International Journal of Molecular Medical Science, 2024, Vol.14, No.2, 106-122 http://medscipublisher.com/index.php/ijmms 110 4) Quorum Sensing: By engineering quorum sensing systems, SynComs can coordinate their behavior and maintain stable population dynamics. This technique allows microbial communities to modulate neurotransmitter production collectively, based on cell density and environmental conditions (Scott and Hasty, 2016). 5) Mathematical Modeling and Computational Tools: Predictive models and computational tools are used to design and optimize SynComs. These models help in understanding the complex interactions within microbial consortia and guide the engineering of stable and functional communities (Zomorrodi and Segrè, 2016). 4.3 Advantages of using engineered SynComs over natural microbial communities Engineered SynComs offer several advantages over natural microbial communities: 1) Predictability and Control: SynComs are designed to have predictable behaviors and functions, reducing the variability often seen in natural communities. This predictability is crucial for therapeutic applications where consistent outcomes are necessary (Karkaria et al., 2021). 2) Targeted Functionality: SynComs can be engineered to perform specific functions, such as the production of particular neurotransmitters, which might not be achievable with natural microbial communities. This targeted functionality allows for precise interventions in the gut-brain axis (Kang et al., 2020). 3) Stability: Engineered communities can be designed to be more stable and resilient to environmental changes compared to natural communities. This stability ensures that the desired functions are maintained over time and under varying conditions (Scott and Hasty, 2016). 4) Scalability and Reproducibility: SynComs can be scaled up and reproduced consistently, which is advantageous for clinical and industrial applications. This scalability ensures that large populations can be managed and utilized effectively for therapeutic purposes (Zomorrodi and Segrè, 2016). 5) Safety: Engineered SynComs can be designed to minimize the risk of pathogenicity and unwanted side effects. By using non-pathogenic strains and incorporating safety switches, the potential for adverse effects can be reduced (Dinan and Cryan, 2017; Strandwitz, 2018; Huang and Wu, 2021). 5 Applications of SynComs in Mental Health 5.1 SynComs for anxiety and depression management Synthetic microbial communities (SynComs) have shown potential in managing anxiety and depression by modulating the gut-brain axis. The gut microbiome plays a crucial role in the production of neurotransmitters such as serotonin and gamma-aminobutyric acid (GABA), which are essential for mood regulation. Studies have demonstrated that specific microbial strains can influence these neurotransmitter levels, thereby alleviating symptoms of anxiety and depression. For instance, a study investigating the use of Microbial Ecosystem Therapeutic-2 (MET-2), which comprises 40 strains of bacteria, showed promising results in treating major depressive disorder and generalized anxiety disorder. Participants who received MET-2 capsules daily for eight weeks exhibited significant improvements in depression and anxiety symptoms, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) and the Generalized Anxiety Disorder 7-item scale (GAD-7). Furthermore, studies have linked specific gut microbial compositions to mental health profiles. For example, reduced diversity of gut microbiota, particularly a decrease in Fusicatenibacter saccharivorans, has been associated with increased anxiety and depression symptoms. This finding suggests that enhancing the abundance of beneficial microbes could alleviate these symptoms. 5.2 Role of SynComs in neurodevelopmental and neurodegenerative disorders The application of SynComs in neurodevelopmental and neurodegenerative disorders is an emerging area of research. Neurodevelopmental disorders such as autism and attention deficit hyperactivity disorder (ADHD) are often associated with cognitive and emotional regulation impairments. SynComs could potentially improve these
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