The Role of Genetically Engineered Probiotics for Treatment of Inflammatory Bowel Disease: A Systematic Review

Abstract

Background: Many preclinical studies have demonstrated the effectiveness of genetically modified probiotics (gm probiotics) in animal models of inflammatory bowel disease (IBD). Objective: This systematic review was performed to investigate the role of gm probiotics in treating IBD and to clarify the involved mechanisms. Methods: PubMed, Web of Science, Cochrane Library, and Medline were searched from their inception to 18 September 2022 to identify preclinical and clinical studies exploring the efficacy of gm probiotics in IBD animal models or IBD patients. Two independent researchers extracted data from the included studies, and the data were pooled by the type of study; that is, preclinical or clinical. Results: Forty-five preclinical studies were included. In these studies, sodium dextran sulfate and trinitrobenzene sulfonic acid were used to induce colitis. Eleven probiotic species have been genetically modified to produce therapeutic substances, including IL-10, antimicrobial peptides, antioxidant enzymes, and short-chain fatty acids, with potential therapeutic properties against colitis. The results showed generally positive effects of gm probiotics in reducing disease activity and ameliorating intestinal damage in IBD models; however, the efficacy of gm probiotics compared to that of wild-type probiotics in many studies was unclear. The main mechanisms identified include modulation of the diversity and composition of the gut microbiota, production of regulatory metabolites by beneficial bacteria, reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of oxidative stress activity in the colon, and improvement of intestinal barrier integrity. Moreover, only one clinical trial with 10 patients with Crohn’s disease was included, which showed that L. lactis producing IL-10 was safe, and a decrease in disease activity was observed in these patients. Conclusions: Gm probiotics have a certain efficacy in colitis models through several mechanisms. However, given the scarcity of clinical trials, it is important for researchers to pay more attention to gm probiotics that are more effective and safer than wild-type probiotics to facilitate further clinical translation.

Next-Generation Probiotics as Novel Therapeutics for Improving Human Health: Current Trends and Future Perspectives

“…Ongoing clinical trials are actively exploring the potential of genetically modified probiotics, particularly in the context of treating IBD. Noteworthy examples include a 2006 phase I clinical trial conducted by Braat et al, which assessed the safety and efficacy of a genetically modified L. lactis strain [ 187 , 188 ]. Additionally, Kang et al’s 2018 study delved into the capabilities of engineered probiotics for IBD treatment [ 174 ].…”

“…These collective efforts underscore the ongoing endeavors to develop and assess the potential of genetically modified probiotics for therapeutic purposes. In conclusion, the genetically modified probiotics have the potential to treat a variety of diseases including IBD, diarrhea, Parkinson’s disease, metabolic diseases, cancer, and bacterial infections such as H. pylori , and C. difficile [ 174 , 188 ]. Nevertheless, it is crucial to acknowledge that the safety and efficacy of these probiotics remain under investigation.…”

Advancements in hydrogel-based drug delivery systems for the treatment of inflammatory bowel disease: a review

“…Probiotics, represented by Lactobacillus , Bifidobacterium , and Saccharomyces boulardii show outstanding effects in regulating intestinal flora. 99 However, most probiotics have weak adhesion to the intestinal mucosa and are rapidly excreted from the gastrointestinal tract, leading to low utilization efficiency. Furthermore, precise delivery of probiotics to inflammatory areas while maintaining their high activity remains a considerable challenge.…”

Designer probiotics: Opening the new horizon in diagnosis and prevention of human diseases

“…For example, probiotics have been engineered to produce IL-10, a cytokine that has potent anti-inflammatory effects. These probiotics have been shown to reduce inflammation and improve symptoms in animal models of IBD and other inflammatory conditions (de Moreno de LeBlanc et al, 2011;Pesce et al, 2022;Zhang et al, 2023). Nitric oxide (NO) is another prime candidate for the detection of cellular inflammation because of its omnipresence in both inflammatory and anti-inflammatory states (Leonard et al, 1998;Maeda & Akaike, 1998;Perner, 2001).…”