International Journal of Clinical Case Reports 2024, Vol.14, No.2, 66-78 http://medscipublisher.com/index.php/ijccr 70 SynComs constructed with beneficial microbial strains can enhance nutrient acquisition, increase crop yield in agricultural settings, and demonstrate similar benefits in human gut health (Wang et al., 2021). Additionally, they produce antimicrobial compounds that enhance the host's immune response and protect against pathogens (Yin et al., 2022). By understanding the ecological theories and community assembly rules, researchers can design SynComs that are more stable and effective under various environmental conditions (Martins et al., 2023). This approach has been shown to be effective in both plant and human microbiomes, where well-structured SynComs can lead to better colonization and long-term stability (De Souza et al., 2020; Marín et al., 2021). Enhanced biofilm formation and improved colonization of the gut are some benefits observed with SynComs (Sun et al., 2023). The use of computational methods, including machine learning, further aids in identifying the best combinations of microbes for desired phenotypes, enhancing the overall functionality of the SynComs (De Souza et al., 2020). 3.3 Genetic modifications to improve resilience and colonization of probiotics Genetic modifications are crucial for improving the resilience and colonization capabilities of probiotics. By introducing specific genetic signatures designed to improve the ability of probiotics to tolerate stress conditions such as acids, bile salts, and oxidative stress, probiotics can become more resistant to environmental stress and colonize the gut more effectively (van Leeuwen et al., 2023). For example, engineered probiotics with enhanced biocontainment mechanisms and logic-gating systems can better survive and function in the complex gut environment (Dou and Bennett, 2018). Genetic enhancements in stress tolerance mechanisms are crucial for improving probiotic resilience. For example, Saccharomyces boulardii has been genetically modified to increase its secretion of therapeutic proteins, enhancing its effectiveness in treating gastrointestinal disorders (Durmusoglu et al., 2022). Enhancing the ability of probiotics to form biofilms improves their protection from environmental stresses and adherence to the gut mucosa. Biofilm formation is a key factor in probiotic colonization and resilience (Bamunuarachchige et al., 2011). Additionally, genetic modifications can help probiotics to better adhere to the gut mucosa and resist the competitive pressures from native microbial communities (van Leeuwen et al., 2023). This is particularly important for ensuring the long-term efficacy of probiotic treatments, as stable colonization is essential for sustained health benefits (Li et al., 2021; van Leeuwen et al., 2023). Advanced gene editing tools like CRISPR-Cas9 have been used to introduce specific genetic traits that enhance probiotic performance. For instance, Lactobacillus and Bifidobacteriumspecies have been engineered to express genes that confer resistance to bile salts and acidity, improving their survival and colonization in the gut (Yadav et al., 2020). Genetically modified probiotics can be designed to produce therapeutic compounds targeting specific pathogens or modulating the host's immune response. Engineered Escherichia coli strains, for example, have been developed to eliminate Pseudomonas aeruginosa by producing anti-biofilm enzymes and other antimicrobial compounds (Hwang et al., 2017). The engineering of metabolic pathways, enhancement of microbial interactions within SynComs, and genetic modifications to improve resilience and colonization are key mechanisms that can significantly enhance the functionality of probiotics. These approaches leverage advanced tools and methodologies from synthetic biology and computational modeling to create more effective and stable probiotic treatments for gut health improvement. 4 Applications of Engineered SynComs in Gut Health 4.1 SynComs for treating gastrointestinal disorders Engineered synthetic microbial communities (SynComs) have shown significant promise in treating gastrointestinal disorders such as Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). These disorders are often associated with dysbiosis, an imbalance in the gut microbiota. SynComs can be designed to restore this balance by introducing beneficial microbial species that can outcompete pathogenic bacteria and reduce inflammation. For instance, SynComs have been utilized to combat chronic inflammatory bowel diseases by harnessing their potential to modulate the gut-immune axis and reduce inflammation (van Leeuwen et al., 2023). Additionally, engineered probiotics have been developed to produce and deliver therapeutic molecules directly within the gut, offering a targeted approach to treating these disorders (Dou and Bennett, 2018; Huang et al., 2022).
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