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.

Parkinson's disease has long been considered a disorder that primarily affects the brain, as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containing α-synuclein protein. In recent decades, however, accumulating research has revealed that Parkinson's disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut, called the "gut-brain axis." Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in Parkinson's disease patients, with findings including impaired intestinal permeability, heightened inflammation, and distinct gut microbiome profiles and metabolites. Furthermore, α-synuclein deposition has been consistently observed in the gut of Parkinson's disease patients, suggesting a potential role in disease initiation. Importantly, individuals with vagotomy have a reduced Parkinson's disease risk. From these observations, researchers have hypothesized that α-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut-brain axis, leading to Parkinson's disease. This review comprehensively examines the gut's involvement in Parkinson's disease, focusing on the concept of a gut-origin for the disease. We also examine the interplay between altered gut-related factors and the accumulation of pathological α-synuclein in the gut of Parkinson's disease patients. Given the accessibility of the gut to both dietary and pharmacological interventions, targeting gut-localized α-synuclein represents a promising avenue for developing effective Parkinson's disease therapies.

The human gut microbiome, crucial in various diseases, can be utilized to develop diagnostic models through machine learning (ML). The specific tools and parameters used in model construction such as data preprocessing, batch effect removal and modeling algorithms can impact model performance and generalizability. To establish an generally applicable workflow, we divided the ML process into three above-mentioned steps and optimized each sequentially using 83 gut microbiome cohorts across 20 diseases. We tested a total of 156 tool-parameter-algorithm combinations and benchmarked them according to internal- and external- AUCs. At the data preprocessing step, we identified four data preprocessing methods that performed well for regression-type algorithms and one method that excelled for non-regression-type algorithms. At the batch effect removal step, we identified the "ComBat" function from the sva R package as an effective batch effect removal method and compared the performance of various algorithms. Finally, at the ML algorithm selection step, we found that Ridge and Random Forest ranked the best. Our optimized work flow performed similarly comparing with previous exhaustive methods for disease-specific optimizations, thus is generally applicable and can provide a comprehensive guideline for constructing diagnostic models for a range of diseases, potentially serving as a powerful tool for future medical diagnostics.

Gut microbiota, which act as a determinant of pharmacokinetics, have long been overlooked. In recent years, a growing body of evidence indicates that the gut microbiota influence drug metabolism and efficacy. Conversely, drugs also exert a substantial influence on the function and composition of the gut microbiota. Pharmacomicrobiomics, an emerging field focusing on the interplay of drugs and gut microbiota, provides a potential foundation for making certain advances in personalized medicine. Understanding the communication between gut microbiota and antiparkinsonian drugs is critical for precise treatment of Parkinson's disease. Here, we provide a historical overview of the interplay between gut microbiota and antiparkinsonian drugs. Moreover, we discuss potential mechanistic insights into the complex associations between gut microbiota and drug metabolism. In addition, we also draw attention to microbiota-based biomarkers for predicting antiparkinsonian drug efficacy and examine current state-of-the-art knowledge of microbiota-based strategies to optimize drug therapy in Parkinson's disease.

Bidirectional communications between the gut and the brain play an important role in the regulation of food intake, pain perception, mood, and cognitive function. The involved communication pathways are modulated by signals generated by the gut microbiome. Alterations in these communications have been implicated in several chronic brain and gut disorders, including food addiction, mood disorders, neurodevelopmental and neurodegenerative disorders, and functional and inflammatory bowel disorders. The gut microbiome holds great promise for the development of novel therapies normalizing altered brain-gut interactions.

Quantification of the absolute microbial abundance in a human stool sample is crucial for a comprehensive understanding of the microbial ecosystem, but this information is lost upon metagenomic sequencing. While several methods exist to measure absolute microbial abundance, they are technically challenging and costly, presenting an opportunity for machine learning. Here, we observe a strong correlation between DNA concentration and the absolute number of 16S ribosomal RNA copies as measured by digital droplet PCR in clinical stool samples from individuals undergoing hematopoietic cell transplantation (BMT CTN 1801). Based on this correlation and additional measurements, we trained an accurate yet simple machine learning model for the prediction of absolute prokaryotic load, which showed exceptional prediction accuracy on an external cohort that includes people living with Parkinson's disease and healthy controls. We propose that, with further validation, this model has the potential to enable accurate absolute abundance estimation based on readily available sample measurements.

There is strong interest in using the gut microbiome for Parkinson's disease (PD) diagnosis and treatment. However, a consensus on PD-associated microbiome features and a multi-study assessment of their diagnostic value is lacking. Here, we present a machine learning meta-analysis of PD microbiome studies of unprecedented scale (4489 samples). Within most studies, microbiome-based machine learning models accurately classify PD patients (average AUC 71.9%). However, these models are study-specific and do not generalise well across other studies (average AUC 61%). Training models on multiple datasets improves their generalizability (average LOSO AUC 68%) and disease specificity as assessed against microbiomes from other neurodegenerative diseases. Moreover, meta-analysis of shotgun metagenomes delineates PD-associated microbial pathways potentially contributing to gut health deterioration and favouring the translocation of pathogenic molecules along the gut-brain axis. Strikingly, microbial pathways for solvent and pesticide biotransformation are enriched in PD. These results align with epidemiological evidence that exposure to these molecules increases PD risk and raise the question of whether gut microbes modulate their toxicity. Here, we offer the most comprehensive overview to date about the PD gut microbiome and provide future reference for its diagnostic and functional potential.

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.

The human gut harbors thousands of microbial species, each exhibiting significant inter-individual genetic variability. Although many studies have associated microbial relative abundances with human-health-related phenotypes, the substantial intraspecies genetic variability of gut microbes has not yet been comprehensively considered, limiting the potential of linking such genetic traits with host conditions. Here, we analyzed 32,152 metagenomes from 94 microbiome studies across the globe to investigate the human microbiome intraspecies genetic diversity. We reconstructed 583 species-specific phylogenies and linked them to geographic information and species' horizontal transmissibility. We identified 484 microbial-strain-level associations with 241 host phenotypes, encompassing human anthropometric factors, biochemical measurements, diseases, and lifestyle. We observed a higher prevalence of a Ruminococcus gnavus clade in nonagenarians correlated with distinct plasma bile acid profiles and a melanoma and prostate-cancer-associated Collinsella clade. Our large-scale intraspecies genetic analysis highlights the relevance of strain diversity as it relates to human health.

Parkinson's disease (PD) is characterized by early-onset olfactory dysfunction preceding motor symptoms, yet its mechanisms remain elusive. Based on the studies on microbiota-gut-brain axis, the microbiota-nose-brain axis might be involved in the pathogenesis of PD. However relative studies are rare.

By consecutive 14-days intranasally transplanting bacteria, we established mice models exhibiting nasal microbiota dysbiosis (NMD), including animal group received intranasal drops of fecal bacterial suspension from normal mice (NB group) and animal group received intranasal drops of fecal bacterial suspension from PD mice (PB group), with animals that only received anesthesia used as the control group. Then we analyzed the nasal microbiota composition via 16S rRNA sequencing, evaluated the olfactory and motor functions through behavioral experiments, including buried food test, open field test, pole descent test, and traction test. The neuropathology in olfactory-related and PD-related brain regions, including olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum, was also detected by western blotting, immunofluorescence and immunohistochemical experiments using the antibodies of NeuN, TH and GFAP.

16S rRNA sequencing revealed that PB mice were primarily characterized by an increase in bacteria associated with inflammation and PD. Behavioral assessments revealed that mice with NMD demonstrated impairments in the buried food test and pole descent test, indicative of olfactory and motor dysfunction. By detecting NeuN and GFAP expression, we identified neuronal loss and astrocytes activation in olfactory-related brain regions and adjacent structures, including the olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum of both NMD groups, which may contribute to the observed functional disorders. Notably, animals exposed to PD-derived bacteria exhibited more pronounced changes in nasal bacteria, with more severe neuropathology.

We present evidence supporting the microbiota-nose-brain axis, and the NMD-induced astrocyte activation and neurodegenerative pathology along the olfactory pathway may serve as a link between nose and brain.

The aging population worldwide is on the rise, leading to a higher number of Parkinson's disease (PD) cases each year. PD is presently the second most prevalent neurodegenerative disease, affecting an estimated 7-10 million individuals globally. This research aimed to identify mobile genetic elements in human fecal samples using a shotgun metagenomics approach. We identified over 44,000 plasmid contigs and compared plasmid populations between PD patients (n = 68) and controls (n = 68). Significant associations emerged between groups (control vs PD) based on plasmid alpha and beta diversity. Moreover, the gene populations present on plasmids displayed marked differences in alpha and beta diversity between PD patients and controls. We identified a considerable number of phage contigs that were differentially abundant in the two groups. We also developed a predictive machine learning model based on phage abundance data, achieving a mean Area Under the Curve (AUC) of 0.74 with a standard deviation of 0.105 and a mean F1 score of 0.68 with a standard deviation of 0.14 across cross-validation folds, indicating moderate discriminatory power. Additionally, when tested on external data, the model yielded an AUC of 0.74 and an F1 score of 0.8, further demonstrating the predictive potential of phage populations in Parkinson's disease. Further, we improved the continuity and identification of the protein coding regions of the phage contigs by implementing alternative genetic codes.

Parkinson's Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, with emerging research suggesting a critical link between intestinal dysbiosis and PD progression. This review explores the pathophysiological mechanisms underlying PD, such as alpha-synuclein aggregation, mitochondrial dysfunction, neuroinflammation, and oxidative stress, while focusing on the impact of gut dysbiosis on intestinal barrier function and its role in reduced neurochemical production. The clinical features of PD, including dopamine, serotonin, and GABA deficiencies, are examined, with a focus on how dysbiosis contributes to neurotransmitter depletion. Current treatments of PD, such as levodopa and dopamine agonists, are discussed alongside gut health therapies such as probiotics, prebiotics, and Fecal Microbiota Transplantation (FMT). Future therapeutic directions, including synbiotics, engineered microbes, phage therapy, and the integration of machine learning (ML) and artificial intelligence (AI), are explored. The chapter also considers preventive strategies, such as lifestyle adjustments and early gut health monitoring using modern diagnostic tools and biosensors. Furthermore, a strong need for continued research into the gut-brain axis (GBA) to develop more effective, gut-targeted therapies for managing PD is discussed.

Current treatment of Parkinson's Disease (PD) remains symptomatic, and disease-modifying approaches are urgently required. A promising approach is to modify intestinal microbiota and key metabolites of bacterial fermentation: short-chain fatty acids (SCFA), which are decreased in PD. A prospective, controlled pilot study (DRKS00034528) was conducted on 11 couples (PD patient plus healthy spouse as control (CO)). Participants followed a 4-week diet rich in dietary fibre, including intake of the prebiotic Lactulose. Gut metagenomes, faecal and urinary metabolites, and clinical characteristics were assessed. The dietary intervention significantly augmented faecal SCFA and increased Bifidobacteria spp., reducing PD-related gastrointestinal symptoms. The pre-existing bacterial dysbiosis in PD (depletion of Blautia, Dorea, Erysipelatoclostridium) persisted. Bacterial metabolite composition in faeces and urine positively changed with the intervention: Brain-relevant gut metabolic functions involved in neuroprotective and antioxidant pathways, including S-adenosyl methionine, glutathione, and inositol, improved in PD. These promising results warrant further investigation in larger cohorts.

Parkinson's disease (PD) is a multifactorial neurodegenerative disease that is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and by the anomalous accumulation of α-synuclein aggregates into Lewy bodies and Lewy neurites. Research suggests 2 distinct subtypes of PD: the brain-first subtype if the pathology arises from the brain and then spreads to the peripheral nervous system (PNS) and the body-first subtype, where the pathological process begins in the PNS and then spreads to the central nervous system. This review primarily focuses on the body-first subtype. The influence of the gut microbiota on the development of PD has been the subject of growing interest among researchers. It has been suggested that gut inflammation may be closely associated with pathogenesis in PD, therefore leading to the hypothesis that gut microbiota modulation could play a significant role in this process. Nutrition can influence gut health and alter the risk and progression of PD by altering inflammatory markers. This review provides an overview of recent research that correlates variations in gut microbiota composition between patients with PD and healthy individuals with the impact of certain nutrients and dietary patterns, including the Mediterranean diet, the Western diet, and the ketogenic diet. It explores how these diets influence gut microbiota composition and, consequently, the risk of PD. Last, it examines fecal transplantation and the use of prebiotics, probiotics, or synbiotics as potential therapeutic strategies to balance the gut microbiome, aiming to reduce the risk or delay the progression of PD.

The human gut microbiota is diverse and abundant and plays important roles in regulating health by participating in metabolism and controlling physiological activities. The gut microbiota and its metabolites have been shown to affect the functioning of the gut and central nervous system through the microbiota-gut-brain axis. It is well established that microbiota play significant roles in the pathogenesis and progression of Parkinson's disease (PD). Disorders of the intestinal microbiota and altered metabolite levels are closely associated with PD. Here, the changes in intestinal microbiota and effects of metabolites in patients with PD are reviewed. Potential mechanisms underlying intestinal microbiota disorders in the pathogenesis of PD are briefly discussed. Additionally, we outline the current strategies for the treatment of PD that target the gut microbiota, emphasizing the development of promising novel strategies.

This study investigated the effects of fructo-oligosaccharides (FOS) supplementation on the growth performance, blood glucose level, white blood cell count, carcass yield, meat quality, and cecal microbiota of Ross 308 broiler chickens. A completely randomized design was employed; FOS was supplemented in the drinking water at concentrations of 0 %, 0.25 %, and 0.50 %. From 11 to 24 d of age, 0.25 % FOS supplementation significantly increased feed intake (FI), while feed cost per gain (FCG) was significantly reduced at 0.50 % FOS (P < 0.05). During the overall period (1-36 d of age), FOS supplementation significantly improved the European Production Efficiency Factor (EPEF) (P < 0.01), and slowed down the reduction in blood glucose levels after the re-feeding period (2, 3, 4, and 5 h) (P < 0.01). Furthermore, FOS supplementation decreased the heterophil/lymphocyte (H:L) ratio (P < 0.05). However, it had no significant effect on breast meat yield or abdominal fat, but 0.50 % FOS supplementation tended to increase the percentage of cecal weight (P = 0.08). Supplementation with FOS (0.25 % and 0.50 %) significantly reduced breast meat cooking loss (P < 0.05). Regarding cecal microbiota, the FOS-supplemented groups showed increased abundances of Lactobacillaceae and Acidaminococcaceae, whereas the abundances of Lachnospiraceae and Barnesiellaceae were reduced (P < 0.05). In conclusion, drinking water FOS supplementation had a beneficial effect on the overall productive performance and cooking loss of broiler chickens via stress reduction, which may involve an improvement in the gut microbiota.

The gut microbiota can affect both the enteric and the central nervous system, influencing individuals and their brain regulation. In this work, different pieces of scientific evidence are discussed, showing the relationship between changes in the microbiota and neurocognitive deterioration, focussing on Parkinson's disease (PD). Other factors that may cause or contribute to PD aetiology are the interactions between environmental factors and genetic susceptibility. According to the existing literature, there are several methods for the identification of neurocognitive impairment in different neurological diseases. However, such methods do not allow early identification, and therefore, the possibility of using other types of more effective diagnostic biomarkers in PD has also been investigated. Since this disease is characterised by specific microRNA (miRNA) expression, and the gut microbiota is an important factor in both PD and miRNA expression, the aim of this review is thoroughly analysing the role of microbiota and microRNAs in PD development. In addition, the relationship between these two factors and potential treatments will be also discussed.

We systematically tracked early life stages in a military dog birth cohort to investigate canine gut microbiota dynamics related to environmental exposure during growth. This study utilized 16s rRNA amplicon sequencing-based analysis with molecular epidemiology of Enterococcus faecalis within a controlled environment at a military dog training center.

We examined shifts in gut microbiota diversity and taxonomic composition across four growth stages (lactation, weaning, starter, puppy) in three littermate groups. Additionally, E. faecalis dynamics was analyzed to confirm strain sharing among littermate groups.

Gut microbiota changed rapidly during early growth, stabilizing at the puppy stage. This is supported by increased similarity in taxonomic composition among littermate groups, as they experienced an increased shared external environment and consumed the identical diets. E. faecalis strain sharing among littermate groups increased as dogs aged. Nine E. faecalis cluster types were identified; three specific types (type I, II, and IX) dominated in each littermate group during lactation. With greater exposure to the shared external environment, cluster type I gradually assumed dominance across all groups. Despite the dynamic shifts in microbiota, we found five genera within the core microbiota, Bacteroides, Peptoclostridium, Fusobacterium, Lactobacillus, and Blautia.

This study is the first to explore the dynamic nature of early-life canine gut microbiota, illustrating its transition to stability and its resilience to environmental perturbations within the controlled training environment of a military dog birth cohort.

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.

Parkinson's disease (PD) is a neurodegenerative disorder primarily characterized by motor impairment, resulting from the accumulation of α-synuclein and neuronal cell death in the substantia nigra of the midbrain. Emerging evidence suggests that α-synuclein aggregation may originate in the enteric nervous system (ENS) and subsequently propagate to the brain via the vagus nerve. Clinical observations, such as prodromal gastrointestinal dysfunction in PD patients and the increased incidence of PD among individuals with inflammatory bowel disease, support the hypothesis that abnormal intestinal inflammation may contribute to the onset of motor dysfunction and neuropathology in PD. This review examines recent findings on the interplay between intestinal immune cells and α-synuclein aggregation within the framework of gut-originated PD pathogenesis. It begins by discussing evidence linking dysbiosis and intestinal inflammation to α-synuclein aggregation in the ENS. Additionally, it explores the potential role of intestinal immune cells in influencing enteric neurons and α-synuclein aggregation, furthering the understanding of PD development.

The gut-brain axis, i.e. the bidirectional communication system between the gut and the brain, has become of central importance in Parkinson disease (PD) research over the past 20 years.

We aimed to describe the milestones of the gut-brain axis research in PD and the development of theories proposing the involvement of the gastrointestinal tract in PD pathogenesis.

We searched PubMed using the terms 'gut-brain axis' AND 'Parkinson disease', and selected relevant articles to provide the foundation for reconstructing an historical overview of the gut-brain axis research in PD.

Mounting evidence from preclinical, clinical and post-mortem studies suggests that a subgroup of PD patients present with a range of prodromal symptoms (e.g., autonomic dysfunction, rapid eye movement sleep behaviour disorder) which reflect initial accumulation and later spread of pathological α-synuclein rostrally from the gastrointestinal tract ("body-first" PD). Through neural connections along the gut-brain axis, pathological α-synuclein may spread to the brain, producing clinically manifest disease. Recently, two mechanisms involving the gut-brain axis have attracted increasing attention for their role in PD pathogenesis and progression, namely the perturbation of the composition of the microorganisms living in the gut (the gut microbiome), and the dysfunction of enteroendocrine cells.

Treatments targeting the gut-brain axis, especially the gut microbiome and the enteroendocrine cells pathway, could potentially slow disease progression or even prevent disease onset. Among these, pre/probiotics, faecal microbiota transplantation, and glucagon-like peptide-1 receptor agonists, have entered advanced stages of clinical trials in humans and shown potential symptomatic and disease-modifying effects.

The healthy gut microbiome is important in maintaining health and preventing various chronic and metabolic diseases through interactions with the host via different gut-organ axes, such as the gut-brain, gut-liver, gut-immune, and gut-lung axes. The human gut microbiome is relatively stable, yet can be influenced by numerous factors, such as diet, infections, chronic diseases, and medications which may disrupt its composition and function. Therefore, microbial resilience is suggested as one of the key characteristics of a healthy gut microbiome in humans. However, our understanding of its definition and indicators remains unclear due to insufficient experimental data. Here, we review the impact of key drivers including intrinsic and extrinsic factors such as diet and antibiotics on the human gut microbiome. Additionally, we discuss the concept of a resilient gut microbiome and highlight potential biomarkers including diversity indices and some bacterial taxa as recovery-associated bacteria, resistance genes, antimicrobial peptides, and functional flexibility. These biomarkers can facilitate the identification and prediction of healthy and resilient microbiomes, particularly in precision medicine, through diagnostic tools or machine learning approaches especially after antimicrobial medications that may cause stable dysbiosis. Furthermore, we review current nutrition intervention strategies to maximize microbial resilience, the challenges in investigating microbiome resilience, and future directions in this field of research.

Some natural products have been found to have a positive effect on the treatment of Type 2 Diabetes Mellitus (T2DM). The effective mechanism by which these natural products work may be attributed to their ability to alter the gut microbiome. In this study, considering the beneficial properties of resveratrol for T2DM, the mechanism of resveratrol in releasing of T2DM, the correlation between the apparent traits of resveratrol in T2DM mice and the changes in intestinal flora structure were explored. The intervention of resveratrol in different dose did effectively improve the apparent T2DM symptoms in mice, including reduced fasting blood glucose, enhance to both the insulin tolerance and glucose tolerance. Simultaneously, resveratrol can effectively ameliorate the pathological condition of the colon and rectum in T2DM mice, leading to a reduction in intestinal villi swelling and fat vacuoles. The intervention of resveratrol led to changes in the gut flora structure of T2DM mice. Erysipelas and Ileibacterium are crucial taxa of resveratrol involved in maintaining the balance of the gut microbiota. The abundance of Erysipelotrichaceae and Ileibacterium was significantly elevated under the treatment of resveratrol, and the compose of the gut microbiota was more inclined to healthy mice. T2DM symptoms could be alleviated by resveratrol through different mechanisms compared to metformin intervention.

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.

With increased life expectancy, there is an increase in aging population and prevalence of dementia. Ghrelin is a key regulator of spatial memory and cognition. The gut microbiome may affect the circulating levels of unacylated ghrelin (UAG) and acylated ghrelin (AG). Thus, we explore the potential association of the gut microbiome, AG, and cognitive health in the aging dementia patient.

40 dementia patients and 40 controls were recruited. Fecal Microbiome analysis using 16S rRNA sequencing was performed on 18 samples. A mixed-method approach was employed for robust interpretation.

Dementia patients had an increased serum AG and AG/UAG ratio. With the increase in AG among dementia subjects, a significant decrease in species richness was observed. Bifidobacterium longum, Eubacterium biforme, Fecalibacterium prausnitzii, Lactobacillus ruminis, and Prevotella copri contributed to substantial differences in beta-diversity. Blautia obeum was associated with Mini-Mental State Examination (MMSE), and Fecalibacterium prausnitzii was associated with Montreal Cognitive Assessment (MoCA) Scale.

This pilot study indicates a complex interaction between AG, gut microbiome, and cognitive scores. Increased AG corresponds to both dementia and gut dysbiosis, intricately interconnecting the gut-brain axis. The circulating AG and associated gut microbiome might be a putative biomarker for dementia.

Emerging evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The microbiota-gut-brain axis plays a crucial role in the development and progression of PD, and numerous studies have demonstrated the potential therapeutic benefits of modulations in the intestinal microbiota. This review provides insights into the characterization of the gut microbiota in patients with PD and highlights associations with clinical symptoms and underlying mechanisms. The discussion underscores the increased influence of the gut microbiota in the pathogenesis of PD. While the relationship is not fully elucidated, existing research demonstrates a strong correlation between changes in the composition of gut microbiota and disease development, and further investigation is warranted to explain the specific underlying mechanisms.

Parkinson's disease is a chronic neurodegenerative disorder, where pathological protein aggregates largely composed of phosphorylated α-synuclein are implicated in disease pathogenesis and progression. Emerging evidence suggests that the interaction between pro-inflammatory microbial factors and the gut epithelium contributes to α-synuclein aggregation in the enteric nervous system. However, the cellular sources and mechanisms for α-synuclein pathology in the gut are still unclear.

The STC-1 cell line, which models an enteroendocrine population capable of communicating with the gut microbiota, immune and nervous systems, was treated with a TLR4 inhibitor (TAK-242) prior to microbial lipopolysaccharide (LPS) exposure to investigate the role of TLR4 signalling in α-synuclein alterations. Antibodies targeting the full-length protein (α-synuclein) and the Serine-129 phosphorylated form (pS129) were used. Complex, multi-parametric image analysis was conducted through confocal microscopy (with Zen 3.8 analysis) and imaging flow cytometry (with IDEAS® analysis).

Confocal microscopy revealed heterogenous distribution of α-synuclein and pS129 in STC-1 cells, with prominent pS129 staining along cytoplasmic processes. Imaging flow cytometry further quantified the relationship between various α-synuclein morphometric features. Thereafter, imaging flow cytometry demonstrated a dose-specific effect of LPS, where the low (8 μg/mL), but not high dose (32 μg/mL), significantly altered measures related to α-synuclein intensity, distribution, and localisation. Pre-treatment with a TLR4 inhibitor TAK-242 alleviated some of these significant alterations.

This study demonstrates that LPS-TLR4 signalling alters the intracellular localisation of α-synuclein in enteroendocrine cells in vitro and showcases the utility of combining imaging flow cytometry to investigate subtle protein changes that may not be apparent through confocal microscopy alone. Further investigation is required to understand the apparent dose-dependent effects of LPS on α-synuclein in the gut epithelium in healthy states as well as conditions such as Parkinson's disease.

Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the possibility that pathogenic alpha-synuclein (⍺-syn) might develop in the GI tract and subsequently spread to susceptible brain regions. The cellular and mechanistic origins of ⍺-syn propagation in disease are under intense investigation. Experimental LBD models have implicated important contributions from the intrinsic gut microbiome, the intestinal immune system, and environmental toxicants, acting as triggers and modifiers to GI pathologies. Here, we review the primary clinical observations that link GI dysfunctions to LBDs. We first provide an overview of GI anatomy and the cellular repertoire relevant for disease, with a focus on luminal-sensing cells of the intestinal epithelium including enteroendocrine cells that express ⍺-syn and make direct contact with nerves. We describe interactions within the GI tract with resident microbes and exogenous toxicants, and how these may directly contribute to ⍺-syn pathology along with related metabolic and immunological responses. Finally, critical knowledge gaps in the field are highlighted, focusing on pivotal questions that remain some 200 years after the first descriptions of GI tract dysfunction in LBDs. We predict that a better understanding of how pathophysiologies in the gut influence disease risk and progression will accelerate discoveries that will lead to a deeper overall mechanistic understanding of disease and potential therapeutic strategies targeting the gut-brain axis to delay, arrest, or prevent disease progression.

The present study aimed to explore the effect of GF powder on the growth performance, diarrhea rate, antioxidant and immune capacity, and intestinal health of weaned piglets. A total of 144 weaned piglets (8.29 ± 0.11 kg) at 21 d old were randomly assigned to four groups, with each treatment consisting of six replicate pens, with six piglets per pen, and each pen containing three barrows and three gilts. The piglets were fed a basal diet supplement with 0%, 0.4%, 0.6%, and 0.8% GF powder (n = 36). Our results indicated that compared with the basal diet, the F/G and diarrhea rate were remarkably decreased in the 0.8% GF group (p < 0.05). Serum biochemical parameters showed that supplementation with GF significantly increased the content of HDL-C (0.6 and 0.8% levels), IL-6 (0.8% level), IL-10 (0.4, 0.6, and 0.8% levels), Ig G (0.4% level), and Ig A (0.8% level) compared with the basal diet (p < 0.05). The index of antioxidant capacity showed that compared with a basal diet, supplementation with GF significantly decreased serum MDA content (0.4% and 0.8% levels) and jejunal and ileal MDA content (0.4%, 0.6%, and 0.8% levels) (p < 0.05). Additionally, compared with the basal diet, supplementation with GF significantly increased serum and ileal T-AOC content (0.4%, 0.6%, and 0.8% levels), serum T-SOD content (0.4% and 0.8% levels), ileal T-SOD content (0.4%, 0.6%, and 0.8% levels), CAT content (0.4%, 0.6%, and 0.8% levels), and jejunal GSH-Px content (0.8% level) (p < 0.05). The results of gene expression indicate that compared with the basal diet, supplementation with GF significantly increased Nrf 2 (0.4% level), NQO (0.4% level), SOD 1 (0.4% and 0.8% levels), and GCLC (0.4% level) and GCLM (0.8% level) abundance in jejunal mucosa; supplementation with GF significantly increased Nrf 2 (0.4%, 0.6%, and 0.8% levels), HO-1 (0.4% level), NQO (0.8% level), SOD 1 (0.4% and 0.8% levels), and GCLC (0.4% level) and GCLM (0.8% level) abundance in ileal mucosa (p < 0.05). Ulteriorly, the present results indicate that supplementation with GF at the 0.8% level significantly increased the villus height in the jejunum and ileum as well as the villus/crypt ratio in the ileum compared with the basal diet (p < 0.05). Compared with the basal diet, 0.4% GF significantly increased Occludin gene expression in ileal mucosa (p < 0.05), 0.6% GF significantly increased ZO-1, Claudin-1, and Occludin gene expression in jejunal mucosa (p < 0.05), and 0.8% GF significantly increased ZO-1 and Occludin gene expression in jejunal mucosa along with Occludin expression in ileal mucosa (p < 0.05). Furthermore, colonic microbiota composition showed that Shannon, observed species, and Chao 1 indices were significantly increased in the 0.8% GF group compared with the basal diet (p < 0.05). At the phylum level, in comparison with the basal diet, the relative abundance of Firmicutes significantly decreased in the 0.4%, 0.6%, and 0.8% GF groups, and Bacteroidetes increased in the 0.8% GF group (p < 0.05). At the genus level, compared with the basal diet, 0.6% and 0.8% GF significantly increased Prevotella abundance, and 0.6% GF significantly decreased Coprococcus abundance (p < 0.05). At the species level, compared with the basal diet, 0.8% GF significantly increased Prevotella copri abundance, and 0.4%, 0.6%, and 0.8% GF significantly decreased Blautia obeum abundance (p < 0.05). In summary, a dietary supplement with 0.8% Gardeniae Fructus powder significantly decreased the F/G and diarrhea rate and improved antioxidant capacity and intestinal barrier function, which may be associated with the improvement of the relative abundance of Prevotella copri. These findings indicate that Gardeniae Fructus powder may be used as a feed additive in swine weaning.

Gut microbiota plays an important role in multiple human physiological processes and an imbalance in it, including the species, abundance, and metabolites can lead to diseases. These enteric microorganisms modulate immune homeostasis by presenting a myriad of antigenic determinants and microbial metabolites. Medicinal and food homologous (MFH) plants, edible herbal materials for both medicine and food, are important parts of Traditional Chinese Medicine (TCM). MFH plants have drawn much attention due to their strong biological activity and low toxicity. However, the interplay of MFH and gut microbiota in rebalancing the immune homeostasis in combating diseases needs systematic illumination.

The review discusses the interaction between MFH and gut microbiota, including the effect of MFH on the major group of gut microbiota and the metabolic effect of gut microbiota on MFH. Moreover, how gut microbiota influences the immune system in terms of innate and adaptive immunity is addressed. Finally, the immunoregulatory mechanisms of MFH in regulation of host pathophysiology via gut microbiota are summarized.

Literature was searched, analyzed, and collected using databases, including PubMed, Web of Science, and Google Scholar using relevant keywords. The obtained articles were screened and summarized by the research content of MFH and gut microbiota in immune regulation.

The review demonstrates the interaction between MFH and gut microbiota in disease prevention and treatment. Not only do the intestinal microorganisms and intestinal mucosa constitute an important immune barrier of the human body, but also lymphoid tissue and diffused immune cells within the mucosa participate in the response of innate immunity and adaptive immunity. MFH modulates immune regulation by affecting intestinal flora, helps maintain the balance of the immune system and interfere with the occurrence and development of a broad category of diseases.

Being absorbed from the gastrointestinal tract, MFH can have profound effects on gut microbiota. In turn, the gut microbiota also actively participate in the bioconversion of complex constituents from MFH, which could further influence their physiological and pharmacological properties. The review deepens the understanding of the relationship among MFH, gut microbiota, immune system, and human diseases and further promotes the progression of additional relevant research.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and seriously affects the quality of life of elderly patients. PD is characterized by the loss of dopaminergic neurons in the substantia nigra as well as abnormal accumulation of α-synuclein in neurons. Recent research has deepened our understanding of the gut microbiota, revealing that it participates in the pathological process of PD through the gut-brain axis, suggesting that the gut may be the source of PD. Therefore, studying the relationship between gut microbiota and PD is crucial for improving our understanding of the disease's prevention, diagnosis, and treatment. In this review, we first describe the bidirectional regulation of the gut-brain axis by the gut microbiota and the mechanisms underlying the involvement of gut microbiota and their metabolites in PD. We then summarize the different species of gut microbiota found in patients with PD and their correlations with clinical symptoms. Finally, we review the most comprehensive animal and human studies on treating PD through fecal microbiota transplantation (FMT), discussing the challenges and considerations associated with this treatment approach.

Prevotella species, notably Prevotella copri, significantly populate the human gut. In particular, P. copri is prevalent among non-Western populations with diets high in fiber. These species show complex relationships with diverse health aspects, associating with beneficial outcomes, including reduced visceral fat and improved glucose tolerance. Studies implicate various Prevotella species in specific diseases. Prevotella nigrescens and Porphyromonas gingivalis were linked to periodontal disease, promoting immune responses and influencing T helper type 17 (Th17) cells. Prevotella bivia was associated with bacterial vaginosis and a specific increase in activated cells in the vaginal mucosa. In contrast, they have shown substantial potential for inducing connective tissue degradation and alveolar bone resorption. Prevotella's role in neuroinflammatory disorders and autoinflammatory conditions such as Alzheimer's disease and Parkinson's disease has also been noted. The complex relationship between Prevotella and age-related conditions further extends to neurobiological changes in aging, with varying associations with Alzheimer's, Parkinson's, and other inflammatory conditions. Studies have also identified Prevotella to be implicated in cognitive decline in middle aged and the elderly. Future directions in this research area are anticipated to explore Prevotella-associated inflammatory mechanisms and therapeutic interventions. Investigating specific drug targets and immunomodulatory measures could lead to novel therapeutic strategies. Understanding how Prevotella-induced inflammation interacts with aging diseases would offer promising insights for treatments and interventions. This review urges ongoing research to discover therapeutic targets and mechanisms for moderating Prevotella-associated inflammation to further enhance our understanding and improve health outcomes.

Pathological forms of α-synuclein contribute to synucleinopathies, including Parkinson's disease (PD). Most cases of PD arise from gene-environment interactions. Microbiome composition is altered in PD, and gut bacteria are causal to symptoms in animal models. We quantitatively profiled nearly 630 metabolites in the gut, plasma, and brain of α-synuclein-overexpressing (ASO) mice, compared to wild-type (WT) animals, and comparing germ-free (GF) to specific pathogen-free (SPF) animals (n = 5 WT-SPF; n = 6 ASO-SPF; n = 6 WT-GF; n = 6 ASO-GF). Many differentially expressed metabolites in ASO mice are also dysregulated in human PD patients, including amine oxides, bile acids and indoles. The microbial metabolite trimethylamine N-oxide (TMAO) strongly correlates from the gut to the plasma to the brain in mice, notable since TMAO is elevated in the blood and cerebrospinal fluid of PD patients. These findings uncover broad metabolomic changes that are influenced by the intersection of host genetics and microbiome in a mouse model of PD.

Parkinson's disease (PD) has been consistently linked to alterations within the gut microbiome.

Our goal was to identify microbial features associated with PD incidence and progression.

Metagenomic sequencing was used to characterize taxonomic and functional changes to the PD microbiome and to explore their relation to bacterial metabolites and disease progression. Motor and non-motor symptoms were tracked using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and levodopa equivalent dose across ≤5 yearly study visits. Stool samples were collected at baseline for metagenomic sequencing (176 PD, 100 controls).

PD-derived stool samples had reduced intermicrobial connectivity and seven differentially abundant species compared to controls. A suite of bacterial functions differed between PD and controls, including depletion of carbohydrate degradation pathways and enrichment of ribosomal genes. Faecalibacterium prausnitzii-specific reads contributed significantly to more than half of all differentially abundant functional terms. A subset of disease-associated functional terms correlated with faster progression of MDS-UPDRS part IV and separated those with slow and fast progression with moderate accuracy within a random forest model (area under curve = 0.70). Most PD-associated microbial trends were stronger in those with symmetric motor symptoms.

We provide further evidence that the PD microbiome is characterized by reduced intermicrobial communication and a shift to proteolytic metabolism in lieu of short-chain fatty acid production, and suggest that these microbial alterations may be relevant to disease progression. We also describe how our results support the existence of gut-first versus brain-first PD subtypes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Subarachnoid hemorrhage (SAH) is a debilitating condition that leaves survivors with neurological disability for the rest of their lives. No effective treatment for early brain injury (EBI) has been developed. Gut microbiome (GM) impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the GM has an impact on the outcome of SAH brain injury. Here, we wondered whether microbiota could relieve the injury. We changed the microbiota of 8-week-old male rats by administering antibiotic-containing water for 2 weeks. Composition of the GM was profiled by using 16S rRNA. We induced SAH by puncture the internal carotid artery of control rats and rats with altered GM. Additionally, we studied inflammatory cells using HE stains, Intestinal lymphocyte flow cytometry, and Neuroinflammatory factor WB. SAH was significantly averted by alterations in GM using antibiotics. The altered GM significantly increased the intestinal and intracranial inflammation after SAH. This was manifested by Mosin (MSN) inflammatory cytokines. Our findings demonstrated that the brain injury following SAH is associated with GM.

We aimed to assess how antimicrobial exposure affects Parkinson's disease (PD) risk.

A nested case-control study was performed to examine the association between antimicrobial exposure and newly diagnosed PD using the Clinical Practice Research Datalink (CPRD). Each PD case was matched by age, sex, and year of diagnosis (index date) to up to 15 controls. Number of prescribed antimicrobial courses was assessed 1-5, 6-10, and 11-15 years prior to the index date. Logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (ORs) and false discovery rate-adjusted p-values between antimicrobial exposure and risk of PD.

We compared 12,557 PD cases with 80,804 matched controls. We found an inverse dose-response relationship between number of penicillin courses and PD risk across multiple time periods (5+ courses, 1-5 years prior: OR 0.85, 95 % CI 0.76-0.95, p = 0.043; 6-10 years prior: OR 0.84, 95 % CI: 0.73-0.95, p = 0.059; 11-15 years prior: OR 0.87, 95 % CI 0.74-1.02, p = 0.291). The number of macrolide courses was inversely but not significantly associated with PD risk 1-5 years prior to the index date (OR 0.89-0.91, 95 % CI: 0.79-0.99, adjusted p = 0.140-0.167). Exposure to ≥2 courses of antifungals 1-5 years prior was associated with an increased risk of PD (OR 1.16, 95 % CI: 1.06-1.27, p = 0.020).

In a large UK-representative population, the risk of PD was modestly lower among adults who had previously received multiple courses of penicillins in the last 15 years and modestly higher among those exposed to antifungal medicines in recent years.

The emerging function of short-chain fatty acids (SCFAs) in Parkinson's disease (PD) has been investigated in this article. SCFAs, which are generated via the fermentation of dietary fiber by gut microbiota, have been associated with dysfunction of the gut-brain axis and, neuroinflammation. These processes are integral to the development of PD. This article examines the potential therapeutic implications of SCFAs in the management of PD, encompassing their capacity to modulate gastrointestinal permeability, neuroinflammation, and neuronal survival, by conducting an extensive literature review. As a whole, this article emphasizes the potential therapeutic utility of SCFAs as targets for the management and treatment of PD.

There are no cures for neurodegenerative protein conformational diseases (PCDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Emerging evidence suggests the gut microbiota plays a role in their pathogenesis, though the influences of specific bacteria on disease-associated proteins remain elusive. Here, we reveal the effects of 229 human bacterial isolates on the aggregation and toxicity of Aβ1-42, α-synuclein, and polyglutamine tracts in Caenorhabditis elegans expressing these culprit proteins. Our findings demonstrate that bacterial effects on host protein aggregation are consistent across different culprit proteins, suggesting that microbes affect protein stability by modulating host proteostasis rather than selectively targeting disease-associated proteins. Furthermore, we found that feeding C. elegans proteoprotective Prevotella corporis activates the heat shock response, revealing an unexpected discovery of a microbial influence on host proteostasis. Insight into how individual bacteria affect PCD proteins could open new strategies for prevention and treatment by altering the abundance of microbes.

Virulence factor genes (VFGs) play pivotal roles in bacterial infections and have been identified within the human gut microbiota. However, their involvement in chronic diseases remains poorly understood. Here, we establish an expanded VFG database (VFDB 2.0) consisting of 62,332 nonredundant orthologues and alleles of VFGs using species-specific average nucleotide identity ( https://github.com/Wanting-Dong/MetaVF_toolkit/tree/main/databases ). We further develop the MetaVF toolkit, facilitating the precise identification of pathobiont-carried VFGs at the species level. A thorough characterization of VFGs for 5452 commensal isolates from healthy individuals reveals that only 11 of 301 species harbour these factors. Further analyses of VFGs within the gut microbiomes of nine chronic diseases reveal both common and disease-specific VFG features. Notably, in type 2 diabetes patients, long HiFi sequencing confirms that shared VF features are carried by pathobiont strains of Escherichia coli and Klebsiella pneumoniae. These findings underscore the critical importance of identifying and understanding VFGs in microbiome-associated diseases.