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Parkinson's disease (PD) is the second most common neurodegenerative disease, but the existing therapeutic drugs for PD have limitations; thus, there is an urgent need to discover new methods of prevention and treatment. Amomum tsaoko Crevost et Lemarie (AT) is a classic traditional Chinese medicine and food. Its main pharmacological effect is the regulation of the gastrointestinal tract. To date, no studies on the use of AT or its extracts to treat PD have been reported. In this study, a rotenone-induced PD mouse model was utilized to evaluate the protective effect of Amomum tsaoko flavonoids (ATFs) and to elucidate the role of the gut microbiota in this effect. The results demonstrated that ATFs not only ameliorated the motor and constipation symptoms but also reduced the loss of nigrostriatal dopaminergic neurons. Furthermore, ATFs reduced the expression of inflammation-related genes ( TNF-α , IL-1β , IL-6 , COX-2 , and MCP-1 ) and increased the expression of gut barrier-related genes ( Muc-2 , ZO-1 , Occludin , Claudin3 , and Claudin4 ) in the colon. Notably, ATFs were able to reverse rotenone-induced gut dysbiosis, including a significant decrease in the abundance of conditionally pathogenic bacteria ( Desulfovibrio , Provotellaceae UCG-001 , the Lachnospiraceae _ NK4A136_group , norank_f_Erysipelotrichacea , and the Eubacterium nodatum group ) and an increase in the abundance of probiotics ( Bifidobacterium and Faecalibaculum ). Interestingly, these genera were found to be significantly associated with PD motor symptoms and constipation indicators. This suggests that ATFs have the potential to alleviate PD symptoms through the modulation of gut microbes. These findings provide a solid foundation for further investigations into the anti-PD mechanism of ATFs and their potential in the prevention and treatment of PD.

Epidemiological and eradication trial evidence indicates that Helicobacter pylori , a major causative factor in peptic ulcer and gastric cancer, is a driver of the hypokinesia of Parkinson's disease (PD). Psychological (cognitive impairment, depression and anxiety) and gastrointestinal (peptic ulceration and constipation) PD features can precede the symptomatic onset of motor features by decades. We hypothesise that the non- H. pylori Helicobacters (NHPH), which have farm, companion and wild animals as their main hosts, can have a role in PD aetiopathogenesis. In those occupationally at risk of NHPH infection, we address whether there is increased mortality with PD, or depression or suicide. Our systematic review gave evidence that occupational exposure to animals/their products is associated with excess mortality with PD. Indeed, whilst livestock farming increased the risk, crop farming decreased it. Moreover, excess mortality from non-Hodgkin lymphoma in livestock farmers is compatible with NHPH being causal. Our scoping review showed that farmers, veterinarians and abattoir workers have an increased risk of depression and suicide; whether their depression is associated with being down the pathway to PD and/or the presence of Helicobacter infection needs investigation. Regarding Helicobacter species specificity, the link between the presence of NHPH in gastric biopsy and PD was described using a ureA polymerase chain reaction (PCR) assay, targeting the most-commonly named NHPH, H. suis . We describe its redesign and optimisation as a probe-based PCR, confirming the exclusion of H. pylori but not H. suis specificity (additionally identifying 6 species of a 22-NHPH-species panel). The exploration of the zoonotic hypothesis requires a non-invasive pan- Helicobacter PCR screen, allowing the detection and molecular grouping of Helicobacter species.

The gut microbiota, a diverse collection of microorganisms in the gastrointestinal tract, plays a critical role in regulating metabolic, immune, and cognitive functions. Disruptions in the composition of these microbial communities, termed dysbiosis, have been linked to various neurodegenerative diseases (NDs), such as Parkinson's disease (PD) and Alzheimer's disease (AD). One of the key pathological features of NDs is neuroinflammation, which involves the activation of microglia and peripheral immune cells. The gut microbiota modulates immune responses through the production of metabolites and interactions with immune cells, influencing the inflammatory processes within the central nervous system. This review explores the impact of gut dysbiosis on neuroinflammation, focusing on the roles of microglia, immune cells, and potential therapeutic strategies targeting the gut microbiota to alleviate neuroinflammatory processes in NDs.

Parkinson's disease (PD) is a complex neurodegenerative disorder. Recent evidence reveals connections between neuroinflammatory processes and intestinal microbiota alterations in the progression of this pathology. This comprehensive review explores the intricate relationships between them, highlighting their combined impact on PD. Neuroinflammation, characterized by immune activation in the central nervous system, is increasingly acknowledged as a critical factor in the development of PD. Concurrently, alterations in the gut microbiota composition have been linked to PD, suggesting a potential modulatory role in disease progression. Thus, bidirectional communication along the gut-brain axis has become pivotal in comprehending the pathogenesis of PD. Furthermore, we explore emerging therapeutic strategies that target these interconnected pathways, providing insights into potential avenues for PD treatment. The elucidation of these intricate relationships establishes a promising foundation for innovative therapeutic strategies aimed at altering disease progression and improving the quality of life for individuals affected by PD.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by numerous motor and non-motor symptoms. Recent data highlight a potential interplay between the gut microbiota and the pathophysiology of PD. The degeneration of dopaminergic neurons in PD leads to motor symptoms (tremor, rigidity, and bradykinesia), with antecedent gastrointestinal manifestations, most notably constipation. Consequently, the gut emerges as a plausible modulator in the neurodegenerative progression of PD. Key molecular changes in PD are discussed in the context of the gut-brain axis. Evidence suggests that the alterations in the gut microbiota composition may contribute to gastroenteric inflammation and influence PD symptoms. Disturbances in the levels of inflammatory markers, including tumor necrosis factor-α (TNF α), interleukin -1β (IL-1β), and interleukin-6 (IL-6), have been observed in PD patients. These implicate the involvement of systemic inflammation in disease pathology. Fecal microbiota transplantation emerges as a potential therapeutic strategy for PD. It may mitigate inflammation by restoring gut homeostasis. Preclinical studies in animal models and initial clinical trials have shown promising results. Overall, understanding the interplay between inflammation, the gut microbiota, and PD pathology provides valuable insights into potential therapeutic interventions. This review presents recent data about the bidirectional communication between the gut microbiome and the brain in PD, specifically focusing on the involvement of inflammatory biomarkers.

There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological disorders. We performed a systematic review of the different microbiota altered in a wide range of neurological disorders (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and stroke). Fifty-two studies were included representing 5496 patients. At the genus level, the most frequently involved microbiota are Akkermansia, Faecalibacterium, and Prevotella. The overlap between the pathologies was strongest for MS and PD, sharing eight genera (Akkermansia, Butyricicoccus, Bifidobacterium, Coprococcus, Dorea, Faecalibacterium, Parabacteroides, and Prevotella) and PD and stroke, sharing six genera (Enterococcus, Faecalibacterium, Lactobacillus, Parabacteroides, Prevotella, and Roseburia). The identification signatures overlapping for AD, PD, and MS raise the question of whether these reflect a common etiology or rather common consequence of these diseases. The interpretation is hampered by the low number and low power for AD, ALS, and stroke with ample opportunity for false positive and false negative findings.

Increasing evidence suggests that the gut microbiota and the brain are closely connected via the so-called gut-brain axis. Small intestinal bacterial overgrowth (SIBO) is a gut dysbiosis in which the small intestine is abundantly colonized by bacteria that are typically found in the colon. Though not a disease, it may result in intestinal symptoms caused by the accumulation of microbial gases in the intestine. Intestinal inflammation, malabsorption and vitamin imbalances may also develop. SIBO can be eradicated by one or several courses of antibiotics but reappears if the predisposing condition persists. Parkinson's disease (PD) is a common neurodegenerative proteinopathy for which disease modifying interventions are not available. Sporadic forms may start in the gut years before the development of clinical features. Increased gastrointestinal transit time is present in most people with PD early during the course of the disease, predisposing to gut dysbiosis, including SIBO. The role that gut dysbiosis may play in the etiopathogenesis of PD is not fully understood yet. Here, we discuss the possibility that SIBO could contribute to the progression of PD, by promoting or preventing neurodegeneration, thus being a potential target for treatments aiming at slowing down the progression of PD. The direct symptomatic impact of SIBO and its impact on symptomatic medication are also briefly discussed.

The exact etiology of Parkinson's disease (PD) remains largely unknown, but more and more research suggests the involvement of the gut microbiota. Interestingly, idiopathic PD patients were shown to have at least a 10 times higher prevalence of Helicobacter suis ( H. suis ) DNA in gastric biopsies compared to control patients. H. suis is a zoonotic Helicobacter species that naturally colonizes the stomach of pigs and non-human primates but can be transmitted to humans. Here, we investigated the influence of a gastric H. suis infection on PD disease progression through a 6-hydroxydopamine (6-OHDA) mouse model. Therefore, mice with either a short- or long-term H. suis infection were stereotactically injected with 6-OHDA in the left striatum and sampled one week later. Remarkably, a reduced loss of dopaminergic neurons was seen in the H. suis/ 6-OHDA groups compared to the control/6-OHDA groups. Correspondingly, motor function of the H. suis -infected 6-OHDA mice was superior to that in the non-infected 6-OHDA mice. Interestingly, we also observed higher expression levels of antioxidant genes in brain tissue from H. suis -infected 6-OHDA mice, as a potential explanation for the reduced 6-OHDA-induced cell loss. Our data support an unexpected neuroprotective effect of gastric H. suis on PD pathology, mediated through changes in oxidative stress.

Background: Parkinson's disease (PD) is currently the second most common neurodegenerative disorder, burdening about 10 million elderly individuals worldwide. The multifactorial nature of PD poses a difficult obstacle for understanding the mechanisms involved in its onset and progression. Currently, diagnosis depends on the appearance of clinical signs, some of which are shared among various neurologic disorders, hindering early diagnosis. There are no effective tools to prevent PD onset, detect the disease in early stages or accurately report the risk of disease progression. Hence, there is an increasing demand for biomarkers that may identify disease onset and progression, as treatment-based medicine may not be the best approach for PD. Over the last few decades, the search for molecular markers to predict susceptibility, aid in accurate diagnosis and evaluate the progress of PD have intensified, but strategies aimed to improve individualized patient care have not yet been established., Conclusions: Genomic variation, regulation by epigenomic mechanisms, as well as the influence of the host gut microbiome seem to have a crucial role in the onset and progress of PD, thus are considered potential biomarkers. As such, the human nuclear and mitochondrial genome, epigenome, and the host gut microbiome might be the key elements to the rise of personalized medicine for PD patients.

Progressive degeneration of neurons and aggravation of dopaminergic neurons in the substantia nigra pars compacta results in the loss of dopamine in the brain of Parkinson's disease (PD) patients. Numerous therapies, exhibiting transient efficacy have been developed; however, they are mostly accompanied by side effects and limited reliability, therefore instigating the need to develop novel optimistic treatment targets. Significant therapeutic targets have been identified, namely: chaperones, protein Abelson, glucocerebrosidase-1, calcium, neuromelanin, ubiquitin-proteasome system, neuroinflammation, mitochondrial dysfunction, and the kynurenine pathway (KP). The role of KP and its metabolites and enzymes in PD, namely quinolinic acid (QUIN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranillic acid (3-HAA), kunurenine-3-monooxygenase (KMO), etc. has been reported. The neurotoxic QUIN, N-methyl-D-aspartate (NMDA) receptor agonist, and neuroprotective KYNA-which antagonizes QUIN actions-primarily justify the Janus-faced role of KP in PD. Moreover, KP has been reported to play a biomarker role in PD detection. Therefore, the authors detail the neurotoxic, neuroprotective, and immunomodulatory neuroactive components, alongside the upstream and downstream metabolic pathways of KP, forming a basis for a therapeutic paradigm of the disease while recognizing KP as a potential biomarker in PD, thus facilitating the development of a suitable target in PD management.

The immune system has been increasingly recognized as a major contributor in the pathogenesis of Parkinson's disease (PD). The double-edged nature of the immune system poses a problem in harnessing immunomodulatory therapies to prevent and slow the progression of this debilitating disease. To tackle this conundrum, understanding the mechanisms underlying immune-mediated neuronal death will aid in the identification of neuroprotective strategies to preserve dopaminergic neurons. Specific innate and adaptive immune mediators may directly or indirectly induce dopaminergic neuronal death. Genetic factors, the gut-brain axis and the recent identification of PD-specific T cells may provide novel mechanistic insights on PD pathogenesis. Future studies to address the gaps in the identification of autoantibodies, variability in immunophenotyping studies and the contribution of gut dysbiosis to PD may eventually provide new therapeutic targets for PD.

Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. The highly bidirectional communication between the brain and the gut is markedly influenced by the microbiome through integrated immunological, neuroendocrine and neurological processes. The gut microbiota and its relevant metabolites interact with the host via a series of biochemical and functional inputs, thereby affecting host homeostasis and health. Indeed, a dysregulated microbiota-gut-brain axis in PD might lie at the basis of gastrointestinal dysfunctions which predominantly emerge many years prior to the diagnosis, corroborating the theory that the pathological process is spread from the gut to the brain. Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs primarily found in microorganisms and a dysregulation in their signaling may be implicated in α-synucleinopathy, such as PD. An overstimulation of the innate immune system due to gut dysbiosis and/or small intestinal bacterial overgrowth, together with higher intestinal barrier permeability, may provoke local and systemic inflammation as well as enteric neuroglial activation, ultimately triggering the development of alpha-synuclein pathology. In this review, we provide the current knowledge regarding the relationship between the microbiota-gut⁻brain axis and TLRs in PD. A better understanding of the dialogue sustained by the microbiota-gut-brain axis and innate immunity via TLR signaling should bring interesting insights in the pathophysiology of PD and provide novel dietary and/or therapeutic measures aimed at shaping the gut microbiota composition, improving the intestinal epithelial barrier function and balancing the innate immune response in PD patients, in order to influence the early phases of the following neurodegenerative cascade.