International Journal of Molecular Medical Science, 2024, Vol.14, No.2, 106-122 http://medscipublisher.com/index.php/ijmms 108 Figure 1 The complex interactions between the gut microbiota and the gut-brain axis (Adapted from Ma et al., 2019) Image caption: A shows that short-chain fatty acids (SCFAs) promote the generation of regulatory T cells (Tregs) by modulating the Foxp3 promoter, while inhibiting the formation of pro-inflammatory T cells; B explains that under germ-free conditions or with antibiotic use, the maturation of microglia is inhibited, affecting the anti-inflammatory effects in the nervous system; C indicates that specific probiotics can promote neurogenesis in the hippocampus; D demonstrates that under germ-free conditions, the permeability of the blood-brain barrier (BBB) increases, and the colonization of microbiota or the use of SCFAs can restore its normal permeability; E emphasizes that the vagus nerve interacts with the gut microbiota directly and indirectly, influencing brain function (Adapted from Ma et al., 2019) Additionally, microbial metabolites such as short-chain fatty acids (SCFAs), tryptophan metabolites, and peptidoglycans can modulate these communication pathways. These mechanisms collectively ensure a dynamic and responsive interaction between the gut and the brain. 2.3 Role of the gut microbiota in modulating these communication pathways The gut microbiota, comprising trillions of microorganisms, plays a pivotal role in modulating the communication pathways of the GBA. The microbiota influences neural communication by interacting with the ENS and modulating vagal signaling (Cryan et al., 2019; Kuwahara et al., 2020). It also affects endocrine pathways by influencing the release of hormones such as serotonin, which is predominantly produced in the gut (Gao et al., 2019; Margolis et al., 2021). The immune system is another critical interface, with the gut microbiota modulating immune responses and maintaining the integrity of the intestinal barrier (Wang and Wang, 2016; Hattori and Yamashiro, 2021). Dysbiosis, or an imbalance in the gut microbiota, has been linked to various neurological and psychiatric disorders, including anxiety, depression, and autism (Wiley et al., 2017; Cryan et al., 2019). Probiotics, prebiotics, and other microbial-based interventions are being explored as potential therapeutic strategies to restore balance in the GBA and improve mental health outcomes (Wiley et al., 2017; Suganya and Koo, 2020). The intricate interplay between the gut microbiota and the GBA underscores the importance of maintaining a healthy and diverse microbial community for optimal brain function and mental health. 3 Neurotransmitter Production in the Gut 3.1 Overview of neurotransmitters produced in the gut The gut is a significant site for the production of various neurotransmitters, including serotonin, dopamine, and gamma-aminobutyric acid (GABA). These neurotransmitters play critical roles in maintaining gastrointestinal (GI) homeostasis and facilitating communication along the gut-brain axis. Serotonin, for instance, is predominantly produced in the gut, with approximately 90% of the body's total serotonin synthesized by enterochromaffin cells in the gastrointestinal tract (Strandwitz, 2018; Liu and Huang, 2019). Dopamine, another critical neurotransmitter, is also produced in the gut, albeit in smaller quantities compared to the brain (Strandwitz, 2018; Bhatia et al., 2023). GABA, which plays a crucial role in inhibiting neural activity, is synthesized by certain gut bacteria, contributing to the overall pool of this neurotransmitter in the body (Strandwitz, 2018; Bhatia et al., 2023).
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