A Bibliometric and Visualized Analysis of Research Trends in the Relationship between Neurological Disorders and Gut Microbiota (2000-2024)

GUO Yangyang¹, ZHANG Linlin², SHI Guangzhi¹, ZHANG Jindong³*

¹Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
²Department of Neurocritical Care, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
³Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China

Corresponding author: ZHANG Jindong, Attending physician/Research assistant; E-mail: zhangjd@bjmu.edu.cn

Abstract

Background: Neurological disorders severely impact patients' quality of life. These disorders have multifactorial etiologies, including genetic, infectious, and immunological factors. Emerging evidence highlights the role of gut microbiota in these disorders through the gut-brain axis. However, the research hotspots and trends in this field remain inadequately characterized.

Objective: This study aims to conduct a visual analysis of the literature related to neurological disorders and gut microbiota, with the goal of understanding the current research landscape both domestically and internationally. Furthermore, it seeks to explore the research hotspots and emerging trends, thereby providing a reference for future studies.

Methods: Relevant literature was retrieved from the Web of Science Core Collection database from January 1, 2000 to July 29, 2024. Using CiteSpace software, a visual analysis was performed from multiple aspects, including publication volume, co-citation analysis, highly cited papers, citation burst papers, keyword co-occurrence, national collaboration, institutional collaboration, and author collaboration.

Results: A total of 5,239 articles were included, with a steady increase in publication volume since 2012, surpassing 1,000 articles in 2022. The research hotspots primarily concentrate on Parkinson's disease, Alzheimer's disease, ischemic stroke, and amyotrophic lateral sclerosis. Citation analysis reveals that the relationship between gut microbiota and CNS diseases has become a prominent research focus in recent years. Moreover, co-occurrence analysis of keywords further highlights the frequent appearance of important research topics such as short-chain fatty acids, the gut-brain axis, and gut microbiota dysbiosis, indicating a high level of attention to these areas. High-citation articles and citation burst analysis show that the research trend is centered on the mechanisms through which gut microbiota influence neurodegenerative diseases and other CNS disorders, particularly focusing on the regulatory roles of short-chain fatty acids, gut microbiota diversity, and the gut-brain axis.

Conclusion: CiteSpace-based bibliometric analysis suggests a potential association between gut microbiota and neurological disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. Modulation of gut microbiota may offer a promising therapeutic avenue for the management of these conditions. Further longitudinal studies and clinical trials are warranted to validate this hypothesis and to elucidate the underlying mechanisms by which the gut microbiota influences neurological disease pathogenesis.

Key words: Nervous system diseases; Gut microbiota; CiteSpace; Bibliometric; Visual analysis

Neurological disorders represent a broad group of conditions affecting the central and peripheral nervous systems, including Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, multiple sclerosis (MS), and stroke [1-5]. These diseases, which may involve genetic, infectious, traumatic, immunological, or environmental factors, can cause diverse symptoms such as muscle weakness, numbness, memory loss, language difficulties, and behavioral changes, severely impacting patients' daily functioning and social participation [6]. Despite significant progress in understanding their etiology and pathogenesis, challenges remain in early diagnosis, effective treatment, and disease progression intervention.

Recent research has increasingly demonstrated a close bidirectional interaction between gut microbiota and the nervous system, influencing brain activity, behavior, and levels of neurotransmitter receptors and neurotrophic factors [7-11]. The gut-brain axis serves as a critical pathway connecting the gut and central nervous system (CNS), participating in the development and progression of various neurological diseases [6,12-15]. Gastrointestinal physiology and motility are subject to bidirectional influence from both local gut and CNS signals. Neurotransmitters, immune signals, hormones, and neuropeptides produced in the gut can reciprocally regulate brain function [16]. Often termed the "second brain," the gut communicates with the brain through complex neural, immune, and endocrine pathways [17]. Dysbiosis of gut microbiota may exacerbate neurological disease progression by modulating immune responses, affecting neurotransmitter metabolism and release, and influencing CNS function through microbial metabolites such as short-chain fatty acids (SCFAs) [5,18-20]. For instance, studies have found that gut microbial disturbances in PD patients correlate with α-synuclein aggregation in the brain, a hallmark pathological feature of PD [21]. AD research has similarly shown that alterations in gut microbiota correlate with abnormal deposition of amyloid-β and tau proteins in the brain, key pathological features of AD [22]. Additionally, immune-related neurological diseases such as MS exhibit correlations between gut microbial communities and immune dysfunction [4]. Therefore, investigating the relationship between gut microbiota and neurological disorders not only enhances understanding of disease pathogenesis but also provides potential directions for exploring novel therapeutic strategies.

As research on the relationship between neurological diseases and gut microbiota deepens, systematic literature analysis becomes crucial for understanding advances and future trends in this field. Bibliometrics and scientific knowledge mapping provide effective methods for researchers to reveal research hotspots, knowledge structures, and evolutionary trends through quantitative analysis of large volumes of literature [23]. Tools such as CiteSpace have been widely applied in biomedical research to help researchers visually identify academic frontiers and potential research opportunities [24].

This study employs the information visualization software CiteSpace to conduct a comprehensive knowledge mapping analysis of literature related to neurological diseases and gut microbiota from 2000 to 2024, aiming to reveal research hotspots, academic development trends, and future research directions. Through this analysis, we hope to provide researchers with a panoramic review of the field and offer theoretical foundations and data support for future basic and clinical research.

1.1 Literature Source

This study conducted literature retrieval through the Web of Science Core Collection database using advanced search mode, focusing on the subject terms "neurological disorders" and "gut microbiota." The specific search strategies were as follows:

#1: Neurological disorders
TS=("Neurodegenerative disease" OR "Neurological disorder" OR "Central nervous system disorder" OR Neuroinflammation OR "Alzheimer's disease" OR "Parkinson's disease" OR "Multiple sclerosis" OR "Amyotrophic lateral sclerosis" OR ALS OR "Huntington's disease" OR Epilepsy OR Dementia OR "Cognitive impairment" OR Stroke OR "Brain injury" OR "Spinal cord injury" OR "Peripheral neuropathy" OR "Tourette syndrome" OR "Cerebrovascular disease" OR "Ischemic stroke" OR "Hemorrhagic stroke" OR "Transient ischemic attack" OR TIA OR "Vascular dementia" OR "Cerebral small vessel disease" OR "Intracerebral hemorrhage" OR "Subarachnoid hemorrhage" OR "Cavernous malformation" OR "Arteriovenous malformation" OR Neurofibromatosis OR "Brain tumor" OR Glioma OR Glioblastoma OR Astrocytoma OR Meningioma OR Medulloblastoma OR "Pituitary adenoma" OR Schwannoma OR Neuroblastoma OR Ependymoma OR "Primary CNS lymphoma" OR "Spinal cord tumor" OR "Spinal glioma" OR "Spinal meningioma" OR "Spinal schwannoma" OR "Spinal ependymoma" OR "Metastatic brain tumor")

#2: Gut microbiota
TS=("Gut microbiota" OR "Gut microbiome" OR "Gut microorganisms" OR "Gut bacteria" OR "Gut metagenome" OR "Gut fungi" OR "Gut pathogens" OR "Gut beneficial bacteria" OR "Gut viruses" OR "Gut microbiota metabolites" OR "Gut bacteriophages" OR "Gut probiotics" OR "Gut symbiotic bacteria" OR "Gut microecology" OR "Gut microenvironment" OR "Microbiota-gut-brain axis" OR "Brain-gut axis" OR "Lung-gut axis" OR "Kidney-gut axis" OR "Fecal microbiota transplantation" OR "Gut microbiota colonization")

All search terms employed exact retrieval methods, with the search timeframe spanning January 1, 2000 to July 29, 2024. Document types were limited to original research articles and reviews, while conference proceedings were excluded. Only English-language publications were included in the retrieval results.

1.2 Research Tools and Methods

This study utilized CiteSpace 6.3.R6, an information visualization software developed by CHEN et al. [24-25], to generate knowledge mapping visualizations of the included literature. The analysis encompassed research hotspots and trends (keyword clustering analysis, literature co-citation analysis, keyword co-occurrence and burst analysis), national/regional and institutional collaboration network analysis, and author collaboration network analysis.

Specific parameter settings were as follows: time span from 2000 to 2024, with a single time slice of 1 year; threshold set at Top N=50, and the pathfinder network scaling method was employed for pruning.

2.1 Publication Statistics in Neurological Disorders and Gut Microbiota Research (2000-2024)

From 2000 to 2024, a total of 85,278 articles on gut microbiota were published (annual publication trends shown in [FIGURE:1]). Analysis across different disciplinary fields revealed that neuroscience and clinical neurology published 2,987 (3.50%) and 1,073 (1.26%) articles respectively, ranking 11th and 34th among all disciplines ([FIGURE:2]). Statistical analysis of literature specifically related to neurological disorders and gut microbiota showed that from 2000 to 2024, 5,239 articles were included, with citations totaling 124, reflecting the逐年增长 and increasing academic influence of research in this field ([FIGURE:3]).

2.2 Co-citation Clustering Network in Neurological Disorders and Gut Microbiota Literature

The visualized clustering map of the reference co-citation network generated by CiteSpace is presented in [FIGURE:4]. The co-citation network is divided into multiple clusters, with closely connected references within the same cluster and relatively loose connections between different clusters. Cluster labels were generated using the log-likelihood ratio (LLR) test. The network's modularity value (Q value) is 0.8144, indicating clear classification within the professional scientific domain [23]. Meanwhile, the mean silhouette value (S value) of the clusters is 0.9341, reflecting high consistency and reliability of the clustering results [23]. Generally, Q > 0.3 and S > 0.5 indicate good clustering quality, demonstrating that this study's clusters have significant structure and high reliability [26].

The 16 largest clusters in the co-citation network, sorted by the number of members in each cluster, are: Parkinson's disease, depression, Alzheimer's disease, autoimmunity, multiple sclerosis, ischemic stroke, obesity, asthma, epilepsy, amyotrophic lateral sclerosis, gut microbiota, short-chain fatty acids, Akkermansia muciniphila, preterm, minerals, and immune signaling ([TABLE:1]). All clusters exhibit high homogeneity and high silhouette scores, indicating good internal consistency of the clustering results. The average publication year of the clusters further reflects the cutting-edge nature and timeliness of these research areas.

Temporal trend analysis shows that since 2020, PD, AD, ischemic stroke, and amyotrophic lateral sclerosis remain concentrated areas of research ([FIGURE:5]). The sustained attention to the relationship between these diseases and gut microbiota demonstrates that research in this field maintains high activity and significant clinical relevance.

2.3 Analysis of Highly Cited Articles

Among highly cited literature, research in the PD field is particularly prominent ([FIGURE:6]), with 4 of the top 10 most frequently cited articles focusing on this area ([TABLE:2]), reflecting strong researcher interest in gut microbiota in PD. SAMPSON et al. [21] demonstrated that α-synuclein aggregation is closely associated with motor dysfunction in PD, with gut microbiota playing a key role in this process. The study found that antibiotics could alleviate PD symptoms, while microbial reconstitution might exacerbate the condition, revealing the central role of the gut-brain axis in PD. Similarly, SCHEPERJANS et al. [27] analyzed gut microbiota in PD patients and healthy controls, finding that significant reduction in Prevotellaceae correlated with motor symptom severity, further highlighting the important position of gut microbiota in PD pathogenesis. UNGER et al. [28] supplemented this field by noting significantly decreased SCFA levels in PD patients, suggesting that microbial changes might affect PD development through intestinal function. Additionally, KESHAVARZIAN et al. [29] showed that α-synuclein aggregation and inflammatory changes in the colon of PD patients reflect that pro-inflammatory dysbiosis may be closely related to disease progression. These studies consistently emphasize the potential role of gut microbiota in PD, providing important biomarkers and intervention targets for future therapeutic strategies.

Beyond PD, gut microbiota is also crucial for maintaining CNS homeostasis and regulating immune function. ERNY et al. [30] demonstrated that microbiota deficiency leads to microglial dysfunction in germ-free mice, revealing the important role of gut microbiota in maintaining microglial homeostasis. SCFAs are identified as key molecules regulating microglial function, suggesting that host microbiota may regulate neural health and immune homeostasis through SCFAs. Furthermore, studies have found that germ-free mice exhibit increased blood-brain barrier (BBB) permeability from fetal stages, while exposure to pathogen-free gut microbiota can improve this permeability, demonstrating long-term interactions between gut microbiota and the BBB [31]. These studies provide new directions for understanding how gut microbiota regulates neural function and immune balance.

AD research has also revealed significant changes in gut microbiota. Studies show that AD patients have markedly decreased microbial diversity, accompanied by reduced Firmicutes and Bifidobacteria and increased Bacteroidetes, changes that correlate with AD biomarkers in cerebrospinal fluid, suggesting a potential role of gut microbiota in AD progression [32]. Meanwhile, cognitively impaired patients show increased pro-inflammatory gut flora (e.g., Escherichia/Shigella), elevated pro-inflammatory cytokines, and reduced anti-inflammatory cytokines. This gut microbiota imbalance is closely associated with brain amyloid deposition and peripheral inflammation [22]. These findings provide potential targets for early diagnosis and intervention in AD.

In MS research, changes in gut microbiota are also closely related to immune regulation. JANGI et al. [4] analyzed gut microbiota in MS patients and healthy controls, finding increased abundance of Methanobrevibacter and Akkermansia and significant reduction of Butyricimonas in MS patients. These changes are closely associated with expression of immune-related genes, revealing that gut microbiota may participate in MS pathogenesis by regulating T cell and monocyte function. Additionally, increased methane levels in exhaled breath correlate with increased intestinal Methanobrevibacter, further suggesting the important role of gut microbiota in MS.

In recent years, gut-brain axis research has received increasing attention, with the microbiome being widely studied as a key regulator of this axis. CRYAN et al. [33] demonstrated that the gut microbiome communicates with the brain through multiple mechanisms, such as the immune system, tryptophan metabolism, and the vagus nerve. These mechanisms are influenced by various factors in early life, such as infection, antibiotic use, and environmental stress, which significantly alter microbiome composition in later stages, thereby affecting neurodevelopment and function. These findings not only associate gut microbiota with various neuropsychiatric disorders but also provide insights for future microbiota-based therapeutic strategies.

2.4 Citation Bursts

Recent research has primarily focused on the role of gut microbiota in neurodegenerative diseases. Literature in the field of neurological disorders and gut microbiota from 2022-2024 was sorted by citation burst intensity, with results shown in [TABLE:3] [1-3,34-42]. In PD, ROMANO et al. [2] found significant dysbiosis in PD patients, characterized by enrichment of Lactobacillus, Akkermansia, and Bifidobacterium and reduction of SCFA-producing bacteria such as Faecalibacterium, potentially leading to a pro-inflammatory state and associated gastrointestinal symptoms. AHO et al. [34] compared fecal samples from PD patients and healthy controls, finding elevated calprotectin levels and reduced SCFA levels in PD patients, which were associated with age and symptoms, revealing potential changes in microbe-host interactions.

Additionally, SRIVASTAV et al. [35] showed that probiotic mixtures can protect dopaminergic neurons and increase butyrate levels, thereby improving neurodegeneration. In AD research, KESIKA et al. [3] noted that gut microbiota influences disease mechanisms through the gut-brain axis, and improving microbial composition may become a preventive strategy for AD. COLOMBO et al. [36] found that SCFAs promote Aβ deposition in AD mouse models, emphasizing their important role in the gut-brain axis. LING et al. [37] analyzed fecal microbiota in AD patients and found significantly reduced microbial diversity, suggesting that gut microbiota imbalance may serve as a non-invasive biomarker for AD. MARIZZONI et al. [38] found that blood levels of lipopolysaccharide and SCFAs positively correlate with AD-related brain pathology. DEN et al. [39] conducted a meta-analysis showing that probiotics can significantly improve cognitive performance in AD patients, possibly by reducing inflammatory and oxidative biomarkers. Regarding stroke, TAN et al. [1] found that gut microbiota and SCFAs are dysregulated in acute ischemic stroke patients, suggesting SCFAs may serve as prognostic markers. XU et al. [40] demonstrated that post-stroke gut microbiota dysbiosis is associated with stroke prognosis, emphasizing the potential value of the gut-brain axis in treatment. These studies collectively reveal the importance of gut microbiota in neurodegenerative diseases and its prospects as an intervention target.

2.5 Keyword Co-occurrence

Keywords provide accurate depiction of research hotspots during specific periods and can clearly illustrate research status. [FIGURE:7] shows keywords with high co-occurrence rates, where larger font size indicates higher frequency. Gut microbiota, PD, AD, multiple sclerosis, oxidative stress, SCFAs, and microbiota-gut-brain axis are the most frequent terms, reflecting the main research focuses in this field.

2.6 Collaboration Network

A total of 104 countries/regions have published relevant papers. Ranked by publication quantity, the top 5 countries/regions are China (1,953 articles), United States (1,336 articles), Italy (409 articles), United Kingdom (256 articles), and Germany (230 articles). [FIGURE:8] displays the collaboration network among countries/regions, comprising 104 nodes and 396 connections. Nodes and connections represent countries/regions and their collaborative relationships, respectively. Larger nodes indicate greater publication volume, while wider connections indicate stronger collaboration.

2.7 Institutional Collaboration

From 2006-2024, 515 institutions published papers in this field. The top 9 institutions (with >50 publications) are Zhejiang University, Harvard Medical School, Capital Medical University, Shanghai Jiao Tong University, Southern Medical University, Chinese Academy of Sciences, Central South University, Nanjing Medical University, and University of California, San Francisco. The institutional network map shows 515 nodes and 1,740 connections, representing institutions and their collaborative relationships, demonstrating active cooperation among different institutions ([FIGURE:9]).

2.8 Author Collaboration

From 2006-2024, a total of 696 authors published papers in this field. ZHANG XIN has the most publications (20), ranking first, followed by LIU JIAMING (18). LI JING, KIM DONG-HYUN, and SUN JING are tied for third place (16 each). The author collaboration network is shown in [FIGURE:10], containing 696 nodes and 971 collaboration lines, with relatively limited collaboration among individual authors.

Discussion

This study systematically summarizes the potential associations between gut microbiota and neurological disorders through bibliometric analysis using CiteSpace, and reveals research hotspots and frontier trends in this field. Although the relationship between gut microbiota and neurological diseases has received widespread attention, current research remains in preliminary stages, requiring further exploration of specific mechanisms and more explicit guidance for future research priorities.

3.1 Trends in Highly Cited Literature and Citation Bursts

Analysis of highly cited literature reveals that several studies on gut microbiota and neurological diseases have established a solid theoretical foundation in recent years. Particularly, some studies have elucidated the mechanisms of the gut-brain axis through animal models and clinical trials, such as the close relationships between SCFAs, gut microbiota diversity, dysbiosis, and neurodegenerative diseases (e.g., PD, AD) [21,29]. These studies have not only produced profound academic impact but also provided potential intervention targets for clinical treatment.

Citation burst analysis shows that with advances in gut microbiota research, some articles have received numerous citations within short timeframes. These articles typically focus on specific mechanisms linking gut microbiota to CNS diseases, particularly regarding the role of SCFAs, regulation of immune responses by gut microbiota, and direct effects on brain function [1,34,36,40]. Additionally, clinical trials targeting gut microbiota interventions have begun to attract increasing attention [35], indicating that research in this field is expanding from basic science toward clinical application.

3.2 Research Hotspots: Gut Microbiota, SCFAs, and Gut-Brain Axis

Keyword co-occurrence analysis further reveals the frequent appearance of research themes including gut microbiota, SCFAs, and gut-brain axis, reflecting the main concerns of this field. SCFAs, particularly butyrate, acetate, and propionate, are considered biologically important metabolites produced by gut microbiota [35]. Increasing evidence indicates that SCFAs can affect the nervous system not only through influencing intestinal barrier function and modulating the immune system but also by regulating neurotransmitter levels in the brain, thereby affecting the development of neurodegenerative diseases [5,18-20].

The gut-brain axis, as a bridge between gut microbiota and the CNS, has become an important research direction in this field. Gut microbes communicate with the brain through neural, immune, and endocrine pathways, influencing neurodevelopment, behavior, emotional regulation, and disease processes. This mechanism provides new perspectives for understanding the association between gut microbiota and neurological diseases and may offer theoretical foundations for future clinical interventions.

3.3 In-depth Analysis: The Relationship Between Dysbiosis and Neurological Diseases

Increasing evidence indicates that gut microbiota dysbiosis has become an important risk factor for multiple neurological diseases. AD, PD, MS, and ischemic stroke all exhibit characteristics associated with specific gut microbial disturbances. Microbiota participate in neuropathological processes through multiple mechanisms, including influencing inflammatory responses, neurotransmitter metabolism, barrier system homeostasis, and microbial metabolites, suggesting the key role of the microbiota-gut-brain axis in neurological diseases.

3.3.1 Dysbiosis is associated with early diagnosis, inflammation, and metabolic disorders in AD:

A study of 476 Chinese participants (covering 5 pathological stages of AD) identified through fecal metagenomic analysis that over 10% of microbial species and gene families changed significantly during AD progression, closely associated with neuroinflammation and neurotransmitter disturbances [43]. Specific microbial gene families (e.g., those involved in carbohydrate and amino acid metabolism) showed high discriminatory ability in AD diagnosis (cross-validation AUC=0.80, independent validation AUC=0.75) and were associated with genera such as Alistipes and Bacteroides. Fecal microbiota transplantation (FMT) experiments further confirmed that microbiota from AD patients could accelerate cognitive decline in 5xFAD mice, suggesting that gut microbiota may become an important target for intervening in AD progression [43]. Additionally, a team from Capital Medical University led by LIU Xicheng found that in AD model mice, reduction of Bacteroides ovatus and increase of Clostridium correlated positively with Aβ deposition. Supplementation with B. ovatus or its metabolite lysophosphatidylcholine (LPC) could improve cognitive impairment and reduce AD pathology by regulating ferroptosis-related pathways through the GPR119 receptor [44]. Another study in 3×Tg-AD mice revealed that with aging, butyrate-producing bacteria decreased and cecal butyrate levels declined, preceding cognitive impairment and tau abnormalities. Oral administration of the butyrate prodrug tributyrin could improve memory function and delay pathological progression [45].

3.3.2 Intertwined mechanisms of microbiota-amino acid metabolism-inflammation in PD:

PD-related studies indicate that gut microbiota plays an important role in its pathogenesis and progression. A study of 106 PD patients and 114 controls found that plasma branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were significantly reduced in PD patients, negatively correlating with clinical stage. Gut function analysis suggested that genes involved in BCAA biosynthesis (e.g., ilvB, ilvC, ilvD, ilvN) were less abundant in advanced PD patients, indicating that microbial metabolic disorders and amino acid imbalance may be one of the pathogenic mechanisms of PD [46]. A prospective metabolomics study from the EPIC4PD cohort further indicated that pre-onset microbial metabolites (such as valine, butyrate, and propionate metabolic pathways) were associated with PD risk, particularly significant in males, smokers, and obese individuals, suggesting these metabolites may serve as early predictive biomarkers for PD [47].

In terms of clinical intervention, a Chinese randomized double-blind placebo-controlled study showed that FMT treatment could significantly improve autonomic and gastrointestinal symptoms in mild-to-moderate PD patients and increase gut microecological complexity without serious adverse events [48]. However, results from a Finnish randomized controlled trial were inconsistent, with the FMT group showing no advantage in clinical score improvement and higher gastrointestinal adverse reactions (53% vs. 7%), suggesting that donor selection may be an important factor affecting FMT efficacy [49]. These discrepancies may also be related to differences in study design, such as different primary endpoint assessment dimensions (overall symptoms vs. single motor symptoms), FMT administration methods (nasointestinal tube vs. enema combined with oral capsules), sample sizes, and follow-up duration. Furthermore, donor microbiota composition and its matching with recipients may also critically influence FMT clinical outcomes.

Experimental studies also support the role of gut microbiota in PD pathogenesis. For example, supplementation with the butyrate-producing bacterium B. producta could inhibit microglial activation and improve motor dysfunction in PD model mice by regulating the RAS-NF-κB signaling pathway [50]; while transplantation of microbiota from PD patients into mice could induce loss of tyrosine hydroxylase-positive neurons in the midbrain, motor dysfunction, and reduction of Th17 cells, suggesting that microbiota can affect the CNS through immune-inflammatory mechanisms [51].

3.3.3 Exploration of microbial mechanisms in other neurological diseases:

Besides AD and PD, other neurological diseases also show close associations with gut microbiota. For example, MS patients exhibit significant reduction of bile acid-metabolizing microbiota, and these metabolites can induce Treg differentiation and inhibit Th17 inflammation, suggesting their key role in immune homeostasis [52]. The acute phase of ischemic stroke can lead to gut microbiota dysbiosis and intestinal barrier damage, triggering "leaky gut," endotoxemia, and bacterial translocation; while microbial metabolites (such as SCFAs, TMAO, and lipopolysaccharide) can activate inflammatory pathways and affect brain function [53]. Multiple barrier systems in the microbiota-gut-brain axis (intestinal epithelial barrier, blood-brain barrier, and blood-cerebrospinal fluid barrier) play central roles in maintaining nervous system homeostasis. Barrier function integrity depends on regulation by SCFAs, tryptophan metabolites, bile acids, polyamines, and other microbial metabolites. Increased barrier permeability is a key pathological link in multiple neurological diseases (such as AD, PD, and stroke), further illustrating the potential of microbiota-mediated barrier function regulation in preventing neurodegenerative diseases [54].

Current research has preliminarily revealed close connections between gut microbiota dysbiosis and neurological diseases, covering multiple aspects including metabolic pathway disorders, inflammatory activation, and barrier dysfunction. However, most evidence still derives from animal experiments or cross-sectional studies, lacking large-scale, long-term follow-up population studies and standardized clinical trials. Therefore, future research should further explore the mechanisms of gut microbiota dysbiosis in neurological diseases and develop targeted intervention approaches, such as dietary regulation, microbiome modulation, and miRNA-based precision therapy, to find new prevention and treatment strategies for neurological diseases.

This study systematically summarizes the potential associations between gut microbiota and neurological diseases through bibliometric analysis and reveals research hotspots and frontier trends in this field. CiteSpace-based analysis suggests that gut microbiota intervention may open new directions for treating neurological diseases, but further validation through more longitudinal studies and clinical trials is needed. Future research should strengthen translation from basic to clinical science and promote the application of gut microbiota in neurological disease treatment.

Author Contributions: GUO Yangyang was responsible for literature data analysis, figure production, quality control and verification, manuscript writing and revision, and overall responsibility for the paper; ZHANG Linlin was responsible for literature retrieval, screening, and deduplication; SHI Guangzhi was responsible for data verification, quality control, and manuscript revision; ZHANG Jindong was responsible for topic selection, manuscript revision, overall structure control, final approval, and overall responsibility for the paper.

Conflict of Interest: The authors declare no conflict of interest.

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(Received: 2025-04-10; Revised: 2025-07-16)
(Editor: MAO Yamin)