Search Results (1,006)

Tauroursodeoxycholic acid (TUDCA), a bile acid conjugate, has been suggested to improve cognition in models of Alzheimer’s disease (AD), although its underlying mechanisms remain unclear. This study aimed to evaluate the effects of TUDCA and its potential pathways in APP/PS1 mice. Behavioral tests, assessments of amyloid-β (Aβ) deposition, neuroinflammation, peripheral inflammatory responses, intestinal barrier integrity, and gut microbiota composition were performed, along with pseudo-sterile mouse experiments and fecal microbiota transplantation (FMT). The expression of genes related to the TLR4/NF-κB/NLRP3 pathway was also examined. TUDCA significantly ameliorated cognitive impairments, reduced Aβ accumulation, and suppressed inflammatory responses in both the central nervous system and peripheral tissues. It improved intestinal barrier function and reshaped gut microbial composition by reducing pro-inflammatory taxa. FMT demonstrated that TUDCA-modulated microbiota contributed to improved learning and memory in AD mice, whereas antibiotic-induced pseudo-sterility indicated that TUDCA also exerted cognitive benefits independent of gut flora. Moreover, TUDCA inhibited the activation of the TLR4/NF-κB/NLRP3 pathway. In conclusion, TUDCA alleviates AD-related cognitive deficits partly through modulation of the microbiota–gut–brain axis while also acting via microbiota-independent mechanisms, supporting its potential as a promising therapeutic strategy for AD. Full article

Parkinson’s disease (PD), the second most common neurodegenerative disorder globally, relies primarily on dopamine replacement therapy for conventional treatment. This approach fails to reverse core pathological processes and is associated with long-term side effects. Recent research on the microbiota-gut-brain axis (MGBA) has revealed that PD pathology may originate in the gut, forming a vicious cycle from the gut to brain through α-synuclein propagation, gut dysbiosis, intestinal barrier disruption, and neuroinflammation. This offers a novel perspective for managing PD through dietary interventions that modulate the gut microbiome. However, single probiotic or prebiotic interventions show limited efficacy. This review systematically introduces the novel concept of “synbiotics combining medicinal plant polysaccharides with probiotics,” aiming to integrate traditional “medicinal food” wisdom with modern microbiome science. The article systematically elucidates the pathological mechanisms of MGBA dysfunction in PD and the intervention mechanisms of probiotics and emphasizes the structural and functional advantages of medicinal plant polysaccharide as superior prebiotics. The core section delves into the multifaceted synergistic mechanisms between these two components: enhancing probiotic colonization and vitality, optimizing microbial metabolic output, synergistically reinforcing the intestinal and blood-brain barriers, and jointly regulating immune and neuroinflammation. This approach targets the MGBA to achieve multi-level intervention for PD. Full article

The gut microbiota has emerged as a central regulator of the gut–brain axis, profoundly influencing neural, immune, and metabolic homeostasis. Increasing evidence indicates that disturbances in microbial composition and function contribute to the onset and progression of neurodegenerative diseases (NDs) through mechanisms involving neuroinflammation, oxidative stress, and impaired neurotransmission. Gut dysbiosis is characterized by a loss of microbial diversity, a reduction in beneficial commensals, and an enrichment of pro-inflammatory taxa. These shifts alter intestinal permeability and systemic immune tone, allowing microbial metabolites and immune mediators to affect central nervous system (CNS) integrity. Metabolites such as short-chain fatty acids (SCFAs), tryptophan derivatives, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO) modulate blood–brain barrier (BBB) function, microglial activation, and neurotransmitter synthesis, linking intestinal imbalance to neuronal dysfunction and cognitive decline. Disruption of this gut–brain communication network promotes chronic inflammation and metabolic dysregulation, key features of neurodegenerative pathology. SCFA-producing and tryptophan-metabolizing bacteria appear to exert neuroprotective effects by modulating immune responses, epigenetic regulation, and neuronal resilience. The aim of this work was to comprehensively explore the current evidence on the bidirectional communication between the gut microbiota and the CNS, with a focus on identifying the principal molecular, immune, and metabolic mechanisms supported by the strongest and most consistent data. By integrating findings from recent human studies, this review sought to clarify how microbial composition and function influence neurochemical balance, immune activation, and BBB integrity, ultimately contributing to the onset and progression of neurodegenerative processes. Collectively, these findings position the gut microbiota as a dynamic interface between the enteric and CNS, capable of influencing neurodegenerative processes through immune and metabolic signaling. Full article

Down Syndrome Regression Disorder (DSRD) is a rare but severe neuropsychiatric condition characterized by abrupt loss of speech, autonomy, and cognitive abilities in individuals with Down syndrome, often associated with immune dysregulation and gut–brain axis dysfunction. We report the case of an 11-year-old girl with Down syndrome who developed developmental regression at age five, in temporal proximity to a family transition (the birth of a younger sibling), with loss of continence, language, and comprehension, alongside persistent behavioral agitation and gastrointestinal symptoms. Laboratory assessment revealed Giardia duodenalis infection, elevated fecal calprotectin and secretory IgA, and microbial imbalance with overgrowth of Streptococcus anginosus and S. sobrinus. The patient received a single oral dose of tinidazole (2 g), daily folinic acid (1 mg/kg), and a 90-day course of transcranial and abdominal photobiomodulation (PBM) (1064 nm, 10 min per site). Post-treatment, stool analysis showed normalized inflammation markers and restoration of beneficial bacterial genera (Bacteroides, Bifidobacterium, Lactobacillus) with absence of Enterococcus growth. Behaviorally, she exhibited marked recovery: CARS-2-QPC decreased from 106 to 91, ABC from 63 to 31, and ATEC from 62 to 57, alongside regained continence, speech, and fine-motor coordination. These outcomes suggest that abdominal and transcranial PBM, by modulating mitochondrial metabolism, mucosal immunity, and microbiota composition, may facilitate systemic and neurobehavioral recovery in DSRD. This translational case supports further investigation of PBM as a non-invasive, multimodal therapy for neuroimmune regression in genetic and developmental disorders including validation through future randomized controlled clinical trials. Full article

Background: Alzheimer’s disease (AD), a progressive brain disorder, is the most common form of dementia and necessitates the development of effective intervention strategies. Ginseng-Natto composite fermentation products (GN) have demonstrated beneficial bioactivities in mouse models of AD; however, the underlying mechanism of action through which GN ameliorates AD requires further elucidation. Methods: Mice received daily intragastric administration of low- or high-dose GN for 4 weeks, followed by intraperitoneal injection of scopolamine to induce the AD model. The pharmacological effects of GN were systematically evaluated using the Morris water maze test, ELISA, and H&E staining. To further investigate the underlying mechanisms, 16S rRNA gene sequencing and metabolomics were employed to analyze the regulatory effects of GN on the gut–brain axis. Additionally, Western blotting was performed to assess the impact of GN on blood–brain barrier (BBB) integrity. Results: GN intervention significantly ameliorated cognitive deficits and attenuated neuropathological injury in AD mice, restoring the brain levels of acetylcholine (ACh), acetylcholinesterase (AChE), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) to normal ranges. GN reshaped the gut microbiota by promoting beneficial bacteria and inhibiting pro-inflammatory strains. It also regulated key metabolic pathways related to amino acid and unsaturated fatty acid metabolism. This metabolic remodeling restored the compromised BBB integrity by upregulating tight junction proteins (ZO-1, Occludin and Claudin-1). Conclusions: Our findings demonstrate that GN ameliorates AD through a gut-to-brain pathway, mediated by reshaping the microbiota-metabolite axis and repairing the BBB. Thus, GN may represent a promising intervention candidate for AD. Full article

Background: Growing evidence indicates that oral microbiome dysbiosis contributes to systemic inflammation, immune activation, and neural dysfunction. These processes may influence the onset and progression of major neuropsychiatric and neurodegenerative disorders. This review integrates clinical, epidemiological, and mechanistic findings linking periodontal pathogens and oral microbial imbalance to Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, and anxiety. Methods: A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar to identify recent studies examining alterations in the oral microbiota, microbial translocation, systemic inflammatory responses, blood–brain barrier disruption, cytokine signaling, and neural pathways implicated in brain disorders. Results: Evidence from human and experimental models demonstrates that oral pathogens, particularly Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, can disseminate systemically, alter immune tone, and affect neural tissues. Their virulence factors promote microglial activation, cytokine release (IL-1β, IL-6, TNF-α), amyloid-β aggregation, and α-synuclein misfolding. Epidemiological studies show associations between oral dysbiosis and cognitive impairment, motor symptoms in PD, and alterations in mood-related taxa linked to stress hormone profiles. Immunometabolic pathways, HPA-axis activation, and the oral–gut–brain axis further integrate these findings into a shared neuroinflammatory framework. Conclusions: Oral dysbiosis emerges as a modifiable contributor to neuroinflammation and brain health. Periodontal therapy, probiotics, prebiotics, synbiotics, and targeted inhibitors of bacterial virulence factors represent promising strategies to reduce systemic and neural inflammation. Longitudinal human studies and standardized microbiome methodologies are still needed to clarify causality and evaluate whether restoring oral microbial balance can modify the course of neuropsychiatric and neurodegenerative disorders. Full article

Alzheimer’s disease (AD) represents an increasingly severe global health challenge. Recently, the role of the gut–brain axis in AD pathogenesis has garnered significant attention. Dysbiosis of the gut microbiota can exacerbate core pathologies such as neuroinflammation, amyloid beta (Aβ) deposition, and tau hyperphosphorylation through neural, endocrine, and immune pathways. Polyphenolic compounds have emerged as a focal point in neuroprotective research owing to their pronounced anti-inflammatory and antioxidant properties. Notably, polyphenols exert effects not only by directly influencing the central nervous system (CNS) but also through indirectly modulating the composition and function of the gut microbiota, thereby impacting bidirectional gut–brain communication. This dual mechanism offers a potential avenue for their application in the prevention and treatment of AD. This review aims to compile recent research on the relationship between polyphenols and the gut microbiota. We assessed the literature from PubMed, Google Scholar, and Web of Science databases, published from the establishment of the database to 24 November 2025. The keywords used include “Polyphenols”, “Gut–brain axis”, “Gut microbiota”, “Alzheimer’s disease”, “Epigallocatechin gallate”, “Quercetin”, “Curcumin”, “Ferulic acid”, “Resveratrol”, “Anthocyanin”, “Myricetin”, “Chlorogenic acid”, etc. This review discusses the various mechanisms by which polyphenols influence AD through modulating the gut microbiota. Polyphenols and gut microbiota exhibit critical bidirectional interactions. On one hand, the bioavailability and activity of polyphenols are highly dependent on metabolic conversion by gut microbiota. On the other hand, polyphenols selectively promote the proliferation of beneficial bacteria such as bifidobacteria and lactobacilli like prebiotics, while inhibiting the growth of pathogenic bacteria. This reshapes the intestinal microecology, enhances barrier function, and regulates beneficial metabolites. Utilizing a nanotechnology-based drug delivery system, the pharmacokinetic stability and brain targeting efficacy of polyphenols can be significantly enhanced, providing innovative opportunities for the targeted prevention and management of AD. Full article

Background: Unhealthy diets characterized by high salt, fat, and fructose content are established risk factors for metabolic and cardiovascular disorders and may have indirect effects on cognitive function. However, the combined impact of a high-salt, high-fat, and high-fructose diet (HSHFHFD) on systemic physiology and brain health remains to be fully elucidated. Methods: Sprague-Dawley (SD) rats received a customized high-salt, high-fat diet supplemented with 30% fructose water for 18 weeks. Physiological and brain parameters were assessed, in combination with multi-omics analyses including brain proteomics and metabolomics, serum metabolomics, and gut microbiota profiling. Results: HSHFHFD significantly elevated blood glucose, blood pressure, and serum levels of TG, TC, and LDL in rats. Serum metabolomic profiling identified over 100 differentially abundant metabolites in the Model group. Proteomics, metabolomics, and gut microbiome integration revealed pronounced alterations in both brain proteomic and metabolomic profiles, with 155 differentially expressed proteins associated with glial cell proliferation and 65 differential metabolites linked to fatty acid and amino acid metabolism, among others. Experimental validation confirmed marked upregulation of GFAP and Bax protein, concomitant with downregulation of ZO-1 and occludin. Furthermore, HSHFHFD perturbed the CREB signaling pathway, leading to diminished BDNF expression. The levels of inflammatory factors, including IL-6, IL-10, IL-1β and TNFα, were significantly elevated in the brain. Oxidative stress was evident, as indicated by elevated malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) activity, and altered NAD⁺/NADH ratio. Additionally, HSHFHFD significantly reduced the abundance of beneficial gut bacteria, including Lactobacillus, Romboutsia, and Monoglobus. Conclusions: HSHFHFD-induced depletion of gut Lactobacillus spp. may disrupt the linoleic acid metabolic pathway and gut–brain axis homeostasis, leading to the impairment of neuroprotective function, blood–brain barrier dysfunction, and exacerbated neuroinflammation and oxidative stress in the brain. These effects potentially increase the susceptibility of rats to neurodegenerative disorders. Full article

Rheumatoid arthritis (RA) is frequently accompanied by depression, a comorbidity arising from the interplay of chronic systemic inflammation, neuroimmune activation, oxidative stress, and dysregulation of the gut–brain axis. Increasing evidence suggests that nanomedicine offers unique opportunities for the integrated management of RA-associated depression by enabling precise modulation of both peripheral inflammation and central nervous system (CNS) pathology. This review outlines the biological mechanisms linking RA and depression—including cytokine cascades, mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and microbial metabolite imbalance—and highlights recent progress in nanocarrier platforms capable of dual-site intervention. Liposomes, polymeric nanoparticles (NPs), exosomes, inorganic nanozymes, and emerging carbon-based nanomaterials have demonstrated the ability to target inflamed synovium, reprogram macrophage phenotypes, traverse the blood–brain barrier (BBB), suppress microglial overactivation, enhance neuroplasticity, and restore gut microbial homeostasis. Furthermore, stimulus-responsive nanoplatforms activated by ROS, pH, enzymes, or hypoxia provide spatiotemporally controlled drug release, thereby improving therapeutic precision. Finally, we discuss integrative designs such as dual-targeting nanomedicines, co-delivery systems, and microbiota-modulating nano-interventions, which offer promising strategies for the comprehensive treatment of RA-associated depression. This review aims to provide mechanistic insights and design principles to guide the development of next-generation nanomedicine for coordinated systemic-central modulation in RA comorbidity. Full article

During the last ten years, the scientific community has increasingly acquired greater knowledge of the importance of oral microbiota, in general, for the physical condition of humans. Not only oral diseases, related to oral dysbiosis, are examined, but also several systemic inflammatory degenerative diseases induced by this condition. This narrative review aims to shed light on the communication mechanisms between the oral cavity and different mucosal compartments, and to explain how the changes in microorganisms may alter their balance, leading to disease. Many potential pathogenic bacteria can induce oral dysbiosis, among them Porphyromonas gingivalis and Fusobacterium nucleatum are the most explored; however, other bacterial species such as Tannerella forsythia, Treponema denticola, Aggregatibacter actinomycetemcomitans and Filifactor alocis are able to give rise to local and systemic diseases through the release of toxins. The two-way communication system between the gastrointestinal tract and the central nervous system, known as the gut–brain axis, is strongly influenced by the gut microbiota and can ultimately be studied even more broadly and in depth if we consider the influence of the oral microbiota on this axis. Taste receptors’ activity also has a significant role, being able to affect a subject’s food choice by interacting with the microbiota. Qualitative and quantitative alterations in microorganisms existing in the main mucosal compartments may easily lead the host to develop systemic degenerative inflammatory diseases. Full article

As one of the few carotenoid-producing microorganisms, Rhodotorula mucilaginosa remains underexplored for its antioxidant activity. This study investigated the effects of R. mucilaginosa JAASSRY on D-galactose-induced aging mice. The high-dose JAASSRY (HR) significantly increased body weight by 9.89% compared to the model group (AM), while reducing organ indices of the spleen, liver, kidneys, and brain (p < 0.01). Compared with the AM group, the HR group exhibited increased serum activities of SOD (20.26%), GSH-Px (9.03%), and CAT (133.01%), with a 24.87% decrease in MDA level. In brain tissue, SOD, GSH-Px, and CAT activities increased by 79.49%, 8.45%, and 60.23%, respectively, while MDA decreased by 8.29%. R. mucilaginosa JAASSRY also dose-dependently alleviated structural damage in the hippocampus and spleen and improved motor strength and learning-memory capacity. Furthermore, R. mucilaginosa JAASSRY increased the abundance of Lactobacillus and reduced Proteobacteria, Helicobacter, and Oscillospira, while enhancing antioxidant capacity by modulating nucleotide, lipid, and carbohydrate metabolism. Lactobacillus and Pediococcus were positively correlated with memory latency and CAT/SOD activities (p < 0.05), whereas Actinormyces and Dehalobacterium showed negative correlations. Notably, HR performed comparably or superiorly to β-carotene in improving cerebral oxidative stress and beneficial microbiota, suggesting its potential in neuroprotection and gut–brain axis regulation. In conclusion, R. mucilaginosa JAASSRY mitigates aging-related oxidative damage and behavioral deficits by modulating gut microbiota structure and function, demonstrating its promise as a β-carotene alternative in animal husbandry and functional foods. Full article

Multiple sclerosis (MS) is a chronic neuroinflammatory and autoimmune disorder of the central nervous system (CNS) whose cause remains unknown. Disease-modifying therapies (DMTs) are the current standard of care, yet growing evidence highlights the importance of complementary lifestyle-based interventions, including nutrition, in modulating disease activity. Given the influence of diet on immune function, several studies have examined its effects in MS, with particular attention to specific dietary patterns and macronutrients. However, fewer studies have focused on micronutrients, bioactive compounds, and minerals and their influence in MS. In this narrative review, we report the latest evidence on micronutrients such as vitamins and essential metals, along with polyphenols and minerals like salt, in both experimental autoimmune encephalomyelitis (EAE) and MS. We also discuss how these dietary components may influence the gut microbiota, which is considered a contributor to disease onset due to its interaction with the immune system in the gut–brain axis. While findings for vitamins B, C, E, and K remain heterogeneous, vitamins A and D show the most consistent immunological and clinical effects, with immunomodulatory, antioxidative, and neuroprotective effects in both EAE and MS. Polyphenols also display anti-inflammatory and neuroprotective properties in EAE and, to a lesser extent, in clinical studies. Lastly, evidence suggests the importance of balanced salt intake and adequate levels of essential metals, as dysregulation may contribute to comorbidities or enhance inflammatory pathways relevant to MS. Although only a limited number of studies have explored these aspects, the gut microbiota appears to be differentially affected by these dietary factors. Overall, advancing our understanding of how these components interact with immune and microbial pathways may support the development of personalized nutritional strategies to complement current therapies and improve patient outcomes. Full article

Major depressive disorder remains a leading cause of disability worldwide, with conventional antidepressants offering incomplete and often transient relief. Mounting evidence highlights disturbances in tryptophan (Trp) metabolism as a key biological axis linking inflammation, neuroplasticity, and mood regulation. Plant-derived compounds that modulate this pathway, including 5-hydroxytryptophan, isoflavones, berberine, and polyphenols, have emerged as promising candidates for integrative treatment strategies. Yet, despite encouraging preclinical and clinical findings, knowledge gaps persist regarding long-term efficacy, mechanistic specificity, and standardized therapeutic protocols. This narrative review explores how Trp modulators influence central and peripheral mechanisms relevant to depression, from serotonergic synthesis and kynurenine shunting to gut–brain–immune interactions. Evidence from animal models and randomized clinical trials is critically synthesized, with particular attention to outcomes on mood stabilization, anxiety reduction, cognitive function, and sleep regulation. Special emphasis is placed on translational potential, methodological limitations, and the need for harmonized research frameworks. Here we highlight that phytochemical interventions represent a mechanistically informed and biocompatible strategy for advancing depression management. By bridging neurobiology and clinical psychiatry, these insights may pave the way for next-generation therapeutics that integrate dietary, microbiota-targeted, and anti-inflammatory approaches. Broader application of this research could ultimately refine personalized psychiatry, expand therapeutic horizons, and contribute to global mental health resilience. Full article

The human gut microbiota plays a key role in neurochemical communication, especially through the gut–brain axis. There is growing evidence that the gut microbiota influences dopamine metabolism through both production and consumption mechanisms. Two key bacterial enzymes are central to this process: tyrosine decarboxylase (TDC), which primarily catalyzes the decarboxylation of tyrosine to tyramine but can also act on L-DOPA to produce dopamine in certain bacterial strains, and aromatic L-amino acid decarboxylase (AADC), which can convert precursors such as L-DOPA, tryptophan, or 5-hydroxytryptophan into bioactive amines including dopamine, tryptamine, and serotonin. Identifying the bacterial families corresponding to TDC and AADC enzymes opens new avenues for clinical intervention, particularly in neuropsychiatric and neurodegenerative disorders, such as Parkinson’s disease. Moreover, elucidating strain-specific microbial contribution and host-microbe interactions may enable personalized therapeutic strategies, such as selective microbial enzyme inhibitors or tailored probiotics, to optimize dopamine metabolism. Emerging technologies, including biosensors and organ-on-chip platforms, offer new tools to monitor and manipulate microbial dopamine activity. This article explores the bacterial taxa capable of producing or consuming dopamine, focusing on the enzymatic mechanisms involved and the methodologies available for studying these processes in vivo. Full article

The intestinal microbiota, a diverse community of microorganisms residing in the human gut, recently attracted considerable attention as a contributing factor to various neurological disorders, including Alzheimer’s Disease (AD). Within the established framework of the gut–brain axis (GBA) concept, it is commonly suggested that dysbiosis, through microbial metabolites entering the brain, affect the cognitive functions in patients with AD. However, evidence for such a role of dysbiosis remains largely associative, and the complexity of the communication channels between the gut and the brain is not fully understood. Moreover, the new players of the GBA are emerging and the AD concept is constantly evolving. The objective of this narrative review is to synthesize the current evidence on the humoral, endocrine, immune, and neural communication mechanisms linking the gut and brain in AD and highlight newly discovered GBA messengers such as microRNAs, extracellular vesicles, T-cells, and the intestinal hormones, including emerging neuroprotective role for glucagon-like peptide-1 (GLP-1). Based on this knowledge, we aimed to develop a conceptual understanding of the GBA function in health and AD. We specify that, in AD, the GBA goes beyond a disrupted microbiome, but operates in conjunction with impaired intestinal secretion, motility, barrier permeability, and neuroinflammatory signaling. These factors are associated with the dysfunction of the hypothalamic–pituitary axis, altered somatic and autonomic neuronal gut regulation, and abnormal, due to memory problems, behavioral aspects of food intake. Identifying the individual profile of key molecular and cellular players contributing to an unbalanced GBA should optimize existing approaches or propose new approaches for the complex therapy of AD. Full article