International Journal of Clinical Case Reports 2024, Vol.14, No.2, 66-78 http://medscipublisher.com/index.php/ijccr 73 Moreover, the integration of advanced computational models and machine learning to predict and optimize SynCom behavior adds another layer of complexity to the engineering process (Kumar et al., 2022; Martins et al., 2023). Figure 2 The contrasting states of the gut-brain axis in conditions of eubiosis (A) and dysbiosis (B) (Adapted from Baldi et al., 2021) Image caption: In eubiosis, a healthy gut microbiota interacts beneficially with brain health, facilitating the production of AHR ligands, SCFAs, and other neuroprotective metabolites like indole and kynurenic acid, which promote gut barrier improvement and reduce inflammation. These actions are supported by the activation of antioxidant enzymes and the SIRT1 pathway, enhancing the integrity of the blood-brain barrier. Conversely, dysbiosis shows increased gut barrier permeability and a reduction in beneficial bacteria, leading to cognitive dysfunction, increased neuroinflammation, and systemic issues such as endotoxemia and low-grade inflammation, which can adversely affect brain health (Adapted from Baldi et al., 2021) 6.2 Safety and ethical considerations The use of genetically modified microbes in SynComs raises several safety and ethical concerns. One major issue is the potential for unintended consequences, such as the horizontal transfer of engineered genes to native gut microbes or the environment, which could lead to unforeseen ecological impacts (Dou and Bennett, 2018; Martins et al., 2023). There is also the risk of engineered microbes evolving in ways that could make them harmful to the host or less effective over time (Landry and Tabor, 2017; van Leeuwen et al., 2023). Ethical considerations include the need for informed consent from individuals receiving these treatments and the potential for unequal access to these advanced therapies, which could exacerbate health disparities (Bober et al., 2018; Kumar et al., 2022). Additionally, public perception and acceptance of genetically modified organisms (GMOs) play a crucial role in the successful implementation of SynCom-based probiotics. Addressing these concerns requires robust safety assessments, transparent communication, and regulatory oversight (Bober et al., 2018; Dou and Bennett, 2018).
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