The educational content in this post, elaborated in collaboration with Bromatech, was independently developed and approved by the GMFH publishing team and editorial board.

What is the rationale for using probiotics in IBD?

A single cause of inflammatory bowel diseases (IBDs), and particularly of ulcerative colitis (UC) and Crohn’s disease (CD), has yet to be identified. However, contributory elements to the pathogenesis of IBD include host genetic susceptibility, the environment and host immune response. Within them, alterations in both the composition and functions of the gut microbiota have been involved in IBD pathogenesis and it is therefore feasible to think that gut microbiota is both the chicken and the egg in IBD.

Robust alterations in the composition and function of the gut microbiota in IBD have suggested that targeting that area with fecal microbiota transplantation, probiotics and phage therapy might be beneficial in IBD.

The rationale of using probiotics in IBD in particular is based on their anti-inflammatory properties (i.e., reducing calprotectin levels), their role in modulating gut microbiota composition (i.e., overcoming the lack of beneficial Lactobacillus and Bifidobacterium seen in patients with IBD), the production of short-chain fatty acids and the strengthening of intestinal barrier integrity.

Other mechanisms are also plausible and include correcting the altered tryptophan metabolism observed in IBD and modulating the expression of heat shock proteins (chaperones). For instance, the levels of heat shock proteins 60 and 10 are increased in colon mucosa of patients with CD and UC in relapse supporting the hypothesis that this is a potential mechanism involved in the development and maintenance of IBD.

That has led to some studies exploring the role of probiotics in shaping the expression of mucosal heat shock proteins in patients with IBD. Some probiotics have shown efficacy in decreasing the levels of heat shock proteins. Other mechanisms of action by which some probiotics may work in UC is by boosting the expression of cytoprotective heat shock proteins 70 and 25, which are decreased in the mucosa by colitis.

 

Probiotics in ulcerative colitis and pouchitis

The latest clinical guidelines from the European Society for Clinical Nutrition and Metabolism (ESPEN) and the World Gastroenterology Organisation agreed that certain bacteria and yeast probiotics are effective and safe for the induction and maintenance of mild to moderately active UC in pediatric and adult populations, but not in the case of severe disease.

Moreover, some probiotic blends with Bifidobacterium and Lactobacillus species coupled with anti-inflammatory drugs may represent an effective approach in mild-to-moderate UC, with beneficial effects that persist after two years of treatment. Specific probiotics can also be as effective as an alternative to conventional therapy (namely, aminosalicylates) and the ESPEN guidelines conclude that “selected probiotics can be used as an alternative to 5-aminosalicylic acid (5-ASA) standard therapy if 5-ASA is not tolerated for the treatment of mild or moderate active disease.”

While the evidence for using probiotics to prevent pouchitis is contradictory, some data suggest certain probiotics may prevent further relapse after the induction of remission with antibiotics and may be used as maintenance treatment for children and adults in remission.

Commensal strains selected for their anti-inflammatory properties such as Faecalibacterium prausnitzii, purified microbial metabolites (i.e., butyrate and tryptophan metabolites) and phage therapy are also promising treatments targeting the microbiota, which could be used in parallel with available treatments that target host inflammatory response.

 

Probiotics in Crohn’s disease

The available evidence is uncertain about the efficacy of probiotics for Crohn’s disease. Currently, the ESPEN clinical guidelines state that “probiotics should not be recommended for treatment of CD, neither for treatment of active disease nor for prevention of relapse in the remission phase or postoperative recurrence of disease.”

 

Probiotics in the form of foods or food supplements: pros and cons

While some studies assessed the efficacy of fermented milks enriched with bifidobacteria in UC, it is not possible to ensure that fermented milks (and other fermented foods) contain the right strains and in an adequate amount with scientific evidence to improve IBD symptoms, and the maintenance of cold temperatures from production to consumption cannot be ensured either.

Moreover, while including fermented foods as part of a well-balanced diet makes sense, the available evidence does not allow for their recommendation in gastrointestinal conditions such as IBD. This is mainly because the microorganisms, byproducts or nutrients responsible for their health benefits are not completely understood.

 

Take-home messages

The gut microbiota is a driver of mucosal inflammation in IBD and contributes with genes and host immune response to the pathogenesis of this gastrointestinal condition.

The latest clinical guidelines from the European Society for Clinical Nutrition and Metabolism and the World Gastroenterology Organisation agreed that certain bacteria and yeast probiotics are effective and safe for the induction and maintenance of mild to moderately active UC.

The available evidence, meanwhile, is uncertain about the efficacy of probiotics for Crohn’s disease.

 

References:

Benech N, Sokol H. Targeting the gut microbiota in inflammatory bowel diseases: where are we? Curr Opin Microbiol. 2023; 74:102319. doi: 10.1016/j.mib.2023.102319.

Naseer M, Poola S, Ali S, et al. Prebiotics and probiotics in inflammatory bowel disease: where are we now and where are we going? Curr Clin Pharmacol. 2020; 15(3):216-233. doi: 10.2174/1574884715666200312100237.

Agus A, Planchais J, Sokol H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe. 2018; 23(6):716-724. doi: 10.1016/j.chom.2018.05.003.

Bellavia M, Tomasello G, Romeo M, et al. Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis. Med Microbiol Immunol. 2013; 202(6):393-406. doi: 10.1007/s00430-013-0305-2.

Rodolico V, Tomasello G, Zerilli M, et al. Hsp60 and Hsp10 increase in colon mucosa of Crohn’s disease and ulcerative colitis. Cell Stress Chaperones. 2010; 15(6):877-884. doi: 10.1007/s12192-010-0196-8.

Tomasello G, Sciumè C, Rappa F, et al. Hsp10, Hsp70, and Hsp90 immunohistochemical levels change in ulcerative colitis after therapy. Eur J Histochem. 2011; 55(4):e38. doi: 10.4081/ejh.2011.e38.

Liu HY, Gu F, Zhu C, et al. Epithelial heat shock proteins mediate the protective effects of Limosilactobacillus reuteri in dextran sulfate sodium-induced colitis. Front Immunol. 2022; 13:865982. doi: 10.3389/fimmu.2022.865982.

Bischoff SC, Bager P, Escher J, et al. ESPEN guideline on clinical nutrition in inflammatory bowel disease. Clin Nutr. 2023; 42(3):352-379. doi: 10.1016/j.clnu.2022.12.004.

Guarner F, Sanders ME, Szajewska H, et al. World Gastroenterology Organisation Global Guidelines. Probiotics and prebiotics. February 2023. Available on: https://www.worldgastroenterology.org/guidelines/probiotics-and-prebiotics/probiotics-and-prebiotics-english

Davide Palumbo V, Romeo M, Marino Gammazza AM, et al. The long-term effects of probiotics in the therapy of ulcerative colitis: a clinical study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016; 160(3):372-377. doi: 10.5507/bp.2016.044.

Staudacher HM, Nevin AN. Fermented foods: fad or favourable addition to the diet? Lancet Gastroenterol Hepatol. 2019; 4(1):19. doi: 10.1016/S2468-1253(18)30392-3.