Microbial-Based and Microbial-Targeted Therapies for Inflammatory Bowel Diseases

Abstract

Inflammatory bowel diseases (IBD), including Crohn's disease, ulcerative colitis, and pouchitis, are chronic, relapsing intestinal inflammatory disorders mediated by dysregulated immune responses to resident microbiota. Current standard therapies that block immune activation with oral immunosuppressives or biologic agents are generally effective, but each therapy induces a sustained remission in only a minority of patients. Furthermore, these approaches can have severe adverse events. Recent compelling evidence of a role of unbalanced microbiota (dysbiosis) driving immune dysfunction and inflammation in IBD supports the therapeutic rationale for manipulating the dysbiotic microbiota. Traditional approaches using currently available antibiotics, probiotics, prebiotics, and synbiotics have not produced optimal results, but promising outcomes with fecal microbiota transplant provide a proof of principle for targeting the resident microbiota. Rationally designed oral biotherapeutic products (LBPs) composed of mixtures of protective commensal bacterial strains demonstrate impressive preclinical results. Resident microbial-based and microbialtargeted therapies are currently being studied with increasing intensity for IBD primary therapy with favorable early results. This review presents current evidence and therapeutic mechanisms of microbiota modulation, emphasizing clinical studies, and outlines prospects for future IBD treatment using new approaches, such as LBPs, bacteriophages, bacterial function-editing substrates, and engineered bacteria. We believe that the optimal clinical use of microbial manipulation may be as adjuvants to immunosuppressive for accelerated and improved induction of deep remission and as potential safer solo approaches to sustained remission using personalized regimens based on an individual patient's microbial profile.

Probiotic Lactobacillus and Bifidobacterium Strains Counteract Adherent-Invasive Escherichia coli (AIEC) Virulence and Hamper IL-23/Th17 Axis in Ulcerative Colitis, but Not in Crohn’s Disease

“…Targeting gut dysbiosis and overly intestinal inflammation with resident microbial-targeted therapies is an attractive strategy for IBD treatment [49,50].…”

Enterobacter Ludwigii Protects Experimental Colitis Through CD103+DC and Treg Cells

“…The intestinal ora in balance is mainly composed of obligate anaerobes, due to a low level of oxygen tension in the distal part of the gastrointestinal tract [31]. Gut microbiota dysbiosis is usually characterized by expansion of aerobes or facultative anaerobes belonging to Proteobacteria and Fusobacteria phylum, and by reduction of obligate anaerobes belonging to Firmicutes phylum [31,32].…”

Discovery of a Novel Multi-Strains Probiotic Formulation with Improved Efficacy toward Intestinal Inflammation

“…Currently, also the probiotics have entered IBD therapy intending to modulate the composition of the intestinal microbiota and the response of the host’s immune system [ 8 ]. Although the mechanisms of action of probiotics are not yet fully understood, many formulations of single strains or combinations of multiple strains are commercially available [ 9 ].…”

“…Although the mechanisms of action of probiotics are not yet fully understood, many formulations of single strains or combinations of multiple strains are commercially available [ 9 ]. The results of clinical trials evaluating the use of probiotics in IBD patients, however, have documented that although probiotics are generally safe, they are only moderately or not effective in treating IBD [ 8 ]. Indeed, while beneficial results have been reported in UC (ulcerative colitis)patients and pouchitis, a substantial lack of efficacy has been documented in CD (Crohn’s disease) patients, highlighting the need to identify single strains or combinations of multiple strain probiotic formulations with improved clinical efficacy that will be beneficial and effective in treating the majority of IBD patients [ 10 , 11 ].…”