBD. Our detailed analysis covered study and participant demographics, along with seven key outcome measures: disease activity index, inflammatory markers, serum cytokines, microbiome composition, adverse effects, and the rates of remission and relapse.

Results: From 6,080 initial search hits, we included 71 studies that assessed various interventions compared to placebo or standard medical therapy. Although there was notable variation in clinical results while assessing different outcomes, overall, probiotics, prebiotics, and synbiotics enhanced the success rates in inducing remission among IBD patients. Furthermore, we noted significant reductions in levels of pro-inflammatory markers and cytokines. Additionally, the requirement for steroids, hospitalization, and poor outcomes in endoscopic and histological scores were significantly reduced in individuals undergoing FMT.

Conclusion: Our investigation highlights the potential of targeting gut microbiota dysbiosis with microbial-based therapies in patients with IBD. We recommend conducting larger, placebo-controlled randomized trials with extended follow-up periods to thoroughly assess these treatments' clinical efficacy and safety before widespread recommendations for clinical application.

References

Duboc H, Rajca S, Rainteau D, Benarous D, Maubert M, Quervain E . Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut. 2012; 62(4):531-9. DOI: 10.1136/gutjnl-2012-302578. View

Rossen N, Fuentes S, van der Spek M, Tijssen J, Hartman J, Duflou A . Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology. 2015; 149(1):110-118.e4. DOI: 10.1053/j.gastro.2015.03.045. View

Darb Emamie A, Rajabpour M, Ghanavati R, Asadolahi P, Farzi S, Sobouti B . The effects of probiotics, prebiotics and synbiotics on the reduction of IBD complications, a periodic review during 2009-2020. J Appl Microbiol. 2020; 130(6):1823-1838. DOI: 10.1111/jam.14907. View

Lichtenstein G, Feagan B, Cohen R, Salzberg B, Diamond R, Price S . Serious infection and mortality in patients with Crohn's disease: more than 5 years of follow-up in the TREAT™ registry. Am J Gastroenterol. 2012; 107(9):1409-22. PMC: 3438468. DOI: 10.1038/ajg.2012.218. View

Li H, Zhou D, Gan R, Huang S, Zhao C, Shang A . Effects and Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics on Metabolic Diseases Targeting Gut Microbiota: A Narrative Review. Nutrients. 2021; 13(9). PMC: 8470858. DOI: 10.3390/nu13093211. View

Sellon R, Tonkonogy S, Schultz M, Dieleman L, Grenther W, Balish E . Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun. 1998; 66(11):5224-31. PMC: 108652. DOI: 10.1128/IAI.66.11.5224-5231.1998. View

Hafer A, Kramer S, Duncker S, Kruger M, Manns M, Bischoff S . Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study. BMC Gastroenterol. 2007; 7:36. PMC: 1995200. DOI: 10.1186/1471-230X-7-36. View

Brezina J, Bajer L, Wohl P, Duricova D, Hrabak P, Novotny A . Fecal Microbial Transplantation versus Mesalamine Enema for Treatment of Active Left-Sided Ulcerative Colitis-Results of a Randomized Controlled Trial. J Clin Med. 2021; 10(13). PMC: 8268406. DOI: 10.3390/jcm10132753. View

Zocco M, Zileri Dal Verme L, Cremonini F, Piscaglia A, Nista E, Candelli M . Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther. 2006; 23(11):1567-74. DOI: 10.1111/j.1365-2036.2006.02927.x. View

10.

Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi S . Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods. 2019; 8(3). PMC: 6463098. DOI: 10.3390/foods8030092. View

11.

Zhang X, Guan X, Tang Y, Sun J, Wang X, Wang W . Clinical effects and gut microbiota changes of using probiotics, prebiotics or synbiotics in inflammatory bowel disease: a systematic review and meta-analysis. Eur J Nutr. 2021; 60(5):2855-2875. DOI: 10.1007/s00394-021-02503-5. View

12.

Dragoni G, Innocenti T, Galli A . Biomarkers of Inflammation in Inflammatory Bowel Disease: How Long before Abandoning Single-Marker Approaches?. Dig Dis. 2020; 39(3):190-203. DOI: 10.1159/000511641. View

13.

Huang M, Chen Z, Lang C, Chen J, Yang B, Xue L . Efficacy of mesalazine in combination with bifid triple viable capsules on ulcerative colitis and the resultant effect on the inflammatory factors. Pak J Pharm Sci. 2019; 31(6(Special)):2891-2895. View

14.

Mariman R, Tielen F, Koning F, Nagelkerken L . The probiotic mixture VSL#3 dampens LPS-induced chemokine expression in human dendritic cells by inhibition of STAT-1 phosphorylation. PLoS One. 2014; 9(12):e115676. PMC: 4278714. DOI: 10.1371/journal.pone.0115676. View

15.

Caldeira L, Borba H, Tonin F, Wiens A, Fernandez-Llimos F, Pontarolo R . Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis. PLoS One. 2020; 15(9):e0238910. PMC: 7500646. DOI: 10.1371/journal.pone.0238910. View

16.

Petrof E, Kojima K, Ropeleski M, Musch M, Tao Y, De Simone C . Probiotics inhibit nuclear factor-kappaB and induce heat shock proteins in colonic epithelial cells through proteasome inhibition. Gastroenterology. 2004; 127(5):1474-87. DOI: 10.1053/j.gastro.2004.09.001. View

17.

Plaza-Diaz J, Ruiz-Ojeda F, Gil-Campos M, Gil A . Mechanisms of Action of Probiotics. Adv Nutr. 2019; 10(suppl_1):S49-S66. PMC: 6363529. DOI: 10.1093/advances/nmy063. View

18.

Zhang L, Liu F, Xue J, Lee S, Liu L, Riordan S . Bacterial Species Associated With Human Inflammatory Bowel Disease and Their Pathogenic Mechanisms. Front Microbiol. 2022; 13:801892. PMC: 8908260. DOI: 10.3389/fmicb.2022.801892. View

19.

Reiff C, Delday M, Rucklidge G, Reid M, Duncan G, Wohlgemuth S . Balancing inflammatory, lipid, and xenobiotic signaling pathways by VSL#3, a biotherapeutic agent, in the treatment of inflammatory bowel disease. Inflamm Bowel Dis. 2009; 15(11):1721-36. DOI: 10.1002/ibd.20999. View

20.

Petersen A, Mirsepasi H, Halkjaer S, Mortensen E, Nordgaard-Lassen I, Krogfelt K . Ciprofloxacin and probiotic Escherichia coli Nissle add-on treatment in active ulcerative colitis: a double-blind randomized placebo controlled clinical trial. J Crohns Colitis. 2014; 8(11):1498-505. DOI: 10.1016/j.crohns.2014.06.001. View