Fig. 2. The common regulatory network of microbial metabolites, inflammatory diseases and CNS disorders.

The common initiating factors for the four neurological diseases are genetic predisposition and environmental factors, which include diet and lifestyle. Under pathogenic conditions, the intestinal barrier can be breached, and systemic inflammatory responses can occur. These changes can be followed by dysbiosis (i.e., decreased gut microbial diversity leading to decreased levels of beneficial microbes). For example, consumption of a diet high in calories and fat but low in dietary fiber can accelerate pathogenic dysbiosis. As a result, decreased levels of beneficial gut microbial metabolites such as SCFAs, Trp metabolites and phytochemicals are produced, and simultaneously, the production of harmful metabolites such as long-chain fatty acids (LCFAs), certain bile acid metabolites, and toxic microbial metabolites increases, thereby affecting immune and tissue cells in both the intestine and CNS. These changes can decrease immune tolerance, which is important for preventing autoimmune diseases, and exacerbate pathogenic immune responses mediated by inflammatory cells such as Th17 and Th1 cells. These pathogenic inflammatory responses can contribute to tissue damage (demyelination in MS), neuronal cell death (PD and AD), and neuronal synapse development (ASD). Moreover, certain microbial metabolites regulate neurotransmission and, therefore, can directly affect neurological activity.