Major depression (MD) significantly impacts individual well-being and society. The vagus nerve plays a pivotal role in the gut-brain axis, facilitating bidirectional communication between these systems. Recent meta-analyses suggest potential antidepressant effects of probiotics, although their mechanisms remain unclear. This study aimed to assess the impact of a multi-species probiotic (OMNi-BiOTiC® STRESS Repair) on vagus nerve function in 43 MD patients and 43 healthy controls (HC). Participants received either probiotics or placebo twice daily. Serum and stool samples were collected at baseline, 7 days, 28 days, and 3 months. Vagus nerve (VN) function was evaluated using 24-hour electrocardiography (ECG) for heart rate variability (HRV), alongside stool microbiome analysis via 16S rRNA sequencing. After 3 months, MD patients receiving probiotics demonstrated significantly improved morning VN function compared to HC. MD participants who were in the probiotic group showed a significant increase in Christensellales, particularly Akkermansia muciniphila along with improved sleep parameters (use of sleep medication, sleep latency) as measured by the Pittsburgh Sleep Quality Inventory (PSI). This study highlights potential physiological benefits of probiotics in MD, potentially mediated through VN stimulation. Understanding these mechanisms could lead to novel therapeutic approaches for MD management.

Intracranial aneurysms (IAs) are a significant clinical concern, with detection rates increasing due to advances in imaging technologies. However, precise mechanisms underlying their pathophysiology remain incompletely understood. Recent evidence suggests a pivotal role of oral microbiota dysbiosis, particularly periodontal pathogens, in systemic inflammation that may contribute to IA development and rupture.

This review aims to critically evaluate the association between oral microbiota dysbiosis and the pathogenesis of IAs, with a focus on the molecular and immunological mechanisms by which oral pathogens influence vascular pathology.

We conducted a comprehensive analysis of the literature regarding the impact of oral microbial dysbiosis on IA pathophysiology, emphasizing the role of specific pathogenic species, such as Porphyromonas gingivalis. The review explores how these pathogens may mediate chronic inflammation through hematogenous spread, gut microbiome alterations, and neuroinflammatory processes, leading to vascular remodeling and cerebrovascular instability.

The findings suggest that oral microbial dysbiosis, particularly the presence of pathogenic bacteria, is implicated in the systemic inflammatory response that exacerbates the structural integrity of the cerebrovascular wall. Chronic inflammatory states induced by oral pathogens contribute to extracellular matrix degradation, impaired vascular remodeling, and an increased susceptibility to IA rupture.

The findings highlight the importance of maintaining oral microbiota homeostasis as a potential therapeutic target for preventing IAs. Interventions aimed at restoring oral microbial balance may represent a novel strategy for reducing the burden of IA formation and rupture, highlighting the need for an integrated approach to oral health and IAs prevention.

The gut is exposed to a wide range of proteins, including ingested proteins and those produced by the resident microbiota. While ingested prion-like proteins can propagate across species, their implications for disease development remain largely unknown. Here, we apply a multidisciplinary approach to examine the relationship between the biophysical properties of exogenous prion-like proteins and the phenotypic consequences of ingesting them. Through computational analysis of gut bacterial proteins, we identified an enrichment of prion-like sequences in Helicobacter pylori. Based on these findings, we rationally designed a set of synthetic prion-like sequences that form amyloid fibrils, interfere with amyloid-beta-peptide aggregation, and trigger prion propagation when introduced in the yeast Sup35 model. When C. elegans were fed bacteria expressing these prion-like proteins, they lost associative memory and exhibited increased lipid oxidation. These data suggest a link between memory impairment, the conformational state of aggregates, and oxidative stress. Overall, this work supports gut microbiota as a reservoir of exogenous prion-like sequences, especially H. pylori, and the gut as an entry point for molecules capable of triggering cognitive dysfunction.

The influence of the gut microbiome on the human brain, especially its associations with psychiatric disorders, has emerged as a focal area in contemporary neuroscience and psychiatry research. In this study, we employed a mediation Mendelian randomization approach to delve into the potential causal relationships between gut microbiota and psychiatric disorders, with a focus on the mediating role of brain structural changes. We harnessed genetic data from large - scale genome - wide association studies to analyze how 196 gut microbiota taxa affect ten psychiatric disorders via alterations in 3,143 brain structures. Our key findings revealed significant bidirectional causal relationships. In the gut microbiota - brain structure relationship, certain gut microbiota taxa, such as Bacteroides and Marvinbryantia, were associated with changes in brain activity and white matter integrity respectively. Conversely, brain structures like the right hippocampus and left superior cerebellar peduncle influenced gut microbiota composition. Regarding gut microbiota and psychiatric disorders, we identified numerous associations. For example, the genus Prevotellaceae was significantly associated with an increased risk of Autism Spectrum Disorder, while Ruminococcaceae UCG005 showed a protective effect. In Panic Disorder, Alistipes was positively associated, and for Schizophrenia, both protective (Barnesiella) and risk - associated (Phascolarctobacterium) genera were found. Moreover, through mediation analysis, we found that brain structures mediated the effects of gut microbiota on five psychiatric disorders, including bipolar disorder and anorexia nervosa. In these cases, the influence of gut microbiota on the disorders was fully transmitted through changes in brain structure. Overall, our research clarifies the role of the microbiota - gut - brain axis in mental health. It offers a new perspective on how intestinal microbes impact brain physiology and psychiatric pathology. These findings not only deepen our understanding of the biological interactions between the gut and brain but also suggest that targeted gut microbiota modifications could be novel therapeutic strategies for mental health disorders.

The management of dry eye disease remains a challenge due to its multifactorial nature and the involvement of chronic inflammation. Exploring the connection between gut health and eye inflammation is essential for developing more effective, holistic treatment strategies.

Dry eye disease is considered to have an inflammatory component. The gut microbiome plays an important role in the regulation of low-grade chronic inflammation in different parts of the body including the eye. Probiotics and prebiotics are recognised for their beneficial effects on gut health and have been previously reported to alleviate dry eye symptoms. This study aimed to further investigate the impact of these supplements on tear and blood serum inflammatory biomarkers.

In this double-masked, randomised trial (registration number ACTRN12624000444583), 41 dry eye participants received either the probiotic and prebiotic supplements (treatment group, n = 23), or their respective placebos (control group, n = 18), for a duration of four months. The participants were followed up at one month and four months, and again one month after treatment cessation. Tear levels of inflammatory markers matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase-1 (TIMP-1), and serum C-reactive protein levels were determined. The MMP-9:TIMP-1 ratio also was calculated.

No significant changes in MMP-9, TIMP-1, or C-reactive protein levels were observed in either group during treatment (p > 0.05). Post-treatment, MMP-9 levels rose in the treatment group (p < 0.05), and MMP-9:TIMP-1 ratios increased in both groups (p < 0.05).

No significant changes were found in the examined biomarkers in either group during the intervention. The apparent post-treatment rise in these markers requires further investigation, particularly in light of reported associations between MMP-9, inflammation, and ocular discomfort.

Despite explosive rise in allergies, little is known about early life gut microbiota effects on postnatal respiratory function. We hypothesized that Enterobacteriaceae-dominant gut microbiota from eczemic infants increases Type 2 inflammation and decreases lung function in transplanted mice, while Bacteroidaceae-dominant gut microbiota from non-eczemic infants is protective. Fecal microbiota transplants (FMT) from eczemic infants "Infant A" and non-eczemic infants "Infant B" were successfully transplanted into germ-free C57BL/6 mice, passing to offspring unchanged. Infant A and B, Adult C-human-derived (positive control), and Mouse (negative control) microbiotas all in C57BL/6 mice were tested for effects on airway function in nonallergic (phosphate-buffered saline [PBS]) and allergic (house dust mite [HDM]) conditions. Baseline lung mechanics in mice with human microbiotas (HUmicrobiota) were significantly impaired compared to Mouse microbiota controls (MOmicrobiota) with or without HDM; respiratory system resistance (Rrs) was increased (P < 0.05-P < 0.01), and respiratory system compliance (Crs) was decreased (P < 0.05-P < 0.01). HUMicrobiota mice showed a statistically significant impairment compared to MOmicrobiota mice in lung parameters Rrs, Ers, Rn, and G at baseline, and at multiple methacholine (MCh) doses with baseline removed. Impairment manifested as increased small airway resistance and tissue resistance. HDM significantly elevated IL-4, eosinophils, lung inflammation, and mucus cell metaplasia, and decreased macrophages and lung function (P < 0.05) in mice of all microbiotas, yet each HUmicrobiota produced distinct features. Infant B and Adult C mice had elevated basal levels of total IgE compared to MOmicrobiota and Infant A mice (P < 0.05). In HUmicrobiota mice given HDM, only Adult C had elevated IL-5 and IL-13 (P < 0.05), only Adult C and Infant B mice had elevated neutrophils (P < 0.05), and only Infant A had elevated lymphocytes (P < 0.01).

Fecal microbiota transplants (FMT) of three distinct human communities to germ-free mice exacerbated inflammation and decreased lung function in their offspring. Taxa formerly described to induce an allergic response (agonists) and pro-inflammatory taxa were abundant in HUmicrobiotas compared to MOmicrobiota controls, while taxa formerly described to reduce allergic responses (antagonists) and anti-inflammatory taxa were numerous in MOmicrobiotas and low in HUmicrobiotas. Thus, we largely rejected our hypotheses because data supported multiple pro-inflammatory allergy agonists functioning in a community-wide fashion to impair lung function in the absence of antagonistic anti-inflammatory taxa. Structure of HUmicrobiotas played a key role in determining varied allergic responses and resulting lung impairment, yet, strikingly, all mice with HUmicrobiotas had impaired lung function even in the absence of allergens. Using a comparative approach, we showed that composition of gut microbiota can alter innate/immune regulation in the gut-lung axis to increase baseline lung function responses and the risk of allergic sensitization.

Convergent data across species paint a compelling picture of the critical role of the gut and its resident microbiota in several brain functions and disorders. The chemicals mediating communication along these sophisticated highways of the brain-gut-microbiome (BGM) axis include both microbiota metabolites and classical neurotransmitters. Amongst the latter, GABA is fundamental to brain function, mediating most neuronal inhibition. Until recently, GABA's role and specific molecular targets in the periphery within the BGM axis had received limited attention. Yet, GABA is produced by neuronal and non-neuronal elements of the BGM, and recently, GABA-modulating bacteria have been identified as key players in GABAergic gut systems, indicating that GABA-mediated signalling is likely to transcend physiological boundaries and species. We review the available evidence to better understand how GABA facilitates the integration of molecularly and functionally disparate systems to bring about overall homeostasis and how GABA perturbations within the BGM axis can give rise to multi-system medical disorders, thereby magnifying the disease burden and the challenges for patient care. Analysis of transcriptomic databases revealed significant overlaps between GABAAR subunits expressed in the human brain and gut. However, in the gut, there are notable expression profiles for a select number of subunits that have received limited attention to date but could be functionally relevant for BGM axis homeostasis. GABAergic signalling, via different receptor subtypes, directly regulates BGM homeostasis by modulating the excitability of neurons within brain centres responsible for gastrointestinal (GI) function in a sex-dependent manner, potentially revealing mechanisms underlying the greater prevalence of GI disturbances in females. Apart from such top-down regulation of the BGM axis, a diverse group of cell types, including enteric neurons, glia, enteroendocrine cells, immune cells and bacteria, integrate peripheral GABA signals to influence brain functions and potentially contribute to brain disorders. We propose several priorities for this field, including the exploitation of available technologies to functionally dissect components of these GABA pathways within the BGM, with a focus on GI and brain-behaviour-disease. Furthermore, in silico ligand-receptor docking analyses using relevant bacterial metabolomic datasets, coupled with advances in knowledge of GABAAR 3D structures, could uncover new ligands with novel therapeutic potential. Finally, targeted design of dietary interventions is imperative to advancing their therapeutic potential to support GABA homeostasis across the BGM axis.

Chronic pain is a prevalent condition, impacting nearly one-fifth of the global population. Despite the availability of various clinical treatments, each comes with inherent limitations, and few offer a complete cure, resulting in a significant social and economic burden. Therefore, it is important to determine the pathogenesis and causes of chronic pain. Numerous studies have shown a close link between the intestinal microflora and chronic pain. The gut microbiota can exert their effects on chronic pain through both central and peripheral mechanisms and is able to communicate with the brain through its own components or metabolites. They also can regulate chronic pain by affecting pro- and anti-inflammatory cells. This review is aimed at reviewing the connection between gut flora and different types of chronic pain, including visceral pain, neuropathic pain, inflammatory pain, musculoskeletal pain, migraine, and chronic cancer pain; exploring the central and peripheral mechanisms of the influence of gut flora on chronic pain; and attempting to provide novel treatment options for chronic pain, that is, the gut microbiota can be regulated by probiotics, fecal microbial transplantation, and natural products to treat chronic pain. By examining the intricate relationship between gut flora and chronic pain, the review sought to pave the way for new treatment strategies that target the gut microbiota, offering hope for more effective pain management.

Tumor is one of the leading causes of death worldwide. The occurrence and development of tumors are related to multiple systems and factors such as the immune system, gut microbiota, and nervous system. The immune system plays a critical role in tumor development. Studies have also found that the gut microbiota can directly or indirectly affect tumorigenesis and tumor development. With increasing attention on the tumor microenvironment in recent years, the nervous system has emerged as a novel regulator of tumor development. Some tumor therapies based on the nervous system have also been tested in clinical trials. However, the nervous system can not only directly interact with tumor cells but also indirectly affect tumor development through the gut microbiota. The nervous system-mediated gut microbiota can regulate tumorigenesis, growth, invasion, and metastasis through the immune system. Here, we mainly explore the potential effects of the nervous system-gut microbiota-immune system axis on tumorigenesis and tumor development. The effects of the nervous system-gut microbiota-immune system axis on tumors involve the nervous system regulating immune cells through the gut microbiota, which can prevent tumor development. Meanwhile, the direct effects of the gut microbiota on tumors and the regulation of the immune system by the nervous system, which can affect tumor development, are also reviewed.

Early life adversity has been studied widely, but still understudied is the impact of positive early life experiences. Emerging evidence suggests that humanity's millions-year-old evolved developmental niche (EDN) supports healthy biopsychosocial development. The EDN includes positive touch, responsive relationships, a welcoming social climate, social embeddedness, and self-directed free play. We examined the relation between EDN components and cardiac vagal regulation, the online biomarker for psychopathology, health, and a correlate of positive parenting behaviors. Women (N = 78; 84% white/Euro-American) self-reported their childhood EDN history, and their respiratory sinus arrhythmia (RSA) was assessed across non-stimulating and stressful conditions, providing indexes of both cardiac vagal tone and cardiac vagal flexibility. Three latent growth curve models demonstrated that childhood history of social embeddedness and positive home climate outperformed the other EDN components. A higher positive home climate predicted higher cardiac vagal tone, whereas greater social embeddedness predicted vagal flexibility, buffering against stress and supporting faster rates of recovery from stress. EDN-consistent childhoods, specifically experiencing a positive home climate and social embeddedness, may promote overall cardiac vagal tone and vagal flexibility in women years later. Ecological contexts that support EDN provision may support physiological adaptations that protect against stress and promote stress resilience in adulthood.

Alzheimer's disease (AD) is a major devastating neurodegenerative disorder afflicting majorly the geriatric population. Emerging studies augur the connection of gut dysbiosis and circadian disruption with the early onset of AD. Gut dysbiosis is characterized by dysregulated gut microbiota signature and compromised intestinal integrity, which provokes the translocation of bacterial metabolites into the systemic circulation. Noteworthy, gut-derived metabolites like calprotectin, trimethylamine-N-oxide, kynurenine, isoamylamine, and short-chain fatty acids play a key role in AD pathogenesis. Circadian dysregulation also corresponds with the exacerbated AD pathogenesis by accumulating Aβ and tau proteins. Moreover, circadian dysregulation is one of the causative factors for gut dysbiosis. This review discusses the complex interplay between the microbiota-gut-brain axis, circadian rhythmicity, and the emergence of AD. We reviewed preclinical and clinical studies on AD describing potential biomarkers of gut dysbiosis and circadian dysregulation. The identification of new biomarkers associated with the microbiota-gut-brain axis and circadian rhythmicity may help in early diagnosis and development of targeted therapies for mitigating neurodegenerative AD.

Crohn's disease (CD) and ulcerative colitis (UC) are the two major entities of inflammatory bowel disease (IBD). These disorders are known for their relapsing disease course and severe gastrointestinal symptoms including pain, diarrhoea and bloody stool. Accumulating evidence suggests that IBD is not only restricted to the gastrointestinal tract and that disease processes are able to reach distant organs including the brain. In fact, up to 35 % of IBD patients also suffer from neuropsychiatric disorders such as generalized anxiety disorder and major depressive disorder. Emerging research in this area indicates that in many cases these neuropsychiatric disorders are a secondary condition as a consequence of the disturbed communication between the gut and the brain via the microbiota-gut-brain axis. In this review, we summarise the current knowledge on IBD-associated neuropsychiatric disorders. We examine the role of different pathways of the microbiota-gut-brain axis in the development of CNS disorders highlighting altered neural, immunological, humoral and microbial communication. Finally, we discuss emerging therapies targeting the microbiota-gut-brain axis to alleviate IBD and neuropsychiatric symptoms including faecal microbiota transplantation, psychobiotics, microbial metabolites and vagus nerve stimulation.

Pediatric asthma, a prevalent chronic disease with rising global incidence, imposing substantial healthcare and socioeconomic burdens. Emerging evidence highlights the gut-lung axis as a pivotal therapeutic target, with microbiota dysbiosis implicated in immune dysregulation and airway hyperresponsiveness. This systematic review evaluated the efficacy and safety of probiotics, prebiotics, synbiotics, and postbiotics in pediatric asthma management.

A comprehensive search of PubMed, Cochrane library, Web of Science, and Embase was conducted up to 2nd January 2025. Inclusion criteria encompassed randomized controlled trials (RCTs) evaluating the therapeutic use of probiotics, prebiotics, synbiotics, or postbiotics in children and/or adolescents (<18 years) with asthma.

Eighteen studies (13 RCTs, n = 2,419 participants) were analyzed, focusing on children aged < 18 years. Probiotic interventions, predominantly Lactobacillus (5 studies) and Bifidobacterium (5 studies), demonstrated significant reductions in asthma exacerbations and improved pulmonary function, with strain-specific effects linked to Th2 cytokine suppression and gut-lung axis modulation. Postbiotics, including bacterial lysates (OM-85 BV, PMBL®), attenuated airway hyperresponsiveness and systemic inflammation. Synbiotics reduced viral respiratory infections and healthcare utilization. However, there is still a lack of direct RCTs to explore the therapeutic effects of prebiotics on pediatric asthma. Key limitations include methodological heterogeneity (dosing: 108-1010 CFU/day; duration: 8 weeks-12 months) and risk of bias (3 low-risk, 12 with concerns).

Our findings underscored the potential of microbiota-targeted therapies but highlight the need for standardized protocols, strain-specific trials, and pediatric prebiotic research. Future studies should integrate multi-omics to elucidate mechanisms and optimize personalized interventions.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42025641318, identifier: CRD42025641318.

The development of nucleic acid and protein drugs for oral delivery has lagged behind their production for conventional nonoral routes. Over the past decade, the evolution of DNA- and RNA-based technologies combined with the innovation of state-of-the-art delivery vehicles for nucleic acids has brought rapid advancements to the biopharmaceutical field. Nucleic acid therapies have the potential to achieve long-lasting effects, or even cures, by inhibiting or editing genes, which is not possible with conventional small-molecule drugs. However, challenges and limitations must be addressed before these therapies can provide cures for chronic conditions and rare diseases, rather than only offering temporary relief. Nucleic acids and proteins face premature degradation in the acidic, enzyme-rich stomach environment and are rapidly cleared by the liver. To overcome these challenges, various delivery vehicles have been developed to transport therapeutic compounds to the intestines, where the active compounds are released and gut microbiota and mucosal immune system also play an important role. This review provides a comprehensive overview of the promises and pitfalls associated with the oral route of administration of biologics, current delivery systems, applications of orally delivered therapeutics, and the challenges and considerations for translation of nucleic acid and protein therapeutics into clinical practice.

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.

Recent studies have highlighted the potential influence of gut dysbiosis on traumatic brain injury (TBI) outcomes. Alterations in the abundance and diversity of Lactobacillus species may affect immune dysregulation, neuroinflammatory responses, anxiety- and depressive-like behaviors, and neuroprotective mechanisms activated in response to TBI.

This study aims to evaluate the protective and preventive effects of Pan-probiotic (PP) treatment on the inflammatory response during both the acute and chronic phases of TBI.

Males and female mice underwent controlled cortical impact (CCI) injury or sham. They received a PP mixture in drinking water containing strains of Lactobacillus plantarum, L. reuteri, L. helveticas, L. fermentum, L. rhamnosus, L. gasseri, and L. casei. In the acute group, mice received PP or vehicle (VH) treatment for 7 weeks before TBI, continuing until 3 days post-injury (dpi). In the chronic group, treatment began 2 weeks before TBI and was extended through 35 dpi. The taxonomic microbiome profiles of fecal samples were evaluated using 16S rRNA V1-V3 sequencing analysis, and Short-chain fatty acids (SCFAs) were measured. Immunohistochemical, in situ hybridization, and histological analyses were performed to assess neuroinflammation post-TBI, while behavioral assessments were conducted to evaluate sensorimotor and cognitive functions.

Our findings suggest that a 7-week PP administration induces specific microbial changes, including increased abundance of beneficial bacteria such as Lactobacillaceae, Limosilactobacillus, and Lactiplantibacillus. PP treatment reduces lesion volume and cell death at 3 dpi, elevates SCFA levels at 35 dpi, and decreases microglial activation at both time points, particularly in males. Additionally, PP treatment improved motor recovery in males and alleviated depressive-like behaviors in females.

Our findings indicate that PP administration modulates microbiome composition, reduces neuroinflammation, and improves motor deficits following TBI, with these effects being particularly pronounced in male mice.

Billions of microorganisms inhabit the human gut and maintain overall health. Recent research has revealed the intricate interaction between the brain and gut microbiota through the microbiota-gut-brain axis (MGBA) and its effect on neurodegenerative disorders (NDDs). Alterations in the gut microbiota, known as gut dysbiosis, are linked to the development and progression of several NDDs. Studies suggest that the gut microbiota may be a viable target for improving cognitive health and reducing hallmarks of brain aging. Numerous pathways including hypothalamic-pituitary-adrenal axis stimulation, neurotransmitter release disruption, system-wide inflammation, and increased intestinal and blood-brain barrier permeability connect gut dysbiosis to neurological conditions. Metabolites produced by the gut microbiota influence neural processes that affect brain function. Clinical interventions depend on the capacity to understand the equilibrium between beneficial and detrimental gut microbiota, as it affects both neurodegeneration and neuroprotection. The importance of the gut microbiota and its metabolites during brain aging and the development of neurological disorders is summarized in this review. Moreover, we explored the possible therapeutic effects of the gut microbiota on age-related NDDs. Highlighting various pathways that connect the gut and the brain, this review identifies several important domains where gut microbiota-based interventions could offer possible solutions for age-related NDDs. Furthermore, prebiotics and probiotics are discussed as effective alternatives for mitigating indirect causes of gut dysbiosis. These therapeutic interventions are poised to play a significant role in improving dysbiosis and NDDs, paving the way for further research.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the abnormal accumulation of alpha-synuclein (α-Syn). Recent research emphasizes the significant role of the gut microbiota, the diverse community of microbes living in the intestines, in modulating α-Syn pathology. This review explores the bi-directional communication along the microbiota-gut-brain axis, highlighting the paradoxical impact of two gut microbiota metabolites-functional bacterial amyloids (FuBA) and vitamins-on neurodegenerative diseases, particularly PD. FuBA contributes to PD pathogenesis by promoting α-Syn aggregation, while vitamins offer neuroprotection through their anti-amyloidogenic, antioxidant, and anti-inflammatory properties. Understanding these processes could lead to precision clinical approaches and novel strategies for managing and preventing PD.

Lacticaseibacillus casei IDCC 3451 (3451) was evaluated for its effects on the gut-brain axis using Caenorhabditis elegans (C. elegans) and mouse models of stress and inflammation. In C. elegans, 3451 extended lifespans by 25 %, improved motility, and chemotaxis, enhanced survival under pathogen challenge, and reduced amyloid beta accumulation by 42 %. Transcriptomic profiling revealed upregulation of genes involved in neurotransmitter signaling and serine/threonine pathways. In the unpredictable chronic mild stress (UCMS) mouse model, 3451 administration increased the time spent in the center of the open field by 65 % and reduced immobility in the forced swim test by 32 %, indicating anxiolytic and antidepressant effects. Serum levels of aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) were decreased by 18 % and 24 %, respectively. Additionally, 3451 restored the expressions of 5HT1AR, GABAR, and tight junction proteins, including ZO-1 and Claudin1. Metabolomic analysis showed increased glycine and decreased palmitic acid levels, associated with an increased abundance of Ruminococcus and Akkermansia. In the dextran sulfate sodium (DSS)-induced colitis model, 3451 reduced the disease activity index by 36 %, improved colon histology, increased goblet cell preservation, and upregulated ZO-1 and IL-10 expression. Threonine levels were also increased and correlated with a higher abundance of Coprococcus. These findings demonstrate that 3451 improved behavioral and intestinal outcomes through coordinated modulation of host signaling, metabolite production, and gut microbial composition, highlighting its therapeutic potential for managing IBD and neurobehavioral disorders.

This narrative review presents the role of antioxidants in regulating the gut microbiota and the impact on the gut-brain axis, with a particular focus on neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). These diseases are characterised by cognitive decline, motor dysfunction, and neuroinflammation, all of which are significantly exacerbated by oxidative stress. This review elucidates the contribution of oxidative damage to disease progression and explores the potential of antioxidants to mitigate these pathological processes through modulation of the gut microbiota and associated pathways. Based on recent studies retrieved from reputable databases, including PubMed, Web of Science, and Scopus, this article outlines the mechanisms by which antioxidants influence gut health and exert neuroprotective effects. Specifically, it discusses how antioxidants, including polyphenols, vitamins, and flavonoids, contribute to the reduction in reactive oxygen species (ROS) production and neuroinflammation, thereby promoting neuronal survival and minimising oxidative damage in the brain. In addition, the article explores the role of antioxidants in modulating key molecular pathways involved in oxidative stress and neuroinflammation, such as the NF-κB, Nrf2, MAPK, and PI3K/AKT pathways, which regulate ROS generation, inflammatory cytokine expression, and antioxidant responses essential for maintaining cellular homeostasis in both the gut and the central nervous system. In addition, this review explores the complex relationship between gut-derived metabolites, oxidative stress, and neurodegenerative diseases, highlighting how dysbiosis-an imbalance in the gut microbiota-can exacerbate oxidative stress and contribute to neuroinflammation, thereby accelerating the progression of such diseases as AD and PD. The review also examines the role of short-chain fatty acids (SCFAs) produced by beneficial gut bacteria in modulating these pathways to attenuate neuroinflammation and oxidative damage. Furthermore, the article explores the therapeutic potential of microbiota-targeted interventions, including antioxidant delivery by probiotics and prebiotics, as innovative strategies to restore microbial homeostasis and support brain health. By synthesising current knowledge on the interplay between antioxidants, the gut-brain axis, and the molecular mechanisms underlying neurodegeneration, this review highlights the therapeutic promise of antioxidant-based interventions in mitigating oxidative stress and neurodegenerative disease progression. It also highlights the need for further research into antioxidant-rich dietary strategies and microbiota-focused therapies as promising avenues for the prevention and treatment of neurodegenerative diseases.

The gut-brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut-brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy.

The gut microbiome has emerged as a novel and intriguing focus in mood disorder research. Emerging evidence demonstrates the significant role of the gut microbiome in influencing mental health, suggesting a bidirectional communication between the gut and the brain. This review examines the latest findings on the gut-microbiota-brain axis and elucidates how alterations in gut microbiota composition can influence this axis, leading to changes in brain function and behavior. Although dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation have yielded encouraging results, significant advances are needed to establish next-generation approaches that precisely target the neurobiological mechanisms of mood disorders. Future research must focus on developing personalized treatments, facilitated by innovative therapies and technological progress, which account for individual variables such as age, sex, drug history, and lifestyle. Highlighting the potential therapeutic implications of targeting the gut microbiota, this review emphasizes the importance of integrating microbiota research into psychiatric studies to develop more effective and personalized treatment strategies for mood disorders.

PM2.5, recognized as a potential pathogenic factor for nervous system diseases, remains an area with many unknowns, particularly regarding its effects on human health. After five-month real-ambient PM2.5 exposure, we observed no significant pathological damage to the lung, liver, spleen, or kidney tissues. However, PM2.5 exposure led to neuronal degeneration in the hippocampal CA1 region of Brown Norway (BN) rats. The level of IL-6, IL-13, IL-1β, IL-12, IL-4, GRO/KC, MIP-1α, CM-CSF significantly increased in lung lavage fluid (P < 0.05 for all). Notably, we detected a slight impairment in spatial learning ability, as evidenced by the Barnes maze training outcomes. There were no significant changes in the bacterial community in lung lavage fluid (P = 0.621), but the bacterial community in the gut significantly changed (P < 0.001), with more species identified (P < 0.05). The metabolomic analysis revealed 147 and 149 significantly changed metabolites in the pulmonary system and serum, respectively (P < 0.05). PM2.5 exposure caused a decrease in Nervonic acid (NA) in both the lung and serum, which likely contributed to spatial learning impairment (P < 0.01). The correlation between lung metabolites, gut bacterial species, and serum metabolites indicated that PM2.5 exposure likely impaired spatial learning through the lung-gut-brain axis pathway. Lung and serum metabolic disorders and intestinal microbial imbalance occurred in BN rats post-five-month real-ambient PM2.5 exposure. There were two potential ways that PM2.5 exposure caused the decline of spatial learning ability in wild-type BN rats: (1) PM2.5 exposure led to a significant decrease of neuroprotective Nervonic acid in lung and serum metabolites. (2) PM2.5 exposure likely led to reduced spatial learning ability through the lung-gut-brain axis.

Alzheimer's disease (AD) is a cognitive disease with high morbidity and mortality. In AD patients, the diversity of the gut microbiota is altered, which influences pathology through the gut-brain axis. Probiotic therapy alleviates pathological and psychological consequences by restoring the diversity of the gut microbial flora. This study addresses the role of altered gut microbiota in the progression of neuroinflammation, which is a major hallmark of AD. This process begins with the activation of glial cells, leading to the release of proinflammatory cytokines and the modulation of cholinergic anti-inflammatory pathways. Short-chain fatty acids, which are bacterial metabolites, provide neuroprotective effects and maintain blood‒brain barrier integrity. Furthermore, the gut microbiota stimulates oxidative stress and mitochondrial dysfunction, which promote AD progression. The signaling pathways involved in gut dysbiosis-mediated neuroinflammation-mediated promotion of AD include cGAS-STING, C/EBPβ/AEP, RAGE, TLR4 Myd88, and the NLRP3 inflammasome. Preclinical studies have shown that natural extracts such as Ganmaidazao extract, isoorentin, camelia oil, Sparassis crispa-1, and xanthocerasides improve gut health and can delay the worsening of AD. Clinical studies using probiotics such as Bifidobacterium spp., yeast beta-glucan, and drugs such as sodium oligomannate and rifaximine have shown improvements in gut health, resulting in the amelioration of AD symptoms. This study incorporates the most current research on the pathophysiology of AD involving the gut microbiota and highlights the knowledge gaps that need to be filled to develop potent therapeutics against AD.

The association between constipation and suicidal ideation remains inadequately explored. This study aims to investigate the potential correlation between constipation and suicidal ideation in US adults, while assessing the mediating role of depression.For this cross-sectional study, a total of 13,493 adults aged 20 years and older were included from the National Health and Nutrition Examination Survey 2005-2010. The definition of constipation was defined by considering the consistency or frequency of stool. The ninth item on the Patient Health Questionnaire-9 (PHQ-9) evaluated suicidal ideation, and depression was evaluated using the PHQ-8 score. Adjusted odds ratios (ORs) were calculated using multivariate logistic regression models. Sensitivity analysis was performed to ensure stable results. Furthermore, study employed mediation analysis to examine the effect of constipation on suicidal ideation through depression. The bootstrapping method was used to assess the significance of the mediation effect. After controlling for demographic factors, risk behaviors, comorbidities, dietary intake, and relevant medications, constipation was associated with an increased risk of suicidal ideation (OR 1.41, 95%CI 1.08-1.83, P = 0.011). Sensitivity analyses showed the stability of the results. Moreover, mediation analysis demonstrated a significant direct effect of constipation on suicidal ideation (P = 0.016), with depression playing a partial mediating role in this interaction (40.81%, P < 0.0001). In conclusion, this study demonstrated a significant association between constipation and suicidal ideation, with depression serving as a partial mediator in this relationship. Further prospective longitudinal studies are essential to establish a definitive causal relationship between these factors so as to guide the development and implementation of targeted intervention strategies.

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with its progression intricately linked to gut microbiota dysbiosis. Disruptions in microbial homeostasis contribute to tumor initiation, immune suppression, and inflammation, establishing the microbiota as a key therapeutic target. Fecal microbiota transplantation (FMT) has emerged as a transformative approach to restore microbial balance, enhance immune responses, and reshape the tumor microenvironment. This review explores the mechanisms underlying FMT's therapeutic potential, evaluates its advantages over other microbiota-based interventions, and addresses challenges such as donor selection, safety concerns, and treatment standardization. Looking forward, the integration of FMT into personalized CRC therapies requires robust clinical trials and the identification of predictive biomarkers to optimize its efficacy and safety.

Microbiota encompasses a diverse array of microorganisms inhabiting specific ecological niches. Gut microbiota significantly influences physiological processes, including gastrointestinal motor function, neuroendocrine signalling, and immune regulation. They play a crucial role in modulating the central nervous system and bolstering body defence mechanisms by influencing the proliferation and differentiation of innate and adaptive immune cells. Given the potential consequences of antibiotic therapy on gut microbiota equilibrium, there is a need for prudent antibiotic use to mitigate associated risks. Observational studies have linked increased antibiotic usage to various pathogenic conditions, including obesity, inflammatory bowel disease, anxiety-like effects, asthma, and pulmonary carcinogenesis. Addressing dysbiosis incidence requires proactive measures, including prophylactic use of β-lactamase drugs (SYN-004, SYN-006, and SYN-007), hydrolysing the β-lactam in the proximal GIT for maintaining intestinal flora homeostasis. Prebiotic and probiotic supplementations are crucial in restoring intestinal flora equilibrium by competing with pathogenic bacteria for nutritional resources and adhesion sites, reducing luminal pH, neutralising toxins, and producing antimicrobial agents. Faecal microbiota transplantation (FMT) shows promise in restoring gut microbiota composition. Rational antibiotic use is essential to preserve microflora and improve patient compliance with antibiotic regimens by mitigating associated side effects. Given the significant implications on gut microbiota composition, concerted intervention strategies must be pursued to rectify and reverse the occurrence of antibiotic-induced dysbiosis. Here, antibiotics-induced microbiota dysbiosis mechanisms and their systemic implications are reviewed. Moreover, proposed interventions to mitigate the impact on gut microflora are also discussed herein.

The microbiota-gut-brain axis is a complex communication system that plays a crucial role in influencing various aspects of our physical and mental health. The goal of this study was to determine the extent to which individual differences in resting measures of vagally-mediated heart rate variability (HRV) and cortisol levels were associated with psychometric and specific gut microbiota characteristics in seventy-five (38 females) healthy individuals. Participants were assessed for vagally-mediated HRV, daily salivary cortisol levels, psychometric characteristics, and gut microbiota composition. Using a categorical approach based on the median split of HRV and cortisol values, we identified an association between low vagally-mediated HRV, greater depressive symptomatology, and altered gut microbiota (e.g., a higher abundance of Prevotella and a smaller abundance of Faecalibacterium, Alistipes, and Gemmiger). This suggests that vagally-mediated HRV may be a useful biomarker of microbiota-gut brain axis function, and that low vagally-mediated HRV may play an important role in the bidirectional link between gut dysbiosis and depression. On the other hand, daily cortisol parameters (e.g., cortisol awakening response, diurnal cortisol slope) were associated either with higher anxiety and perceived stress, or with a specific gut microbiota profile. Therefore, their utility as biomarkers of microbiota-gut-brain axis function needs further scrutiny.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that connects the central nervous system (CNS) and the gastrointestinal system. Our study aimed to explore the correlation between the intestinal microbiota and demyelinating diseases from a bibliometric perspective, focusing on research since 2014.

A comprehensive search was carried out on the Web of Science Core Collection (WoSCC) to locate studies on the intestinal microbiota and demyelinating diseases, with a focus on publications from 1 January 2014 to 29 March 2024. We visualized and analyzed the data using VOSviewer, CiteSpace, and Charticulator.

We gathered 429 scholarly articles on the intestinal microbiota and demyelinating disorders published in the past 10 years. Research concerning the intestinal microbiota and demyelinating diseases has demonstrated a consistent increase in frequency over time. The USA has the highest number of publications, while Canada has the highest average number of citations, reaching as high as 3,429, which is greater than that of the USA. Moreover, the journal with the highest number of publications was Frontiers in Immunology, with 33 publications and 1,494 citations. The majority of the scholars focused on "multiple sclerosis" and "gut microbiota," which are the primary keywords in the field of the intestinal microbiota and demyelinating diseases.

This study conducted a comprehensive analysis of existing research investigating the correlation between the intestinal microbiota and demyelinating diseases. Using advanced bibliometric tools such as VOSviewer and CiteSpace, this study analyzed the intricate relationship between the intestinal microbiota and the pathogenesis of demyelinating conditions. In addition, the study used literature statistical analysis to identify research hotspots and future directions in the field.

The search for biological markers that can be reliably linked to aggression and antisocial behavior has been central to the work of biological criminology. One such marker, uric acid, has long been suspected to play a causative role in promoting anger, irritability, aggression, and violence. Here, in this perspective article, we revisit some of the historical interest in uric acid as a compound relevant to brain and behavior, and reflect these early accounts off emergent scientific research. Advances in brain sciences, including neuropsychiatry and neuromicrobiology, have allowed for a more sophisticated understanding of potential mechanistic pathways linking uric acid with cognition and behavior. The updated science suggests that some of the early ideas surrounding uric acid and criminology had credibility. The available research strongly suggests that uric acid, as a potential biomarker of risk, is worthy of further research and close scrutiny. Informed by emergent gut-brain-microbiome research, we argue that certain aspects of early-to-mid-20th-century biological criminology were prematurely abandoned. From a legalome perspective, further advances surrounding uric acid and other gut-brain biomarkers can aid in shaping more humane, scientifically grounded policies that recognize the interplay between biology and environment.

The human gut flora of trillions of bacteria is vital for general health and greatly influences digestion, immune system function, and brain development. Through neuronal, hormonal, and immunological channels, the gut-brain axis (GBA), a bidirectional communication network, links the gut microbiota to the central nervous system (CNS). This relationship has been linked to affective diseases, including depression and anxiety, as well as mental health issues. This review explores the intricate relationship between gut bacteria and mood disorders, focusing on how gut microbiota-host interactions, immune system modulation, and neurotransmitter control support mental health. The function of important microbial metabolites, including short-chain fatty acids (SCFAs), in preserving blood-brain barrier integrity and modulating neuroinflammation is covered in this review. It also examines the bidirectional impact between gut health and mental health, including how dysbiosis could aggravate mood disorders and how depressed states might change the composition of gut bacteria. Furthermore, we discuss how psychotropic drugs affect gut flora and consider other elements such as nutrition and lifestyle that affect gut microbiome composition. Potential paths for treating mood disorders through gut microbiota modification are presented as emerging treatment techniques, including probiotics, nutritional therapies, and precision medicine. The development of new therapeutic approaches for mood disorders depends on the awareness of the GBA. Gut bacteria significantly affect mental health through immune modulation, neurotransmitter generation, and other intricate processes. Future studies should concentrate on large, varied populations to better understand these interactions and to create customized treatments that combine gut microbiota modulation with conventional mental health therapies.

Microglia, the brain's resident macrophages, are key mediators of neuroinflammation, responding to immune pathogens and toxins. They play a crucial role in clearing cellular debris, regulating synaptic plasticity, and phagocytosing amyloid-β (Aβ) plaques in Alzheimer's disease (AD). Recent studies indicate that microglia not only exhibit intrinsic circadian rhythms but are also regulated by circadian clock genes, influencing specific functions such as phagocytosis and the modulation of neuroinflammation. Disruption of the circadian rhythm is closely associated with AD pathology. In this review, we will provide an overview of how circadian rhythms regulate microglia-mediated neuroinflammation in the progression of AD, focusing on the pathway from the central nervous system (CNS) and the peripheral immune system. We also discuss potential therapeutic targets, including hormone modulation, lifestyle interventions, and anti-inflammatory therapies, aimed at maintaining brain health in AD. This will shed light on the involvement of circadian rhythm in AD and explore new avenues for AD treatment.

The gut microbiota, the complex community of microorganisms that inhabit the gastrointestinal tract, has emerged as a key player in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD). AD is characterized by progressive cognitive decline and neuronal loss, associated with the accumulation of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation in the brain. Increasing evidence suggests that alterations in the composition and function of the gut microbiota, known as dysbiosis, may contribute to the development and progression of AD by modulating neuroinflammation, a chronic and maladaptive immune response in the central nervous system. This review aims to comprehensively analyze the current role of the gut microbiota in regulating neuroinflammation and glial cell function in AD. Its objective is to deepen our understanding of the pathogenesis of AD and to discuss the potential advantages and challenges of using gut microbiota modulation as a novel approach for the diagnosis, treatment, and prevention of AD.

Huntington's disease (HD) is a currently incurable neurogenerative disorder and is typically characterized by progressive movement disorder (including chorea), cognitive deficits (culminating in dementia), psychiatric abnormalities (the most common of which is depression), and peripheral symptoms (including gastrointestinal dysfunction). There are currently no approved disease-modifying therapies available for HD, with death usually occurring approximately 10-25 years after onset, but some therapies hold promising potential. HD subjects are often burdened by chronic diarrhea, constipation, esophageal and gastric inflammation, and a susceptibility to diabetes. Our understanding of the microbiota-gut-brain axis in HD is in its infancy and growing evidence from preclinical and clinical studies suggests a role of gut microbial population imbalance (gut dysbiosis) in HD pathophysiology. The gut and the brain can communicate through the enteric nervous system, immune system, vagus nerve, and microbiota-derived-metabolites including short-chain fatty acids, bile acids, and branched-chain amino acids. This review summarizes supporting evidence demonstrating the alterations in bacterial and fungal composition that may be associated with HD. We focus on mechanisms through which gut dysbiosis may compromise brain and gut health, thus triggering neuroinflammatory responses, and further highlight outcomes of attempts to modulate the gut microbiota as promising therapeutic strategies for HD. Ultimately, we discuss the dearth of data and the need for more longitudinal and translational studies in this nascent field. We suggest future directions to improve our understanding of the association between gut microbes and the pathogenesis of HD, and other 'brain and body disorders'.

Background: The human gastrointestinal tract is home to a wide variety of microorganisms. For some decades now, bacteria known as probiotics have been added to various foods because of their beneficial effects for human health. Evidence indicates that probiotics significantly regulate gut microbiota, which is vital for digestion, metabolism, immune function, and mental health. Methods: We conducted a narrative review of available original research published in PubMed for the past ten years focusing on recent advancements that provide a thorough understanding of the relationship between the gastrointestinal system and the brain. Results: Recent advances in research have focused on the importance of gut microbiota in influencing mental health. The microbiota-gut-brain axis is a complex, bidirectional communication network linking the central nervous system and the gastrointestinal tract, which highlights how the gut and brain are deeply interconnected and influence each other in ways that affect our overall health, emotions, and behavior. This powerful link is a major area of research as scientists discover more about how gut health can impact mental well-being. Conclusions: A comprehensive understanding of microbiota composition and mechanisms involved in these interactions between the gut and the brain could shape future medical and therapeutic approaches. It would balance scientific explanation with clinical relevance, offering insights into how understanding the brain-gut axis can revolutionize our approach to treating mental health and gastrointestinal disorders.

Recent studies have focused on improving our understanding of gut microbiome dysbiosis and its impact on cognitive function. However, the relationship between gut microbiome composition, accelerated brain atrophy, and cognitive function has not yet been fully explored.

We recruited 292 participants from South Korean memory clinics to undergo brain magnetic resonance imaging, clinical assessments, and collected stool samples. We employed a pretrained brain age model- a measure associated with neurodegeneration. Using cluster analysis, we categorized individuals based on their microbiome profiles and examined the correlations with brain age, Mental State Examination (MMSE) scores, and the Clinical Dementia Rating Sum of Box (CDR-SB).

Two clusters were identified in the microbiota at the phylum level that showed significant differences on a few microbiotas phylum. Greater gut microbiome dysbiosis was associated with worse cognitive function including MMSE and CDR-SB; this effect was partially mediated by greater brain age even when accounting for chronological age, sex, and education.

Our findings indicate that brain age mediates the link between gut microbiome dysbiosis and cognitive performance. These insights suggest potential interventions targeting the gut microbiome to alleviate age-related cognitive decline.

Tumors of the central nervous system (CNS), especially gliomas, pose a significant clinical challenge due to their aggressive nature and limited therapeutic options. Emerging research highlights the critical role of the gut microbiota in regulating CNS health and disease. The composition of the gut microbiota is essential for maintaining CNS homeostasis, as it modulates immune responses, oxidative status, and neuroinflammation. The microbiota-gut-brain axis, a bidirectional communication network, plays a pivotal role in cancer and CNS disease treatment, exerting its influence through neural, endocrine, immunological, and metabolic pathways. Recent studies suggest that the gut microbiota influences the solidification of the tumor microenvironment and that dysbiosis may promote glioma development by modulating systemic inflammation and oxidative stress, which contributes to tumorigenesis and CNS tumor progression. This review interrogates the impact of the gut microbiota on glioma, focusing on critical pathways such as NF-κB, MAPK, PI3K/Akt/mTOR, and Kynurenine/AhR that drive tumor proliferation, immune evasion, and therapy resistance. Furthermore, we explore emerging therapeutic strategies, including probiotics and microbiota-based interventions, which show potential in modulating these pathways and enhancing immunotherapies such as checkpoint inhibitors. By focusing on the multifaceted interactions between the gut microbiota, oxidative stress, and CNS tumors, this review highlights the potential of microbiota-targeted therapies and their manipulation to complement and enhance current treatments.