From the Gut to the Brain: Is Microbiota a New Paradigm in Parkinson's Disease Treatment?

Parkinson's disease (PD) is recognized as the second most prevalent primary chronic neurodegenerative disorder of the central nervous system. Clinically, PD is characterized as a movement disorder, exhibiting an incidence and mortality rate that is increasing faster than any other neurological condition. In recent years, there has been a growing interest concerning the role of the gut microbiota in the etiology and pathophysiology of PD. The establishment of a brain-gut microbiota axis is now real, with evidence denoting a bidirectional communication between the brain and the gut microbiota through metabolic, immune, neuronal, and endocrine mechanisms and pathways. Among these, the vagus nerve represents the most direct form of communication between the brain and the gut. Given the potential interactions between bacteria and drugs, it has been observed that the therapies for PD can have an impact on the composition of the microbiota. Therefore, in the scope of the present review, we will discuss the current understanding of gut microbiota on PD and whether this may be a new paradigm for treating this devastating disease.

Association between increased and decreased gut microbiota abundance and Parkinson's disease: A systematic review and subgroup meta-analysis.

OBJECTIVE: The objective of the study was to systematically investigate the association between gut microbiota (GM) abundance and Parkinson's disease (PD). METHODS: PubMed, Medline, Cochrane Library and other literature datebase platforms were searched for eligible studies in the English-language from conception to March 1, 2024. Studies evaluating the association between GM and PD were included. The results of the included studies were analyzed using a random effects model with calculation of the mean difference (MD) with the 95 % confidence interval to quantify the incidence of differences in abundance of various bacterial families in PD patients. Continuous models were used to analyze the extracted data. RESULTS: A total of 14 studies with 1045 PD cases and 821 healthy controls were included for data extraction and meta-analysis. All the included studies exhibited reasonable quality. The included studies reported the data on the ratios of 10 families of GM. Of these 10 microbiota families, Bifidobacteriaceae, Ruminococcaceae, Rikenellaceae, Lactobacillaceae, Verrucomicrobiaceae and Christensenellaceae were found to have increased ratios according to the pooled ratios, while Prevotellaceae, Lachnospiraceae, Erysipelotrichaceae and Faecalibacterium were decreased in PD cases. CONCLUSION: Patients in the PD cohort exhibited distinctive microbiota compositions compared to healthy individuals, with unique differential patterns in gut microbiome abundance at the phylum, family, and genus levels that may be associated wtih PD pathogenesis.

Role of the Gut Microbiome and Bacterial Amyloids in the Development of Synucleinopathies.

Less than ten years ago, evidence began to accumulate about association between the changes in the composition of gut microbiota and development of human synucleinopathies, in particular sporadic form of Parkinson's disease. We collected data from more than one hundred and thirty experimental studies that reported similar results and summarized the frequencies of detection of different groups of bacteria in these studies. It is important to note that it is extremely rare that a unidirectional change in the population of one or another group of microorganisms (only an elevation or only a reduction) was detected in the patients with Parkinson's disease. However, we were able to identify several groups of bacteria that were overrepresented in the patients with Parkinson's disease in the analyzed studies. There are various hypotheses about the molecular mechanisms that explain such relationships. Usually, α-synuclein aggregation is associated with the development of inflammatory processes that occur in response to the changes in the microbiome. However, experimental evidence is accumulating on the influence of bacterial proteins, including amyloids (curli), as well as various metabolites, on the α-synuclein aggregation. In the review, we provided up-to-date information about such examples.

Interplay of human gastrointestinal microbiota metabolites: Short-chain fatty acids and their correlation with Parkinson's disease.

Short-chain fatty acids (SCFAs) are, the metabolic byproducts of intestinal microbiota that, are generated through anaerobic fermentation of undigested dietary fibers. SCFAs play a pivotal role in numerous physiological functions within the human body, including maintaining intestinal mucosal health, modulating immune functions, and regulating energy metabolism. In recent years, extensive research evidence has indicated that SCFAs are significantly involved in the onset and progression of Parkinson disease (PD). However, the precise mechanisms remain elusive. This review comprehensively summarizes the progress in understanding how SCFAs impact PD pathogenesis and the underlying mechanisms. Primarily, we delve into the synthesis, metabolism, and signal transduction of SCFAs within the human body. Subsequently, an analysis of SCFA levels in patients with PD is presented. Furthermore, we expound upon the mechanisms through which SCFAs induce inflammatory responses, oxidative stress, abnormal aggregation of alpha-synuclein, and the intricacies of the gut-brain axis. Finally, we provide a critical analysis and explore the potential therapeutic role of SCFAs as promising targets for treating PD.

Discovery of a Gut Bacterial Metabolic Pathway that Drives α-Synuclein Aggregation.

Parkinson's disease (PD) etiology is associated with aggregation and accumulation of α-synuclein (α-syn) proteins in midbrain dopaminergic neurons. Emerging evidence suggests that in certain subtypes of PD, α-syn aggregates originate in the gut and subsequently spread to the brain. However, mechanisms that instigate α-syn aggregation in the gut have remained elusive. In the brain, the aggregation of α-syn is induced by oxidized dopamine. Such a mechanism has not been explored in the context of the gastrointestinal tract, a niche harboring 46% of the body's dopamine reservoirs. Here, we report that Enterobacteriaceae, a bacterial family prevalent in human gut microbiotas, induce α-syn aggregation. More specifically, our in vitro data indicate that respiration of nitrate by Escherichia coli K-12, which results in production of nitrite that mediates oxidation of Fe2+ to Fe3+, creates an oxidizing redox potential. These oxidizing conditions enabled the formation of dopamine-derived quinones and α-syn aggregates. Exposing nitrite, but not nitrate, to enteroendocrine STC-1 cells induced aggregation of α-syn that is natively expressed in these cells, which line the intestinal tract. Taken together, our findings indicate that bacterial nitrate reduction may be critical for initiating intestinal α-syn aggregation.

Relationship among Parkinson's disease, constipation, microbes, and microbiological therapy.

This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson's disease (PD), a prevalent non-motor symptom contributing significantly to patients' morbidity. A marked alteration in the gut microbiota, predominantly an increase in the abundance of Proteobacteria and Bacteroidetes, is observed in PD-related constipation. Conventional treatments, although safe, have failed to effectively alleviate symptoms, thereby necessitating the development of novel therapeutic strategies. Microbiological interventions such as prebiotics, probiotics, and fecal microbiota transplantation (FMT) hold therapeutic potential. While prebiotics improve bowel movements, probiotics are effective in enhancing stool consistency and alleviating abdominal discomfort. FMT shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with PD. Despite promising developments, the causal relationship between changes in gut microbiota and PD-related constipation remains elusive, highlighting the need for further research in this expanding field.

Gut Microbiota Composition in Patients with Neurodegenerative Disorders (Parkinson's and Alzheimer's) and Healthy Controls: A Systematic Review.

This systematic review aims to provide a comprehensive understanding of the current literature regarding gut microbiota composition in patients with Parkinson's disease (PD) and Alzheimer's disease (AD) compared to healthy controls. To identify the relevant studies, a thorough search of PubMed, Medline, and Embase was conducted following the PRISMA guidelines. Out of 5627 articles, 73 studies were assessed for full-text eligibility, which led to the inclusion of 42 studies (26 PD and 16 AD studies). The risk of bias assessment showed a medium risk in 32 studies (20 PD studies and 12 AD studies), a low risk in 9 studies (5 PD studies and 4 AD studies), and 1 PD study with a high risk. Among the PD studies, 22 out of 26 studies reported a different gut microbiota composition between the PD cases and the healthy controls, and 15 out of 16 AD studies reported differences in gut microbiota composition between the AD cases and the healthy controls. The PD and AD studies consistently identified the phyla Bacteroidetes, Firmicutes, and Proteobacteria as prevalent in the gut microbiota in both the healthy groups and the case groups. Microbial dysbiosis was specifically characterized in the PD studies by a high abundance of Akkermansia, Verrucomicrobiaceae, Lachnospiraceae, and Ruminococcaceae in the cases and a high abundance of Blautia, Coprococcus, Prevotellaceae, and Roseburia in the controls. Similarly, Bacteroides and Acidobacteriota were abundant in the AD cases, and Acidaminococcaceae, Firmicutes, Lachnospiraceae, and Ruminiclostridium were abundant in the AD controls. The microbial signature assessment showed the association of several microbial taxa, including Akkermansia, Lachnospiraceae, Verrucomicrobiaceae, Bifidobacterium, Ruminococcacea, and Verrucomicrobia with PD and Ruminococcaceae, Bacteroides, and Actinobacteria with AD. The microbial diversity evaluations in the PD and AD studies indicated comparable alpha diversity in some groups and distinct gut microbiota composition in others, with consistent beta diversity differences between the cases and the controls across multiple studies. The bacterial signatures identified in this study that are associated with PD and AD may offer promising prospects for efficient management and treatment approaches.

Microorganismos relacionados con un mayor riesgo de presentar la enfermedad de Parkinson / Microorganisms associated with increased risk of Parkinson's disease

La enfermedad de Parkinson es un trastorno neurológico degenerativo que afecta a más de 7 millones de personas en todo el mundo. Se desconoce su etiología, aunque se acepta que existe una susceptibilidad genética a agentes ambientales. Estos agentes ambientales incluyen hongos, bacterias y virus. Tres microorganismos están directamente relacionados con un mayor riesgo estadístico de presentar enfermedad de Parkinson: el género de hongos Malassezia, la bacteria Helicobacter pylori y el virus de la hepatitis C. Estos microorganismos, si el huésped es vulnerable por susceptibilidad genética o debilidad inmunológica, pueden acceder al sistema nervioso, infectarlo y causar neuroinflamación crónica con neurodegeneración. Otros microorganismos se relacionan desde una vertiente epidemiológica con la enfermedad, destacando los virus influenza tipo A, de la encefalitis japonesa tipo B, de San Luis y del Nilo Occidental. Estos virus pueden afectar al sistema nervioso causando encefalitis, cuya consecuencia puede ser un parkinsonismo. En este artículo se hace una revisión de los mencionados agentes infecciosos y su papel en la enfermedad de Parkinson.(AU)

Parkinson's disease is a neurodegenerative disorder that affects more than 7 million people worldwide. Its aetiology is unknown, although the hypothesis of a genetic susceptibility to environmental agents is accepted. These environmental agents include fungi, bacteria, and viruses. Three microorganisms are directly associated with a significantly increased risk of developing Parkinson's disease: the fungal genus Malassezia, the bacterium Helicobacter pylori, and the hepatitis C virus. If the host is vulnerable due to genetic susceptibility or immune weakness, these microorganisms can access and infect the nervous system, causing chronic neuroinflammation with neurodegeneration. Other microorganisms show an epidemiological association with the disease, including the influenza type A, Japanese encephalitis type B, St Louis, and West Nile viruses. These viruses can affect the nervous system, causing encephalitis, which can result in parkinsonism. This article reviews the role of all these microorganisms in Parkinson's disease.(AU)

Metagenomics of the Gut Microbiome in Parkinson's Disease: Prodromal Changes.

OBJECTIVE: Prior studies on the gut microbiome in Parkinson's disease (PD) have yielded conflicting results, and few studies have focused on prodromal (premotor) PD or used shotgun metagenomic profiling to assess microbial functional potential. We conducted a nested case-control study within 2 large epidemiological cohorts to examine the role of the gut microbiome in PD. METHODS: We profiled the fecal metagenomes of 420 participants in the Nurses' Health Study and the Health Professionals Follow-up Study with recent onset PD (N = 75), with features of prodromal PD (N = 101), controls with constipation (N = 113), and healthy controls (N = 131) to identify microbial taxonomic and functional features associated with PD and features suggestive of prodromal PD. Omnibus and feature-wise analyses identified bacterial species and pathways associated with prodromal and recently onset PD. RESULTS: We observed depletion of several strict anaerobes associated with reduced inflammation among participants with PD or features of prodromal PD. A microbiome-based classifier had moderate accuracy (area under the curve [AUC] = 0.76 for species and 0.74 for pathways) to discriminate between recently onset PD cases and controls. These taxonomic shifts corresponded with functional shifts indicative of carbohydrate source preference. Similar, but less marked, changes were observed in participants with features of prodromal PD, in both microbial features and functions. INTERPRETATION: PD and features of prodromal PD were associated with similar changes in the gut microbiome. These findings suggest that changes in the microbiome could represent novel biomarkers for the earliest phases of PD. ANN NEUROL 2023;94:486-501.

What Are the Key Gut Microbiota Involved in Neurological Diseases? A Systematic Review.

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.

[A role of human microbiota in the development of neurodegenerative diseases]. / Rol' mikrobioty cheloveka v razvitii neirodegenerativnykh zabolevanii.

Improving the quality of life in developed countries has contributed to an increase in its duration, which has led to an increase in the number of reported cases of Alzheimer's disease (AD) and Parkinson's disease (PD) in the world. Today, there are 26.6 million patients with AD in the world and it is suspected that by 2050 the number of such patients may increase four times. Additionally, PD in different countries is recorded among people above 60-65 years old at a level of 167 to 5703 per 100.000 population. The latest studies have made it possible to formulate the main mechanisms of the «microbiota-gut-brain¼ axis associated with the pathogenesis of some neurodegenerative diseases. In this review, we summarize the currently available information on the possible role of the gut microbiota in the AD and PD development. It was shown that oxidative stress is one of the main pathogenetic mechanisms of the development of neurodegenerative diseases. In addition, the deposition of lipopolysaccharides of gram-negative bacteria and amyloid of microbial origin in the brain tissue of patients with impaired permeability of the intestinal barrier plays an important role in AD. In PD, the synthesis of α-synuclein produced by bacteria and neuroinflammation are of the greatest importance. Knowledge of these mechanisms will allow the development of psychobiotics, which will reduce the risk of neurodegeneration in AD and PD.

Infections and Changes in Commensal Bacteria and the Pathogenesis of Parkinson's Disease.

The cause of Parkinson's disease (PD) is unknown, but environmental factors are purported to influence risk. Interest in PD as a sequel of infection dates back to reports of parkinsonism arising from encephalitis lethargica. The objective of this paper is to review the literature as it relates to infections and changes in microbiome and the genesis of PD. There is evidence to support prior infection with Helicobacter pylori, hepatitis C virus, Malassezia, and Strep pneumonia in association with PD. A large number of studies support an association between changes in commensal bacteria, especially gut bacteria, and PD. Extant literature supports a role for some infections and changes in commensal bacteria in the genesis of PD. Studies support an inflammatory mechanism for this association, but additional research is required for translation of these findings to therapeutic options.

Bacterial Butyrate in Parkinson's Disease Is Linked to Epigenetic Changes and Depressive Symptoms.

BACKGROUND: The gut microbiome and its metabolites can impact brain health and are altered in Parkinson's disease (PD) patients. It has been recently demonstrated that PD patients have reduced fecal levels of the potent epigenetic modulator butyrate and its bacterial producers. OBJECTIVES: Here, we investigate whether the changes in the gut microbiome and associated metabolites are related to PD symptoms and epigenetic markers in leucocytes and neurons. METHODS: Stool, whole blood samples, and clinical data were collected from 55 PD patients and 55 controls. We performed DNA methylation analysis on whole blood samples and analyzed the results in relation to fecal short-chain fatty acid concentrations and microbiota composition. In another cohort, prefrontal cortex neurons were isolated from control and PD brains. We identified genome-wide DNA methylation by targeted bisulfite sequencing. RESULTS: We show that lower fecal butyrate and reduced counts of genera Roseburia, Romboutsia, and Prevotella are related to depressive symptoms in PD patients. Genes containing butyrate-associated methylation sites include PD risk genes and significantly overlap with sites epigenetically altered in PD blood leucocytes, predominantly neutrophils, and in brain neurons, relative to controls. Moreover, butyrate-associated methylated-DNA regions in PD overlap with those altered in gastrointestinal (GI), autoimmune, and psychiatric diseases. CONCLUSIONS: Decreased levels of bacterially produced butyrate are related to epigenetic changes in leucocytes and neurons from PD patients and to the severity of their depressive symptoms. PD shares common butyrate-dependent epigenetic changes with certain GI and psychiatric disorders, which could be relevant for their epidemiological relation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neuroprotection of chicoric acid in a mouse model of Parkinson's disease involves gut microbiota and TLR4 signaling pathway.

Chicoric acid (CA), a polyphenolic acid obtained from chicory and purple coneflower (Echinacea purpurea), has been regarded as a nutraceutical to combat inflammation, viruses and obesity. Parkinson's disease (PD) is a common neurodegenerative disorder, and the microbiota-gut-brain axis might be the potential mechanism in the pathogenesis and development of PD. The results obtained in this study demonstrated that oral pretreatments of CA significantly prevented the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor dysfunctions and death of nigrostriatal dopaminergic neurons along with the inhibition of glial hyperactivation and the increment in striatal neurotrophins. 16S rRNA sequence results showed that CA significantly reduced MPTP-induced microbial dysbiosis and partially restored the composition of the gut microbiota to normal, including decreased phylum Bacteroidetes and genera Parabacteroide, as well as increased phylum Firmicutes, genera Lactobacillus and Ruminiclostridium. Besides, CA promoted colonic epithelial integrity and restored normal SCFA production. We also observed that proinflammatory cytokines such as TNF-α and IL-1ß in the serum, striatum and colon were reduced by CA, indicating that CA prevented neuroinflammation and gut inflammation, in which the suppression of the TLR4/MyD88/NF-κB signaling pathway might be the underlying molecular mechanism. These findings demonstrated that CA had neuroprotective effects on MPTP-induced PD mice possibly via modulating the gut microbiota and inhibiting inflammation throughout the brain-gut axis.

Axillary Microbiota Is Associated with Cognitive Impairment in Parkinson's Disease Patients.

Cognitive impairment (CI) is among the most common non-motor symptoms of Parkinson's disease (PD), with a substantially negative impact on patient management and outcome. The development and progression of CI exhibits high interindividual variability, which requires better diagnostic and monitoring strategies. PD patients often display sweating disorders resulting from autonomic dysfunction, which has been associated with CI. Because the axillary microbiota is known to change with humidity level and sweat composition, we hypothesized that the axillary microbiota of PD patients shifts in association with CI progression, and thus can be used as a proxy for classification of CI stages in PD. We compared the axillary microbiota compositions of 103 PD patients (55 PD patients with dementia [PDD] and 48 PD patients with mild cognitive impairment [PD-MCI]) and 26 cognitively normal healthy controls (HC). We found that axillary microbiota profiles differentiate HC, PD-MCI, and PDD groups based on differential ranking analysis, and detected an increasing trend in the log ratio of Corynebacterium to Anaerococcus in progression from HC to PDD. In addition, phylogenetic factorization revealed that the depletion of the Anaerococcus, Peptoniphilus, and W5053 genera is associated with PD-MCI and PDD. Moreover, functional predictions suggested significant increases in myo-inositol degradation, ergothioneine biosynthesis, propionate biosynthesis, menaquinone biosynthesis, and the proportion of aerobic bacteria and biofilm formation capacity, in parallel to increasing CI. Our results suggest that alterations in axillary microbiota are associated with CI in PD. Thus, axillary microbiota has the potential to be exploited as a noninvasive tool in the development of novel strategies. IMPORTANCE Parkinson's disease (PD) is the second most common neurodegenerative disease. Cognitive impairment (CI) in PD has significant negative impacts on life quality of patients. The emergence and progression of cognitive impairment shows high variability among PD patients, and thus requires better diagnostic and monitoring strategies. Recent findings indicate a close link between autonomic dysfunction and cognitive impairment. Since thermoregulatory dysfunction and skin changes are among the main manifestations of autonomic dysfunction in PD, we hypothesized that alterations in the axillary microbiota may be useful for tracking cognitive impairment stages in PD. To our knowledge, this the first study characterizing the axillary microbiota of PD patients and exploring its association with cognitive impairment stages in PD. Future studies should include larger cohorts and multicenter studies to validate our results and investigate potential biological mechanisms.

The Role of the Western Diet and Oral Microbiota in Parkinson's Disease.

The type of diet not only affects the composition of the oral microflora but is also one of the more critical factors associated with an increased risk of Parkinson's disease, PD. This study compared diet preferences and oral microbiota profiles in patients with PD vs. healthy controls. This study compared the oral microbiota composition of 59 patients with PD and 108 healthy controls (without neurodegeneration) using 16S rRNA gene amplicon sequencing. According to results, oral microbiota in patients with PD is different compared from healthy controls. In particular, decreased abundance of Proteobacteria, Pastescibacteria, and Tenercutes was observed. The oral cavity of patients with PD was characterized by the high relative abundance of bacteria from the genera Prevotella, Streptococcus, and Lactobaccillus. There were also differences in food preferences between patients with PD and healthy controls, which revealed significantly higher intake of margarine, fish, red meat, cereals products, avocado, and olives in the patients with PD relative to healthy controls. Strong positive and negative correlations between specific food products and microbial taxa were identified.

Composition of intestinal flora affects the risk relationship between Alzheimer's disease/Parkinson's disease and cancer.

An increasing number of epidemiological studies have shown that there is a significant inverse relationship between the onset of Alzheimer's disease/Parkinson's disease (AD/PD) and cancer, but the mechanism is still unclear. Considering that intestinal flora can connect them, we tried to explain this phenomenon from the intestinal flora. This review briefly introduced the relationship among AD/PD, cancer, and intestinal flora, studied metabolites or components of the intestinal flora and the role of intestinal barriers and intestinal hormones in AD/PD and cancer. After screening, a part of the flora capable of participating in the occurrence processes of the three diseases at the same time was obtained, the abundance changes of the special flora in AD/PD and various types of cancers were summarized, and they were classified according to the flora function and abundance, which in turn innovatively and reasonably explained the fact that AD/PD and cancer showed certain antagonism in epidemiological statistics from the perspective of intestinal flora. This review also proposed that viewing the risk relationship between diseases from the perspective of intestinal flora may provide new research ideas for the treatment of fecal microbiota transplantation (FMT) and related diseases.

Altered gut microbiota in Parkinson's disease patients with motor complications.

INTRODUCTION: Parkinson's disease (PD) is associated with gut dysbiosis. However, whether gut dysbiosis can cause motor complications is unclear. METHODS: Subjects were enrolled from four independent movement disorder centers in Japan. We performed 16S ribosomal RNA gene sequence analysis of gut microbiota. Relative abundance of gut microbiota and relationships between them and clinical characteristics were statistically analyzed. Analysis of co-variance (ANCOVA) was used to assess altered gut microbiota associated with wearing-off or dyskinesia. RESULTS: We enrolled 223 patients with PD. Wearing-off was noted in 47.5% of patients and dyskinesia in 21.9%. We detected 98 genera of bacteria. Some changes in the gut microbiota were observed in patients with PD and motor complications. After Bonferroni correction, patients with wearing-off showed decreased relative abundance of Lachnospiraceae Blautia (p < 0.0001) and increased relative abundance of Lactobacillaceae Lactobacillus (p < 0.0001), but patients with dyskinesia no longer showed significant changes in the gut microbiota. Adjustment with two models of confounding factors followed by ANCOVA revealed that age (p < 0.0001), disease duration (p = 0.01), and wearing-off (p = 0.0004) were independent risks for the decreased relative abundance of Lachnospiraceae Blautia, and wearing-off (p = 0.009) was the only independent risk factor for the increased relative abundance of Lachnospiraceae Lactobacillus. CONCLUSION: Relative abundance of Lachnospiraceae Blautia and Lactobacillaceae Lactobacillus was significantly decreased and increased, respectively, in the gut microbiota of PD patients with motor complications. This indicates that an altered gut microbiota is associated with the development of motor complications in patients with advanced PD.

An altered microbiome in a Parkinson's disease model Drosophila melanogaster has a negative effect on development.

Parkinson's disease (PD) is the second most common neurodegenerative disease, besides Alzheimer's Disease, characterized by multiple symptoms, including the well-known motor dysfunctions. It is well-established that there are differences in the fecal microbiota composition between Parkinson's disease (PD) patients and control populations, but the mechanisms underlying these differences are not yet fully understood. To begin to close the gap between description and mechanism we studied the relationship between the microbiota and PD in a model organism, Drosophila melanogaster. First, fecal transfers were performed with a D. melanogaster model of PD that had a mutation in the parkin (park25) gene. Results indicate that the PD model feces had a negative effect on both pupation and eclosion in both control and park25 flies, with a greater effect in PD model flies. Analysis of the microbiota composition revealed differences between the control and park25 flies, consistent with many human studies. Conversely, gnotobiotic treatment of axenic embryos with feces-derived bacterial cultures did not affect eclosure. We speculate this result might be due to similarities in bacterial prevalence between mutant and control feces. Further, we confirmed a bacteria-potentiated impact on mutant and control fly phenotypes by measuring eclosure rate in park25 flies that were mono-associated with members of the fly microbiota. Both the fecal transfer and the mono-association results indicate a host genotype-microbiota interaction. Overall, this study concludes functional effects of the fly microbiota on PD model flies, providing support to the developing body of knowledge regarding the influence of the microbiota on PD.

Gastric Helicobacter suis Infection Partially Protects against Neurotoxicity in A 6-OHDA Parkinson's Disease Mouse Model.

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.