International Journal of Molecular Medical Science, 2024, Vol.14, No.2, 106-122 http://medscipublisher.com/index.php/ijmms 113 Figure 2 demonstrates the various factors influencing the composition and diversity of the gut microbiota. These factors include geographic location, host genetics, exercise, stress, antibiotic use, age, diet, and mode of delivery. Geographic location and host genetics establish the foundational characteristics of an individual's gut microbiota; exercise helps enhance microbial diversity; stress may disrupt microbial balance. Antibiotic use significantly reduces microbiota diversity, impacting gut health. The gut microbiota varies considerably across different ages, with distinct microbial structures present at each life stage from infancy to old age. Diet directly affects the composition of gut microbiota, while the mode of delivery (such as vaginal birth or cesarean section) plays a crucial role in the early establishment of the microbiota. These factors collectively determine the health and function of an individual's gut microbiota. Foster et al. (2017) highlighted that diet is a critical factor influencing the gut-brain axis. Microorganisms communicate with the brain through pathways such as the vagus nerve, gut hormone signaling, the immune system, tryptophan metabolism, and short-chain fatty acids. Alterations in the early gut microbiome can have profound impacts on later health, including stress-related physiological and behavioral changes. The study also explored the role of the microbiome in stress-related diseases such as anxiety, depression, and irritable bowel syndrome, proposing that psychobiotics might serve as an intervention to improve mental health. The Table 1 demonstrates the effects of targeting the gut microbiota on depression and anxiety in both clinical and preclinical studies. Clinical evidence indicates that the prebiotic B-GOS and various probiotics such as Lactobacillus and Bifidobacterium have significant effects on improving cognitive processing, mood, and reducing psychological stress, while also decreasing physiological stress responses like cortisol levels. Preclinical studies further support these findings, showing improvements in depression-like and anxiety-like behaviors in animal models treated with prebiotics and probiotics, along with corresponding physiological changes such as reduced corticosterone and pro-inflammatory cytokine levels. These results suggest that the potential role of the gut microbiota in mental health warrants further exploration. Environmental factors such as stress and exposure to antibiotics can also impact gut microbiota composition and function, thereby influencing the effectiveness of SynComs. For example, stress can alter the gut microbiota and increase gut permeability, leading to changes in neurotransmitter levels and brain function (Petra et al., 2015). Similarly, antibiotic use can disrupt gut microbiota composition, affecting the production of neurotransmitters and other neuroactive compounds (Gao et al., 2019). Lifestyle factors, including physical activity and sleep patterns, also play a crucial role in modulating gut microbiota and SynCom efficacy. Regular physical activity has been shown to promote a healthy gut microbiota composition, which can enhance the production of beneficial neurotransmitters (Wijdeveld et al., 2020). Adequate sleep is essential for maintaining gut microbiota balance and optimal neurotransmitter production, thereby supporting mental health (Gao et al., 2019). 7 Clinical Studies and Performance Evaluation 7.1 Overview of preclinical and clinical trials involving SynComs for mental health The exploration of synthetic microbial communities (SynComs) in modulating mental health through the gut-brain axis has gained significant traction in recent years. Preclinical studies have demonstrated the potential of SynComs in altering neurotransmitter levels and influencing behavior. For instance, germ-free rodent models and those subjected to antibiotic treatments have shown that the absence or alteration of gut microbiota can significantly impact anxiety and depression-like behaviors, suggesting a critical role of gut microbes in mental health (Huang and Wu, 2021; Socała et al., 2021). Clinical trials, although still in their nascent stages, have begun to explore the efficacy of SynComs in human subjects. These studies aim to translate the promising results observed in animal models to human applications, focusing on conditions such as depression, anxiety, and irritable bowel syndrome (IBS) (Foster et al., 2017; Martin et al., 2018; Iannone et al., 2019).
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