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The humoral route involves transporting bacterial products and pro-inflammatory cytokines from the gut to the CNS , causing central alfa-synuclein misfolding by inducing neuroinflammation
Dysbiosis, along with the release of Lipopolysaccharides (LPS) and inflammatory factors, with reactive oxygen/ nitrogen species and a leaky gut, induces misfolding of Alfa-Synuclein (SNCA). Misfolding Alfa-Synuclein (SNCA) resulted in abnormal aggregation and truncated fragments in the Enteric Nervous System (ENS) of Morbus Parkinson / Parkinson's Disease (PD) patients
The vagus nerve serves as a bidirectional communication pathway between the brain and the gut. It transmits signals for alfa-synuclein accumulation from the enteric nervous system to the central nervous system. Once these signals reach the central nervous system, neurons there initiate the over-expression, accumulation, and aggregation of alfa-synuclein
The aggregated and truncated fragments are transported from the Enteric Nervous System (ENS) to the Central Nervous System (CNS) via the vagus nerve and autonomic enteric fibers at a speed of 5-10 mm/day. It subsequently spreads through the brainstem, midbrain, basal forebrain and finally reaches the cortical areas
Due to an increase in Alfa-Synuclein (SNCA) aggregation in the Substantia nigra Pars compacta, eosinophilic Lewy bodies are formed in the cytoplasm, and mitochondrial dysfunction occurs in the Dopaminergic neurons resulting in their degradation, which stimulates an inflammatory response of the microglia. These pathological changes result in oxidative stress in the brain, which triggers cell apoptosis, and thus is involved in the initiation and progression of PD
The increase in oxidative stress further oxidizes and intensifies the abnormal Alfa-Synuclein (SNCA) aggregation in the brain
Recent evidence supports the involvement of the microbiota-gut-brain axis in the pathogenesis of Morbus Parkinson / Parkinson's Disease (PD). We propose that a pro-inflammatory intestinal environment, caused by intestinal hyper-permeability and/or microbial dysbiosis, initiates or exacerbates PD pathogenesis. One factor that can cause intestinal hyper-permeability and dysbiosis is chronic stress, which has been shown to accelerate neuronal degeneration and motor deficits in Parkinsonism rodent models.
TLR-4 knockout rotenone mice showed less pro-inflammatory microglia, less dopaminergic cell loss and less behaviour deficits compared with wild-type-rotenone
Recent studies indicate a strong correlation between the gut-brain axis and Morbus Parkinson / Parkinson's Disease (PD). The communication between the gastrointestinal system (GIT) and the central nervous system is bidirectional. It is hypothesized that PD may originate in the gut and spread to the brain via the vagus nerve, facilitating the propagation of alfa-synuclein, which targets the brain. The presence of Lewy bodies in the olfactory bulb, dorsal motor vagal nerve, and the enteric nervous system (ENS) of the gut suggests a peripheral and central correlation.
Microbiota-gut-brain axis in Morbus Parkinson / Parkinson's Disease (PD) means that neural and humoral communication routes link gut microbial dysbiosis with brain function in Morbus Parkinson / Parkinson's Disease (PD)
Morbus Parkinson / Parkinson's Disease (PD) is a progressively debilitating neurodegenerative disorder characterized by alfa-synucleinopathy, which affects all parts of the brain-gut axis, including the central, autonomic, and enteric nervous systems. The highly bidirectional communication between the brain and the gut is significantly influenced by the gut microbiota through integrated immunological, neuroendocrine, and neurological processes
Leaky gut promotes the increased translocation of pathogenic bacterial components (e.g., lipopolysaccharides (LPS)) and SCFAs from the intestinal mucosa into the systemic circulation. This translocation activates innate immunity, characterized by the production of pro-inflammatory cytokines, resulting in systemic inflammation and abnormal gut function. Systemic pro-inflammatory cytokines can cross the Blood Brain Barrier (BBB) and activate innate immune cells, particularly microglia and Astroglia / Astrocytes, leading to neuroinflammation. These mechanisms potentially impair central nervous system (CNS) function, causing alterations in cognition, behavior, and stress responses, which may ultimately contribute to or exacerbate Parkinson's Disease (PD).
Microbiota-based therapies, such as Antibiotics (J01), probiotics, and fecal microbiota transplantation (FMT), may inhibit the progression of Morbus Parkinson / Parkinson's Disease (PD) by addressing the underlying gut microbiota imbalances.
The Gram-negative Prevotellaceae play a role in enhancing mucin production within the intestinal mucosal layer. Consequently, a reduction in the abundance of Prevotellaceae might result in diminished mucin synthesis and heightened intestinal permeability. This can lead to greater exposure to bacterial antigens and endotoxins, which may trigger excessive alfa-synuclein expression in the colon and potentially in the brain as well.
During the first stages of Morbus Parkinson / Parkinson's Disease (PD), neurons of the ENS and the olfactory bulbs (OB) were found to contain aggregated and Phosphorylated Alfa-synuclein
see also:
Aberrant Folding / Misfolding & Alfa-Synuclein (SNCA)
Aggregation & Alfa-Synuclein (SNCA)
Alfa-Synuclein (SNCA) & Enteric nervous system (ENS)
Alfa-Synuclein (SNCA) & Morbus Parkinson / Parkinson's Disease (PD)
Brain-Gut-Microbiome-Axis / Gut-Brain Axis & Enteric nervous system (ENS)
Dysbiosis & Enteric nervous system (ENS)
Enteric Nervous System (ENS) & Neurodegeneration / Neurodegenerative Diseases (NDDs)
Enteric nervous system (ENS) & Neurological and Related Central Nervous System Disorders
Fecal Microbiota Transplantation (FMT) & Morbus Parkinson / Parkinson's Disease (PD)
Mitochondrial Dysfunction & Morbus Parkinson / Parkinson's Disease (PD)
Morbus Parkinson / Parkinson's Disease (PD) & Neuroinflammation
Morbus Parkinson / Parkinson's Disease (PD) & Pathogenicity / Pathology