International Journal of Molecular Medical Science, 2024, Vol.14, No.2, 106-122 http://medscipublisher.com/index.php/ijmms 109 3.2 Microbial involvement in neurotransmitter synthesis and regulation The gut microbiota plays a pivotal role in the synthesis and regulation of neurotransmitters. Various gut bacteria are capable of producing neurotransmitters directly. For example, certain strains of Lactobacillus and Bifidobacterium can produce GABA, while other bacteria can synthesize serotonin and dopamine (Strandwitz, 2018; Liu and Huang, 2019; Bhatia et al., 2023). Additionally, the gut microbiota can influence the availability of precursors for neurotransmitter synthesis. The metabolism of aromatic amino acids (AAAs) by gut bacteria can affect the levels of tryptophan and tyrosine, which are precursors for serotonin and dopamine, respectively (Gao et al., 2018; Gao et al., 2019). This microbial modulation of neurotransmitter precursors can subsequently impact neurotransmitter levels in the brain (Gao et al., 2018; Gao et al., 2019). 3.3 Impact of Gut-Derived neurotransmitters on brain function and mental health Gut-derived neurotransmitters have a profound impact on brain function and mental health. The gut-brain axis facilitates bidirectional communication between the gut and the brain, allowing gut-derived neurotransmitters to influence central nervous system activities. For instance, alterations in gut microbiota composition have been linked to changes in brain neurotransmitter levels, which can affect mood and behavior (Chen et al., 2021; Huang and Wu, 2021; Socała et al., 2021). Studies have shown that Alterations in gut serotonin levels have been linked to conditions like irritable bowel syndrome (IBS) and depression. Serotonergic pathways in the gut can influence central serotonergic activity, impacting mood and behavior (Kumar et al., 2020). Increased GABA production in the gut, particularly under conditions like hepatic encephalopathy, can affect brain inhibition and lead to altered neural activity (Altaib et al., 2021). Moreover, interventions targeting the gut microbiota, such as the use of probiotics, prebiotics, or antibiotics, have been shown to alter neurotransmitter levels and improve symptoms of mental health disorders (Dinan and Cryan, 2017; Strandwitz, 2018; Huang and Wu, 2021). 4 Engineering Synthetic Microbial Communities (SynComs) for Neurotransmitter Modulation 4.1 Definition and principles of SynComs Synthetic microbial communities (SynComs) are engineered consortia of microorganisms designed to perform specific functions that natural microbial communities may not efficiently achieve. These communities are constructed using principles of synthetic biology, which involves the design and assembly of genetic components to create new biological systems or reprogram existing ones. SynComs can be tailored to produce desired metabolites, including neurotransmitters, by incorporating specific microbial strains with known metabolic capabilities (Petra et al., 2015; Dinan and Cryan, 2017; Huang and Wu, 2021). 4.2 Techniques for engineering SynComs to enhance neurotransmitter production Several techniques are employed to engineer SynComs for enhanced neurotransmitter production such as serotonin, dopamine, and gamma-aminobutyric acid (GABA): 1) Genetic Engineering: This involves the insertion, deletion, or modification of genes within microbial genomes to enhance their ability to produce specific neurotransmitters. For example, genes responsible for the production of serotonin, dopamine, and gamma-aminobutyric acid (GABA) can be inserted into microbial genomes to boost their production (Strandwitz, 2018; Baj et al., 2019; Huang and Wu, 2021). 2) Synthetic Biology: This broad field includes techniques such as the design of synthetic gene circuits and metabolic pathways that can control and optimize microbial behavior. Synthetic biology approaches enable the creation of complex genetic networks that regulate neurotransmitter production in response to environmental signals or internal cellular states (Kang et al., 2020). 3) Metabolic Engineering: This involves the optimization of metabolic pathways within microorganisms to increase the yield of neurotransmitters. By redirecting metabolic fluxes and eliminating competing pathways, the production of target neurotransmitters can be maximized (Dinan and Cryan, 2017; Margolis et al., 2021; Socała et al., 2021).
RkJQdWJsaXNoZXIy MjQ4ODYzNQ==