Review of PD. Parkinson's disease (PD), first described in 1817, is the second most prevalent neurodegenerative disorder following Alzheimer's disease, affecting 1% of individuals >60 years of age. The rising global prevalence and aging population highlight the need to understand its complexities, making it a focus of contemporary neuroscience research. This section provides a comprehensive analysis of the history, epidemiology and clinical significance of PD (1).

Parkinson's disease affects 1-2% of individuals aged ≥55 years, primarily affecting movement due to the loss of dopamine-producing neurons in the substantia nigra. This disrupts the basal ganglia network, causing motor symptoms (2). Factors such as oxidative stress, mitochondrial dysfunction and protein accumulation contribute to neuronal death. Lewy bodies, abnormal protein aggregates, are another prominent degenerative feature of PD, causing neurodegeneration (3).

PD exhibits a wide range of motor and non-motor symptoms. The primary motor symptoms include tremors, bradykinesia, rigidity and postural instability. These are analyzed based on their progression, variation among patients, and affect daily life. Non-motor symptoms, such as cognitive dysfunction, depression, sleep disturbances, autonomic dysfunction and sensory abnormalities, sometimes manifest prior to onset of motor symptoms and significantly affect the quality of life of patients (4). PD presents a diverse range of symptoms and rates of progression, complicating diagnosis and treatment. Personalized medicine approaches, which consider genetic, molecular, and environmental factors, are crucial for improving patient outcomes.

PD is multifactorial, involving genetics, mitochondrial dysfunction, oxidative stress, neuroinflammation and gut microbiome alterations. Recent research suggests that the gut-brain axis (GBA) and mitochondrial dysfunction are interconnected in PD (5). The microbiome can influence mitochondrial function via metabolites such as short-chain fatty acids (SCFAs), and vice versa, and mitochondrial stress can affect the gut barrier and microbiome composition. Some mitochondrial disorders (e.g., POLG mutations) present with parkinsonian symptoms, which further supports the relevance (5). The exact cause of PD remains unknown, although multiple variables are considered to play a role. While the majority of PD cases are idiopathic, genetic mutations in the LRRK2, PARK7 and SNCA genes have been linked to familial PD. Certain genetic mutations and having close relatives with PD increase the risk of developing the disease. Additionally, environmental toxins and factors, such as pesticides, heavy metals and herbicides can enhance susceptibility (6).

Age is a critical risk factor for PD, with individuals aged >60 years being more likely to develop it. Notably, males are more prone to the disease than females, which may suggest sex-related differences in its pathogenesis (7). Variations in disease progression between male and female patients support the hypothesis that different pathogenic mechanisms or variations in the same mechanism may exist (8).

There is currently no reliable test available for PD; however, diagnosis relies on medical history, symptoms, neurological examination and dopamine-enhancing medication response. Misdiagnosis is common; however, neuroimaging techniques and biomarker initiatives, such as cerebrospinal fluid analysis for α-synuclein (α-syn), are being explored (3).

Although there is no cure for PD, medications help control symptoms. The most frequently used drug, levodopa, converts to dopamine in the brain. Other treatments include dopamine agonists, MAO-B inhibitors and anticholinergics (9). Surgical options, such as deep brain stimulation, involve implanting electrodes in the brain to manage motor symptoms (10). Additionally, physical therapy improves mobility, balance and flexibility, while speech therapy benefits those with speech and swallowing difficulties (11). In summary, an interdisciplinary approach to PD care involves medical treatments, lifestyle modifications, and support from family, friends, and community resources.

The present study aimed to summarize the published evidence on the role of the microbiome in the pathogenesis of PD. Initial research revealed that individuals with PD have a distinct gut microbiota composition compared to healthy controls. Consequently, marked changes in the gut microbiota between patients with PD and healthy individuals need to be investigated.

Another key finding is that certain bacterial groups are associated with the severity of both motor and non-motor symptoms of PD. Therefore, the association between the gut microbiota and clinical symptoms of PD warrants investigation. Additionally, the mechanisms through the gut microbiota influences the pathogenesis of PD need to be elucidated. Changes in the gut microbiota may lead to the development of neuroinflammation and the accumulation of α-syn, which significantly affects PD. It is equally essential to promote the discovery of novel diagnostic biomarkers and therapeutic targets, if feasible. These hypotheses and questions are discussed in the present review.

The present review article discusses the development of PD and the contribution of the microbiome to its pathology. Specifically, to conduct the review, sources from various scientific websites (such as PubMed) were reviewed, and relevant written reports were examined that highlighted the differences in the microbiome between a healthy individual and one suffering from PD. The present review compares the composition of the gut microbiome and related biological markers in patients with PD and healthy controls, using a case-control methodology. By focusing on both motor and non-motor symptoms, this approach aims to identify connections between gut microbiome dysfunction and the pathogenesis of PD. The findings were processed and reported herein. Equally important was the inclusion of other factors that contributed to the progression of the pathology of the disease in relation to the microbiome. Through the integration of microbiological, clinical data and biomarkers, this approach aims to offer a comprehensive method for researching the association between the gut microbiome and PD. In order to provide potential pathways for targeted therapeutic interventions for the microbiome, the present review discusses how gut dysbiosis may contribute to the onset and progression of PD.

The theory of the GBA has garnered significant attention over recent decades, highlighting the profound impact of the gastrointestinal system on brain function and vice versa. The central nervous system (CNS), comprising the brain and spinal cord, serves as the primary control center for processing and coordinating information (16). It communicates with the gut through various pathways to regulate physiological processes and behaviors. The GBA is a bidirectional communication network that links the CNS to the gastrointestinal tract. This system integrates neurological, endocrine, and immune pathways, with the gut microbiota playing a pivotal role in modulating these connections (17). Understanding the GBA is essential for elucidating the mechanisms underlying numerous physiological processes and the pathophysiology of a wide range of conditions, including mental health disorders, neurodegenerative diseases, and gastrointestinal issues (18).

The vagus nerve serves as the primary neurological connection between the gut and the brain. It transmits sensory information from the gastrointestinal tract to the brain, while delivering motor commands from the brain to regulate gut activities. Additionally, other nerves, such as spinal afferents, contribute to this transmission (19). Hormones and neuropeptides also function as chemical messengers in the GBA. For example, ghrelin and leptin are gut-derived hormones that regulate hunger and energy balance by acting on the hypothalamus. The gut microbiota transforms dietary components into bioactive compounds, such as SCFAs, bile acids and neurotransmitter precursors. These metabolites can influence brain function by crossing the blood-brain barrier or interacting with peripheral receptors (20).

Emerging evidence suggests that the GBA may be implicated in the pathological mechanisms underlying PD. Gastrointestinal symptoms often precede motor symptoms and the diagnosis of PD, and alterations in the gut microbiota may influence the accumulation of α-syn, a hallmark of the disease (21). While the GBA presents opportunities for therapeutic intervention, further research is required to fully understand its role and develop effective treatments.

The term ‘neuroinflammation’ refers to inflammation occurring within the brain and CNS, primarily as a result of immune system activation in response to various stimuli. These stimuli may include diseases, toxins, or physical injuries. Dysbiosis, an imbalance in the gut microbiome, has been identified as a key factor in triggering or exacerbating neuroinflammation in numerous cases. Understanding the association between the gut microbiome and neuroinflammation is crucial to elucidating the mechanisms through which gut health affects brain function and contributes to neuropsychiatric and neurodegenerative diseases (22).

The immune system of the brain uses neuroinflammation as a defense mechanism against harmful stimuli. Key components include microglia, astrocytes and cytokines. Microglia are the primary immune cells, releasing pro-inflammatory cytokines to protect neurons. Astrocytes regulate inflammation and prevent damage but may promote it under certain conditions. Molecules, such as TNF-α, IL-1β and IL-6 play critical roles in immune responses. However, chronic neuroinflammation damages neurons and accelerates neurodegenerative processes (20).

The gut microbiota, a vast community of microorganisms in the body, particularly in the gut, has been linked to neuroinflammation. Dysbiosis, caused by an overgrowth of certain bacterial strains or reduced diversity of beneficial bacteria, has been associated with conditions, such as rheumatoid arthritis, colitis, hypertension and multiple sclerosis (MS). Studies using experimental autoimmune encephalomyelitis, a key animal model of MS, have highlighted the importance of microbial metabolites, such as tryptophan or SCFAs. In PD, neuroinflammation is increasingly linked to gut dysbiosis, which may exacerbate both motor and non-motor symptoms (23). Gut bacteria influence CNS physiology and inflammation through mechanisms, such as the vagus nerve, immune pathways and microbial metabolites or products, as presented in Table I. Dysbiosis disrupts these pathways, leading to neuroinflammation and changes in the permeability of the blood-brain barrier (24). Reducing neuroinflammation is vital for maintaining brain health and preventing or mitigating neurological disorders, including PD, MS, Alzheimer's disease and depression. Strategies to achieve this include dietary modifications, pharmacological treatments, alternative therapies and lifestyle changes (25).

Promoting gut health indirectly reduces neuroinflammation through the GBA. Prebiotics (e.g., fiber from fruits, vegetables and whole grains) nourish beneficial gut bacteria, while probiotic-rich foods (e.g., yogurt, kefir and fermented vegetables) support a balanced gut microbiome. Regular cardiovascular activities, such as walking, jogging, cycling or swimming, when performed three to five times a week, also m reduce neuroinflammation (15). Chronic stress is a major contributor to neuroinflammation, as it stimulates the hypothalamic-pituitary-adrenal axis and promotes pro-inflammatory cytokine production. Therefore, a multifaceted approach involving dietary adjustments, stress reduction, regular exercise and, when necessary, pharmacological interventions, can mitigate neuroinflammation. This combined strategy protects against the development of neurodegenerative diseases and enhances overall mental well-being (24).

The association between the microbiome and α-syn, a protein linked to PD, has garnered significant interest within the scientific community. This connection suggests that gut health plays a crucial role in the development and progression of neurodegenerative diseases (26). The α-syn protein is typically found in neurons, although it has the capacity to misfold and aggregate into toxic clumps known as Lewy bodies, a hallmark of PD. These aggregates contribute to motor symptoms and neurodegeneration associated with the disease. The enteric nervous system (ENS), which governs gastrointestinal functions, and the brain both contain α-syn (27).

Research indicates that α-syn aggregates may form in the gut years before symptoms manifest in the brain. This raises the possibility that the causes of PD may, in some cases, originate in the gut (28). For instance, constipation, a common gastrointestinal symptom, often precedes the motor symptoms of PD by several years. According to this hypothesis, misfolded α-syn may originate in the gut, travel along the vagus nerve, and ultimately reach the brain, contributing to the neurodegeneration seen in Parkinson's disease. Dysbiosis, or an imbalance in the gut microbiome, may facilitate the misfolding of α-synuclein. Imbalances in gut bacteria can increase intestinal permeability, often referred to as a ‘leaky gut’, allowing bacterial endotoxins, such as lipopolysaccharide (LPS) to enter the bloodstream (26). This chronic low-grade inflammation can influence the brain via systemic and gut-specific inflammatory pathways, activating immune cells in the ENS and contributing to the production and aggregation of misfolded α-synuclein in the nervous system (29).

Research using mouse models of PD has revealed that germ-free mice exhibit a reduced α-syn aggregation and less severe motor impairments compared to mice with a normal gut microbiome. Conversely, transplanting gut microbiota from patients with PD into germ-free mice increases α-syn aggregation and exacerbates motor symptoms, indicating a potential role of specific microbial communities in disease progression (30).

SCFAs, typically anti-inflammatory, may in some cases contribute to neuroinflammation and α-syn aggregation, particularly in the context of dysbiosis. Certain Gram-negative bacteria in the gut produce LPS, a potent inflammatory agent, capable of crossing the blood-brain barrier and influencing neuroinflammation and protein misfolding (25). Furthermore, serotonin synthesis, a neurotransmitter affected in PD, is linked to tryptophan metabolism, which is modulated by the gut flora. Alterations in tryptophan metabolism may exacerbate neuroinflammation and α-syn-associated pathology (28).

On the other hand, beneficial bacteria, such as Lactobacillus and Bifidobacterium, are associated with improved gut health and reduced inflammation. These bacteria may exert neuroprotective effects by mitigating α-synuclein aggregation and promoting a balanced immune response (24).

The association between the microbiome and α-syn underscores the significance of gut health in neurodegenerative diseases, such as PD. By increasing gut permeability, activating immune responses and generating pro-inflammatory agents, dysbiosis may facilitate the misfolding and aggregation of α-syn. Addressing gut dysbiosis through microbiome-targeted therapies may provide a promising avenue for mitigating or reversing the progression of PD.

Multiple clinical studies have consistently demonstrated significant alterations in the gut microbiota composition of patients with PD compared to that of healthy individuals. In one of the earliest comprehensive studies, Scheperjans et al (31) analyzed the gut microbiota of 72 patients with PD and 72 matched controls. They observed a marked reduction in the amount of Prevotellaceae, a family of beneficial bacteria associated with gut health, in patients with PD. Prevotella species produce SCFAs, which possess anti-inflammatory properties and help maintain the integrity of the gut barrier. The diminished abundance of Prevotellaceae in patients with PD suggests a possible connection between gut dysbiosis and the neuroinflammatory processes characteristic of the disease (32).

Keshavarzian et al (33) further investigated the gut microbiota of 38 patients with PD and 34 healthy controls, confirming a decrease in the number of beneficial bacteria, such as Lactobacillus and Bifidobacterium. These bacteria support gut barrier integrity and immune balance. Their study also identified an increase in the amount of Enterobacteriaceae, a bacterial family known to produce LPS, potent endotoxins that can induce systemic inflammation and neuroinflammation in patients with PD (33).

Several studies have highlighted the association between gut microbiota composition and the severity of motor symptoms in PD. For instance, Heintz-Buschart and Wilmes (34) analyzed 197 patients with PD and 130 controls, identifying a significant association between increased levels of Proteobacteria, particularly Enterobacteriaceae, and greater motor dysfunction. Similarly, Hill-Burns et al (35) reported that patients with PD with more severe motor symptoms exhibited higher levels of Lachnospiraceae and Akkermansia, suggesting that specific microbial communities may influence both disease onset and symptom progression.

The GBA, a crucial communication link between the gastrointestinal tract and the CNS, is affected by neurodegenerative disorders such as PD, with gut dysbiosis causing increased permeability.

Forsyth et al (26) conducted one of the first clinical studies linking PD with increased intestinal permeability. They found that patients with PD exhibited a significantly higher gut permeability, as evidenced by the presence of bacterial products in the bloodstream, compared to healthy controls. This finding underscores the potential of gut inflammation and barrier dysfunction as early contributors to the pathogenesis of PD (26).

Animal studies also support these findings. Perez-Pardo et al (36) demonstrated that gastrointestinal inflammation and microbiota changes in mice induced α-syn aggregation in the gut, which subsequently travelled to the brain. Although conducted in animal models, these results align with human clinical data, further strengthening the connection between gut dysbiosis, inflammation and PD (37).

PD often begins with non-motor symptoms, such as depression, cognitive decline and gastrointestinal disturbances. Sampson et al (38) found a significant association between gut dysbiosis and non-motor symptoms in PD, including gastrointestinal dysfunction. Their study on 103 patients with PD and 103 controls revealed a higher prevalence of pro-inflammatory bacteria, such as Proteobacteria, and a reduction in SCFA-producing bacteria in patients with PD (38).

Finally, the composition of the gut microbiome has been linked to cognitive decline in patients with PD. Unger et al (39) reported that patients with cognitive impairment had a distinct gut microbiota composition compared to those without cognitive decline, including a reduction in anti-inflammatory bacteria. This suggests that gut dysbiosis may contribute to cognitive symptoms in PD (39).

Patients with PD often exhibit a decrease in microbial diversity, or alpha diversity, which is linked to various diseases and dysbiosis (27). The diversity of the gut microbiome is crucial for identifying neurological disorders. Patients with PD exhibit significant changes in their gut microbiome composition, which are linked to symptoms such as neuroinflammation, intestinal barrier dysfunction and pathological lesions such as α-syn protein accumulation. The association between neurological disorders and gut microbiome diversity is not yet understood (40).

Patients with PD have a distinct gut microbiome composition, with varying levels of certain bacteria, suggesting a potential link between dysbiosis and disease severity. Prevotellaceae bacteria, known for producing anti-inflammatory SCFAs, such as butyrate, produce lower concentrations in patients with PD, potentially causing inflammation and increased intestinal permeability, also known as leaky gut (41).

Furthermore, pathogenic bacteria that induce inflammation, such as Escherichia coli and Klebsiella, are members of the Enterobacteriaceae family and produce endotoxins, such as LPS. Elevated levels of Enterobacteriaceae have been associated with increased inflammation in the stomach and CNS, leading to neurodegeneration in individuals with PD. Additionally, a bacterium known as Akkermansia muciniphila breaks down mucus and promotes the regeneration of the intestinal mucosa. While Akkermansia is considered beneficial, its high abundance in individuals with PD may lead to the excessive breakdown of intestinal mucus, thereby increasing intestinal barrier permeability and promoting inflammation (19).

Furthermore, hydrogen sulfide produced by Desulfovibrio bacteria is a gas that can damage the intestinal mucosa. Patients with PD have higher levels of these bacteria in their bodies, which is associated with gut dysbiosis and may also contribute to the worsening of motor symptoms in the disease. Furthermore, bacteria from the Ruminococcaceae family aid in the digestion of plant fibers and the production of SCFAs, which are essential for a healthy gut microbiota. Patients with PD often have fewer of these bacteria in their bodies, which may affect digestion and worsen intestinal inflammation (42).

Finally, the Lactobacillaceae family of bacteria is known for its probiotic properties, as well as its role in immune system regulation and lactic acid production. Therefore, patients with PD have significantly various levels of Lactobacillaceae, which may affect the balance of gut flora and inflammatory processes (40-43).

The altered composition of the gut microbiome in patients with PD raises the possibility that gut health, and the neurodegeneration characteristic of the disease are intricately linked. By worsening disease symptoms, gut dysbiosis appears to be associated with inflammation and the accumulation of α-syn, as evidenced by the increase in pathogenic microorganisms, such as Enterobacteriaceae, and the reduction of beneficial bacteria, such as Prevotellaceae (32). Understanding these changes could provide novel therapeutic avenues, including the administration of probiotics or alternative measures aimed at modulating the microbiome.

The composition of the human gut microbiome varies significantly across different populations due to cultural, dietary and geographical factors. These variations have profound implications for the development and progression of diseases, including PD. Diet is one of the most influential factors shaping the gut microbiome. Populations with diets rich in plant-based, fibber-rich foods, such as those in Mediterranean or Asian countries, tend to have higher gut microbiota diversity. Elevated levels of beneficial bacteria, such as Bifidobacterium and Lactobacillus are associated with these diets, which are linked to anti-inflammatory effects and improved gut barrier integrity (14). By contrast, Western diets, characterized by a high consumption of refined sugars, saturated fats and processed foods, are associated with reduced microbial diversity and the increased prevalence of pro-inflammatory bacteria, such as Enterobacteriaceae. These dietary patterns may exacerbate gut dysbiosis, a factor implicated in the pathology of PD (34). Fermented foods, a staple in a number of traditional diets (e.g., kimchi in Korea or kefir in Eastern Europe), are rich in probiotics such as Lactobacillus. These foods support the balance of the gut microbiota and may help mitigate dysbiosis observed in patients with PD. Cultural practices, such as fasting, which alter gut microbiota composition, also have potential therapeutic implications for PD (14). These dietary influences may partially explain why the prevalence and severity of PD vary across regions. For example, it has been suggested that Asian countries have lower prevalence rates of PD compared to Western countries, due to differences in traditional diets and lifestyle factors (40).

Geographical location significantly affects the microbiome through environmental exposures, lifestyle differences and cultural dietary preferences. Rural populations in Africa and South America have a dominant microbiome dominated by fibber-fermenting bacteria, producing essential SCFAs, such as butyrate for gut health and inflammation modulation, while urbanized populations in Europe and North America have lower levels of Prevotella (32).

While these patterns provide valuable insight, individual variability, genetic predispositions and confounding factors, such as the use of medications and socioeconomic status should also be considered. Future research is required to focus on cross-cultural analyses to elucidate the interactions between dietary habits, microbiome composition and the risk of developing PD.

Studies examining the association between the gut microbiome and the onset of PD symptoms are rapidly expanding. According to recent research, dysbiosis or alterations in the gut microbiome, may play a crucial role in the development and progression of PD symptoms. Evidence suggests that the gastrointestinal tract may be an early source of pathology in PD, with gut-related symptoms, such as constipation, sometimes manifesting years prior to the onset of motor symptoms (44).

The ENS and CNS communicate bidirectionally via the GBA, involving the vagus nerve, immune pathways and microbial metabolites. Disruptions in this communication pathway, caused by gut dysbiosis, have been linked to neuroinflammation and neurodegeneration in PD (17,19).

There is a theory suggesting that α-syn may initially accumulate in the ENS as a response to toxins from pathogenic microorganisms. The accumulated α-syn protein may then pass through the vagus nerve and reach the brain, potentially leading to neurodegeneration in PD (44). This notion is supported by the discovery of α-synopathy in the gastrointestinal tissues of patients with PD, even in the preliminary stages of the disease. At the same time, reduced levels of butyrate may render the gut less capable of maintaining a protective barrier, thus increasing intestinal permeability and facilitating the entry of bacterial endotoxins, such as LPS, into the bloodstream. These endotoxins may enter the brain and worsen the symptoms of PD by inducing neuroinflammation and neuronal death.

The vagus nerve, a direct pathway between the stomach and brain, may be involved in transmitting misfolded proteins or inflammatory signals from the stomach to the brain. Studies show that the surgical severing of the vagus nerve reduces the risk of developing PD (45). Gastrointestinal issues, such as constipation, are common in individuals with PD, thus suggesting that gut-related mechanisms may influence the early pathogenesis of the disease. In some cases, α-syn accumulation in the ENS may occur before the brain (46)

There is strong evidence to indicate that the onset and progression of PD symptoms are significantly influenced by the gut microbiota. The misfolding of α-syn, increased intestinal permeability and neuroinflammation appear to be impacted by dysbiosis in patients with PD. Restoring microbial balance through therapies has the potential to alleviate both motor and non-motor symptoms of the disease, making the GBA a promising therapeutic target. In order to fully understand the processes related to the microbiome and PD and to develop effective microbiome-based treatments, further research is warranted (47).

The association between PD and the gut microbiome is becoming increasingly evident, as research indicates that changes in the composition of gut microbes can have a significant effect on the development and progression of the symptoms of the disease (48). The vagus nerve, immune pathways and the production of microbial metabolites, such as SCFAs, are among the communication channels that link the gut and the CNS via the GBA (49).

Notable alterations in gut flora, known as dysbiosis, have been repeatedly reported in patients with PD (50). The amounts of beneficial bacteria, such as Prevotellaceae, are reduced, while potentially harmful bacteria, including Enterobacteriaceae and Akkermansia muciniphila, proliferate (51). The reduction in the amount of Prevotellaceae is associated with the decreased production of SCFAs, such as butyric acid, a crucial compound that maintains gut barrier integrity and possesses anti-inflammatory properties (52). The deficiency of butyric acid makes the gut more permeable, facilitating the entry of harmful compounds into circulation, such as lipopolysaccharides or bacterial endotoxins (53). These molecules can exacerbate neurodegenerative processes in the brain and induce systemic inflammation (54).

The rise in opportunistic infections due to the endotoxins of Enterobacteriaceae bacteria can exacerbate inflammation, potentially affecting the CNS and worsening the symptoms of PD. Increased concentrations of these bacteria are linked to more severe motor symptoms in patients with PD, highlighting their role in the progression pf the disease (22).

PD may be linked to α-syn, a misfolded protein that accumulates in the brain. Recent data suggest that this misfolding may begin in the ENS, be influenced by gut dysbiosis, and then pass through the vagus nerve to the brain. The ‘intestinal origin’ theory suggests microbial imbalances in the gut may cause α-syn accumulation in the brain. The presence of α-syn aggregates in the ENS and the early onset of gastrointestinal issues highlight the importance of gut health in the early development of PD (55).

This knowledge of the GBA in PD has significant therapeutic implications. Probiotics, prebiotics, dietary modifications and fecal microbiota transplantation (FMT) are some examples of microbiome-centered interventions that provide promising means for restoring microbial balance, reducing neuroinflammation and potentially alleviating symptoms of PD. Preliminary resesarch suggests that these approaches can modify the gut microbiome and improve the progression of the disease in both human and animal models (56). The increased synthesis of SCFAs and beneficial bacterial populations can be achieved through the use of probiotics and dietary fibers. This could improve gut health and potentially attenuate the inflammatory cascade associated with neurodegeneration. FMT has exhibited promise in restoring a a healthy gut microbiome, potentially correcting dysbiosis and delaying the progression of PD, despite its experimental nature (57).

In summary, the association between the gut microbiome and PD is a critical area of study that promises cutting-edge therapeutic approaches. Dysbiosis, defined as the overgrowth of pathogenic microbes and the reduction of beneficial bacteria, is considered to be a key factor in the development and progression of PD. Neuroinflammation and the accumulation of α-syn in the brain may be caused by gut imbalances via the GBA, specifically through the vagus nerve and immune pathways. Understanding these processes may lead to the development of novel therapeutic strategies aimed at shaping the gut microbiome, increasing the prospect of better control and possibly even the prevention of PD (40).