Investigation of the relationship between oligodendrocyte damage and intestinal microbiome diversity

Human and animal studies have revealed that the gut microbiome may play a role in the pathology of demyelinating diseases. The majority of research on this subject has sought to elucidate the pathogenesis of demyelination by focusing on the inflammatory process induced by intestinal flora dysbiosis. The understanding fostered by the concept of the "gut-brain-axis" has prompted investigations into the unidirectional effects of intestinal flora dysbiosis on the central nervous system. However, the potential bidirectionality of this axis has not been explored. In this study, the relationship between myelin, the glial component of memory, and intestinal flora was examined bidirectionally under the control of α-synuclein, interleukin-3, and tumor necrosis factor-α markers. Molecular and biochemical investigations of gut dysbiosis effects on myelin production were conducted using polymerase chain reaction and ELISA. Additionally, the impact of hippocampal myelin damage on gut flora was assessed through metagenomic sequencing. Moreover, the influence of the interaction between gut dysbiosis and myelin damage on memory and motor performance was evaluated using behavioral mazes. The findings revealed that antibiotic-induced intestinal dysbiosis suppressed the production of hippocampal myelin basic protein (p = .001) and oligodendrocyte-specific protein (p = .158). Conversely, hippocampal myelin damage was found to cause intestinal dysbiosis by elevating the levels of α-synuclein (p = .001) in vagus samples and α-synuclein (p = .014), tumor necrosis factor-α (p = .035), and interleukin-3 (p = .016) in colon samples. Similarly, gut dysbiosis induced by antibiotics was observed to reduce claudin-5 levels in colon tissue (p = .001), suggesting that inflammation in the intestine could spread to systemic circulation, as indicated by increased plasma α-synuclein levels (p = .001). At the behavioral level, it was demonstrated that myelin damage impairs spatial memory performance and leads to heightened expression of anxiety-like behaviors. Consequently, the notion that myelin is static and solely associated with demyelinating disorders is no longer tenable. The concept of "myelin plasticity," which is increasingly permeating the literature on learning physiology, has been integrated into the "gut-brain axis" studies of synaptic memory theory. As such, the "myelin-microbiome axis" has emerged as a conceptual advancement, providing hypothetical explanations and practical solutions to the unexplained symptoms of early memory impairments in demyelinating diseases.