The gut-brain axis (GBA) denotes the dynamic and bidirectional communication system that connects the gastrointestinal tract and the central nervous system (CNS). This review explored this axis, focusing on the role of microbial diversity and fitness in maintaining gastrointestinal health and preventing neurodegeneration, particularly in Alzheimer's disease (AD). Gut dysbiosis, characterized by the imbalance in populations of beneficial and harmful bacteria, has been associated with increased systemic inflammation, neuroinflammation, and the progression of AD through pathogenic mechanisms involving amyloid deposition, tauopathy, and increased blood-brain barrier (BBB) permeability. Emerging evidence highlighted the therapeutic potential of probiotics, dietary interventions, and intermittent fasting in restoring microbial balance, reducing inflammation, and minimizing neurodegenerative risks. Probiotics and synbiotics are promising in helping improve cognitive function and metabolic health, while dietary patterns like the Mediterranean diet were linked to decreased neuroinflammation and enhanced gut-brain communication. Despite significant advancement, further research is needed to elucidate the specific microbial strains, metabolites, and mechanisms influencing brain health. Future studies employing longitudinal designs and advanced omics technologies are essential to developing targeted microbiome-based therapies for managing AD-related disorders.

Sleep-disordered breathing (SDB) is characterized by recurrent reductions or interruptions in airflow during sleep, termed hypopneas and apneas, respectively. SDB impairs sleep quality and is linked to substantive health issues including cardiovascular and metabolic disorders, as well as cognitive decline. Recent evidence suggests a link between gut microbiota (GM) composition and sleep apnea. Indeed, GM, a community of microorganisms residing in the gut, has emerged as a potential player in various diseases, and several studies have identified associations between sleep apnea and GM diversity along with shifts in bacterial populations. Additionally, the concept of "leaky gut," a compromised intestinal barrier with potentially increased inflammation, has emerged as another key player in the potential bidirectional relationship between GM and sleep apnea. One of the potential effectors could be extracellular vesicles (EVs) underlying gut-brain communication pathways that are relevant to sleep regulation and function. Thus, therapeutic implications afforded by targeting the GM or exosomes for sleep apnea management have surfaced as promising areas of research. This review explores current understanding of the relationship between GM, exosomes and sleep apnea, highlighting key research dynamics and potential mechanisms. A comprehensive review of the literature was conducted, focusing on studies investigating GM composition, intestinal barrier function and gut-brain communication in relation to sleep apnea.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and synaptic dysfunction. The accumulation of amyloid beta (Aβ) plaques and hyperphosphorylated tau protein leads to neuronal dysfunction, neuroinflammation, and glial cell activation. Emerging evidence suggests that peripheral insulin resistance and chronic inflammation, often associated with type 2 diabetes (T2D) and obesity, promote increased proinflammatory cytokines, oxidative stress, and immune cell infiltration. These conditions further damage the blood-brain barrier (BBB) integrity and promote neurotoxicity and chronic glial cell activation. This induces neuroinflammation and impaired neuronal insulin signaling, reducing glucose metabolism and exacerbating Aβ accumulation and tau hyperphosphorylation. Indeed, epidemiological studies have linked T2D and obesity with an increased risk of developing AD, reinforcing the connection between metabolic disorders and neurodegeneration. This review explores the relationships between peripheral insulin resistance, inflammation, and BBB dysfunction, highlighting their role in glial activation and the exacerbation of AD pathology.

Excessive accumulation of reactive oxygen species (ROS) and dysbiosis of gut microbiota are pivotal etiological factors in the pathogenesis of ulcerative colitis (UC) and its associated intestinal and extraintestinal manifestations (e.g., intestinal microthrombosis, anxiety, and depression symptoms). This investigation presents a multifunctional inulin complex (PB/NKase@Inulin gel) incorporating Prussian blue nanozymes (PB NZs) and the thrombolytic agent nattokinase (NKase) for the therapeutic management of dextran sulfate sodium (DSS)-induced UC and its associated intestinal and extraintestinal complications. Following oral administration, the PB/NKase@Inulin gel, characterized by prolonged retention of PB NZs and NKase at inflamed colonic sites, can facilitate continuously ROS scavenging, attenuate oxidative stress damage, effectively reduce pro-inflammatory cytokine levels. Importantly, PB/NKase@Inulin gel can not only robustly inhibit inflammatory microthrombosis formation but also effectively lyses thrombi due to the potent thrombolytic properties of NKase both in vitro and in vivo. Furthermore, the PB/NKase@Inulin gel is able to modulate gut microbiota homeostasis and alleviate multiple stresses responses (including anxiety and depression) in a UC mouse model via microbiota-gut-brain (MGB) axis interactions. Overall, the PB/NKase@Inulin gel offers an innovative paradigm for comprehensive therapeutic interventions in DSS-induced UC and its multifaceted complications.

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.

The number of the patients treated with maintenance hemodialysis (HD) is increasing due to the increasing incidence of end stage renal disease (ESRD). Autologous arteriovenous fistula (AVF) is the preferable modality for long-term vascular access during HD. AVF stenosis is the main cause of AVF dysfunction in HD patients, but its mechanism has not been fully elucidated. Patients with ESRD often have various related complications due to intestinal microbiota disorders and their metabolites, and the intestinal axis reveals various metabolic disorders in patients with chronic kidney disease. This paper analyzes the correlation between intestinal axis abnormalities and AVF stenosis in patients with CKD through three axes: "gut-liver axis," "gut-brain axis," and "gut-spleen axis," to provide clinical significance for elucidating the mechanism of AVF stenosis and for the prevention and treatment of AVF stenosis.

Estrogen receptors (ERs) play a critical role in breast cancer (BC) development and progression, with ERα being oncogenic and ERβ exhibiting tumor-suppressive properties. The interaction between ER signaling and other molecular pathways, such as PI3K/AKT/mTOR, influences tumor growth and endocrine resistance. Emerging research highlights the role of prebiotics in modulating gut microbiota, which may influence estrogen metabolism, immune function, and therapeutic responses in BC. This review explores the impact of prebiotics on estrogen receptor modulation, gut microbiota composition, immune regulation, and metabolic pathways in breast cancer. The potential of prebiotics as adjunctive therapies to enhance treatment efficacy and mitigate chemotherapy-related side effects is discussed. A comprehensive analysis of recent preclinical and clinical studies was conducted, examining the role of prebiotics in gut microbiota modulation, immune regulation, and metabolic reprogramming in breast cancer. The impact of short-chain fatty acids (SCFAs) derived from prebiotic fermentation on epigenetic regulation and endocrine resistance was also evaluated. Prebiotics were found to modulate the gut microbiota-estrogen axis, reduce inflammation, and influence immune responses. SCFAs demonstrated selective estrogen receptor downregulation and metabolic reprogramming, suppressing tumor growth. Synbiotic interventions mitigate chemotherapy-related side effects, improving the quality of life in breast cancer patients. Prebiotics offer a promising avenue for breast cancer prevention and therapy by modulating estrogen metabolism, immune function, and metabolic pathways. Future clinical trials are needed to validate their efficacy as adjunctive treatments in breast cancer management.

Based on the microbiota-gut-brain axis (MGBA) hypothesis, probiotics play an increasingly important role in treating various psychiatric disorders. Schizophrenia (SCZ) is a common mental disease with a complex pathogenesis and is challenging to treat. Although studies have elucidated the mechanisms associated with the interactions between the microbiota-gut-brain axis and SCZ, few have specifically used probiotics as a therapeutic intervention for SCZ. Accordingly, the current study determines whether L. johnsonii YH1136 effectively prevents SCZ-like behavior in mice and identifies the associated key microbes and metabolites. An SCZ mouse model was established by intraperitoneal injection of MK-801; L. johnsonii YH1136 was administered via oral gavage. L. johnsonii YH1136 significantly improves abnormal behaviors, including psychomotor hyperactivity and sociability and alleviates aberrant enzyme expression associated with tryptophan metabolism in SCZ mice. Additionally, L. johnsonii YH1136 upregulates hippocampal brain-derived neurotrophic factor (BDNF) levels while downregulating tryptophan 2,3-dioxygenase (TDO2), indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1), kynurenine aminotransferase 1 (KAT1). Subsequent 16S rRNA sequencing of intestinal contents suggests that L. johnsonii YH1136 modulates the gut flora structure and composition by increasing the relative abundance of Lactobacillus and decreasing Dubosiella in SCZ mice. N-acetylneuraminic acid and hypoxanthine are the key serum metabolites mediating the interaction between the MGBA and SCZ. These results partially reveal the mechanism underlying the effects of L. johnsonii YH1136 on SCZ-like behavior in mice, supporting the development of therapeutic L. johnsonii probiotic formulations against SCZ.

Depression is a widespread disease affecting over 300 million individuals of various ethnicities and socioeconomic backgrounds globally. It frequently strikes early in life and becomes a chronic or recurring lifelong illness. Out of the various hypotheses for the pathophysiology of depression, the gut-brain axis and stress hypothesis are the ones that need to be researched, as psychological stress impairs one or more pathways of the brain-gut axis and is likely to cause brain-gut axis dysfunction and depression. A dysfunctional reciprocal gut-brain relationship may contribute to many diseases, including inflammatory disorders, abnormal stress responses, impaired behavior, and metabolic changes. The hormone ghrelin is a topic of interest concerning the gut-brain axis as it interacts with the gut-brain axis indirectly via the central nervous system or via crossing the blood-brain barrier. Ghrelin release is also affected by the gut microbes, which has also been discussed in the review. This review elaborates on Ghrelin's role in depression and its effect on various aspects like neurogenesis, HPA axis, and neuroinflammation. Furthermore, this review focuses on ghrelin as a potential target for alleviation of depressive symptoms.

Gut microbial essential amino acid (EAA) provisioning to mammalian hosts remains a critical yet poorly understood aspect of host-microbe nutritional interactions, with significant implications for human and animal health. To investigate microbial EAA contributions in mice with reconstituted gut microbiomes, we analyzed stable carbon isotopes (13C) of six EAAs across multiple organs. Germ-free (GF) mice fed a high-protein diet (18%) were compared to conventionalized (CVZ) mice fed a low-protein diet (10%) following fecal microbiota transplantation 30 days prior and a 20-day dietary intervention. We found no evidence for microbial EAA contributions to host tissues, with 13C-EAA fingerprinting revealing nearly identical patterns between GF and CVZ organs. Both groups maintained their expected microbiome statuses, with CVZ gut microbiota dominated by Firmicutes and Bacteroidetes phyla. These findings raise important questions about the functional capacities of reconstituted gut microbiomes. Future studies should investigate longer adaptation periods, varied dietary protein levels, and complementary analytical techniques to better understand the context-dependent nature of microbial EAA provisioning in mammalian hosts.

The blood-brain barrier (BBB) is essential for maintaining brain homeostasis by regulating molecular exchange between the systemic circulation and the central nervous system. However, its dysfunction, often driven by peripheral inflammatory processes, has been increasingly linked to the development and progression of neurodegenerative diseases such as Alzheimer's and Parkinson's. Emerging evidence suggests that the gut-brain axis plays a key role in BBB integrity, with intestinal dysbiosis and chronic inflammation contributing to barrier disruption through immune and metabolic pathways. Furthermore, the selective vulnerability of specific brain regions to BBB dysfunction appears to be influenced by regional differences in vascularization, metabolic activity, and permeability, making certain areas more susceptible to neurodegenerative processes. This review explored the molecular mechanisms linking peripheral inflammation, gut microbiota, and BBB dysfunction, emphasizing their role in neurodegeneration. A comprehensive literature review was conducted using Web of Science, PubMed, Scopus, Wiley, ScienceDirect, and Medline, covering publications from 2015 to 2025. The findings highlight a complex interplay between gut microbiota-derived metabolites, immune signaling, and BBB permeability, underscoring the need for targeted interventions such as microbiome modulation, anti-inflammatory therapies, and advanced drug delivery systems. The heterogeneity of the BBB across different brain regions necessitates the development of region-specific therapeutic strategies. Despite advancements, critical knowledge gaps persist regarding the precise mechanisms underlying BBB dysfunction. Future research should leverage cutting-edge methodologies such as single-cell transcriptomics and organ-on-chip models to translate preclinical findings into effective clinical applications. Addressing these challenges will be crucial for developing personalized therapeutic approaches to mitigate the impact of BBB dysfunction in neurodegenerative diseases.

Ischemic stroke is a cerebrovascular disease with highly incidence. Previous research has demonstrated that apigenin provides protective effects against ischemic stroke. However, it remains unclear whether apigenin can regulate intestinal flora against ischemic stroke.

In this study, we evaluated the regulatory effects of apigenin on intestinal microbiota using a middle cerebral artery occlusion rat model. The protective impact of apigenin on brain damage in ischemic stroke rats was assessed through Nissl staining, hematoxylin and eosin staining, and immunohistochemistry. Additionally, we employed 16S rRNA sequencing to analyze intestinal contents and utilized non-targeted metabolomics to investigate the effects of apigenin on brain metabolites, thereby exploring its mechanism of action. AMPK levels were detected by Western blot and immunohistochemistry. The kit was used to detect oxidative stress and inflammation.

The intervention with apigenin resulted in significant alterations in the intestinal flora, characterized by an increase in the abundance of probiotic species and a decrease in harmful flora, alongside notable changes in brain metabolite profiles. This protective effect is attributed to apigenin's promotion of AMPK expression and enhancement of energy metabolism in the context of ischemic stroke. In addition, apigenin improved oxidative stress and inflammation in ischemic stroke.

These findings suggest that apigenin exerts a protective effect on ischemic stroke through the AMPK signaling pathway by modulating intestinal flora and associated metabolites. Consequently, apigenin emerges as a therapeutic candidate warranting further investigation.

Significance: Hydrogen sulfide (H2S), a ubiquitous small gaseous signaling molecule, plays a critical role in various diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), ischemic stroke, and myocardial infarction (MI) via reducing inflammation, inhibiting oxidative stress, and cell apoptosis. Recent Advances: Uncontrolled inflammation is closely related to pathological process of ischemic stroke, RA, MI, and IBD. Solid evidence has revealed the axes between gut and other organs like joint, brain, and heart, and indicated that H2S-mediated anti-inflammatory effect against IBD, RA, MI, and ischemic stroke might be related to regulating the functions of axes between gut and other organs. Critical Issues: We reviewed endogenous H2S biogenesis and the H2S-releasing donors, and revealed the anti-inflammatory effects of H2S in IBD, ischemic stroke, RA, and MI. Importantly, this review outlined the potential role of H2S in the gut-joint axis, gut-brain axis, and gut-heart axis as a gasotransmitter. Future Direction: The rate, location, and timing of H2S release from its donors determine its potential success or failure as a useful therapeutic agent and should be focused on in the future research. Therefore, there is still a need to explore internal and external sources monitoring and controlling H2S concentration. Moreover, more efficient H2S-releasing compounds are needed; a better understanding of their chemistry and properties should be further developed. Antioxid. Redox Signal. 42, 341-360.

Background: Psychological disorders are prevalent in patients having undergone gastrointestinal cancer surgery, and their emotional status may further deteriorate during subsequent chemotherapy. Psychobiotics are specific probiotics that have the unique characteristics of producing neuroactive substances that are thought to act on the brain-gut axis. The aim of the present study was to evaluate the benefits of a psychobiotic formula on depression and anxiety status, as well as on perceived stress, versus a placebo in patients on a chemotherapy course following gastrointestinal surgery for cancer. Patients: The enrolled patients, allocated to the psychobiotic and placebo groups, were assessed by means of these psychometric tests: Beck's Depression Inventory and the Hamilton Depression Rating 17-item Scale for depression; the General Anxiety Disorder-7 for anxiety; and the Perceived Stress Scale-14 Item for perceived stress at three time-points: upon allocation [T1], after one month of treatment [T2], and two months thereafter [T3]. Results: In total, 266 patients were included. One month of psychobiotic treatment improved [i] depression status by 60.4% [48 depressed patients at T1, reduced to 16 at T3]; [ii] anxiety by 57.0% [72 patients at T1, 26 at T3]; and [iii] stress by 60.4% [42 at T1, 14 at T3]. The placebo-treated patients experienced a deterioration in all parameters studied, i.e., depression increased by 62.9%, anxiety by 39.7%, and stress by 142.5%. Conclusions: Based on these findings, it can be recognized that psychobiotic treatment has great potential for every patient at risk of suffering from depression, anxiety, or stress during the course of surgery/chemotherapy for gastrointestinal cancer.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting approximately 55 million individuals globally. Diagnosis typically occurs in advanced stages, and there are limited options for reversing symptoms. Preventive strategies are, therefore, crucial. Time Restricted Eating (TRE) or Time Restricted Feeding (TRF) is one such strategy. Here we review recent research on AD and TRE/TRF in addition to AD biomarkers and gut microbiota.

A comprehensive review of recent studies was conducted to assess the impact of TRE/TRF on AD-related outcomes. This includes the analysis of how TRE/TRF influences circadian rhythms, beta-amyloid 42 (Aß42), pro-inflammatory cytokines levels, and gut microbiota composition.

TRE/TRF impacts circadian rhythms and can influence cognitive performance as observed in AD. It lowers beta-amyloid 42 deposition in the brain, a key AD biomarker, and reduces pro-ininflammatory cytokines. The gut microbiome has emerged as a modifiable factor in AD treatment. TRE/TRF changes the structure and composition of the gut microbiota, leading to increased diversity and a decrease in harmful bacteria.

These findings underscore the potential of TRE/TRF as a preventive strategy for AD. By reducing Aß42 plaques, modulating pro-inflammatory cytokines, and altering gut microbiota composition, TRE/TRF may slow the progression of AD. Further research is needed to confirm these effects and to understand the mechanisms involved. This review highlights TRE/TRF as a promising non-pharmacological intervention in the fight against AD.

Perioperative neurocognitive dysfunction is a significant concern for population health, impacting postoperative recovery and increasing the financial burden on patients. With an increasing number of surgical procedures being performed, the prevention and management of perioperative neurocognitive dysfunction have garnered significant attention. While factors such as age, lifestyle, genetics, and education are known to influence the development of cognitive dysfunction, recent research has highlighted the role of the gut microbiota in neurological health. An increased abundance of pro-inflammatory gut microbiota can trigger and worsen neuroinflammation, neuronal cell damage, and impaired cellular autophagy. Moreover, the inflammation-promoting gut microbiota can disrupt immune function, impair neuroautophagy, and affect the production and circulation of extracellular vesicles and neurotransmitters. These factors collectively play a role in the onset and advancement of cognitive impairment. This narrative review delves into the molecular mechanisms through which gut microbiota and their derivatives contribute to cognitive impairment, focusing on the impact of anesthesia surgery, changes in gut microbial populations, and perioperative cognitive impairment associations. The study suggests that alterations in the abundance of various bacterial species and their metabolites pre- and post-surgery may be linked to postoperative cognitive impairment. Furthermore, the potential of probiotics or prebiotics in addressing cognitive impairment is discussed, offering a promising avenue for investigating the treatment of perioperative neurocognitive disorders.

Alzheimer's disease (AD) is a progressive, degenerative disorder of the central nervous system. Despite extensive research conducted on this disorder, its precise pathogenesis remains unclear. In recent years, the microbiota-gut-brain axis has attracted considerable attention within the field of AD. The gut microbiota communicates bidirectionally with the central nervous system through the gut-brain axis, and alterations in its structure and function can influence the progression of AD. Consequently, regulating the gut microbiota to mitigate the progression of AD has emerged as a novel therapeutic approach. Currently, numerous studies concentrate on the intrinsic relationship between the microbiota-gut-brain axis and AD. In this paper, we summarize the multifaceted role of the gut microbiota in AD and present detailed therapeutic strategies targeting the gut microbiota, including the treatment of AD with Traditional Chinese Medicine (TCM), which has garnered increasing attention in recent years. Finally, we discuss potential therapeutic strategies for modulating the gut microbiota to alleviate the progression of AD, the current challenges in this area of research, and provide an outlook on future research directions in this field.

The microbiome, comprising the diverse microbial communities inhabiting the human body, has emerged as a critical factor in regulating immune function and inflammation. The relationship between the microbiome and uveitis represents a promising frontier in ophthalmological research, with the microbiome increasingly implicated in disease onset and progression. Research has predominantly focused on the gut microbiome, with animal studies providing evidence that dysbiosis is a key factor in autoimmunity. As the understanding of the microbiome increases, so does the potential for developing innovative treatments that leverage the microbiome's impact on immune and inflammatory processes. Future research will be crucial for deciphering the complexities of the interaction between the microbiome and immune system and for creating effective microbiome-based therapies for those with uveitis. Incorporating microbiome research into clinical practice could transform how uveitis is managed, leading to better and more individualized approaches for management. This review discusses the current understanding of the microbiome-uveitis axis, the promise of microbiome-based diagnostics and therapeutics, and the critical need for large-scale, longitudinal studies. Unlocking the potential of microbiome-targeted approaches may revolutionize the management of uveitis and other inflammatory diseases.

Depression is a mental disorder that significantly impairs both physical and mental health. Recent studies have shown that reactive astrogliosis have gained significant attention for their involvement in the pathophysiology of depression. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hotspots regarding the role of astrocytes in the mechanisms and treatment of depression through bibliometric analysis. The scope of the literature review encompasses both basic and clinical research.

Publications related to astrocytes in depression and treatment from 2014 to 2023 were searched in the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, and the R package "bibliometrix" were used to conduct this bibliometric analysis.

From 2014 to 2023, a total of 1,502 documents from 78 countries on astrocytes in depression and treatment were analyzed from 169 journals, with the most co-cited journals being the Journal of Neuroscience and PNAS. China Medical University was the most productive institution. The analysis identified key authors like Verkhratsky Alexei and Baoman Li, and major co-cited references by Rajkowska and Liddelow. Keywords such as "synaptic plasticity," "astrocytes," and "neuroinflammation" revealed research trends focusing on molecular mechanisms, gut microbiota, and inflammation.

This is the first bibliometric study to comprehensively summarize the research trends and advancements regarding astrocytes in depression and its treatment. Through this bibliometric analysis, we aim to enhance the understanding of the significance of astrocytes in depression research and provide new perspectives and insights for future investigations. We hope that this study will facilitate a broader integration of basic and clinical research, offering novel approaches for the treatment of depression.

Neurodegenerative diseases (NDDs) cause a progressive loss of neurons. Since NDDs are multifactorial, the precise etiology varies on the basis of the type of disease and patient history. Cohort studies and case studies have demonstrated a potential link between viral infections and the onset or progression of NDDs. Recent findings concerning the mechanisms by which neuropathic infections occur have provided more insights into the importance of such connections. In this review, we aim to elaborate on the occurrence of the neuropathic effects of viruses from epidemiological, clinical, and biological perspectives while highlighting potential treatments and challenges. One of the key players in viral neuropathogenesis is neuroinflammation caused by the immune response to the virus; this can occur due to both neurotropic and nonneurotropic viruses. The COVID-19 pandemic has raised concerns about whether vaccines are essential for preventing viruses or whether vaccines may play a part in exacerbating or accelerating NDDs. By classifying viruses and the common NDDs associated with them and further delving into their cellular pathways, this review provides insights to advance the development of potential treatments and diagnostic methods.

The relationship between the gut microbiome and mental health, particularly depression, has gained significant attention. This review explores the connection between microbial metabolites, dysbiosis, and depression. The gut microbiome, comprising diverse microorganisms, maintains physiological balance and influences health through the gut-brain axis, a communication pathway between the gut and the central nervous system.

Dysbiosis, an imbalance in the gut microbiome, disrupts this axis and worsens depressive symptoms. Factors like diet, antibiotics, and lifestyle can cause this imbalance, leading to changes in microbial composition, metabolism, and immune responses. This imbalance can induce inflammation, disrupt neurotransmitter regulation, and affect hormonal and epigenetic processes, all linked to depression.

Microbial metabolites, such as short-chain fatty acids and neurotransmitters, are key to gut-brain communication, influencing immune regulation and mood. The altered production of these metabolites is associated with depression. While progress has been made in understanding the gut-brain axis, more research is needed to clarify causative relationships and develop new treatments. The emerging field of psychobiotics and microbiome-targeted therapies shows promise for innovative depression treatments by harnessing the gut microbiome's potential.

Epigenetic mechanisms, including DNA methylation and histone modifications, are crucial in how the gut microbiota impacts mental health. Understanding these mechanisms offers new prospects for preventing and treating depression through the gut-brain axis.

The hallmarks of Alzheimer's disease (AD) include brain dysfunction and the buildup of amyloid and tau proteins. The onset of dementia is one of the latter symptoms. Imaging diagnostics allowed for the detection of amyloid buildup in the brain 10-20 years before the emergence of overt signs of the disease. The application of imaging diagnostic techniques allowed for this identification. Within the next few decades, the incidence and frequency of this disease are expected to reach epidemic proportions unless measures are done to stop or slow its growth. However, unless action is taken to slow or stop the disease's progression, it will continue to threaten the health of the general public. Recently, there has been some speculation that the gut flora might contribute to the development of AD. Not only that, but the rapidly expanding ischemia etiology is another possible contributor to the issue. Rumor has it that there's a network connecting the brain and the stomach called the "gut-brain-microbiota axis." The hypothesis is based on this network. Furthermore, a large amount of evidence implies that the gut microbiota (GMB) could potentially contribute to the onset of AD. It has been suggested that the GMB could play a role in the onset of AD. This notion has been bolstered by new studies. It is quite probable that this review will address the prospect of a link between the microbiome and AD. This concept could be explored as a potential therapy or preventative measure. Some techniques that show promise as new treatments for AD include changes to the GMB, which can be achieved through dietary changes or positive microflora interventions, and changes to microbiological partners and their products, like amyloid protein.

Background/Objectives: Research on the relationship between gut microbiota (GM) and atopic dermatitis (AD) has seen a growing interest in recent years. The aim of this systematic review was to determine whether differences exist between the GM of adults with AD and that of healthy adults (gut dysbiosis). Methods: We conducted a systematic review based on the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed using PubMed, EMBASE, and Web of Science. Observational and interventional studies were analyzed. Results: Although the studies showed heterogeneous results, some distinguishing characteristics were found in the intestinal microbial composition of adults with dermatitis. Even though no significant differences in diversity were found between healthy and affected adults, certain microorganisms, such as Bacteroidales, Enterobacteriaceae, and Clostridium (perfringens), were more characteristic of the fecal microbiota in adults with AD. Healthy individuals exhibited lower abundances of aerobic bacteria and higher abundances of short-chain fatty acid-producing species and polyamines. Clinical trials showed that the consumption of probiotics (Bifidobacterium and/or Lactobacillus), fecal microbiota transplants, and balneotherapy modified the fecal microbiota composition of participants and were associated with significant improvements in disease management. Conclusions: In anticipation of forthcoming clinical trials, it is essential to conduct meta-analyses that comprehensively evaluate the effectiveness and safety of interventions designed to modify intestinal flora in the context of AD. Preliminary evidence suggests that certain interventions may enhance adult AD management.

To investigate metabolic markers linked to Mycobacterium tuberculosis (M. tb) in the cerebrospinal fluid (CSF) of a South African cohort of paediatric tuberculous meningitis (TBM).

Targeted proton magnetic resonance (1H-NMR) spectroscopy and two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) metabolomics approaches were used to evaluate M. tb-linked metabolites in the CSF of 21 definite cases of TBM and 25 control cases. Uni- and multivariate statistical analyses were performed.

Four statistically significant metabolites were identified to discriminate TBM cases from controls. Mannose and arabinose were found at lower concentrations in the TBM group. Nonanoic acid and propanoic acid were found in higher concentrations in the definite TBM group.

We identified the novel presence of nonanoic acid for the first time as a M. tb-linked marker in the CSF of cases of TBM, possibly as a degradation product of the M. tb cell wall. Propanoic acid can be related to perturbed brain neuro-energetics and neuro-inflammation in TBM cases and is likely a host-response metabolite. Mannose and arabinose-supposed surrogates for lipoarabinomannan, a component of the M. tb cell wall-were not reliable markers for M. tb. Further research should focus on the analysis of fatty acids in the CSF of patients with TBM.

Age-associated alterations in the brain lead to cognitive deterioration and neurodegenerative disorders (NDDs). This review with a particular focus on Alzheimer's disease (AD), emphasizes the burgeoning significance of the gut microbiota (GMB) in neuroinflammation and its impact on the gut-brain axis (GBA), a communication conduit between the gut and the central nervous system (CNS). Changes in the gut microbiome, including diminished microbial diversity and the prevalence of pro-inflammatory bacteria, are associated with AD pathogenesis. Promising therapies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, may restore gut health and enhance cognitive performance. Clinical data remain insufficient, necessitating further research to elucidate causes, enhance therapy, and consider individual variances. This integrative approach may yield innovative therapies aimed at the GMB to improve cognitive function and brain health in older people.

Drug-resistant epilepsy (DRE), also known as intractable epilepsy or refractory epilepsy, is a disease state with long-term poorly controlled seizures attack. Without effective treatment, patients are at an elevated risk of injury, premature death, mental disorders, and poor quality of life, increasing the need for a fresh perspective on the etiology and treatment of DRE. The gut is known to harbor a wide variety of microorganisms that can regulate the host's response to exogenous signals and participate in various physiological and pathological processes in the human body. Interestingly, emerging evidence has uncovered the changes in gut microbiota in patients with epilepsy, particularly those with DRE. In addition, both dietary interventions and specific antibiotic therapy have been proven to be effective in restoring the microecological environment and, more importantly, reducing seizures. Here, we reviewed recent studies on DRE and the involvement of gut microbiota in it, describing changes in the gut microflora composition in patients with DRE and corresponding animal models. Furthermore, the influence of the ketogenic diet, probiotics, fecal microbiota transplantation (FMT), and antibiotics as microbiome-related factors on seizure control and its possible mechanisms are broadly discussed. Finally, we highlighted the significance of gut microbiome in DRE, in order to provide a new prospect for early identification and individualized treatment of patients with DRE.

Gastrointestinal dysfunction frequently occurs following traumatic brain injury (TBI) and significantly increases posttraumatic complications. TBI can lead to alterations in gut microbiota. The neuroprotective effects of hyperbaric oxygen (HBO) have not been well recognized after TBI. The study''s aim was to investigate the impact of HBO on TBI-induced dysbiosis in the gut and the pathological changes in the brain following TBI.

Anesthetized male Sprague-Dawley rats were randomly assigned to three groups: sham surgery plus normobaric air (21% oxygen at 1 atmospheres absolute), TBI (2.0 atm) plus normobaric air, and TBI (2.0 atm) plus HBO (100% oxygen at 2.0 atmospheres absolute) for 60 min immediately after TBI, 24 h later, and 48 h later. The brain injury volume, tumor necrosis factor-α expression in microglia and astrocytes, and neuronal apoptosis in the brain were subsequently determined. The V3-V4 regions of 16S ribosomal rRNA in the fecal samples were sequenced, and alterations in the gut microbiome were statistically analyzed. All parameters were evaluated on the 3rd day after TBI.

Our results demonstrated that HBO improved TBI-induced neuroinflammation, brain injury volume, and neuronal apoptosis. HBO appeared to increase the abundance of aerobic bacteria while inhibiting anaerobic bacteria. Intriguingly, HBO reversed the TBI-mediated decrease in Prevotella copri and Deinococcus spp., both of which were negatively correlated with neuroinflammation and brain injury volume. TBI increased the abundance of these gut bacteria in relation to NOD-lik0065 receptor signaling and the proteasome pathway, which also exhibited a positive correlation trend with neuro inflammation and apoptosis. The abundance of Prevotella copri was negatively correlated with NOD-like receptor signaling and the Proteasome pathway.

Our study demonstrated how the neuroprotective effects of HBO after acute TBI might act through reshaping the TBI-induced gut dysbiosis and reversing the TBI-mediated decrease of Prevotella copri.

Premature infants are more prone to brain injuries owing to incomplete nervous system development and poor adaptation outside the mother's body. Without timely intervention, premature infants with brain injuries often develop intellectual disabilities, causing significant burdens on families and the society. Multiple studies have shown that gut dysbiosis can affect the nervous system, and vice versa. This study aimed to explore the changes in gut microbiota of typical premature infants and those with brain injuries on the third and seventh days after birth using 16 S rRNA technology.

Fecal samples from typical premature infants (non-brain injury group, n = 17) and those with brain injuries (brain injury group, n = 21) were collected on days 1, 3, and 7 after birth for 16 S rRNA sequencing. Alpha diversity analysis was used to evaluate the diversity of gut microbiome. LEfSe and DESeq2 were used to analyze of the microorganisms' characteristics and differentiate the microorganisms between the two groups.

At the phylum level, Firmicutes, Proteobacteria, and Actinobacteria were the dominant flora in both groups. At the genus level, the proportion of Enterococcus in fecal samples of the brain injury group was higher than that of the non-brain injury group on day three after birth; however, the opposite was observed on day seven. Rothia and Lactobacillales were characteristic bacteria of the non-brain injury group on days three and seven after birth, whereas Enterococcus and Bifidobacteria were characteristic bacteria of the brain injury group on days three and seven after birth, respectively. Three days after birth, the Shannon and Simpson indices of the non-brain injury group were significantly higher than those of the brain injury group.

Premature infants with brain injuries have a unique gut microbiota that is different from that of typical premature infants, indicating correlation between brain injuries and gut microbiota.

Salmonellosis, a major global cause of diarrheal diseases, significantly impacts the intestinal microbiome. Probiotic-rich beverages, such as kefir, are increasingly utilized as alternative health-promoting beverages associated with various microbiota benefits. This study investigated the repercussions of daily consumption of household-produced milk kefir on Salmonella enterica serovar Typhimurium infection in C57BL-6 mice.

Kefir consumption pre-infection reduced the presence of inflammatory cells in the colon and altered the cytokine profile by reducing IL-10 and increasing IFN-γ. Despite reducing intestinal inflammation, kefir intake did not yield a prompt response to an acute infection caused by the aggressive pathogen Salmonella. This contributed to increased mortality in the mice, evidenced by higher fecal Salmonella counts post-infection. Metabarcoding analysis demonstrated that the use of kefir before infection increases butyric acid by the higher abundance of Lachnospiraceae and Prevotellaceae families and genus in feces, coupled with an increase in Muribaculaceae family and Bacteroides genus among infected kefir-treated mice. While kefir hinted at microbiota alterations reducing enterobacteria (Helicobacter), decrease IL-10, and increased IFN-γ, butyric acid on pre-infection, the beverage potentially facilitated the systemic translocation of pathogens, intensifying the infection's severity by altering the immune response.

The use of kefir in the dosage of 10% w/v (109 CFU), for acute infections with Salmonella Typhimurium, may not be enough to combat the infection and worsen the prognosis, leaving the intestine less inflamed, favoring the replication and translocation of the pathogen. These findings underscore the importance of prudently evaluating the widespread use of probiotics and probiotic-rich beverages, especially during acute infections, given their potential association with adverse effects during these diseases.

The gut microbiota (GM) produces various molecules that regulate the physiological functionality of the brain through the gut-brain axis (GBA). Studies suggest that alteration in GBA may lead to the onset and progression of various neurological dysfunctions. Moreover, aging is one of the prominent causes that contribute to the alteration of GBA. With age, GM undergoes a shift in population size and species of microflora leading to changes in their secreted metabolites. These changes also hamper communications among the HPA (hypothalamic-pituitary-adrenal), ENS (enteric nervous system), and ANS (autonomic nervous system). A therapeutic intervention that has recently gained attention in improving health and maintaining communication between the gut and the brain is calorie restriction (CR), which also plays a critical role in autophagy and neurogenesis processes. However, its strict regime and lifelong commitment pose challenges. The need is to produce similar beneficial effects of CR without having its rigorous compliance. This led to an exploration of calorie restriction mimetics (CRMs) which could mimic CR's functions without limiting diet, providing long-term health benefits. CRMs ensure the efficient functioning of the GBA through gut bacteria and their metabolites i.e., short-chain fatty acids, bile acids, and neurotransmitters. This is particularly beneficial for elderly individuals, as the GM deteriorates with age and the body's ability to digest the toxic accumulates declines. In this review, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production, physiological conditions, and neurological dysfunctions including neurodegenerative disorders.

Objective: Probiotics have been reported to exert beneficial effects on sleep through the gut-brain axis. Therefore, this randomized, double-blind, placebo-controlled trial assessed the effects of Lacticaseibacillus paracasei 207-27 supplementation on sleep quality and its safety and potential mechanisms. Method and study design: Healthy adults under mild stress aged 18-35 years consumed low or high doses of L. paracasei 207-27 or a placebo for 28 days. Fecal samples, blood samples, and questionnaires were collected at the baseline and the end of the intervention. Sleep quality was measured using wearable devices and Pittsburgh sleep quality index (PSQI) questionnaire. Serum inflammatory markers, corticotropin-releasing hormone, adrenocorticotropic hormone (ACTH), cortisol (COR), γ-aminobutyric acid, and 5-hydroxytryptamine levels were detected using enzyme-linked immunosorbent assay. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Short-chain fatty acids levels were detected using gas chromatography-mass spectrometry. Results: Both the low-dose and high-dose groups exhibited significant improvements in wearable device- measured sleep duration compared to the placebo group. The global scores of PSQI in three groups significantly decreased after intervention without statistical difference between groups. At the phylum level, the low-dose group exhibited a higher relative abundance of Bacteroidota and a lower Firmicutes-to-Bacteroidetes (F/B) ratio. At the genus level, two treatment groups had higher relative abundance of Bacteroides and Megamonas, alongside lower levels of Escherichia-Shigella. Furthermore, the low-dose group exhibited significant increases in acetic acid, propionic acid, butyric acid, and valeric acid levels, while two treatment groups exhibited a significant decrease in COR levels. Correlation analysis revealed that the increased levels of acetic acid and butyric acid in the low-dose group may be associated with decreased ACTH. Conclusion: L. paracasei 207-27 administration in healthy adults resulted in improvements in gut microbiota community and sleep duration. The mechanisms might involve modulation of the gut microbiota structure to regulate the function of the gut-brain axis, including increases in SCFA levels and decreases in hypothalamic-pituitary-adrenal axis activity. The Chinese clinical trial registry number is ChiCTR2300069453 (https://www.chictr.org.cn/showproj.html?proj=191193, registered 16 May 2023 - retrospectively registered).

This study aims to investigate the effect of electroacupuncture (EA) treatment on depression, and the potential molecular mechanism of EA in depression-like behaviors rats.

A total of 40 male Sprague Dawley rats were divided into three groups: normal control, chronic unpredictable mild stress (CUMS), and EA (CUMS + EA). The rats in CUMS and EA groups underwent chronic stress for 10 weeks, and EA group rats received EA treatment for 4 weeks starting from week 7. Body weight and behavioral tests, including the sucrose preference test (SPT), the forced swimming test (FST), and the open field test (OFT) were monitored. Gut microbiota composition was assessed via 16S rDNA sequencing, and lipid metabolism was analyzed by using UPLC-Q-TOF/MS technology.

In comparison to CUMS group, EA could improve the behavior including bodyweight, immovability time, sucrose preference index, crossing piece index and rearing times index. After 4 weeks of EA treatment, 5-HT in hippocampus, serum and colon of depressive rats were simultaneously increased, indicating a potential alleviation of depression-like behaviors. In future studies revealed that EA could regulate the distribution and functions of gut microbiota, and improve the intestinal barrier function of CUMS rats. The regulation of intestinal microbial homeostasis by EA may further affect lipid metabolism in CUMS rats, and thus play an antidepressant role.

This study suggested that EA has potential antidepressant effects by regulating gut microbiota composition and abundance, subsequently affecting lipid metabolism.

The pathogenesis of epilepsy is related to the microbiota-gut-brain axis, but the mechanism has not been clarified. The microbiota-gut-brain axis is divided into the microbiota-gut-brain axis (upward pathways) and the brain-gut-microbiota axis (downward pathways) according to the direction of conduction. Gut microorganisms are involved in pathological and physiological processes in the human body and participate in epileptogenesis through neurological, immunological, endocrine, and metabolic pathways, as well as through the gut barrier and blood brain barrier mediated upward pathways. After epilepsy, the downward pathway mediated by the HPA axis and autonomic nerves triggers "leaky brain "and "leaky gut," resulting in the formation of microbial structures and enterobacterial metabolites associated with epileptogenicity, re-initiating seizures via the upward pathway. Characteristic changes in microbial and metabolic pathways in the gut of epileptic patients provide new targets for clinical prevention and treatment of epilepsy through the upward pathway. Based on these changes, this review further redescribes the pathogenesis of epilepsy and provides a new direction for its prevention and treatment.

An increasing number of people undergo anesthesia and surgery. Perioperative neurocognitive and depressive disorders are common central nervous system complications with similar pathogeneses. These conditions pose a deleterious threat to human health and a significant societal burden. In recent years, numerous studies have focused on the role of the gut microbiota and its metabolites in the central nervous system via the gut-brain axis. Its involvement in perioperative neurocognitive and depressive disorders has attracted considerable attention. This review aimed to elucidate the role of the gut microbiota and its metabolites in the pathogenesis of perioperative neurocognitive and depressive disorders, as well as the value of targeted interventions and treatments.

The Econeurobiology of the brain describes the environment in which an individual's brain develops. This paper explores the complex neural mechanisms that support and evaluate enrichment at various stages of development, providing an overview of how they contribute to plasticity and enhancement of both achievement and health. It explores the deep benefits of enrichment and contrasts them with the negative effects of trauma and stress on brain development. In addition, the paper strongly emphasizes the integration of Gardner's intelligence types into the school curriculum environment. It emphasizes the importance of linking various intelligence traits to educational strategies to ensure a holistic approach to cognitive development. In the field of Econeurobiology, this work explains the central role of the environment in shaping the development of the brain. It examines brain connections and plasticity and reveals the impact of certain environmental factors on brain development in early and mid-childhood. In particular, the six key factors highlighted are an environment of support, nutrition, physical activity, music, sleep, and cognitive strategies, highlighting their potential to improve cognitive abilities, memory, learning, self-regulation, and social and emotional development. This paper also investigates the social determinants of health and education in the context of Econeurobiology. It emphasizes the transformative power of education in society, especially in vulnerable communities facing global challenges in accessing quality education.

Ischemic stroke is a leading cause of morbidity and mortality in older adults. Therefore, in this study, we sought to understand the interplay between the microbiota, gut, and brain in the context of stroke in older adults.

To determine whether gut microbiota from younger individuals promotes recovery through angiogenesis in both elderly stroke patients and aged stroke mice, we explored the changes in gut microbiota and the correlation between short-chain fatty acids (SCFAs) and angiogenesis in the aged stroke population. Then, we altered the gut microbiome in aged mice by transplanting microbiota from younger donors before inducing experimental stroke to explore the mechanism by which gut microbiota-derived SCFAs promote angiogenesis.

Part I: We conducted a single-center, double-blind trial to compare gut microbiota diversity and SCFA levels in fecal samples from older stroke patients with those from younger stroke patients. Additionally, we measured levels of vascular endothelial growth factor (VEGF) and VEGFC levels in plasma to assess their correlation with SCFA levels. Part II: We performed fecal microbiota transplantation (FMT) 3 days before inducing ischemic stroke in aged male mice (16-18) via distal middle cerebral artery occlusion (dMCAO). The FMT was conducted using gut microbiomes from either young donors (2-3 months) or aged donors (16-18 months).

In older stroke patients, gut microbiota diversity was significantly reduced compared to that in younger stroke patients. Furthermore, levels of acetate, a bacterially derived SCFA, were lower and positively correlated with angiogenesis markers (VEGF and VEGF-C). In aged stroke mice, transplantation of young microbiota improved stroke outcomes by promoting angiogenesis, which was facilitated by lymphatic ingrowth into the cortex. This protective effect was linked to gut microbiota-derived acetate, which enhanced lymphangiogenesis by replenishing acetyl coenzyme A.

(a) Gut microbiota-derived acetate promotes angiogenesis post-stroke and (b) lymphatic ingrowth into the cerebral cortex was observed in post-dMCAO mice. These findings suggest that selectively promoting SCFA-producing bacteria, particularly acetate-producers, could be a promising therapeutic strategy to reduce functional impairments in older stroke subjects.

Previous studies have suggested that gut microbiota (GM) may be involved in the pathogenesis of epilepsy through the microbiota-gut-brain axis (MGBA). However, the causal relationship between GM and different epilepsy subtypes and whether circulating inflammatory proteins act as mediators to participate in epileptogenesis through the MGBA remain unclear. Therefore, it is necessary to identify specific GM associated with epilepsy and its subtypes and explore their underlying inflammatory mechanisms for risk prediction, personalized treatment, and prognostic monitoring of epilepsy.

We hypothesized the existence of a pathway GM-inflammatory proteins-epilepsy. We found genetic variants strongly associated with GM, circulating inflammatory proteins, epilepsy and its subtypes, including generalized and partial seizures, from large-scale genome-wide association studies (GWAS) summary data and used Multivariate Mendelian Randomization to explore the causal relationship between the three and whether circulating inflammatory proteins play a mediating role in the pathway from GM to epilepsy, with inverse variance weighted (IVW) method as the primary statistical method, supplemented by four methods: MR-Egger, weighted median estimator (WME), Weighted mode and Simple mode.

16 positive and three negative causal associations were found between the genetic liability of GM and epilepsy and its subtypes. There were nine positive and nine negative causal associations between inflammatory proteins and epilepsy and its subtypes. Furthermore, we found that C-X-C motif chemokine 11 (CXCL11) levels mediated the causal association between Genus Family XIII AD3011 group and epilepsy.

Our study highlights the possible causal role of specific GM and specific inflammatory proteins in the development of epilepsy and suggests that circulating inflammatory proteins may mediate epileptogenesis through the MGBA.

Alzheimer's disease (AD) is the most widespread and irreversible form of dementia and accounts for more than half of dementia cases. The most significant risk factors for AD are aging-related exacerbations, degradation of anatomical pathways, environmental variables and mitochondrial dysfunction. Finding a decisive therapeutic solution is a major current issue. Nuanced interactions between major neuropathological mechanisms in AD in patients and microbiome have recently gained rising attention. The presence of bacterial amyloid in the gut triggers the immune system, resulting in increased immune feedbacks and endogenous neuronal amyloid within the CNS. Also, early clinical research revealed that changing the microbiome with beneficial bacteria or probiotics could affect brain function in AD. New approaches focus on the possible neuroprotective action of disease-modifying medications in AD. In the present review, we discuss the impact of the gut microbiota on the brain and review emerging research that suggests a disruption in the microbiota-brain axis can affect AD by mediating neuroinflammation. Such novel methods could help the development of novel therapeutics for AD.