Meta-analysis of the Parkinson's disease gut microbiome suggests alterations linked to intestinal inflammation.
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ABSTRACT:
SUBMITTER: Romano S
PROVIDER: S-EPMC7946946 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Alzheimer's disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
| S-EPMC5648830 | biostudies-other
Project description:BackgroundParkinson's disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we addressed this question by an analysis of stool samples from the Luxembourg Parkinson's Study (n = 147 typical PD cases, n = 162 controls).ResultsAll individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Stool samples from these individuals were first analysed by 16S rRNA gene sequencing. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include the following. Eight genera and seven species changed significantly in their relative abundances between PD patients and healthy controls. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. Particularly, the relative abundances of Bilophila and Paraprevotella were significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. Furthermore, personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in the predicted secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The predicted microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms.ConclusionOur results suggest that PD-associated alterations of the gut microbiome can translate into substantial functional differences affecting host metabolism and disease phenotype.
| S-EPMC7285525 | biostudies-literature
Project description:Parkinson's disease (PD) is the second most common neurodegenerative disease which significantly influences the life quality of patients. The protein α-synuclein plays an important driving role in PD occurrence and development. Braak's hypothesis suggests that α-synuclein is produced in intestine, and then spreads into the central nervous system through the vagus nerve. The abnormal expression of α-synuclein has been found in inflammatory bowel disease (IBD). Intestinal inflammation and intestinal dysbiosis have been involved in the occurrence and development of PD. The present review aimed to summarize recent advancements in studies focusing on intestinal inflammation and PD, especially the mechanisms through which link intestinal inflammation and PD. The intestinal dysfunctions such as constipation have been introduced as non-motor manifestations of PD. The possible linkages between IBD and PD, including genetic overlaps, inflammatory responses, intestinal permeability, and intestinal dysbiosis, are mainly discussed. Although it is not confirmed whether PD starts from intestine, intestinal dysfunction may affect intestinal microenvironment to influence central nervous system, including the α-synuclein pathologies and systematic inflammation. It is expected to develop some new strategies in the diagnosis and treatment of PD from the aspect of intestine. It may also become an exciting direction to find better ways to regulate the composition of gut microorganism to treat PD.
| S-EPMC8612622 | biostudies-literature
Project description:Acute graft-versus-host disease (aGVHD) is the main complication of hematopoietic stem cell transplantation (HSCT). Changes in gut microbiota composition have been associated with subsequent aGVHD, and reconstitution of healthy microbiota is currently being explored as a therapeutic approach. However, the specific actors in the intestinal ecosystem involved in the pathologic process at the time of aGVHD onset are not yet fully known. We prospectively collected stool samples from patients who underwent allogeneic HSCT. Patients sampled at aGVHD onset were compared with non-GVHD patients. To identify phylogenetic and functional signatures of the disease process, we determined fecal short-chain fatty acid (SFCA) profiles and used high-throughput DNA sequencing and real-time quantitative polymerase chain reaction to assess the microbiota composition. Microbiota alterations were highly specific of gastrointestinal (GI) aGVHD severity. Bacterial biomass and α-diversity were lower in severe aGVHD. We identified several bacterial signatures associated with severe aGVHD at disease onset; a negative correlation was observed with anaerobic bacteria of the Lachnospiraceae, especially the Blautia genus, and Ruminococcaceae families. In parallel, in severe aGVHD patients, we showed a dramatic decrease in the levels of the main SFCAs: acetate (75.8%), propionate (95.8%), and butyrate (94.6%). Mild aGVHD patients were characterized by conserved levels of propionate and Blautia propionate producers. Butyrate was significantly decreased in all GI aGVHD stages, representing a potential diagnostic marker of the disease. Specific microbiota and metabolic alterations were thus associated with aGVHD severity and may be useful for diagnostic and pathophysiologic purposes.
| S-EPMC7218439 | biostudies-literature
Project description:BackgroundAlthough some human studies have reported gut microbiome changes in individuals with Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI), gut microbiome alterations in preclinical AD, i.e., cerebral amyloidosis without cognitive impairment, is largely unknown.ObjectiveWe aimed to identify gut microbial alterations associated with preclinical AD by comparing cognitively normal (CN) older adults with cerebral Aβ deposition (Aβ+ CN) and those without cerebral Aβ deposition (Aβ- CN).MethodsSeventy-eight CN older participants (18 Aβ+ CN and 60 Aβ- CN) were included, and all participants underwent clinical assessment and Pittsburg compound B-positron emission tomography. The V3-V4 region of the 16S rRNA gene of genomic DNA extracted from feces was amplified and sequenced to establish the microbial community.ResultsGeneralized linear model analysis revealed that the genera Megamonas (B = 3.399, q<0.001), Serratia (B = 3.044, q = 0.005), Leptotrichia (B = 5.862, q = 0.024) and Clostridium (family Clostridiaceae) (B = 0.788, q = 0.034) were more abundant in the Aβ+ CN group than the Aβ- CN group. In contrast, genera CF231 (B = -3.237, q< 0.001), Victivallis (B = -3.447, q = 0.004) Enterococcus (B = -2.044, q = 0.042), Mitsuokella (B = -2.119, q = 0.042) and Clostridium (family Erysipelotrichaceae) (B = -2.222, q = 0.043) were decreased in Aβ+ CN compared to Aβ- CN. Notably, the classification model including the differently abundant genera could effectively distinguish Aβ+ CN from Aβ- CN (AUC = 0.823).ConclusionOur findings suggest that specific alterations of gut bacterial taxa are related to preclinical AD, which means these changes may precede cognitive decline. Therefore, examining changes in the microbiome may be helpful in preclinical AD screening.
| S-EPMC9707757 | biostudies-literature
Project description:Gut Microbiome Alterations Drive Distinct Metabolic Expression Patterns in a Cohort of Italian Patients with Parkinson’s Disease
| PRJEB30401 | ENA
Project description:BackgroundThere is mounting evidence for a connection between the gut and Parkinson's disease (PD). Dysbiosis of gut microbiota could explain several features of PD.ObjectiveThe objective of this study was to determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research.MethodsA total of 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways.ResultsIndependent microbial signatures were detected for PD (P = 4E-5), participants' region of residence within the United States (P = 3E-3), age (P = 0.03), sex (P = 1E-3), and dietary fruits/vegetables (P = 0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P = 4E-4), anticholinergics (P = 5E-3), and possibly carbidopa/levodopa (P = 0.05). We found significantly altered abundances of the Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways, including the metabolism of plant-derived compounds and xenobiotics degradation.ConclusionPD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. © 2017 International Parkinson and Movement Disorder Society.
| S-EPMC5469442 | biostudies-literature
Project description:Recent findings suggest an implication of the gut microbiome in Parkinson's disease (PD) patients. PD onset and progression has also been linked with various environmental factors such as physical activity, exposure to pesticides, head injury, nicotine, and dietary factors. In this study, we used a mouse model, overexpressing the complete human SNCA gene (SNCA-TG mice) modeling familial and sporadic forms of PD to study whether environmental conditions such as standard vs. enriched environment changes the gut microbiome and influences disease progression. We performed 16S rRNA DNA sequencing on fecal samples for microbiome analysis and studied fecal inflammatory calprotectin from the colon of control and SNCA-TG mice kept under standard environment (SE) and enriched environment (EE) conditions. The overall composition of the gut microbiota was not changed in SNCA-TG mice compared with WT in EE with respect to SE. However, individual gut bacteria at genus level such as Lactobacillus sp. was a significant changed in the SNCA-TG mice. EE significantly reduced colon fecal inflammatory calprotectin protein in WT and SNCA-TG EE compared to SE. Moreover, EE reduces the pro-inflammatory cytokines in the feces and inflammation inducing genes in the colon. Our data suggest that an enriched social environment has a positive effect on the induction of SNCA mediated inflammation in the intestine and by modulating anti-inflammatory gut bacteria.
| S-EPMC6842954 | biostudies-literature
Project description:BackgroundPsoriasis is a chronic inflammatory condition that predominantly affects the skin and is associated with extracutaneous disorders, such as inflammatory bowel disease and arthritis. Changes in gut immunology and microbiota are important drivers of proinflammatory disorders and could play a role in the pathogenesis of psoriasis. Therefore, we explored whether psoriasis in a Central Asian cohort is associated with alterations in select immunological markers and/or microbiota of the gut.MethodsWe undertook a case-control study of stool samples collected from outpatients, aged 30-45 years, of a dermatology clinic in Kazakhstan presenting with plaque, guttate, or palmoplantar psoriasis (n = 20), and age-sex matched subjects without psoriasis (n = 20). Stool supernatant was subjected to multiplex ELISA to assess the concentration of 47 cytokines and immunoglobulins and to 16S rRNA gene sequencing to characterize microbial diversity in both psoriasis participants and controls.ResultsThe psoriasis group tended to have higher concentrations of most analytes in stool (29/47 = 61.7%) and gut IL-1α was significantly elevated (4.19-fold, p = 0.007) compared to controls. Levels of gut IL-1α in the psoriasis participants remained significantly unaltered up to 3 months after the first sampling (p = 0.430). Psoriasis was associated with alterations in gut Firmicutes, including elevated Faecalibacterium and decreased Oscillibacter and Roseburia abundance, but no association was observed between gut microbial diversity or Firmicutes/Bacteroidetes ratios and disease status.ConclusionsPsoriasis may be associated with gut inflammation and dysbiosis. Studies are warranted to explore the use of gut microbiome-focused therapies in the management of psoriasis in this under-studied population.
| S-EPMC7559734 | biostudies-literature
Project description:Parkinson's disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates of misfolded alpha-synuclein along the cerebral axis. Several studies report the association between intestinal dysbiosis and Parkinson's disease, although a cause-effect relationship remains to be established. Herein, the gut microbiota composition of 64 Italian patients with Parkinson's disease and 51 controls was determined using a next-generation sequencing approach. A real metagenomics shape based on gas chromatography-mass spectrometry was also investigated. The most significant changes within the Parkinson's disease group highlighted a reduction in bacterial taxa, which are linked to anti-inflammatory/neuroprotective effects, particularly in the Lachnospiraceae family and key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, and Blautia The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. Changes were seen in lipids (linoleic acid, oleic acid, succinic acid, and sebacic acid), vitamins (pantothenic acid and nicotinic acid), amino acids (isoleucine, leucine, phenylalanine, glutamic acid, and pyroglutamic acid) and other organic compounds (cadaverine, ethanolamine, and hydroxy propionic acid). Most modified metabolites strongly correlated with the abundance of members belonging to the Lachnospiraceae family, suggesting that these gut bacteria correlate with altered metabolism rates in Parkinson's disease.IMPORTANCE To our knowledge, this is one of the few studies thus far that correlates the composition of the gut microbiota with the direct analysis of fecal metabolites in patients with Parkinson's disease. Overall, our data highlight microbiota modifications correlated with numerous fecal metabolites. This suggests that Parkinson's disease is associated with gut dysregulation that involves a synergistic relationship between gut microbes and several bacterial metabolites favoring altered homeostasis. Interestingly, a reduction of short-chain fatty acid (SCFA)-producing bacteria influenced the shape of the metabolomics profile, affecting several metabolites with potential protective effects in the Parkinson group. On the other hand, the extensive impact that intestinal dysbiosis has at the level of numerous metabolic pathways could encourage the identification of specific biomarkers for the diagnosis and treatment of Parkinson's disease, also in light of the effect that specific drugs have on the composition of the intestinal microbiota.
| S-EPMC7498685 | biostudies-literature