Summary: This review examines the role of gut microbiome-produced short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate in Parkinson's disease (PD) pathogenesis, focusing on their influence on alpha-synuclein aggregation, neuroinflammation, and oxidative stress (ROS/RNS). It highlights that PD patients exhibit lower SCFA levels and suggests probiotics as a potential therapeutic avenue, while also discussing how alpha-synuclein, found in the gut and brain, may drive neuroinflammation and oxidative stress, acting as an early biomarker and a key component of the gut-brain axis in PD.

Summary: This study investigated the link between the gut microbiota genus Blautia and Parkinson's disease (PD), finding a deficiency in Blautia and fecal butyrate levels in PD patients, with Blautia abundance correlating to clinical severity. In preclinical models, supplementation with the butyrate-producing bacterium B. producta demonstrated neuroprotective effects by attenuating neuroinflammation and dopaminergic neuronal death, thereby improving motor dysfunction. The research identified the RAS-NF-κB pathway as a key mechanism, where butyrate inhibits microglial activation in PD. These findings establish a causal relationship between specific gut microbiota and PD, suggesting a novel microbiota-based therapeutic approach.

Summary: This study investigated the impact of a prebiotic, fiber-rich diet on motor deficits and neuroinflammation in alpha-synuclein overexpressing (ASO) mice, a model for Parkinson's disease (PD). The findings indicate that the prebiotic diet attenuated motor deficits, reduced alpha-synuclein aggregation in the substantia nigra, and shifted the gut microbiome towards a healthier profile. Crucially, the diet also reduced microglial activation, reversing pro-inflammatory states and promoting protective microglial subsets in the substantia nigra and striatum. The beneficial effects were dependent on microglia, as their depletion abolished the diet's positive impact on motor symptoms, highlighting a novel microglia-dependent interaction between diet and PD-like motor deficits.

Summary: This review discusses Parkinson's disease (PD) as a neurodegenerative disorder where alpha-synuclein aggregates are found in both the substantia nigra and the enteric nervous system, suggesting the pathology may originate in the gut. It highlights the role of the gut microbiome, noting that dysbiosis is associated with changes in the enteric and central nervous systems, potentially leading to dopaminergic neuron loss through mechanisms such as neurotoxin release, reduced neuroprotective factors, and inflammatory/autoimmune responses.

Summary: This review synthesizes existing studies on the role of intestinal dysbiosis in Parkinson's disease (PD), suggesting that PD may originate in the gut and that alterations in the gut microbiota can promote its development and progression. The paper focuses on how microbiota, their metabolites, and components contribute to inflammation, barrier failure, microglial activation, and alpha-synuclein pathology in PD. It concludes that intestinal dysbiosis is present in PD and likely involved in pathogenesis through mechanisms like barrier destruction, inflammation, oxidative stress, and molecular mimicry, while also noting the potential of gastrointestinal microbial therapy as a novel treatment, though further clinical studies are needed.

Summary: This narrative review examines the gut-brain axis's role in Alzheimer's and Parkinson's diseases, focusing on trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite. TMAO, produced from dietary choline and carnitine, is linked to increased neuroinflammation, protein misfolding, and cognitive decline. The review details TMAO's impact on amyloid-beta and tau pathologies in Alzheimer's, and its effect on alpha-synuclein conformation and aggregation in Parkinson's, noting TMAO's ability to cross the blood-brain barrier and activate pro-inflammatory pathways like NF-kB. It also explores the interaction between TMAO and microRNAs (miRNAs) in neurodegenerative processes, suggesting the gut microbiome-miRNA-brain axis as a mechanistic link and potential source for biomarkers. The paper also briefly mentions neuroradiology techniques and animal models for studying these pathologies, concluding that modulating the gut-brain communication pathway offers potential therapeutic strategies.

Summary: This review discusses how changes in the gastrointestinal microbiome (GM) in Parkinson's disease (PD) lead to alpha-synuclein (α-syn) misfolding and aggregation in the intestine, which is then transported via the vagus nerve to the central nervous system (CNS). In the substantia nigra, this abnormal α-syn stimulates microglial activation and causes dopaminergic neuron dysfunction, contributing to neuroinflammation and oxidative stress, creating a positive feedback loop that exacerbates PD progression. The review also touches upon clinical therapeutic strategies targeting the GM and α-syn accumulation.

Summary: This study investigated urolithins, anti-inflammatory metabolites produced by gut microbes, as potential biomarkers for gut dysbiosis and disease stage in Parkinson's disease (PD). Researchers analyzed stool and urine samples from 52 PD patients and 117 controls, assessing gut microbiota composition and urolithin profiles before and after walnut consumption. They found that individuals who were urolithin non-producers (metabotype-0) increased with disease severity, and these patients, along with those with more severe PD, exhibited altered gut microbiomes characterized by increased pro-inflammatory bacteria and reduced protective bacteria. The findings suggest that urolithin detection is a feasible, non-invasive method to reflect gut dysbiosis and intestinal inflammation in PD, potentially aiding diagnostics and therapeutic strategies.

Summary: This review critically assesses studies on how dietary interventions modulate the gut microbiota in relation to neuroinflammation and neurodegenerative diseases like Parkinson's and Alzheimer's. It highlights that diet influences gut microbiota composition, permeability, and metabolite synthesis, which in turn affect host homeostasis and disease progression. While specific diets like ketogenic, Mediterranean, and vegetarian diets show potential for Parkinson's disease by impacting gut inflammation, the Western diet is associated with reduced microbial diversity and increased neuroinflammation. The review emphasizes the need for more research to understand the complex interactions between diet, gut microbiota, and neuroinflammation in these diseases.

Summary: This review article explores the transmission of alpha-synuclein from the gut to the brain as a key mechanism in Parkinson's disease (PD). It highlights how environmental factors entering the body can lead to alpha-synuclein misfolding and Lewy pathology in the gut's enteric nervous system, which then travels to the brain via the vagus nerve. The paper notes the bidirectional gut-brain connection and the prevalence of gastrointestinal issues, such as gut inflammation, in early-stage PD patients. The review aims to detail the signaling pathways involved in this gut-brain link and discuss current therapeutic strategies for PD.

Summary: This study investigated the temporal stability of gut microbiota alterations in Parkinson's disease (PD) patients and their relationship to disease progression. Collecting stool samples and clinical data from 64 PD patients and 64 controls twice over an average of 2.25 years, the researchers used 16S rRNA gene sequencing. They found significant differences in microbial communities between PD patients and controls that persisted over the follow-up period, identifying specific taxa like Roseburia, Prevotella, and Bifidobacterium as differentially abundant. While differentially abundant taxa related to disease progression were inconsistent, there was some evidence suggesting different enterotypes and a decrease in Prevotella in faster-progressing patients, though longer follow-up is needed for confirmation.

Summary: This critical review explores the role of gut microbiota dysfunction in Parkinson's disease (PD) pathophysiology, proposing it as a source of reliable, non-invasive early diagnostic biomarkers. It highlights the microbiota-gut-brain axis's influence on brain activity and dopamine synthesis, and how alpha-synuclein pathology in the enteric nervous system leads to increased intestinal permeability, oxidative stress, and local inflammation, contributing to PD symptoms like constipation. The paper posits that chronic low-grade gut inflammation can trigger blood-brain barrier leakage, immune cell activation, and subsequent neuroinflammation in the central nervous system. It suggests that non-motor symptoms, correlated with neuroimaging or behavioral indices, could serve as early biomarkers, and calls for future research to identify specific gut microbes and develop novel therapeutic strategies.

Summary: This review examines the role of the gut microbiome in aging and neurodegenerative diseases, including Parkinson's disease, by analyzing preclinical and clinical studies. It discusses how gut dysbiosis, influenced by factors like diet and lifestyle, affects brain function via the brain-gut microbiota axis. The paper also explores strategies for modulating the gut microbiome, such as probiotics, dietary interventions, fecal microbiota transplantation, and physical activity, to address aging and prevent neurodegenerative conditions.

Summary: This study analyzed the gut microbiota composition in 350 individuals, including idiopathic Parkinson's disease (PD) patients (stratified by duration and drug-naïve status), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and healthy controls (HC), using 16S rRNA sequencing. While unadjusted comparisons revealed differences between PD and HC, these were reduced after accounting for confounders like diet. Notably, lower abundance of Lachnospiraceae was observed in de novo PD patients and persisted across disease duration, while decreased Lachnospiraceae and increased Lactobacillaceae and Christensenellaceae were associated with a worse clinical profile, including cognitive impairment and gait disturbances. The findings suggest the gut microbiota can modulate PD pathogenesis and clinical variability, emphasizing the need for prospective studies in de novo PD patients to clarify dysbiosis effects on disease progression.

Summary: This study investigated gastrointestinal inflammation in Parkinson's disease (PD) by measuring immune and angiogenesis-related proteins in stool samples from 156 PD patients and 110 controls. PD patients reported more digestive issues, and analysis revealed elevated levels of vascular endothelial growth factor receptor 1, interleukin-1α, and CXCL8 in their stool. After accounting for confounders like sex, BMI, smoking, and probiotic use, multivariate analysis confirmed increased levels of interleukin-1α, CXCL8, interleukin-1β, and C-reactive protein in PD patients' stool, indicating the presence of intestinal inflammation. These findings suggest that stool immune factors could serve as early biomarkers for PD.

Summary: This paper reviews the gut microbiota-brain axis (GMBA) in Parkinson's disease (PD), noting that non-motor symptoms can precede motor symptoms by up to 20 years and suggesting PD pathology may originate in the gastrointestinal tract. The GMBA facilitates communication between the gut microbiota and the brain via the immune system, amino acid metabolism, and neurological pathways. Microbial metabolites, such as amino acids (e.g., glutamate, tryptophan), are identified as signaling molecules that can influence nerve cell communication and basal ganglia function in PD. The study aims to compile and analyze existing evidence on gut microbiota-derived amino acid metabolic changes associated with PD.