scholarly journals The impact of dextran sodium sulphate and probiotic pre-treatment in a murine model of Parkinson’s disease

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Zach Dwyer ◽  
Melany Chaiquin ◽  
Jeffrey Landrigan ◽  
Kiara Ayoub ◽  
Pragya Shail ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Murine Model ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Sodium Sulphate ◽  
Dopamine Neurons ◽  
Dextran Sodium Sulphate ◽  
Pre Treatment ◽  
The Impact

Abstract Background Recent work has established that Parkinson’s disease (PD) patients have an altered gut microbiome, along with signs of intestinal inflammation. This could help explain the high degree of gastric disturbances in PD patients, as well as potentially be linked to the migration of peripheral inflammatory factors into the brain. To our knowledge, this is the first study to examine microbiome alteration prior to the induction of a PD murine model. Methods We presently assessed whether pre-treatment with the probiotic, VSL #3, or the inflammatory inducer, dextran sodium sulphate (DSS), would influence the PD-like pathology provoked by a dual hit toxin model using lipopolysaccharide (LPS) and paraquat exposure. Results While VSL #3 has been reported to have anti-inflammatory effects, DSS is often used as a model of colitis because of the gut inflammation and the breach of the intestinal barrier that it induces. We found that VSL#3 did not have any significant effects (beyond a blunting of LPS paraquat-induced weight loss). However, the DSS treatment caused marked changes in the gut microbiome and was also associated with augmented behavioral and inflammatory outcomes. In fact, DSS markedly increased taxa belonging to the Bacteroidaceae and Porphyromonadaceae families but reduced those from Rikencellaceae and S24-7, as well as provoking colonic pro-inflammatory cytokine expression, consistent with an inflamed gut. The DSS also increased the impact of LPS plus paraquat upon microglial morphology, along with circulating lipocalin-2 (neutrophil marker) and IL-6. Yet, neither DSS nor VSL#3 influenced the loss of substantia nigra dopamine neurons or the astrocytic and cytoskeleton remodeling protein changes that were provoked by the LPS followed by paraquat treatment. Conclusions These data suggest that disruption of the intestinal integrity and the associated microbiome can interact with systemic inflammatory events to promote widespread brain-gut changes that could be relevant for PD and at the very least, suggestive of novel neuro-immune communication.

scholarly journals Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 772
Author(s):  
Javier Conde ◽  
Marlene Schwarzfischer ◽  
Egle Katkeviciute ◽  
Janine Häfliger ◽  
Anna Niechcial ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Titanium Dioxide ◽  
Genetic Risk ◽  
Intestinal Inflammation ◽  
Sodium Sulphate ◽  
Food Additive ◽  
Wild Type ◽  
Dextran Sodium Sulphate ◽  
Risk Gene ◽  
The Impact

Environmental and genetic factors have been demonstrated to contribute to the development of inflammatory bowel disease (IBD). Recent studies suggested that the food additive; titanium dioxide (TiO2) might play a causative role in the disease. Therefore, in the present study we aimed to explore the interaction between the food additive TiO2 and the well-characterized IBD risk gene protein tyrosine phosphatase non-receptor type 2 (Ptpn2) and their role in the development of intestinal inflammation. Dextran sodium sulphate (DSS)-induced acute colitis was performed in mice lacking the expression of Ptpn2 in myeloid cells (Ptpn2LysMCre) or their wild type littermates (Ptpn2fl/fl) and exposed to the microparticle TiO2. The impact of Ptpn2 on TiO2 signalling pathways and TiO2-induced IL-1β and IL-10 levels were studied using bone marrow-derived macrophages (BMDMs). Ptpn2LysMCre exposed to TiO2 exhibited more severe intestinal inflammation than their wild type counterparts. This effect was likely due to the impact of TiO2 on the differentiation of intestinal macrophages, suppressing the number of anti-inflammatory macrophages in Ptpn2 deficient mice. Moreover, we also found that TiO2 was able to induce the secretion of IL-1β via mitogen-activated proteins kinases (MAPKs) and to repress the expression of IL-10 in bone marrow-derived macrophages via MAPK-independent pathways. This is the first evidence of the cooperation between the genetic risk factor Ptpn2 and the environmental factor TiO2 in the regulation of intestinal inflammation. The results presented here suggest that the ingestion of certain industrial compounds should be taken into account, especially in individuals with increased genetic risk

scholarly journals Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stefano Romano ◽  
George M. Savva ◽  
Janis R. Bedarf ◽  
Ian G. Charles ◽  
Falk Hildebrand ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Short Chain Fatty Acids ◽  
Inflammatory Status

AbstractThe gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.

The impact of device-assisted therapies on the gut microbiome in Parkinson’s disease

2021 ◽  
Author(s):  
Michal Lubomski ◽  
Xiangnan Xu ◽  
Andrew J. Holmes ◽  
Jean Y. H. Yang ◽  
Carolyn M. Sue ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
The Impact

scholarly journals Gut microbiome signatures of risk and prodromal markers of Parkinson’s disease

2019 ◽  
Author(s):  
Sebastian Heinzel ◽  
Velma T. E. Aho ◽  
Ulrike Suenkel ◽  
Anna-Katharina von Thaler ◽  
Claudia Schulte ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
Physical Inactivity ◽  
Disease Onset ◽  
Rem Sleep Behavior Disorder ◽  
Sleep Behavior ◽  
Microbiome Composition ◽  
Β Diversity ◽  
The Impact

AbstractObjectivesAlterations of the gut microbiome in Parkinson’s disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they may be related to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition.MethodsEstablished risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and taxonomic composition in stool samples of 666 elderly TREND study participants.ResultsAmong risk and prodromal markers, physical inactivity, constipation and age showed associations with α- and β-diversity, and for both measures subthreshold parkinsonism and physical inactivity showed interaction effects. Moreover, male sex, possible REM-sleep behavior disorder (RBD), smoking as well as body-mass-index, antidiabetic and urate-lowering medication were associated with β-diversity. Physical inactivity and constipation severity were increased in individuals with the Firmicutes-enriched enterotype. Subthreshold parkinsonism was least frequently observed in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history and the overall prodromal PD probability showed no significant microbiome associations.InterpretationSeveral risk and prodromal markers of PD are associated with changes in gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases.

scholarly journals Interventional Influence of the Intestinal Microbiome Through Dietary Intervention and Bowel Cleansing Might Improve Motor Symptoms in Parkinson’s Disease

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 376 ◽  
Author(s):  
Tobias Hegelmaier ◽  
Marco Lebbing ◽  
Alexander Duscha ◽  
Laura Tomaske ◽  
Lars Tönges ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
Dietary Intervention ◽  
Therapeutic Option ◽  
Vegetarian Diet ◽  
Alpha Synuclein ◽  
Intestinal Microbiome ◽  
Bowel Cleansing ◽  
The Impact

The impact of the gut microbiome is being increasingly appreciated in health and in various chronic diseases, among them neurodegenerative disorders such as Parkinson’s disease (PD). In the pathogenesis of PD, the role of the gut has been previously established. In conjunction with a better understanding of the intestinal microbiome, a link to the misfolding and spread of alpha-synuclein via inflammatory processes within the gut is discussed. In a case-control study, we assessed the gut microbiome of 54 PD patients and 32 healthy controls (HC). Additionally, we tested in this proof-of-concept study whether dietary intervention alone or additional physical colon cleaning may lead to changes of the gut microbiome in PD. 16 PD patients underwent a well-controlled balanced, ovo-lacto vegetarian diet intervention including short fatty acids for 14 days. 10 of those patients received additional treatment with daily fecal enema over 8 days. Stool samples were collected before and after 14 days of intervention. In comparison to HC, we could confirm previously reported PD associated microbiome changes. The UDPRS III significantly improved and the levodopa-equivalent daily dose decreased after vegetarian diet and fecal enema in a one-year follow-up. Additionally, we observed a significant association between the gut microbiome diversity and the UPDRS III and the abundance of Ruminococcaceae. Additionally, the abundance of Clostridiaceae was significantly reduced after enema. Dietary intervention and bowel cleansing may provide an additional non-pharmacologic therapeutic option for PD patients.

The impact of age and gender on the striatal astrocytes activation in murine model of Parkinson’s disease

2009 ◽  
Vol 58 (11) ◽  
pp. 747-753 ◽  
Author(s):  
Agnieszka Ciesielska ◽  
I. Joniec ◽  
I. Kurkowska-Jastrzębska ◽  
A. Cudna ◽  
A. Przybyłkowski ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Murine Model ◽  
Age And Gender ◽  
And Gender ◽  
The Impact

Effects of Sildenafil on Nigrostriatal Dopamine Neurons in a Murine Model of Parkinson's Disease

2008 ◽  
Vol 15 (1) ◽  
pp. 97-107 ◽  
Author(s):  
Kelly L. Janis ◽  
Ryan T. Brennan ◽  
Robert E. Drolet ◽  
Bahareh Behrouz ◽  
Sarah K. Kaufman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Murine Model ◽  
Dopamine Neurons ◽  
Nigrostriatal Dopamine ◽  
Nigrostriatal Dopamine Neurons

The impact of gut microbiome in Parkinson's disease

2021 ◽  
Vol 429 ◽  
pp. 119589
Author(s):  
Nargiza Mansurova ◽  
Yakuthon Madjidova
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
The Impact

scholarly journals Meta-analysis of the gut microbiome of Parkinson's disease patients suggests alterations linked to intestinal inflammation

2020 ◽  
Author(s):  
Stefano Romano ◽  
George M Savva ◽  
Janis R Bedarf ◽  
Ian G Charles ◽  
Falk Hildebrand ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Short Chain Fatty Acids ◽  
Inflammatory Status

The gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson's disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing 10 currently available 16S microbiome datasets to investigate whether underlying alterations in the gut microbiota of PD patients exist. We found consistent alterations in PD-associated microbiome, which are significant and robust to confounders across studies, although differences in microbiome structure between PD and controls are limited. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the families Lachnospiraceae and Ruminococcaceae, which are important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could explain the recurrent gastrointestinal symptoms affecting PD patients.

scholarly journals 091 The impact of device-assisted therapy initiation on the gut microbiome in Parkinson’s disease

2021 ◽  
Author(s):  
Michal Lubomski ◽  
Xiangnan Xu ◽  
Andrew J Holmes ◽  
Jean Yang ◽  
Carolyn M Sue ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
Therapy Initiation ◽  
The Impact
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