Figure 7 - available via license: Creative Commons Attribution 4.0 International
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Cladogram generated by LEfSe shows the taxa differences between PD patients (2) and healthy controls (1). The central yellow dot in each cladogram represents kingdom; each successive circle is one step lower phylogenetically (phylum, class, order, family, and OTU). Regions colored in red indicate taxa enriched in controls compared to those enriched in PD patients marked with green regions.
Source publication
Gut microbiome and colonic inflammation can be associated with the predisposition and progression of Parkinson’s disease (PD). The presented study aimed to compare gastrointestinal microbiota composition between patients diagnosed with PD and treated only with Levodopa to healthy controls. In this prospective study, patients were recruited in 1 aca...
Context in source publication
Context 1
... generated by LEfSe and shown in Figure 7 demonstrates that samples of PD were enriched for Coriobacteriia, Flavobacteriia, Erysipelotrichia, Deltaproteobacteria, Gammaproteobacteria, and Verrucomicrobia, whereas samples from healthy controls were primarily enriched in Clostridia, Firmicutes, and Fusobacteria. Bacterial taxa, whose abundance was significantly different between PD patients and the control group, is displayed as a heated tree included in Figure 8. ...
Citations
... The phylum/family/genus abundance profiling was based on the aggregate counts for each group. Using the method outlined by Rodrguez-Rabassa et al. [16] and Zapała et al., [17] the core microbiome assessment of a taxonomic cluster that represented a sizable fraction of the population and a comparative analysis of the microbiome within and between the groups was examined. ...
... [22] In concordance with other studies, we noted the statistical significance in β diversity, indicating a microbial community profile specific to PD when bacterial richness between PD and HC groups was compared. [17,21] PD-specific gut bacterial profile was consistent with β diversity differences. At the family level, a higher abundance of Christensenellaceae and a lower abundance of Lachnospiraceae are consistent with reports from several earlier studies. ...
Objectives:
Recent advancement in understanding neurological disorders has revealed the involvement of dysbiosis of the gut microbiota in the pathophysiology of Parkinson’s disease (PD). We sequenced microbial DNA using fecal samples collected from PD cases and healthy controls (HCs) to evaluate the role of gut microbiota.
Methods:
Full-length bacterial 16S rRNA gene sequencing of fecal samples was performed using amplified polymerase chain reaction (PCR) products on the GridION Nanopore sequencer. Sequenced data were analyzed using web-based tools BugSeq and MicrobiomeAnalyst.
Results:
We found that certain bacterial families like Clostridia UCG 014, Cristensenellaceae, and Oscillospiraceae are higher in abundance, and Lachinospiracea, Coriobacteriaceae and genera associated with short-chain fatty acid production, Faecalibacterium , Fusicatenibacter , Roseburia and Blautia , are lower in abundance among PD cases when compared with the HC. Genus Akkermansia , Dialister , Bacteroides , and Lachnospiraceae NK4A136 group positively correlated with constipation in PD.
Conclusion:
Observations from this study support the other global research on the PD gut microbiome background and provide fresh insight into the gut microbial composition of PD patients from a south Indian population. We report a higher abundance of Clostridia UCG 014 group, previously not linked to PD.
... Similar to the findings in AD, gut dysbiosis has been observed even in the prodromal phase of PD, with enrichment of A. muciniphila occurring in patients with PD (Keshavarzian et al., 2015;Bedarf et al., 2017;Hill-Burns et al., 2017;Baldini et al., 2020;Cirstea et al., 2020;Zapała et al., 2021). Additionally, an increased number of A. muciniphila has been found in MPTP-induced (Jeon et al., 2021) and rotenone-treated PD mouse models (Dodiya et al., 2020). ...
An accumulating body of evidence suggests that the bacterium Akkermansia muciniphila exhibits positive systemic effects on host health, mainly by improving immunological and metabolic functions, and it is therefore regarded as a promising potential probiotic. Recent clinical and preclinical studies have shown that A. muciniphila plays a vital role in a variety of neuropsychiatric disorders by influencing the host brain through the microbiota-gut-brain axis (MGBA). Numerous studies observed that A. muciniphila and its metabolic substances can effectively improve the symptoms of neuropsychiatric disorders by restoring the gut microbiota, reestablishing the integrity of the gut mucosal barrier, regulating host immunity, and modulating gut and neuroinflammation. However, A. muciniphila was also reported to participate in the development of neuropsychiatric disorders by aggravating inflammation and influencing mucus production. Therefore, the exact mechanism of action of A. muciniphila remains much controversial. This review summarizes the proposed roles and mechanisms of A. muciniphila in various neurological and psychiatric disorders such as depression, anxiety, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, strokes, and autism spectrum disorders, and provides insights into the potential therapeutic application of A. muciniphila for the treatment of these conditions.
... Along with the attention of using Akkermansia muciniphila in compromised intestinal conditions, recent findings from the neurologic field indicated a cautionary use of such probiotic. Different studies revealed an increase in Akkermansia abundance in patients suffering from Parkinson's disease (PD) [16,48,49]. The elevated abundance of Akkermansia seems to be one of the features of the intestinal microbiota in such patients. ...
Akkermansia muciniphila is a mucin-degrading bacterium of the intestinal niche, exerting beneficial effects on the host metabolic profile. Accumulating evidence indicated Akkermansia as a promising therapeutic probiotic against metabolic disorders such as obesity, type 2 diabetes and cardiovascular diseases. However, in specific intestinal microenvironments, its excessive enrichment may be not beneficial. Conditions like inflammatory bowel disease (IBD), Salmonella typhimurium infection or post-antibiotic reconstitution may not benefit from Akkermansia supplementation. Furthermore, using Akkermansia in patients with endocrine and gynecological disorders—such as polycystic ovary syndrome (PCOS) or endometriosis—that have a higher risk of developing IBD, should be critically evaluated. In addition, a cautionary note comes from the neurological field, as the gut microbiota of patients suffering from Parkinson’s disease or multiple sclerosis exhibits a characteristic signature of Akkermansia municiphila abundance. Overall, considering these controversial points, the use of Akkermansia should be evaluated on an individual basis, avoiding risking unexpected effects.
... We hypothesized that the participation of the above three genera in the immune response and the modulation of intestinal permeability could be important for disease pathogenesis of RBD and PD. In line with our findings, increased Eubacterium was observed in another microbiome study of PD [55]. The increase of Gordonibacter also complied with another study, which suggested its increase in mild PD [56]. ...
Rapid eye movement sleep behavior disorder (RBD) has a close relationship with Parkinson's disease (PD) and was even regarded as the most reliable hallmark of prodromal PD. RBD might have similar changes in gut dysbiosis to PD, but the relationship between RBD and PD in gut microbial alterations is rarely studied. In this study, we aim to investigate whether there are consistent changes between RBD and PD in gut microbiota, and find some specific biomarkers in RBD that might indicate phenoconversion to PD. Alpha-diversity showed no remarkable difference and beta-diversity showed significant differences based on the unweighted (R = 0.035, P = 0.037) and weighted (R = 0.0045, P = 0.008) UniFrac analysis among idiopathic RBD (iRBD), PD with RBD, PD without RBD and normal controls (NC). Enterotype distribution indicated iRBD, PD with RBD and PD without RBD were Ruminococcus-dominant while NC were Bacteroides-dominant. 7 genera (4 increased: Aerococcus, Eubacterium, Gordonibacter and Stenotrophomonas, 3 decreased: Butyricicoccus, Faecalibacterium and Haemophilus) were consistently changed in iRBD and PD with RBD. Among them, 4 genera (Aerococcus, Eubacterium, Butyricicoccus, Faecalibacterium) remained distinctive in the comparison between PD with RBD and PD without RBD. Through clinical correlation analysis, Butyricicoccus and Faecalibacterium were found negatively correlated with the severity of RBD (RBD-HK). Functional analysis showed iRBD had similarly increased staurosporine biosynthesis to PD with RBD. Our study indicates that RBD has similar gut microbial changes to PD. Decreased Butyricicoccus and Faecalibacterium might be potential hallmarks of phenoconversion of RBD to PD.
... These findings suggest that PD may originate within the gut. Some studies suggest that A. muciniphila abundance is significantly increased in PD, which contrasts with previous indications that A. muciniphila has beneficial effects in most diseases [104,105]. A. muciniphilaconditioned medium (CM) leads to ROS production and α-synuclein aggregation in enteroendocrine cells by increasing intracellular Ca + levels (Fig. 3) [105]. However, the methods of these studies are limited. ...
Akkermansia muciniphila (A. muciniphila) has drawn much attention as an important gut microbe strain in recent years. A. muciniphila can influence the occurrence and development of diseases of the endocrine, nervous, digestive, musculoskeletal, and respiratory systems and other diseases. It can also improve immunotherapy for some cancers. A. muciniphila is expected to become a new probiotic in addition to Lactobacillus and Bifidobacterium. An increase in A. muciniphila abundance through direct or indirect A. muciniphila supplementation may inhibit or even reverse disease progression. However, some contrary findings are found in type 2 diabetes mellitus and neurodegenerative diseases, where increased A. muciniphila abundance may aggravate the diseases. To enable a more comprehensive understanding of the role of A. muciniphila in diseases, we summarize the relevant information on A. muciniphila in different systemic diseases and introduce regulators of A. muciniphila abundance to promote the clinical transformation of A. muciniphila research.
... Multiple 16S rRNA gene sequence assays in patients with PD have also revealed a link with the gut microbiome [67,68]. These studies have consistently found that A. muciniphila is significantly enriched in patients with PD. ...
Akkermansia muciniphila (A. muciniphila) is an anaerobic bacterium that widely colonizes the mucus layer of the human and animal gut. The role of this symbiotic bacterium in host metabolism, inflammation, and cancer immunotherapy has been extensively investigated over the past 20 years. Recently, a growing number of studies have revealed a link between A. muciniphila, and aging and aging-related diseases (ARDs). Research in this area is gradually shifting from correlation analysis to exploration of causal relationships. Here, we systematically reviewed the association of A. muciniphila with aging and ARDs (including vascular degeneration, neurodegenerative diseases, osteoporosis, chronic kidney disease, and type 2 diabetes). Furthermore, we summarize the potential mechanisms of action of A. muciniphila and offer perspectives for future studies.
... We hypothesized that their participation in the immune response and the modulation of intestinal permeability could be important for the disease pathogenesis. Increased Eubacterium was also reported in another microbiome studs of PD 29 . Among those 7 genera, 4 common taxa (2 increased: Aerococcus and Eubacterium, 2 decreased: Butyricicoccus and Faecalibacterium) were distinctive between PD with RBD and PD without RBD. ...
Background
Rapid eye movement sleep behavior disorder (RBD) has close relationship with Parkinson’s disease (PD), and even was regarded as the most reliable hallmark of prodromal PD. RBD might have similar changes in neuroimaging and gut dysbiosis to PD, but the relationship between RBD and PD in gut microbial alteration is rarely studied. In this study, we aimed to investigate whether there are the consistent changes between RBD and PD in gut microbiota, and find some specific biomarkers in RBD that might indicate phenoconversion to PD.
Results
This case-control study assessed microbiota of fecal samples from 35 idiopathic RBD (iRBD), 30 de novo PD with RBD, 64 PD without RBD and 60 normal controls (NCs) by 16S ribosomal RNA amplicon sequencing (16S rRNA) and quantitative real-time PCR (qPCR). Alpha-diversity showed no remarkable difference and beta-diversity showed significant differences based on the unweighted (R = 0.035, P = 0.037) and weighted (R = 0.0045, P = 0.008) UniFrac analysis among four groups. Enterotype distribution showed Ruminococcus was dominant in iRBD, PD with RBD and PD without RBD, while NC was Bacteroides-dominant. 7 genera (4 increased: Aerococcus, Eubacterium, Gordonibacter and Stenotrophomonas, 3 decreased: Butyricicoccus, Faecalibacterium and Haemophilus ) were consistently changed in iRBD and PD with RBD. Among them, 4 genera (Aerococcus, Eubacterium, Butyricicoccus, Faecalibacterium) remained distinctive in the comparison between PD with RBD and PD without RBD. Butyricicoccus and Faecalibacterium were found negatively correlated with the severity of RBD, and Stenotrophomonas was found positively related to RBD disease duration. Functional analysis showed iRBD had similarly increased staurosporine biosynthesis to PD with RBD.
Conclusions
RBD has similar gut microbial changes to PD. Decreased Butyricicoccus and Faecalibacterium might be specific to RBD, and also potential hallmark of phenoconversion of RBD to PD.
... Alterations in the gut microbiota composition is strongly associated with PD. The gut microbial diversity with certain phyla, including Firmicutes, Bacteroidetes, and Fusobacteria, was deformed in patients with Parkinson's symptoms compared to the control [222]. ...
The gut–brain axis is a bidirectional communication network connecting the gastrointestinal tract and central nervous system. The axis keeps track of gastrointestinal activities and integrates them to connect gut health to higher cognitive parts of the brain. Disruption in this connection may facilitate various neurological and gastrointestinal problems. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Misfolded protein aggregates that cause cellular toxicity and that aid in the collapse of cellular proteostasis are a defining characteristic of neurodegenerative proteinopathies. These disorders are not only caused by changes in the neural compartment but also due to other factors of non-neural origin. Mounting data reveal that the majority of gastrointestinal (GI) physiologies and mechanics are governed by the central nervous system (CNS). Furthermore, the gut microbiota plays a critical role in the regulation and physiological function of the brain, although the mechanism involved has not yet been fully interpreted. One of the emerging explanations of the start and progression of many neurodegenerative illnesses is dysbiosis of the gut microbial makeup. The present understanding of the literature surrounding the relationship between intestinal dysbiosis and the emergence of certain neurological diseases, such as Alzheimer's disease, Parkinson’s disease, Huntington's disease, and multiple sclerosis, is the main emphasis of this review. The potential entry pathway of the pathogen-associated secretions and toxins into the CNS compartment has been explored in this article at the outset of neuropathology. We have also included the possible mechanism of undelaying the synergistic effect of infections, their metabolites, and other interactions based on the current understanding.
... Akkermansia muciniphila is a bacterial genus belonging to the family of Verrucomicrobiaceae that is frequently found increased in patients with PD compared to controls [65,69,[78][79][80][81]. Although Akkermansia muciniphila possesses the beneficial ability to convert mucin into SCFAs [82], its mucin degrading activity might also damage the gut-barrier triggering in-flammation and promoting gut permeability [83,84]. ...
... Among Chinese people, Parasutterella and Bilophila wadsworthia were more abundant in 39 PD patients compared to their healthy spouses [64], while the Northeastern Han population with PD showed reduced Bacteroides, as well as increased Ruminococcaceae and Lachnospiraceae NK4A [65]. These latter results, although in constrast with the previously described studies reporting lower levels of Lachnospiraceae and Ruminococcus among patients [59,69,81], could be explained as a population specific trait or may be a result of the small sample size. Furthermore, it has been reported that the Australian signature consists of decreased Colidextribacter, Agathobaculum, Kineothrix, Roseburia and Intestinibacter in favor of enriched Synergistetes and Proteobacteria, which elicit inflammation [50,66]. ...
The bidirectional interaction between the gut microbiota (GM) and the Central Nervous System, the so-called gut microbiota brain axis (GMBA), deeply affects brain function and has an important impact on the development of neurodegenerative diseases. In Parkinson’s disease (PD), gastrointestinal symptoms often precede the onset of motor and non-motor manifestations, and alterations in the GM composition accompany disease pathogenesis. Several studies have been conducted to unravel the role of dysbiosis and intestinal permeability in PD onset and progression, but the therapeutic and diagnostic applications of GM modifying approaches remain to be fully elucidated. After a brief introduction on the involvement of GMBA in the disease, we present evidence for GM alterations and leaky gut in PD patients. According to these data, we then review the potential of GM-based signatures to serve as disease biomarkers and we highlight the emerging role of probiotics, prebiotics, antibiotics, dietary interventions, and fecal microbiota transplantation as supportive therapeutic approaches in PD. Finally, we analyze the mutual influence between commonly prescribed PD medications and gut-microbiota, and we offer insights on the involvement also of nasal and oral microbiota in PD pathology, thus providing a comprehensive and up-to-date overview on the role of microbial features in disease diagnosis and treatment.
... One of the major differences observed was the decrease in Akkermansia and Lactobacillus genera from TCE treated rats, compared to the relatively common increase found in human PD studies (E. M. Romano et al. 2021;Wallen et al. 2020;Zapała et al. 2021), though at least one or more studies report decreases in either genus Qian et al. 2018). While the most obvious source of variation is likely rodent to human translation, MRL +/+ mice exposed to TCE in drinking water displayed a significant elevation in Akkermansia within the gut microbiome compared to control (Hui ). ...
Microbial alterations within the gut microbiome appear to be a common feature of individuals with Parkinson’s disease (PD), providing further evidence for the role of the gut-brain axis in PD development. As a major site of contact with the environment, questions have emerged surrounding the cause and effect of alterations to the gut microbiome by environmental contaminants associated with PD risk, such as pesticides, metals, and organic solvents. Recent data from our lab shows that ingestion of the industrial byproduct and environmental pollutant trichloroethylene (TCE) induces key Parkinsonian pathology within aged rats, including the degeneration of dopaminergic neurons, α-synuclein accumulation, neuroinflammation, and endolysosomal deficits. As TCE is the most common organic contaminant within drinking water, we postulated that ingestion of TCE associated with PD-related neurodegeneration may alter the gut microbiome to a similar extent as observed in persons with PD. To assess this, we collected fecal samples from adult rats treated with 200 mg/kg TCE over 6 weeks via oral gavage and analyzed the gut microbiome via whole genome shotgun sequencing. Our results showed changes in gut microorganisms reflective of the microbial signatures observed in individuals with idiopathic PD, such as decreased abundance of short-chain fatty acid producing Blautia and elevated lactic-acid producing Bifidobacteria, as well as genera who contain species previously reported as opportunistic pathogens such as Clostridium. From these experimental data, we postulate that TCE exposure within contaminated drinking water could induce alterations of the gut microbiome that contributes to chronic disease risk, including idiopathic PD.
Abstract Figure
