Redrawing the gut map: evolving probiotic approaches to microbiota modulation in inflammatory bowel disease

Inflammatory bowel disease (IBD), comprising Ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disorder of the gastrointestinal tract (GIT) that occurs due to several factors, including, but not limited to, gut microbiota dysbiosis, immune dysregulation, and environmental factors. Despite significant advances in IBD pharmacotherapy, patients often experience treatment failures due to suboptimal treatment responses, frequent relapses, and are also susceptible to developing several adverse effects (AEs), highlighting the need for developing alternative therapies. A growing body of evidence necessitates the importance of maintaining gut microbiome homeostasis, which is commonly disrupted in IBD. Probiotics have emerged as promising adjunctive IBD therapies due to their capacity to modulate immune responses, restore gut microbial balance, and preserve mucosal barrier integrity. Multiple probiotic strains, including Escherichia coli (E. coli) Nissle 1917, Lacticaseibacillus rhamnosus GG, Bifidobacterium longum (B. longum), Saccharomyces cerevisiae var. boulardii (S. boulardii), and combination formulations, such as VSL#3 (Lactobacillus, Bifidobacterium, and Streptococcus thermophilus), have demonstrated superior efficacy in inducing and maintaining remission in comparison with placebo and comparable efficacy with conventional treatments, such as mesalazine. While the efficacy of probiotics has been demonstrated in UC through several clinical studies, evidence supporting their use in CD remains inconsistent, with studies yielding mixed or inconclusive results. This highlights the necessity for additional carefully designed, large-scale studies specifically targeting CD patients to better understand the therapeutic potential of probiotics in a broader context. Finally, emerging innovations in genetic engineering and clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9 (CRISPR/Cas9) technology offer exciting prospects for the development of precision probiotics, which could possess both diagnostic and treatment benefits and further expand the clinical utility of probiotics in IBD treatment.