Human microbiota form a biofilm with substantial consequences for health and disease. Numerous studies have indicated that microbial communities produce functional amyloids as part of their biofilm extracellular scaffolds. The overlooked interplay between bacterial amyloids and the host may have detrimental consequences for the host, including neurodegeneration. This work gives an overview of the biofilm-associated amyloids expressed by the gut microbiota and their potential role in neurodegeneration. It discusses the biofilm-associated proteins (BAPs) of the gut microbiota, maps the amyloidogenic domains of these proteins, and analyzes the presence of bap genes within accessory genomes linked with transposable elements. Furthermore, the evidence supporting the existence of amyloids in the gut are presented. Finally, it explores the potential interactions between BAPs and α-synuclein, extending the literature on amyloid cross-kingdom interactions. Based on these findings, this study propose that BAP amyloids act as transmissible catalysts, facilitating the misfolding, accumulation, and spread of α-synuclein aggregates. This review contributes to the understanding of complex interactions among the microbiota, transmissible elements, and host, which is crucial for developing novel therapeutic approaches to combat microbiota-related diseases and improve overall health outcomes.

Necrotic enteritis (NE) in broiler chickens leads to significant economic losses in poultry production. This study examined the inhibitory effects of usnic acid and tannic acid on coccidia, sporozoite, and Clostridium perfringens and assessed their influence on growth performance and intestinal health in NE-challenged broilers through in vitro and in vivo experiments.

The in vitro experiment included 5 treatment groups: the negative control (NC), 2 μmol/L diclazuril (DZ), 30 μmol/L usnic acid (UA), 90 μmol/L tannic acid (TA), and 15 μmol/L usnic acid + 45 μmol/L tannic acid (UTA) groups. The in vivo experiment involved 320 broilers divided into four groups: PC (NE-challenged), SA (500 mg/kg salinomycin premix + NE-challenged), UA (300 mg/kg usnic acid + NE-challenged), and UTA (300 mg/kg usnic acid + 500 mg/kg tannic acid + NE-challenged) groups.

In the in vitro study, the UA, TA, and UTA treatments significantly increased apoptosis in coccidian oocysts and sporozoites, lowered the mitochondrial membrane potential (P < 0.05), and disrupted the oocyst structure compared with those in the NC group. UA and TA had inhibitory effects on C. perfringens, with the strongest inhibition observed in the UTA group. The in vivo results demonstrated that the SA group presented significantly improved growth performance on d 13, 21, and 28 (P < 0.05), whereas the UA and UTA groups presented improvements on d 13 and 21 (P < 0.05). The SA, UA, and UTA treatments reduced the intestinal lesion scores by d 28 and the fecal coccidian oocyst counts from d 19 to 21 (P < 0.05). Compared with the PC group, the UA and UTA groups presented lower intestinal sIgA levels and CD8+ cell percentages (P < 0.05), with a trend toward a reduced CD3+ cell percentage (P = 0.069). The SA, UA, and UTA treatments significantly reduced the serum diamine oxidase activity, crypt depth, and platelet-derived growth factor levels in the intestinal mucosa while increasing the villus height to crypt depth ratio and number of goblet cells (P < 0.05). The UTA treatment also significantly increased the acetate and butyrate concentrations in the cecum (P < 0.05). With respect to the gut microbiota, significant changes in β diversity in the ileum and cecum were observed in the SA, UA, and UTA groups, indicating that the microbial community compositions differed among the groups. Romboutsia dominated the SA group, Bacillales dominated the UA group, and Lactobacillales and Lachnospirales dominated the UTA group in the ileal microbiota. In the cecal microbiota, Lactobacillus, Butyricicoccus, and Blautia abundances were significantly elevated in the UTA group (P < 0.05).

Usnic acid and tannic acid induce apoptosis in coccidia and sporozoites by lowering the mitochondrial membrane potential. Both usnic acid alone and in combination with tannic acid alleviate NE-induced adverse effects in broilers by modulating intestinal immunity, altering the microbial composition, and improving intestinal barrier function. Compared with usnic acid alone, the combination of usnic acid and tannic acid had superior effects, providing a promising basis for the development of effective feed additive combinations.

Background: The gut-brain axis (GBA) is a complex bidirectional communication system that links the gastrointestinal tract and the central nervous system. Essential oils (EOs) have emerged as promising natural compounds capable of modulating this axis. Methods: A comprehensive analysis of the recent literature was conducted, focusing on studies investigating the effects of EOs on the GBA. Particular attention was given to the endocannabinoid system, the role of cannabis-derived EOs, and other plant-based EOs with potential neuroprotective and gut microbiota-modulating effects. Results: Among the EOs analyzed, cannabis essential oil (CEO) gained attention for its interaction with cannabinoid receptors (CBR1 and CBR2), modulating gut motility, immune responses, and neurotransmission. While acute administration of the CEO reduces inflammation and gut permeability, chronic use has been associated with alterations in gut microbiota composition, potentially impairing cognitive function. Other EOs, such as those from rosemary, lavender, eucalyptus, and oregano, demonstrated effects on neurotransmitter modulation, gut microbiota balance, and neuroinflammation, supporting their potential therapeutic applications in GBA-related disorders. Conclusions: EOs demonstrate promising potential in modulating the GBA through mechanisms including neurotransmitter regulation, gut microbiota modulation, and anti-inflammatory activity. At the same time, phytocannabinoids offer therapeutic value; their long-term use warrants caution due to potential impacts on microbiota. Future research should aim to identify EO-based interventions that can synergistically restore GBA homeostasis and mitigate neurodegenerative and gastrointestinal disorders.

Ginsenoside CK (CK) is a metabolite of natural diol ginsenoside in the intestine, which has a unique chemical structure and pharmacological activity. CK has great potential in the treatment of neurologic dysfunction diseases. However, the therapeutic effect and potential mechanism of CK on Parkinson's disease (PD) have not been studied. Accordingly, this study used microbiome analysis to correlate behavioral, physiological and biochemical indices, and combined with WB to elucidate the mechanism of CK's improvement on PD. CK showed significant therapeutic effects on PD mice, which improved behavioral abnormalities such as spatial memory ability and motor coordination in PD mice, increased the activities of T-AOC and GSH-Px, decreased the MDA content, thus alleviating oxidative stress injury, suppressed the levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α, and activated the expression of anti-inflammatory factor IL-2, which then exerted against neuroinflammation, inhibited the apoptosis of dopaminergic neurons in the substantia nigra of PD mice, increased the expression of TH, and prevented the aggregation of α-Syn in the substantia nigra. Microbiomics analysis showed that CK treatment could reshape the gut microbiota of PD mice by increasing the abundance of probiotics (Bacteroides anomalies) and decreasing the number of pathogenic bacteria (Actinomycetes). Correlation analysis showed that gut microbiota had potential correlation with behavioral, physiological and biochemical indexes. Western blot results showed that CK inhibited the expression levels of apoptotic proteins Bax, caspase-3, and Bcl-2, which revealed that CK treatment could improve the dysfunction of MPTP-induced PD mice from the molecular level. Collectively, these findings will provide a basis for further development of CK as an anti-PD drug.

Parkinson's disease (PD) is a neurodegenerative disorder characterised by motor and non-motor symptoms. Recent evidence suggests a role for gut microbiome composition and diversity in PD aetiology. This study aimed to explore the association between the gut microbiome and PD in a South African population. Gut microbial sequencing data (cases: n = 16; controls: n = 42) was generated using a 16S rRNA gene (V4) primer pair. Alpha- and beta-diversity were calculated using QIIME2, and differential abundance of taxa was evaluated using Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC). Beta-diversity was found to differ significantly between cases and controls, with depletion in the relative abundance of Faecalibacterium, Roseburia, Dorea, and Veillonella, and enrichment of the relative abundance of Akkermansia and Victivallis. Our study found a reduction in butyrate-producing bacteria (e.g. Faecalibacterium and Roseburia) and an increase in mucin-degrading bacteria (Akkermansia) in PD cases compared to controls. These alterations might be associated with heightened gut permeability and inflammation. Longitudinal studies should address the question of whether these microbiome differences are a risk factor for, or are consequent to, the development of PD.

Alpha-synuclein aggregation, a hallmark of Parkinson's disease (PD), is hypothesized to often begin in the enteric or peripheral nervous system in "body-first" PD and progresses through the vagus nerve to the brain, therefore REM sleep behavior disorder (RBD) precedes the PD diagnosis. In contrast, "brain-first" PD begins in the central nervous system. Evidence that gut microbiome imbalances observed in PD and idiopathic RBD exhibit similar trends supports body-first and brain-first hypothesis and highlights the role of microbiota in PD pathogenesis. However, further investigation is needed to understand distinct microbiome changes in body-first versus brain-first PD over the disease progression.

Our investigation involved 104 patients with PD and 85 of their spouses as healthy controls (HC), with 57 patients (54.8%) categorized as PD-RBD(+) and 47 patients (45.2%) as PD-RBD(-) based on RBD presence before the PD diagnosis. We evaluated the microbiome differences between these groups over the disease progression through taxonomic and functional differential abundance analyses and carbohydrate-active enzyme (CAZyme) profiles based on metagenome-assembled genomes. The PD-RBD(+) gut microbiome showed a relatively stable microbiome composition irrespective of disease stage. In contrast, PD-RBD(-) microbiome exhibited a relatively dynamic microbiome change as the disease progressed. In early-stage PD-RBD(+), Escherichia and Akkermansia, associated with pathogenic biofilm formation and host mucin degradation, respectively, were enriched, which was supported by functional analysis. We discovered that genes of the UDP-GlcNAc synthesis/recycling pathway negatively correlated with biofilm formation; this finding was further validated in a separate cohort. Furthermore, fiber intake-associated taxa were decreased in early-stage PD-RBD(+) and the biased mucin-degrading capacity of CAZyme compared to fiber degradation.

We determined that the gut microbiome dynamics in patients with PD according to the disease progression depend on the presence of premotor RBD. Notably, early-stage PD-RBD(+) demonstrated distinct gut microbial characteristics, potentially contributing to exacerbation of PD pathophysiology. This outcome may contribute to the development of new therapeutic strategies targeting the gut microbiome in PD. Video Abstract.

Parkinson's disease (PD) is a complex neurodegenerative disorder with debilitating non-motor symptoms, including gastrointestinal dysfunction, cardiovascular abnormalities, mood and anxiety disorders, cognitive decline, sleep disturbances, respiratory dysfunction, and pain. Despite their significant impact on quality of life, these symptoms are often inadequately addressed. Propolis is a natural bee-derived product, rich in bioactive compounds with anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective properties, which holds potential in PD due to its multitarget and multipathway actions, addressing various underlying mechanisms of non-motor symptom diseases. Preclinical and clinical studies suggest that propolis may influence key pathological mechanisms in PD's non-motor symptoms. Evidence points to its potential benefits in improving cognition, mood disorders, gastrointestinal health, and alleviating cardiovascular and sleep-related issues. Although research on propolis in non-motor symptoms of PD remains scarce, findings from related conditions suggest its ability to influence mechanisms associated with these symptoms. This review underscores the underexplored therapeutic potential of propolis in non-motor symptoms of PD, drawing on existing evidence and advocating for further research to fully assess its role in addressing these symptoms and improving patient outcomes.

The microbiota-gut-brain axis has been proposed as a potential modulator of mood disorders such as major depression. Complex bidirectional biochemical activities in this axis have been posited to participate in adverse mood disorders. Environmental and genetic factors have dominated recent discussions on depression. The prescription of antibiotics, antidepressants, adverse negative DNA methylation reactions and a dysbiotic gut microbiome have been cited as causal for the development and progression of depression. While research continues to investigate the microbiome-gut-brain axis, this review will explore the state of persistence of gut bacteria that underpins bacterial dormancy, possibly due to adverse environmental conditions and/or pharmaceutical prescriptions. Bacterial dormancy persistence in the intestinal microbial cohort could affect the role of bacterial epigenomes and DNA methylations. DNA methylations are highly motif driven exerting significant control on bacterial phenotypes that can disrupt bacterial metabolism and neurotransmitter formation in the gut, outcomes that can support adverse mood dispositions.

Epidemiological studies reveal that inflammatory bowel disease (IBD) is associated with an increased risk of Parkinson's disease (PD). Gut dysbiosis has been documented in both PD and IBD, however it is currently unknown whether gut dysbiosis underlies the epidemiological association between both diseases. To identify shared and distinct features of the PD and IBD microbiome, we recruited 54 PD, 26 IBD, and 16 healthy control individuals and performed the first joint analysis of gut metagenomes. Larger, publicly available PD and IBD metagenomic datasets were also analyzed to validate and extend our findings. Depletions in short-chain fatty acid (SCFA)-producing bacteria, including Roseburia intestinalis, Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium rectale, as well depletion in SCFA-synthesis pathways were detected across PD and IBD datasets, suggesting that depletion of these microbes in IBD may influence the risk for PD development.

The gut microbiome comprises a vast community of microbes inhabiting the human alimentary canal, playing a crucial role in various physiological functions. These microbes generally live in harmony with the host; however, when dysbiosis occurs, it can contribute to the pathogenesis of diseases, including osteoporosis. Osteoporosis, a systemic skeletal disease characterized by reduced bone mass and increased fracture risk, has attracted significant research attention concerning the role of gut microbes in its development. Advances in molecular biology have highlighted the influence of gut microbiota on osteoporosis through mechanisms involving immunoregulation, modulation of the gut-brain axis, and regulation of the intestinal barrier and nutrient absorption. These microbes can enhance bone mass by inhibiting osteoclast differentiation, inducing apoptosis, reducing bone resorption, and promoting osteoblast proliferation and maturation. Despite these promising findings, the therapeutic effectiveness of targeting gut microbes in osteoporosis requires further investigation. Notably, gut microbiota has been increasingly studied for their potential in early diagnosis, intervention, and as an adjunct therapy for osteoporosis, suggesting a growing utility in improving bone health. Further research is essential to fully elucidate the therapeutic potential and clinical application of gut microbiome modulation in the management of osteoporosis.

Parkinson's disease (PD) is a progressive disease that requires effective staging management. The role of intestinal microbiota in PD has been studied, but its changes at different stages are not clear. In this study, meta- analysis, bioinformatics analysis and in vivo simulation were used to explore the intestinal microbiota distribution of PD patients and models at different stages. Two PD models at different stages were established in rotenone-treated rats and MPTP-induced mice. The differences in the intestinal microbiota among the different stages of PD patients or models were compared and analyzed. There were significant differences between PD patients and controls, including Actinobacteriota, Deltaproteobacteria, Clostridiales, Lachnospiraceae, Parabacteroides, etc. Through bioinformatics analysis, we revealed significant differences between PD patients at different stages and controls, including Actinobacteriota, Methanobacteria, Erysipelotrichales, Prevotellaceae, Parabacteroides, Parabacteroides gordonii, etc. Through meta-analysis, we found that Actinobacteriota and Erysipelotrichaceae had significantly increased in the chronic MPTP model, while Prevotellaceae had significantly decreased. PD rats and mice presented significant damage to motor function, coordination, autonomous activity ability and gastrointestinal function, and the damage in the late group was greater than that in the early group. There were significant differences in intestinal microbiota between PD patients or models at different stages and the control groups. In the early stage, the dominant microbiota are Akkermansia, Alistipes, Anaerotruncus, Bilophila, Rikenellaceae, Verrucomicrobia and Verrucomicrobiae, whereas in the late stage, the dominant microbiota are Actinobacteriota and Erysipelotrichaceae. These differences can lay a foundation for subsequent research on the treatment and mechanism of PD at different stages.

Exercise is a widely recognized non-pharmacological treatment for Parkinson's Disease (PD). The bidirectional regulation between the brain and peripheral organs has emerged as a promising area of research, with the mechanisms by which exercise impacts PD closely linked to the interplay between peripheral signals and the central nervous system.

This review aims to summarize the mechanisms by which exercise influences peripheral-central crosstalk to improve PD, discuss the molecular processes mediating these interactions, elucidate the pathways through which exercise may modulate PD pathophysiology, and identify directions for future research.

This review examines how exercise-induced cytokine release promotes neuroprotection in PD. It discusses how exercise can stimulate cytokine secretion through various pathways, including the gut-brain, muscle-brain, liver-brain, adipose-brain, and bone-brain axes, thereby alleviating PD symptoms. Additionally, the potential contributions of the heart-brain, lung-brain, and spleen-brain axes, as well as multi-axis crosstalk-such as the brain-gut-muscle and brain-gut-bone axes-are explored in the context of exercise therapy. The study highlights the need for further research into peripheral-central crosstalk and outlines future directions to address challenges in clinical PD therapy.

Bacterial biofilms, which are complex communities of microorganisms encapsulated in a self-produced extracellular matrix, play critical roles in various diseases. Recent research has underscored the dualistic nature of amyloids, structural proteins within these biofilms, in human health, particularly highlighting the significant role in neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's disease (PD). These amyloids modulate the immune response by inducing the production of interleukin-10 (IL-10), which plays a role in anti-inflammatory processes. Additionally, they inhibit the aggregation of human amyloids and enhance the integrity of the intestinal barrier. Detrimentally, they exacerbate neuroinflammation by elevating inflammatory cytokines and promoting the aggregation of human amyloid proteins-amyloid-β (Aβ) in AD and α-synuclein (αS) in PD-through a process known as cross-seeding. Moreover, bacterial amyloids have also been shown to stimulate the production of anti-curli/DNA antibodies, which are implicated in the pathogenesis of autoimmune diseases. Given their dualistic nature, bacterial amyloids may, under specific conditions, function as beneficial proteins for human health. This understanding holds promise for the development of targeted therapeutic strategies aimed at modulating bacterial amyloids in the context of neurodegenerative diseases, such as AD and PD.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, affecting 1-2% of people over age 65. The risk of developing PD dramatically increases with advanced age, indicating that aging is likely a driving factor in PD neuropathogenesis. Several age-associated biological changes are also hallmarks of PD neuropathology, including mitochondrial dysfunction, oxidative stress, and neuroinflammation. Accumulation of senescent cells is an important feature of aging that contributes to age-related diseases. How age-related cellular senescence affects brain health and whether this phenomenon contributes to neuropathogenesis in PD is not yet fully understood. In this review, we highlight hallmarks of aging, including mitochondrial dysfunction, loss of proteostasis, genomic instability and telomere attrition in relation to well established PD neuropathological pathways. We then discuss the hallmarks of cellular senescence in the context of neuroscience and review studies that directly examine cellular senescence in PD. Studying senescence in PD presents challenges and holds promise for advancing our understanding of disease mechanisms, which could contribute to the development of effective disease-modifying therapeutics. Targeting senescent cells or modulating the senescence-associated secretory phenotype (SASP) in PD requires a comprehensive understanding of the complex relationship between PD pathogenesis and cellular senescence.

This review discusses findings related to neurological disorders, gut microbiota, and bariatric surgery, focusing on neurotransmitters, neuroendocrine, the pathophysiology of bacteria contributing to disorders, and possible therapeutic interventions. Research on neurotransmitters suggests that their levels are heavily influenced by gut microbiota, which may link them to neurological disorders such as Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Depression, and Autism spectrum disorder. The pathophysiology of bacteria that reach and influence the central nervous system has been documented. Trends in microbiota are often observed in specific neurological disorders, with a prominence of pro-inflammatory bacteria and a reduction in anti-inflammatory types. Furthermore, bariatric surgery has been shown to alter microbiota profiles similar to those observed in neurological disorders. Therapeutic interventions, including fecal microbiota transplants and probiotics, have shown potential to alleviate neurological symptoms. We suggest a framework for future studies that integrates knowledge from diverse research areas, employs rigorous methodologies, and includes long-trial clinical control groups.

Previous studies have suggested a link between gut microbiota and iron-deficiency anemia (IDA). However, interpreting these findings is difficult due to various factors that influence microbiome composition and the limitations of observational studies, such as confounding variables and reverse causation. This study aims to explore the causal relationship between gut microbiota and IDA using Mendelian randomization (MR) to overcome these limitations. We conducted a 2-sample MR analysis using data from genome-wide association studies from the MiBioGen Consortium and the UK Biobank. The gut microbiome data included 211 genus-level microbes linked to single-nucleotide polymorphisms from 18,340 participants in the MiBioGen Consortium. The outcome data for IDA were obtained from 484,598 participants in the UK Biobank, with 2941 cases and 481,657 controls. We assessed causal relationships using various MR techniques, primarily inverse variance weighting, and performed sensitivity analyses to confirm the robustness of our results. Nine genus-level gut microbes were significantly associated with IDA (P < .05). Protective factors included Clostridia, Actinomycetaceae, Pasteurellaceae, Oscillospira, Prevotella, and Roseburia, while risk factors included Ruminococcus gnavus group, Hungatella, and Parasutterella. Sensitivity analyses showed the reliability of these findings without significant variability. This study provides evidence for a causal relationship between specific gut bacteria and IDA risk, identifying potential targets for therapies aimed at improving outcomes for those with IDA. Further research is needed to clarify the bacteria involved.

Parkinson's disease (PD) is a progressive neurological disorder with an increasing prevalence in aging populations. Identifying effective therapeutic targets and treatments remains a critical challenge. This study aimed to discover potential therapeutic targets and design novel compounds for PD treatment. Gene expression analysis was conducted using diverse datasets, including microarray, mRNA sequencing, and miRNA sequencing. While no common genes were identified across all datasets, the RNA-seq dataset GSE-135036 was prioritized. The investigation focused on downregulated miRNAs targeting upregulated mRNAs, revealing that hsa-mir-5585 regulates Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) within the Shigellosis pathway. Given RIPK1's role in cell death and inflammation, it emerged as a promising therapeutic target for PD. To identify RIPK1 inhibitors, 67 compounds were screened via molecular docking, with CHEMBL-3109201 exhibiting the highest binding affinity. A structurally similar compound, CHEMBL-76328382, also demonstrated strong interactions. A fragment-based drug design approach generated two novel compounds, BI-1215 and BI-146, which, along with RIPK1-IN-4 and CHEMBL-70909876, were shortlisted based on docking scores and ADME profiles. Molecular dynamics simulations confirmed the stability of CHEMBL-70909876 and BI-1215, with RMSD fluctuations between 0.005 and 0.2 nm. MM-PBSA analysis further validated their superior thermodynamic stability and binding affinity compared to other candidates. This study offers novel insights into PD pathogenesis and potential therapeutic interventions, marking a significant step toward effective treatment strategies for this debilitating disorder.

The trillions of microbial populations residing in the gut have recently shown that they can be used as a remedy for various diseases. The gut microbiota-brain-axis interface is one unique pathway that the microbiota demonstrates its medicinal value. This medicinal value is further seen when there is a decline in gut microbial diversity (dysbiosis). Dysbiosis leads to neurodegenerative disorders (NDDs). The objective of this review is to ascertain the clinical significance of gut microbiota induced therapeutic strategies. While navigating this important area of interest, we will elucidate the research gaps, the prospects and the potential reverse interventions of the studied NDDs. In addition to our previous work, relevant literature published in English were searched and retrieved from the PubMed database. The 'gut microbiota and Neurodegenerative disorders' were used as keywords during the search period. The Filters applied are: Abstract, Full text, Meta-Analysis, Randomized Controlled Trial, Reviews, in the last 5 years. The articles were analyzed in our unrelenting quest to make sense of the prospects and research gap in gut microbiota-brain-axis. This chapter is a result of this meticulous work. More convincing data from researches on gut microbiota-brain-axis are required to provide clinical significance including neuroimaging studies. Addressing the structural (pathological footprints) and the functional changes (diseases manifestation) involving gut microbiota-brain-axis require a holistic approach. While the pharmacological therapies such as chemotherapeutic and chemobiotic treatment approaches come with low success rates, non-pharmacological interventions are found to be more useful in reversing NDDs. The inability to detect NDDs at an early stage in their clinical history, makes preventive medicinal approaches the must needed and best intervention strategy. Gut-driven treatments have a lot to offer in the management of refractory neurologic diseases.

Given that Parkinson's disease is a progressive disorder, with symptoms that worsen over time, our goal is to enhance the diagnosis of Parkinson's disease by utilizing machine learning techniques and microbiome analysis. The primary objective is to identify specific microbiome signatures that can reproducibly differentiate patients with Parkinson's disease from healthy controls.

We used four Parkinson-related datasets from the NCBI repository, focusing on stool samples. Then, we applied a DADA2-based script for amplicon sequence processing and the Recursive Ensemble Feature Selection (REF) algorithm for biomarker discovery. The discovery dataset was PRJEB14674, while PRJNA742875, PRJEB27564, and PRJNA594156 served as testing datasets. The Extra Trees classifier was used to validate the selected features.

The Recursive Ensemble Feature Selection algorithm identified 84 features (Amplicon Sequence Variants) from the discovery dataset, achieving an accuracy of over 80%. The Extra Trees classifier demonstrated good diagnostic accuracy with an area under the receiver operating characteristic curve of 0.74. In the testing phase, the classifier achieved areas under the receiver operating characteristic curves of 0.64, 0.71, and 0.62 for the respective datasets, indicating sufficient to good diagnostic accuracy. The study identified several bacterial taxa associated with Parkinson's disease, such as Lactobacillus, Bifidobacterium, and Roseburia, which were increased in patients with the disease.

This study successfully identified microbiome signatures that can differentiate patients with Parkinson's disease from healthy controls across different datasets. These findings highlight the potential of integrating machine learning and microbiome analysis for the diagnosis of Parkinson's disease. However, further research is needed to validate these microbiome signatures and to explore their therapeutic implications in developing targeted treatments and diagnostics for Parkinson's disease.

Gut microbiota with co-abundant behaviors is considered belonging to the same guild in micro-ecosystem. In this study, we established co-abundance networks of operational taxonomic units (OTUs) among 2944 Chinese adults from the Shanghai Men's and Women's Health Studies and observed a positive connection-dominated scale-free network using Sparse Correlations for Compositional data (SparCC). The closeness centrality was negatively correlated with other degree-based topological metrics in the network, indicating the isolated modularization of the bacteria. A total of 130 guilds were constructed, with a high modularity of 0.68, and retaining more diversity of OTUs than genus classification. The scores of guild structure similarity for comparisons between all, the healthy and the unhealthy subjects were higher than those derived from randomized permutations, suggesting a robust guild structure. We further used the constructed 130 guilds as the aggregation units to identify gut microbiota that may be associated with type 2 diabetes, and found that the OTUs in 21 significant guilds relevant to diabetes belonged to 19 of 41 (46.3%) previously reported genera (derived from Disbiome database), while only 10 (24.4%) showed different abundances between diabetes patients and healthy subjects in genus-based analysis. Our study reveals modularization of gut microbiota as guilds in Chinese populations, and demonstrates advantages of guild-based analysis in identifying diabetes-related gut bacteria. The analytical method based on microbial networks should be widely used to deepen our understanding of the role of gut microbiota in human health.

The online version contains supplementary material available at 10.1007/s43657-024-00211-8.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by motor symptoms and non-motor symptoms. It has been found that intestinal issues usually precede motor symptoms. Microorganisms in the gastrointestinal tract can affect central nervous system through the microbiota-gut-brain axis. Accumulating evidence has shown that disturbances in the microbiota-gut-brain axis are linked with PD. Thus, this pathway appears to be a promising therapeutic target for treatment of PD.

In this review, we mainly described gut dysbiosis in PD and their underlying mechanisms for mediating neuroinflammation and peripheral immune response in PD pathology and futher discussed the potential small-molecule compounds and genic therapeutic strategies targeting the microbiota-gut-brain axis and their applications in PD.

Studies have found that some small molecule compounds and alterations of inflammation-related genes can improve the motor and non-motor symptoms of PD by improving the microbiota-gut-brain axis, which may provide potentially beneficial drugs and molecular targets for the therapies of PD.

First isolated during World War I, Escherichia coli Nissle 1917 (ECN) is an intensively studied bacterium that produces several factors that can inhibit pathogenic bacteria to promote gut health. These findings have led to its commercialization as a probiotic bacterium widely available for human consumption. Notably, the genome of ECN is highly analogous to many extraintestinal pathogenic E. coli (ExPEC) strains that do cause diseases in humans. Both ECN and ExPEC carry the sat gene which encodes a cytotoxic serine autotransporter toxin (Sat). Given that the role of ECN Sat in human disease has been poorly studied, we sought to implement the nematode C. elegans as a model for analyzing how ECN Sat may impact human neurodegenerative disease. Using multiple C. elegans disease models, we find that ECN Sat induces significantly higher neurodegeneration in several C. elegans models we tested. Although preliminary, our early findings suggest that careful studies are paramount to assess the impact of ECN to humans susceptible of neurodegenerative disease to determine the long-term safety of ECN as a commercial probiotic.

Recent evidence links gut microbiota alterations to neurodegenerative disorders, including Parkinson's disease (PD). Replenishing the abnormal composition of gut microbiota through gut microbiota-based interventions "prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT)" has shown beneficial effects in PD. These interventions increase gut metabolites like short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1), which may protect dopaminergic neurons via the gut-brain axis. Neuroprotective effects of these interventions are mediated by several mechanisms, including the enhancement of neurotrophin and activation of the PI3K/AKT/mTOR signaling pathway, GLP-1-mediated gut-brain axis signaling, Nrf2/ARE pathway, and autophagy. Other pathways, such as free fatty acid receptor activation, synaptic plasticity improvement, and blood-brain and gut barrier integrity maintenance, also contribute to neuroprotection. Furthermore, the inhibition of the TLR4/NF-кB pathway, MAPK pathway, GSK-3β signaling pathway, miR-155-5p-mediated neuroinflammation, and ferroptosis could account for their protective effects. Clinical studies involving gut microbiota-based interventions have shown therapeutic benefits in PD patients, particularly in improving gastrointestinal dysfunction and some neurological symptoms. However, the effectiveness in alleviating motor symptoms remains mild. Large-scale clinical trials are still needed to confirm these findings. This review emphasizes the neuroprotective mechanisms of gut microbiota-based interventions in PD as supported by both preclinical and clinical studies.

Previous research has consistently shown that high-fat diet (HFD) consumption can lead to the development of colonic inflammation. Neohesperidin (NHP), a naturally occurring flavanone glycoside in citrus fruits, has anti-inflammatory properties. However, the efficacy and mechanism of NHP in countering prolonged HFD-induced inflammation remains unclear. In this study, rats on HFD were intragastrically administered (i.g.) with NHP for 12 consecutive weeks. Results indicate that this natural compound is effective in reducing colorectal inflammation at doses of 40-80 mg/kg body weight (BW) by i.g. administration, with significant decreases in inflammation markers such as TNF-α and IL-1β levels. It also improved intestinal mucosal tissue integrity and reduced HFD-stimulated colorectal inflammation via the JAK2/STAT3 pathway. Furthermore, intestinal microbiota sequencing results show that NHP intervention significantly downregulated the Firmicutes/Bacteroidetes ratio. This ratio is closely related to the preventive role in the context of glycolipid metabolism disorder. Compared with fecal cultures of rats from the HFD group, after 48 h in vitro fermentation, those from the NHP group had distinct microbiota composition and notably higher concentrations of SCFAs. Collectively, these observations suggest that 80 mg/kg BW NHP possesses biological activities in downregulating HFD-induced colorectal inflammation by regulating intestinal flora and promoting SCFAs formation.

Emerging evidence suggests that changes in the composition of the gut microbiota may play an important role in the pathogenesis of Parkinson's disease (PD). Paeonia lactiflora Pall., a traditional Chinese medicinal herb belonging to the genus Paeonia, is commonly used in Chinese medicinal practice for the treatment of PD. However, the specific mechanisms of its action remain poorly understood. This study aimed to further determine the neuroprotective properties of Paeonia lactiflora Pall. water extract (PWE) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, and to investigate its potential implications for the pathogenesis of PD. A PD mouse model was established via the intraperitoneal administration of MPTP, followed by the assessment of motor function using behavioral tests. Western blotting and histopathological analysis were used to measure the levels of dopaminergic (DAergic) neurodegeneration-related factors in the midbrain (containing the substantia nigra (SN)) and striatum. 16S rRNA gene sequencing and metabolomic analysis were applied to identify differences in the gut microbiota and metabolites, respectively. Our results indicate that PWE effectively protects against MPTP-induced motor deficits, loss of DAergic neurons, blood-brain barrier (BBB) damage, and neuroinflammation in PD. The protective effects of PWE against PD are mediated through modulation of the gut microbiota, specifically by an increase in the abundance of the genus Dubosiella. In this study, we selected D. newyorkensis as a representative strain of the genus, and determined its therapeutic effects in an MPTP-induced PD mouse model. Our preliminary findings suggest that the neuroprotective effects of D. newyorkensis may be related to the production of serum indoleacetic acid.

Dysbiosis of the gut microbiota is closely associated with neurodegenerative diseases, including Huntington's disease (HD). Gut microbiome-derived metabolites are key factors in host-microbiome interactions. This study aimed to investigate the crucial gut microbiome and metabolites in HD and their correlations. Fecal and serum samples from 11 to 26 patients with HD, respectively, and 16 and 23 healthy controls, respectively, were collected. The fecal samples were used for shotgun metagenomics while the serum samples for metabolomics analysis. Integrated analysis of the metagenomics and metabolomics data was also conducted. Firmicutes, Bacteroidota, Proteobacteria, Uroviricota, Actinobacteria, and Verrucomicrobia were the dominant phyla. At the genus level, the presence of Bacteroides, Faecalibacterium, Parabacteroides, Alistipes, Dialister, and Christensenella was higher in HD patients, while the abundance of Lachnospira, Roseburia, Clostridium, Ruminococcus, Blautia, Butyricicoccus, Agathobaculum, Phocaeicola, Coprococcus, and Fusicatenibacter decreased. A total of 244 differential metabolites were identified and found to be enriched in the glycerophospholipid, nucleotide, biotin, galactose, and alpha-linolenic acid metabolic pathways. The AUC value from the integrated analysis (1) was higher than that from the analysis of the gut microbiota (0.8632). No significant differences were found in the ACE, Simpson, Shannon, Sobs, and Chao indexes between HD patients and controls. Our study determined crucial functional gut microbiota and potential biomarkers associated with HD pathogenesis, providing new insights into the role of the gut microbiota-brain axis in HD occurrence and development.

Background: Parkinson's disease (PD) is a neurodegenerative disorder that progressively damages the autonomic and central nervous systems, leading to hallmark symptoms such as resting tremor, bradykinesia, and rigidity. Despite extensive research, the underlying cause of PD remains unclear, and current treatments are unable to halt the progression of the disease. In this retrospective study, based on historical electronic health records (EHR) from a national health provider covering the period from 2003 to 2023, we investigated the impact of vaccination and medication purchases on PD occurrence and severity. Methods: Using a case-control design, we compared the vaccination histories of 1446 PD patients with 7230 matched controls to assess the association between vaccination and PD onset. Additionally, we explored statistical associations between vaccination, medication purchases, and PD severity over an average of 9 years of follow-up, utilizing a machine learning algorithm to quantify disease severity based on annual antiparkinsonian medication purchases. Results: Our analysis revealed a significant reduction in PD occurrence following tetanus-diphtheria (Td) vaccination, with an adjusted odds ratio of 0.17 (95% CI [0.04, 0.70]) for PD onset within 5 years post-vaccination. Furthermore, a time-dependent relationship was identified between the duration since vaccination and both the rate of PD onset and disease progression. Notably, we observed that antimicrobial treatments significantly influenced disease severity, consistent with the antibiotic sensitivity profile of Clostridium tetani. Conclusions: These findings support the hypothesis that tetanus vaccination and/or C. tetani eradication may reduce PD occurrence and slow its progression, suggesting promising directions for future research in PD prevention and treatment.

The impressive achievements made in the last century in extending the lifespan have led to a significant growth rate of elderly individuals in populations across the world and an exponential increase in the incidence of age-related conditions such as cardiovascular diseases, diabetes mellitus type 2, and neurodegenerative diseases. To date, geroscientists have identified 12 hallmarks of aging (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, impaired macroautophagy, mitochondrial dysfunction, impaired nutrient sensing, cellular senescence, stem cell exhaustion, defective intercellular communication, chronic inflammation, and gut dysbiosis), intricately linked among each other, which can be targeted with senolytic or senomorphic drugs, as well as with more aggressive approaches such as cell-based therapies. To date, side effects seriously limit the use of these drugs. However, since rejuvenation is a dream of mankind, future research is expected to improve the tolerability of the available drugs and highlight novel strategies. In the meantime, the medical community, healthcare providers, and society should decide when to start these treatments and how to tailor them individually.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.

Associations between the gut microbiota and Parkinson's disease (PD) have been widely investigated. However, the replicable biomarkers for PD diagnosis across multiple populations remain elusive. Herein, we performed a meta-analysis to investigate the pivotal role of the gut microbiome in PD and its potential diagnostic implications. Six 16S rRNA gene amplicon sequence datasets from five independent studies were integrated, encompassing 550 PD and 456 healthy control samples. The analysis revealed significant alterations in microbial composition and alpha and beta diversity, emphasizing altered gut microbiota in PD. Specific microbial taxa, including Faecalibacterium, Roseburia, and Coprococcus_2, known as butyrate producers, were notably diminished in PD, potentially contributing to intestinal inflammation. Conversely, genera such as Akkermansia and Bilophila exhibited increased relative abundances. A network-based algorithm called NetMoss was utilized to identify potential biomarkers of PD. Afterwards, a classification model incorporating 11 optimized genera demonstrated high performance. Further functional analyses indicated enrichment in pathways related to neurodegeneration and metabolic pathways. These findings illuminate the intricate relationship between the gut microbiota and PD, offering insights into potential therapeutic interventions and personalized diagnostic strategies.

Early detection of Parkinson's disease (PD), a neurodegenerative disease with central and peripheral nerve involvement, ensures timely treatment access. Microbes influence nervous system health and are altered in PD.

We examined gut and mouth microbiomes from recently diagnosed patients in a geographically diverse, matched case-control, shotgun metagenomics study.

Here, we show greater alpha-diversity in 445 PD patients versus 221 controls. The microbial signature of PD includes overabundance of 16 OTUs, including Streptococcus mutans and Bifidobacterium dentium, and depletion of 28 OTUs. Machine learning models indicate that subspecies level oral microbiome abundances best distinguish PD with reasonably high accuracy (area under the curve: 0.758). Microbial networks are disrupted in cases, with reduced connectivity between short-chain fatty acid-producing bacteria the the gut. Importantly, microbiome diversity metrics are associated with non-motor autonomic symptom severity.

Our results provide evidence that predictive oral PD microbiome signatures could possibly be used as biomarkers for the early detection of PD, particularly when there is peripheral nervous system involvement.

The gut microbiota offers numerous benefits to the human body, including the promotion of nutrient absorption, participation in metabolic processes, and enhancement of immune function. Recent studies have introduced the concept of the gut-organ axis, which encompasses interactions such as the gut-brain axis, gut-liver axis, and gut-lung axis. This concept underscores the complex interplay between gut microbiota and various organs and tissues, including the brain, heart, lungs, liver, kidneys, muscles, and bones. Growing evidence indicates that gut microbiota can influence the onset and progression of multi-organ system diseases through their effects on the gut-organ axis. Traditional Chinese medicine has demonstrated significant efficacy in regulating the gastrointestinal system, leveraging its unique advantages. Considerable advancements have been made in understanding the role of gut microbiota and the gut-organ axis within the mechanisms of action of traditional Chinese medicine. This review aims to elucidate the roles of gut microbiota and the gut-organ axis in human health, explore the potential connections between traditional Chinese medicine and gut microbiota, and examine the therapeutic effects of traditional Chinese medicine on the microbiota-gut-organ axis. Furthermore, the review addresses the limitations and challenges present in current research while proposing potential directions for future investigations in this area.

Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.

Depression and Parkinson's disease share pathogenetic characteristics, meaning that they can impact each other and exacerbate their respective progression. From a pathogenetic perspective, depression can develop into Parkinson's disease and is a precursor symptom of Parkinson's disease; Parkinson's disease is also often accompanied by depression. From a pharmacological perspective, the use of antidepressants increases the risk of developing Parkinson's disease, and therapeutic medications for Parkinson's disease can exacerbate symptoms of depression. Therefore, identifying how Parkinson's disease and depression impact each other in their development is key to formulating preventive measures and targeted treatment. One commonality in the pathogenesis of depression and Parkinson's disease are alterations in the gut microbiota, with mechanisms interacting in neural, immune inflammatory, and neuroendocrine pathways. This paper reviews the role of gut microbiota in the pathogenesis of depression and Parkinson's disease; conducts a study of the relationship between both conditions and medication; and suggests that dysregulated gut microbiota may be a key factor in explaining the relationship between Parkinson's disease and depression. Finally, on the basis of these findings, this article hopes to provide suggestions that new ideas for the prevention and treatment of depression and Parkinson's disease.

Parkinson's Disease (PD) is a prevalent neurodegenerative disorder characterized by motor and non-motor symptoms. Emerging evidence suggests that gut microbiota alterations, specifically involving short-chain fatty acids (SCFAs) like butyrate, may influence PD pathogenesis and symptomatology. This Systematic Review aims to synthesize current research on the role of butyrate in modulating motor symptoms and its neuroprotective effects in PD, providing insights into potential therapeutic approaches. A systematic literature search was conducted in April 2024 across databases, including ScienceDirect, Scopus, Wiley, and Web of Science, for studies published between 2000 and 2024. Keywords used were "neuroprotective effects AND butyrate AND (Parkinson disease OR motor symptoms)". Four authors independently screened titles, abstracts, and full texts, applying inclusion criteria focused on studies investigating butyrate regulation and PD motor symptoms. A total of 1377 articles were identified, with 40 selected for full-text review and 14 studies meeting the inclusion criteria. Data extraction was performed on the study population, PD models, methodology, intervention details, and outcomes. Quality assessment using the SYRCLE RoB tool highlighted variability in study quality, with some biases noted in allocation concealment and blinding. Findings indicate that butyrate regulation has a significant impact on improving motor symptoms and offers neuroprotective benefits in PD models. The therapeutic modulation of gut microbiota to enhance butyrate levels presents a promising strategy for PD symptom management.

Gut microbiota disturbances may influence cognitive function, increasing uremic toxins and inflammation in dialysis patients; therefore, we aimed to evaluate the association of the gut microbiota profile with cognitive impairment (CI) in patients on automated peritoneal dialysis (APD). In a cross-sectional study, cognitive function was evaluated using the Montreal Cognitive Assessment in 39 APD patients and classified as normal cognitive function and CI. The gut microbiota was analyzed using the 16S rRNA gene sequencing approach. All patients had clinical, biochemical and urea clearance evaluations. Eighty-two percent of patients were men, with a mean age of 47 ± 24 years and 11 (7-48) months on PD therapy; 64% had mild CI. Patients with CI were older (53 ± 16 vs. 38 ± 14, p = 0.006) and had a higher frequency of diabetes mellitus (56% vs. 21%, p = 0.04) and constipation (7% vs. 48%, p = 0.04) and lower creatinine concentrations (11.3 ± 3.7 vs. 14.9 ± 5.4, p = 0.02) compared to normal cognitive function patients. Patients with CI showed a preponderance of S24_7, Rikenellaceae, Odoribacteraceae, Odoribacter and Anaerotruncus, while patients without CI had a greater abundance of Dorea, Ruminococcus, Sutterella and Fusobacteria (LDA score (Log10) > 2.5; p < 0.05). After glucose and age adjustment, Odoribacter was still associated with CI. In conclusion, patients with CI had a different gut microbiota characterized by the higher abundance of indole-producing and mucin-fermenting bacteria compared to normal cognitive function patients.

Akkermansia muciniphila (A. muciniphila) and its derivatives, including extracellular vesicles (EVs) and outer membrane proteins, are recognized for enhancing intestinal balance and metabolic health. However, the mechanisms of Akkermansia muciniphila's action and its effects on the microbiome are not well understood. In this study, we examined the influence of A. muciniphila and its derivatives on gastrointestinal (GI) and metabolic disorders through a meta-analysis of studies conducted on mouse models. A total of 39 eligible studies were identified through targeted searches on PubMed, Web of Science, Science Direct, and Embase until May 2024. A. muciniphila (alive or heat-killed) and its derivatives positively affected systemic and gut inflammation, liver enzyme level, glycemic response, and lipid profiles. The intervention increased the expression of tight-junction proteins in the gut, improving gut permeability in mouse models of GI and metabolic disorders. Regarding body weight, A. muciniphila and its derivatives prevented weight loss in animals with GI disorders while reducing body weight in mice with metabolic disorders. Sub-group analysis indicated that live bacteria had a more substantial effect on most analyzed biomarkers. Gut microbiome analysis using live A. muciniphila identified a co-occurrence cluster, including Desulfovibrio, Family XIII AD3011 group, and Candidatus Saccharimonas. Thus, enhancing the intestinal abundance of A. muciniphila and its gut microbial clusters may provide more robust health benefits for cardiometabolic, and age-related diseases compared with A. muciniphila alone. The mechanistic insight elucidated here will pave the way for further exploration and potential translational applications in human health.

Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans.

In a case-control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer's disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating.

The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes.

Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.

The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson's disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis.

Natural compounds can positively impact health, and various studies suggest that they regulate glucose‒lipid metabolism by influencing short-chain fatty acids (SCFAs). This metabolism is key to maintaining energy balance and normal physiological functions in the body. This review explores how SCFAs regulate glucose and lipid metabolism and the natural compounds that can modulate these processes through SCFAs. This provides a healthier approach to treating glucose and lipid metabolism disorders in the future.

This article reviews relevant literature on SCFAs and glycolipid metabolism from PubMed and the Web of Science Core Collection (WoSCC). It also highlights a range of natural compounds, including polysaccharides, anthocyanins, quercetins, resveratrols, carotenoids, and betaines, that can regulate glycolipid metabolism through modulation of the SCFA pathway.

Natural compounds enrich SCFA-producing bacteria, inhibit harmful bacteria, and regulate operational taxonomic unit (OTU) abundance and the intestinal transport rate in the gut microbiota to affect SCFA content in the intestine. However, most studies have been conducted in animals, lack clinical trials, and involve fewer natural compounds that target SCFAs. More research is needed to support the conclusions and to develop healthier interventions.

SCFAs are crucial for human health and are produced mainly by the gut microbiota via dietary fiber fermentation. Eating foods rich in natural compounds, including fruits, vegetables, tea, and coarse fiber foods, can hinder harmful intestinal bacterial growth and promote beneficial bacterial proliferation, thus increasing SCFA levels and regulating glucose and lipid metabolism. By investigating how these compounds impact glycolipid metabolism via the SCFA pathway, novel insights and directions for treating glucolipid metabolism disorders can be provided.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by numerous motor and non-motor symptoms. Recent data highlight a potential interplay between the gut microbiota and the pathophysiology of PD. The degeneration of dopaminergic neurons in PD leads to motor symptoms (tremor, rigidity, and bradykinesia), with antecedent gastrointestinal manifestations, most notably constipation. Consequently, the gut emerges as a plausible modulator in the neurodegenerative progression of PD. Key molecular changes in PD are discussed in the context of the gut-brain axis. Evidence suggests that the alterations in the gut microbiota composition may contribute to gastroenteric inflammation and influence PD symptoms. Disturbances in the levels of inflammatory markers, including tumor necrosis factor-α (TNF α), interleukin -1β (IL-1β), and interleukin-6 (IL-6), have been observed in PD patients. These implicate the involvement of systemic inflammation in disease pathology. Fecal microbiota transplantation emerges as a potential therapeutic strategy for PD. It may mitigate inflammation by restoring gut homeostasis. Preclinical studies in animal models and initial clinical trials have shown promising results. Overall, understanding the interplay between inflammation, the gut microbiota, and PD pathology provides valuable insights into potential therapeutic interventions. This review presents recent data about the bidirectional communication between the gut microbiome and the brain in PD, specifically focusing on the involvement of inflammatory biomarkers.