Damian Sendler: For people with Parkinson’s disease, one of the most debilitating non-motor symptoms is gastrointestinal distress (PD). Pathogenetically, it has been suggested that the gastrointestinal tract is the first site of pathological changes in Parkinson’s disease (PD). Pathology in Parkinson’s disease (PD) may be exacerbated by inflammation and changes in the gut microbiota. However, in Parkinson’s disease, the mechanisms underlying this “gut-brain” axis are still unknown.. Patients with Parkinson’s disease may experience a wide range of gastrointestinal symptoms, which can impair their quality of life and cause them emotional pain. Neurological outcomes can be negatively impacted by gastrointestinal disorders, which can limit the ability of patients to respond to medications. Though gastrointestinal disorders in Parkinson’s disease (PD) are receiving more attention in research, little is known about them, and treatment options are limited as a result. This review summarizes our knowledge of the importance of the “gut-brain” axis in the pathogenesis of Parkinson’s disease, discusses the impact of gastrointestinal disorders in patients with Parkinson’s disease, and offers clinical guidance for their management.
Damian Jacob Sendler: Neurodegenerative disorder Parkinson disease (PD) affects 1% of the global population over the age of 60 [1]. It has been established that the progression of dopaminergic nigrostriatal innervation deficits and the presence of Lewy bodies and abnormal -synuclein aggregates in various brain regions characterize Parkinson’s disease (PD) [2]. As a result of dopaminergic loss in the striatum, Parkinson’s disease (PD) sufferers develop a variety of motor and nonmotor symptoms, including tremors, bradykinesia, rigidity, and posture and gait impairment [3]. A major source of disability and decreased quality of life, PD-related GI disorders are important factors in the clinical care of PD patients, making them central considerations. PD pathogenesis may be influenced by gut inflammation and changes in the intestinal microbiota, according to a growing body of evidence [4].
Dr. Sendler: GI disorders and Parkinson’s disease are discussed in this review. The role of the GI tract in the pathogenesis of Parkinson’s disease (PD) is summarized, and the “gut-brain” axis is discussed. Finally, we discuss the most important PD-related digestive issues and their practical effects on neurological function.
It was proposed in 2003 that Parkinson’s disease may be caused by an unknown neurotropic pathogen that can cross the mucosal barrier of the GI tract, cause abnormal -synuclein aggregation in the enteric nervous system (ENS), and then spread retrogradely axonal transport through the vagus nerve (VN) to both DMV and the brain [5]. Initial neuropathological findings of LBs in the DMV of PD patients supported this hypothesis [6]. Five people with brain LBs pathology had gastric -synuclein immunoreactive inclusions in their myenteric Auerbach and submucosal Meissner plexuses [7]. A mechanistic basis for Braak’s hypothesis was provided by evidence that misfolded -synuclein can act as a template, causing additional -synuclein to misfold and form insoluble inclusions that can spread from neuron to neuron [8,9].
Patients in the prodromal or manifest stages of Parkinson’s disease (PD) have been studied for the past two decades to determine whether or not they have gastrointestinal accumulations of -synuclein aggregates. However, results from these studies have been mixed. In patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD), a predispositional marker of Parkinson’s disease, phosphorylated -synuclein deposition has been found in the submucosal nerve fibers or ganglia, as well as in the ENS of gastric, duodenal, and colonic biopsies taken from PD patients years before the onset of motor signs [10, 11–13]. Because of this, it is possible that PD’s prodromal phase has pathogenic changes. Despite this, only a few cases of gastrointestinal -synuclein pathology have been reported [14]. Comparing the intestinal samples of PD patients and healthy age-matched controls, similar -synuclein or phosphorylated—synuclein immunoreactivity was also reported [15,16], although quantitative morphometry could detect differences in the amount and pattern of phosphorylated—synuclein aggregates in both groups [16]. One explanation for the wide range of pathological findings is that there are no standard immunohistochemical protocols, different GI tract sites are examined, and the peripheral nervous system has a wide and heterogeneous distribution. It is possible to resolve some of these discrepancies by applying new functional imaging technologies, such as the quantification of acetylcholinesterase density in peripheral organs by using the PET tracer, [11C]-donepezil, to the parasympathetic gut innervation, which is a validated method [18]. The cholinergic innervation of the intestine is impaired during the prodromal phase of Parkinson’s disease (PD), as evidenced by studies on early-stage PD patients [19, 20] and in a cohort of patients with iRBD [21, 22]. Some of these findings have been confirmed in patients with and without prodromal RBD who have recently been diagnosed with Parkinson’s disease (PD) (i.e. prior to parkinsonism). The 123I-metaiodobenzylguanidin (MIBG) heart:mediastinum ratios of PD patients with prodromal RBD were reduced, as were the colon [11C]-donepezil uptake values, the enlarged colon volumes, and the delayed colonic transit times [21]. Although RBD and iRBD patients had similar MIBG and donepezil PET scans, it was surprising that the two groups had similar results. There is a subset of Parkinson’s disease (PD) patients (those without prodromal RBD) that does not fit into the “gut-brain” theory because they have primary loss of putaminal FDOPA uptake with secondary sympathetic and parasympathetic denervation (thus following a “brain-first” trajectory), but these findings also confirm the existence of a “gut-first” subtype in the general population of PD sufferers. -synuclein pathology may begin in the enteric and parasympathetic nervous systems, resulting in prodromal GI disorders such as constipation, and then spread to the sympathetic nervous system and lower brainstem, resulting in prodromal RBD [21].
How does -synucleinopathy get to the brain if it starts in the gut? -synuclein may be transported from the ENS to the brain via the VN, according to some researchers. Preganglionic efferents from the DMV in rats express -synuclein and form synapses with intrinsic neurons in the stomach and duodenum myenteric plexus that are -synuclein-positive [22]. The involvement of the VN has been confirmed in animal models of Parkinson’s disease. It has been shown that low dose rotenone injections in the stomach caused a rise in the ENS and spread to the DMV and SNpc with selective dopaminergic cell loss [23] when injected into mice [24, 25]. Mice pre-treated with hemi-vagotomy were able to prevent some of these pathological effects and motor deficits [24]. Similarly, in experiments evaluating the effects of injections of recombinant adeno-associated viral vectors (AAV) that express adenosynuclein in the VN of the rat neck or pathological forms of adenosynuclein in the gut, similar results supporting a caudo-rostral spread were also found. Pathological -synuclein was injected into the intestinal wall of rats, which led to the spread of -synuclein to the VN, DMV, and brain stem in a time-dependent manner in the later experiments [26]. An inoculation of -synuclein pre-formed fibrils (PFF) into the mouse GI tract caused LB-like aggregates in the DMV, but no further caudo-rostral propagation was observed afterward [27]. When dopaminergic cells in the duodenum and pyloric muscle layer of mice were administered PFF to cause pathological -synuclein propagation up to and onto the SNpc, motor deficits developed [28]. Truncal vagotomy prevented the caudo-rostral spread of pathological -synuclein and the beginning of behavioral deficits. For example, in another mouse model, duodenal -synuclein PFF inoculation was capable of interfering with digestion, increasing phosphorylated myenteric -synuclein, and reducing striatal dopamine in aged mice [29].
People who have undergone vagotomy have a higher risk of developing Parkinson’s disease compared to those who have not had the procedure, according to large population-based studies (for a comprehensive review of this topic, the reader is directed elsewhere [30]). Vagotomy, particularly truncal vagotomy, may reduce the risk of developing Parkinson’s disease (PD) more than five years after the procedure [31,32]. The vermiform appendix is the first place where enteric -synuclein aggregation occurs because of its high content of -synuclein, the lack of a blood-tissue barrier in the mucosa, and the connection with vagal efferents [34]. Some studies have found that appendicitis can delay the onset of Parkinson’s disease and even reduce the risk of developing the disease by 19.3% [35,36]. According to these findings, patients who underwent appendicitis were more likely to develop Parkinson’s disease (PD) than those who did not have the procedure [37,38]. Vagotomy appears to have a protective role, while appendicitis appears to have a less clear association with PD risk reduction.
A “leaky” intestinal epithelial barrier may allow factors such as bacterial lipopolysaccharide (LPS) to enter the gut lumen and reach the ENS, despite the fact that it is supposed to keep the pro-inflammatory contents of the intestine out of the bloodstream. Colonic (but not small intestine) barrier permeability appears to be increased in patients with Parkinson’s disease [39].
Sugar that is ingested orally is excreted in the urine, which can be used to evaluate the barrier function of various intestinal sites. In the small intestine, changes in mannitol and lactulose excretion reflect changes in permeability, while changes in colonic permeability are evaluated using either sucralose or chromium-labeled EDTA [39]. PD patients had higher 24-hour urinary excretion of sucralose than did controls [40], but there were no differences in the excretion of mannitol or lactulose in the urine [41], suggesting that the colon was the only organ with increased permeability.
It is also possible to measure alpha-1-antitrypsin and zonulin in the feces, which can be used to evaluate the intestinal barrier in vivo. The increased faecal concentration of the tight junction-associated cytoplasmic protein zonulin (Zonulin) is a sign of weakened intestinal barrier integrity [39]. Because proteins are lost to the intestinal lumen when alpha-1-antitrypsin levels are detected in the feces, it is also considered a measure of mucosal barrier integrity [39]. PD patients had higher levels of faecal alpha-1-antitrypsin and zonulin in a case-control study compared to age-matched controls [42]. It’s worth noting that none of these studies differentiates between damage to and loss of epithelial cells and dysfunctional tight junctions in terms of mucosal barrier disruption [39]. Tight junction proteins expression in colonic biopsies of Parkinson’s disease (PD) patients was examined in order to address the problem, and it was discovered that occludin, but not zonulin, was significantly lower in PD patients and that there was an abnormal subcellular distribution of tight junction proteins [43] or reduced zonulin [40] compared to controls.
Furthermore, the association between PD and IBD suggests that intestinal inflammation may play a role in PD pathogenesis. According to a recent meta-analysis, people with IBD have a 28% higher risk of developing Parkinson’s disease (RR 1.41, 95% CI 1.19–1.66) than people without the disease (controls) [44]. Crohn’s disease and Parkinson’s disease both have shared alleles in the LRRK2 gene (OMIM 609007), which supports the idea that the two diseases may share pathogenetic pathways involving the dysregulation of intestinal barrier/immune system dysregulation. Another finding in favor of a role for systemic inflammation in PD pathogenesis was found in IBD patients receiving anti-tumor necrosis factor therapy, who had a 78% lower risk of developing PD than those who did not (adjusted incidence rate ratio, 0.22; 95% CI, 0.05–0.88) [46].
Interest in the role of the gut microbiome in the pathological changes seen in Parkinson’s disease (PD) has grown since the focus on the digestive tract as a primary site of -synucleinopathy. This is supported by animal studies, according to what we know so far. There was a correlation between the presence of microbes in a mouse model of Parkinson’s disease (PD) that overexpressed -Synuclein and microglial activation and brain -Synuclein pathology and antibiotic treatment [47]. To make matters worse, when given to germ-free mice, specific microbiota metabolites were found to increase neuroinflammation and motor symptoms, and transplanting this microbial community into these mice caused more motor dysfunction than receiving the microbiota from healthy human donors [47]. Fecal transplantation from 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-treated mice to normal mice impaired motor functions and decreased striatal dopamine levels, while transplantation of normal mice’s faecal microbiota to MPTP mice reduced motor dysfunction, restored striatal dopamine and serotonin levels and reduced the activation of microglia and astrocytes [48].
Damian Jacob Markiewicz Sendler: What evidence can be found in the human population? There are numerous reports that the intestinal microbiome of PD patients differs from that of healthy individuals, despite several limitations in the design of studies of the human microbiome (differences in geographical background, age, sex, diet, medications, the occurrence of gastrointestinal symptoms influencing the gut microbiome composition). There was an increase in Lactobacillales, including the genera Akkermansia and Bifidiobacterium [49,50], and a decrease in the genus Prevotella, Lachnospirae, and the short-chain fatty acid-producing genera Blautia and Roseburia [49–51]. What these studies did not address is whether these changes are a direct result of the disease or a result of the disease itself. Prodromal biomarkers for Parkinson’s disease (PD) may be found in the gut microbiome of patients with iRBD or elderly people, according to preliminary findings from studies evaluating the composition of the gut microbiome.
For now, we don’t know how gut microbes can be detected in the digestive tract and lead to the development of PD, if these findings hold up when applied to larger groups of people who are at risk. Enteroendocrine cells may play a role here, according to some theories. In the small intestine and colon, enteroendocrine cells, which are specialized intestinal cells, can detect nutrients and bacterial byproducts that have been ingested [54]. In addition, their membranes contain voltage-gated ion channels, which allow them to be electrically excitable [55, 56]. In light of the recent discovery that enteroendocrine cells express -synuclein and synapses with the VN, we may speculate that once stimulated by gut bacteria signaling, these cells may trigger -synucleinopathy within the EN and then spread it to the brain via the VN. For example, patients with Parkinson’s disease (PD) have an increased permeability of the gut wall, which allows bacteria by-products or toxins (such as bacterial LPS) to enter and trigger synucleinopathy [59]. PD patients may also have higher levels of pro-inflammatory cytokines in their serum as a result of the leaky gut syndrome, which may allow bacterial byproducts to enter the bloodstream and increase systemic inflammation. It’s possible that this pro-inflammatory state contributes to BBB disruption, activation of microglial cells, and eventual death of nigral dopaminergic cells [61]. Hopefully, further research testing these hypotheses will shed light on the pathogenetic mechanisms that underlie Parkinson’s disease.
Damian Sendler
Symptomatic DGE is known as gastroparesis, which is defined as reduced stomach motility in the absence of mechanical obstruction [66]. However, despite the fact that only 15–45 percent of Parkinson’s patients report symptoms indicative of gastroparesis (such as nausea, vomiting, postprandial bloating and early satiety, as well as abdominal pain), DGE is found in 70–100 percent of PD patients [69]. In this case, the pathophysiology is likely multifactorial. However, the involvement of Cajal interstitial cells (the gastric pacemaker cells) in the pathogenesis of DGE is less clear [70–71]. [70,71]. Levodopa and anticholinergics, two common PD medications, can cause DGE in a dose-dependent manner [71,72], and the interaction of certain macronutrients (particularly fats) with receptors in the small intestine can further inhibit gastric emptying [73].
Levodopa absorption occurs in the proximal duodenum, so DGE is the limiting factor in this process [66]. An association was found between peak-time gastric emptying rates and plasma levodopa peak delay levels in a study of 31 PD patients, suggesting that DGE and “delayed on-time” are linked directly [74]. Motor fluctuations have been linked to higher rates of DGE in another study comparing PD patients with and without motor fluctuations [75]. DGE is only one of a number of factors and conditions that affect levodopa bioavailability related to the GI tract, which will be discussed in detail in the dedicated section below. In particular, diet is a major determinant because levodopa competes for active-transport systems in the small intestine and at the BBB with LNAA, such as phenylalanine, tyrosine, and tryptophan, which are associated with suboptimal motor response [76]. In light of these facts, it is obvious that detecting and treating PD-related gastroparesis is critical not only to alleviate the gastrointestinal symptoms of this condition but also to improve levodopa bioavailability and, as a result, motor function..
Gastroparesis in Parkinson’s disease (PD) is most commonly treated with dietary modifications. When combined with high-quality carbohydrates (starch), fat intake can improve gastric emptying patterns and thus levodopa bioavailability. Taking levodopa 30–45 minutes before a meal may also aid in the absorption of the drug. Levodopa bioavailability has been increased in advanced PD stages by redistribution of daily protein intake to the evening hours and/or restriction of daily protein intake [78,79]. In 30–90% of PD patients, motor fluctuations improved and the levodopa daily dose was reduced by 75 percent [78]. Long-term adherence to low-protein diets, on the other hand, necessitates close monitoring to prevent nutritional complications like weight loss and malnutrition [71]. In two small open-label studies, Rikkunshito dietary herb extract was administered. According to two different studies, improvements in DGE had no effect on motor fluctuations [83,84], but these findings contradict each other.
Treatment for gastroparesis relies heavily on prokinetic agents. D2 dopamine receptor blocker domperidone, which does not cross the blood-brain barrier, has been shown to be effective in the management of gastroparesis in Parkinson’s disease (PD) without worsening motor symptoms [85, 86]. International Parkinson and Movement Disorder Society (MDS) EBM Committee has updated its recommendations on PD treatment, saying that domperidone “possibly useful” in the treatment of PD-related gastroparesis, but that specialized monitoring is needed due to potentially life-threatening arrythmias caused by QT elongation [87]. In PD, metoclopramide, the only FDA-approved medication for gastroparesis, is contraindicated because it can cross the BBB and block central dopaminergic receptors [71]…. In a small open-label trial on five patients with advanced PD, mosapride, a selective 5-hydroxytryptamine type 4 (5-HT4) agonist, was beneficial in reducing gastric emptying rates, prolonging “on” time and reducing motor fluctuations [88]. Gastroparesis associated with Parkinson’s disease (PD) may benefit from the use of the prokinetic hormone ghrelin. In addition to increasing hunger and food intake, ghrelin stimulates the production of growth hormone in the stomach [89]. Both ghrelin and ghrelin receptor agonists have been successfully used in the treatment of gastroparesis associated with a variety of diseases, including diabetes [91,92], because of their ability to stimulate gastric emptying in humans. Preclinical evidence shows that ghrelin and ghrelin agonists [93,94] reduce levodopa-induced DGE and increase plasma levels of levodopa, but no studies have evaluated ghrelin in PD patients with gastroparesis to date. It has also been suggested that macrolides, which are powerful prokinetics, could be used to treat PD-related gastroparesis, but so far clinical evidence is lacking to support their use in routine practice.
Damian Jacob Sendler
To summarize, there are only a few options for treating gastroparesis caused by Parkinson’s disease. A review of conditions and medications known to delay gastric emptying should be conducted before any dietary changes are made. Patients with advanced stages and problematic motor fluctuations should be encouraged to reduce their protein intake or restrict their protein intake to the evening hours, but this should be done under close supervision to prevent any long-term complications. Some patients may benefit from the judicious use of domperidone, always accompanied by cardiac safety monitoring. Ghrelin, 5-HT4 agonists, and macrolides all have a role to play in the treatment of obesity.
Having an increased concentration of bacteria (above 105 colony-forming units/mL) and/or the presence of colonic-type bacteria in the small intestine (SIBO) is associated with this condition. Patients with Parkinson’s disease (PD) are more likely to have SIBO (25–54%), which has been linked to an increased risk of motor complications and fluctuations [105,110,111].
SIBO’s role in the development of Parkinson’s disease (PD) remains a mystery. For example, previous studies have been limited in their interpretation due to factors such as the lack of standard protocols for breath tests for SIBO [111], or changes in SIBO status that occur during the disease course [107,112]. Increased intestinal permeability in SIBO-positive patients facilitates bacterial translocation, creates a proinflammatory environment, and ultimately promotes neurodegeneration (e.g. abnormal accumulation of -synuclein in enteric neurons) [111]. [112]. SIBO may affect levodopa bioavailability, either because of inflammation in the peripheral tissues or because levodopa is partially metabolized [63]. This final hypothesis has been supported by recent studies reporting the impact of the small intestine microbiome on peripheral levodopa conversion. Levodopa decarboxylation to dopamine occurs in the small intestine by a bacterial enzyme called tyrosine decarboxylase (tyrDC) [113], which is encoded in several species’ genomes. In human gut microbiota samples, only Enterococcus faecalis and tyrDC were associated with levodopa and dopamine metabolism, respectively, of all the identified bacterial species [114].
Damien Sendler: The possibility that eradicating SIBO could help improve motor function in people with Parkinson’s disease is therefore alluring. It has been found that rifaximin 400 mg three times a day, taken for one week, improved motor fluctuations (off” time and “delayed on”). However, there were no changes in levodopa pharmacokinetic parameters [105]. Another RCT of rifaximin in SIBO-positive PD patients with at least four hours of “off” time per day has been designed to evaluate “off” time reduction. It’s unfortunate that the results of this trial were unsatisfactory. SIBO eradication studies in Parkinson’s disease (PD) are notoriously difficult to design, and this study shows how difficult it can be to recruit patients, as well as the unexplained change to SIBO negativity that occurred in patients given placebo [112].
Despite the evidence pointing to a link between SIBO and motor decline in Parkinson’s disease, it has yet to be determined whether or not an antibiotic regimen should be used to eradicate SIBO. Considering that Enterococcus faecalis and the activity of the tyrDC enzyme may serve as biomarkers for monitoring levodopa efficacy, the impact of tyrDC manipulation on levodopa efficacy in Parkinson’s disease patients merits further study [114].
It has been shown that constipation, one of the most common PD-related GI disorders, can begin 20 years before motor symptoms [115,116]. It is more common in older patients with more advanced stages of Parkinson’s disease (PD) [117,118,119]. Chronic constipation has been linked to a wide range of health problems, including depression and anxiety [120], as well as intestinal volvulus, pseudo-obstruction, megacolon, and faecal impaction.
Constipation prevalence in Parkinson’s disease studies ranges from 8 percent to 70 percent and can be described by patients as hard stools, reduced bowel movements, bloating, abdominal pain, and straining during defecation [122]. Constipation associated with Parkinson’s disease (PD) can be caused by either colonic slow transit or anorectal dysfunction [121]. Cell death and accumulation of -synuclein in the parasympathetic and sympathetic neurons that innervate the entire colon, as well as increased colonic inflammation and permeability, are the underlying mechanisms. Furthermore, it is possible that PD-related constipation and changes in the gut microbiome have a direct relationship. Congestion is reduced in germ-free transgenic mice compared to mice with a complex microbiota in preclinical studies [47]. Constipation in Parkinson’s disease (PD) patients has been linked to a specific gut microbiome signature in clinical studies [123,124]. It has been found that several taxa such as Dorea and Oscillospira, Akkermansia, and Ruminococcaceae have been found to be associated with chronic constipation and stool consistency [123]. Researchers found that the Lactobacillaceae family increased, but the Faecalibacterium family decreased, when constipation was induced [124]. However, other studies failed to find a link between certain types of gut microbiota and constipation [125]. Despite these discrepancies, altering the gut microbiota may be a promising treatment for constipation in Parkinson’s disease.
It is possible to alleviate constipation by manipulating the gut microbiota through diet, probiotics, and prebiotic fibers [126]. Dietary insoluble fibers (dietetic supplements containing 375 mg wheat, 70 mg pectin, 2.5 mg dimethylpolyoxyhexane-900 [127]; or psyllium [128]) have been studied in the treatment of constipation in patients with Parkinson’s disease (PD). Although the small sample sizes of both studies (n = 19, and n = 7 patients) may have underpowered these findings, beneficial effects were reported on some constipation-related measures (severity, stool frequency or weight) [127,128]. [127] Interestingly, both at 2 weeks and 2 months, insoluble fiber-enriched diet improved motor function as well as plasma levodopa levels in both groups. Probiotics’ impact on PD-related constipation has only recently been studied. Microorganisms, either live or attenuated, with multiple putative benefits for intestinal homeostasis are known as probiotics [129]. Probiotics have been shown to reduce motor impairment and protect dopaminergic neurons in animal models of Parkinson’s disease [130,131]. Probiotics have been studied for constipation associated with Parkinson’s disease in three studies, two of which were randomized controlled trials (RCTs). Treatment with multi-strain or single-strain probiotic has been shown to improve several measures related to constipation (spontaneous bowel movements, stool consistency, patient quality of life and treatment satisfaction) [132–134]. [132–134]. Probiotics and prebiotic fiber are now considered “clinically useful” by the MDS EBM Committee, and their use in clinical practice is deemed a “acceptable risk without specialized monitoring” [87] on the basis of these findings. However, it is not yet known if these treatments can improve other outcomes, such as motor symptoms.
Two randomized controlled trials (RCTs) looked at the osmotic laxative macrogol [135] and the chrolide type 2 channel activator lubiprostone [136]. Stool frequency and consistency, gastrointestinal symptoms were all improved with both treatments [135,136], but there were no improvements in motor function. Congestion in patients with Parkinson’s disease (PD) may benefit from macrogol and lubiprostone.
To summarize, treating PD-related constipation clinically is difficult, and the currently available treatments do not meet the ultimate goal of patient satisfaction [137]. We think the best approach to take is a personalized one that includes both non-pharmacological and pharmacological options. There are nonpharmacological measures that can be used as first-line treatment, such as increasing physical activity, increasing fluid and fiber intake, and discontinuing aggravating medications (e.g. opioids and amantadine) [118,138]. Probiotics and prebiotic fibers, followed by lubiprostone and macrogol, could be considered at the individual level when previous strategies have failed, despite the absence of formal guidelines at this time.
The gut-brain axis in Parkinson’s disease is depicted schematically in the figure below. Patients with Parkinson’s disease (PD) have been shown to have a more pro-inflammatory gut microbiome composition. In patients with Parkinson’s disease (PD), the increased permeability of the gastrointestinal tract could expose neurons within the ENS to bacterial-derived pro-inflammatory products; the activation of enteric glial cells (EGC) within the gastrointestinal tract of PD patients, seen in the early stages of the disease, might contribute to amplify the intestinal barrier impairment and facilitate the spread of pathological -synuclein within the ENS. It is also possible that the EECs dispersed throughout the gut epithelium detect bacterial products, and that these cells serve as an initial site of -synuclein aggregation, which can be transferred to the VN later. Pathological -synuclein can reach the vagal nerve and, due to its cell-to-cell transmission properties, retrogradely propagate to the brain either through the ENS or by direct synapsing. Parkinson’s disease symptoms are caused by the spread of pathological -synuclein throughout the brain, which results in the loss of nigrostriatal dopaminergic neurons. Lipopolysaccharide (LPS), short-chain fatty acids (SCFA), enteric nervous system (ENS), and enteric glial cell (EGC) are some of the terms used to describe the various cell types in the digestive tract.
Many diseases, including Parkinson’s, have an impact on the digestive system, which can lead to severe disability, decreased quality of life, and an increased risk of death. Levodopa bioavailability and motor function are strongly influenced by some of the most common gastrointestinal (GI) symptoms associated with Parkinson’s disease (PD). The burden of motor fluctuations experienced by people with Parkinson’s disease can be lessened by making evaluation and treatment of these conditions a top priority. As a result of therapeutic interventions involving the gut-brain axis, both the gut and the brain have been found to benefit from the use of dietary soluble fibers. As a result, treating patients with Parkinson’s disease necessitates a multidisciplinary approach involving neurologists, gastroenterologists, internists, and family practitioners.
