Search Results (952)

The bidirectional relationship between the brain and gut microbiota has led to the concept of the microbiota–gut–brain axis. It refers to a system of bilateral communication that integrates neuronal, immunological, and metabolic signals, whose disruption has been linked to the pathogenesis of digestive, metabolic, and neurological disorders, among others. Intestinal dysbiosis (an imbalance in the gut microbiota) can promote a proinflammatory and prothrombotic state, as well as dyslipidaemia and dysglycemia, that increase atherogenic risk and consequently the risk of stroke. Dysbiosis can also lead to neuroinflammatory and neurodegenerative effects, compromising the integrity of the blood–brain barrier and exacerbating brain injury after stroke. Specific bacterial profiles have been associated with varying levels of stroke risk, emphasising the role of gut microbiota-derived vasoactive metabolites such as Trimethylamine N-Oxide (TMAO), phenylacetylglnutamine (PAGln), and short-chain fatty acids (SCFAs), which may serve as biomarkers for stroke risk and severity. Gut microbiota also influences neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), involved in recovery after stroke. Research has explored the potential to modify the gut microbiota to either prevent stroke (by reducing risk) or improve outcomes (by decreasing severity and sequelae). Current scientific evidence supports the role of gut microbiota as a potential diagnostic and prognostic biomarker, as well as a therapeutic target. Full article

Anatoxin-a (ANTX-a), a potent neurotoxin produced by various cyanobacterial species, poses a serious threat to aquatic organisms. This study investigated the neurotoxicity of ANTX-a on juvenile Chinese mitten crab (Eriocheir sinensis). Different from previous studies on vertebrate models or fish liver toxicity, we focused on the microbiota–intestine–brain axis. Results demonstrated that ANTX-a exposure induced significant neurotoxicity, marked by the upregulation of apoptosis-related genes and disruption of neurotransmitter homeostasis. Transcriptomic analysis of thoracic ganglia revealed significant dysregulation of metabolic pathways, characterized by upregulated histidine metabolism (elevated histidine decarboxylase-like) and downregulated lipid metabolism (suppressed sphingomyelin phosphodiesterase-like). Additionally, increased intestinal histamine levels and elevated serum diamine oxidase activity indicated intestinal barrier damage. Intestinal microbiota analysis revealed that the abundance of nerve-related bacteria Tyzzerella and Clostridium sensu stricto 1 changed significantly. In summary, these findings indicate that ANTX-a induced neurotoxicity by affecting neurotransmitter systems and gut health, implicating the microbiota–intestine–brain axis. The results underscore the role of microbiota–intestine–brain communication in cyanotoxin toxicity within aquatic invertebrates and provide new insights into the ecotoxicological risks of cyanobacterial blooms in aquatic invertebrates. Full article

This review examines the diverse ways in which probiotics, defined as live microorganisms that provide health benefits to the host when administered in adequate amounts, contribute to animal health and welfare across both livestock and companion species. By modulating gut microbiota, enhancing immune responses, and suppressing harmful pathogens, probiotics represent an effective strategy for disease prevention and performance improvement without reliance on antibiotics. In livestock production, these beneficial microbes have been shown to optimize feed utilization, support growth, and reduce methane emissions, thereby contributing to more sustainable farming practices. Their role extends beyond productivity, as probiotics also help mitigate antimicrobial resistance (AMR) by offering natural alternatives to conventional treatments. In aquaculture, they further promote environmental sustainability by improving water quality and reducing pathogen loads. For companion animals such as dogs and cats, probiotics are increasingly recognized for their ability to support gastrointestinal balance, alleviate stress through gut–brain axis interactions, and aid in the management of common conditions including diarrhea, food sensitivities, and allergies. The integration of probiotics into veterinary practice thus reflects a growing emphasis on holistic and preventive approaches to animal health. Despite these advances, several challenges remain, including variability in strain-specific efficacy, regulatory limitations, and cost-effectiveness in large-scale applications. Emerging research into precision probiotics, host–microbiome interactions, and innovative delivery methods offers promising avenues to overcome these barriers. As such, probiotics can be regarded not only as functional supplements but also as transformative tools that intersect animal health, productivity, and sustainability. Full article

Environmental sensitivity illnesses—including fibromyalgia syndrome (FMS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and multiple chemical sensitivity (MCS)—are chronic, disabling disorders characterized by hypersensitivity to environmental stimuli, persistent fatigue, widespread pain, and neurocognitive and autonomic dysfunction. Although their diagnostic criteria differ, increasing evidence suggests overlapping clinical features and shared biological mechanisms. A unifying hypothesis highlights the gut–brain–immune axis, where alterations in the intestinal microbiome, epithelial barrier dysfunction, and aberrant immune signaling interact with central sensitization and systemic metabolic dysregulation. Recent studies demonstrate reduced microbial diversity, depletion of anti-inflammatory taxa (e.g., Faecalibacterium prausnitzii, Bifidobacterium), and enrichment of pro-inflammatory Clostridium species across these conditions. These shifts likely alter production of short-chain fatty acids, amino acid metabolites, and complex lipids, with downstream effects on mitochondrial function, neuroinflammation, and host energy metabolism. Moreover, emerging clinical interventions—including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation—suggest a potential role for microbiome-targeted therapies, though controlled evidence remains limited. This review synthesizes current knowledge on microbiome alterations in FMS, ME/CFS, and MCS, emphasizing their convergence on metabolic and immune pathways. By integrating microbial, immunological, and neurophysiological perspectives, we propose a microbiome-centered framework for understanding environmental sensitivity illnesses and highlight avenues for translational research and therapeutic innovation. Full article

Ganoderma lucidum (Lingzhi), a traditional medicinal mushroom, is renowned for its immunomodulatory, anti-inflammatory, and antioxidant properties, primarily attributed to its bioactive components such as polysaccharides and triterpenoids. This review focuses on the mechanisms by which Ganoderma lucidum modulates immune responses, particularly in the context of gut–liver–brain axis disorders. Polysaccharides enhance immune function by activating macrophages, natural killer cells, and T cells, thereby promoting phagocytosis and cytokine production. Triterpenoids contribute through anti-inflammatory and antioxidant activities, inhibiting inflammatory mediators and protecting tissues from damage. Ganoderma lucidum also influences immune regulation via key signaling pathways, including NF-κB and MAPK, and supports immune tolerance, potentially reducing the risk of autoimmune diseases. Additionally, it modulates gut microbiota, which further impacts systemic immunity. Importantly, polysaccharides and triterpenoids demonstrate promising clinical application prospects in metabolic diseases, inflammatory conditions, neurodegenerative disorders, and cancer immunotherapy, attributed to their multi-target immunomodulatory activities and prebiotic properties. Despite promising applications in treating metabolic, inflammatory, and neurodegenerative diseases, further research is needed to fully elucidate the molecular mechanisms and potential of Ganoderma lucidum in precision medicine. This comprehensive analysis underscores the value of Ganoderma lucidum as a multifaceted immunomodulatory agent. Full article

Anxiety and depression are mental disorders with significant global impact, and are especially prominent in women during times of hormonal fluctuations. The microbiota–gut–brain axis (MGB axis) has emerged as a crucial pathway in the pathogenesis of these disorders, as it directly influences the production of neurotransmitters such as serotonin (5-HT), gamma-aminobutyric acid (GABA) and dopamine (DA). In addition, they have shown estrogenic effects through enzymes such as β-glucuronidase, which modulate hormone metabolism and consequently mood. A comprehensive search of recent preclinical studies has found that probiotic intake in female rats led to significant improvements in anxiety- and depression-related behaviors. Similarly, clinical trials in certain populations, particularly women with hormonal imbalances during menopause or premenstrual syndrome, have shown promising results. However, there are still significant problems, such as the individual variability of responses and the need for controlled long-term studies. The development of specific probiotics for hormonal modulation and the implementation of personalized approaches integrating omics and neuroimaging technologies to optimize therapeutic interventions in the field of mental health are promising. Accordingly, a comprehensive search was conducted in scientific databases such as PubMed, ScienceDirect, Scopus and Web of Science. Preclinical studies investigating the estrogenic effects of different probiotic strains in animal models and in controlled clinical trials during chronic treatment were selected, excluding those studies that did not provide access to full text. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with a complex etiology whose exact mechanisms are not fully understood. In recent years, there has been growing interest in the role of the gastrointestinal microbiota in the pathogenesis of AD, particularly in the context of the gut–brain axis. The purpose of this review is to discuss the current state of knowledge regarding potential relationships between the composition of the gut microbiota and the development and progression of AD. Preclinical and clinical studies indicating that microbiota imbalances (dysbiosis) may contribute to increased inflammation, increased permeability of the intestinal and blood–brain barriers, and accumulation of pathological proteins such as beta-amyloid and tau are analyzed. The effects of diet, probiotics and microbiota interventions on cognitive function were also discussed. An attempt was also made to evaluate microbiota disruption as a potential early marker of AD development. Although the mechanisms require further study, the role of the gut microbiota appears to be an important and promising direction in understanding the pathophysiology of AD and developing potential therapeutic and diagnostic strategies. Full article

Obsessive–compulsive disorder (OCD) is a multifactorial condition, and interest in gut–brain interactions is increasing. We conducted a systematic two-step review, registered in PROSPERO (CRD420251083936). Step 1 mapped core OCD biology to gut-relevant pathways, including neuroimmune activation, epithelial barrier function, microbial metabolites, and stress circuitry, to clarify plausible mechanisms. Step 2 synthesized evidence from human and preclinical studies that measured or manipulated microbiota. Searches across PubMed, EMBASE, Web of Science, PsycINFO, and Cochrane (September 2025) yielded 357 biological and 20 microbiota-focused studies. Risk of bias was assessed using the Joanna Briggs Institute checklist for human studies and SYRCLE’s tool for animal studies. Although taxonomic findings in human cohorts were heterogeneous, functional patterns converged: reduced short-chain fatty acid capacity, enrichment of pro-inflammatory pathways, and host markers of barrier disruption and inflammation correlating with OCD severity. Transferring patient microbiota to mice induced OCD-like behaviors with neuroinflammatory changes, partly rescued by metabolites or barrier-supporting strains. Mendelian randomization suggested possible causal contributions at higher taxonomic levels. Diet, especially fiber intake, and psychotropic exposure were major sources of heterogeneity. Evidence supports the microbiota as a modifiable co-factor in a subset of OCD, motivating diet-controlled, stratified clinical trials with composite host–microbe endpoints. Full article

The interaction between microorganisms in the dental microfilm (plaque) at the gingival margin, the immune system, and the brain is vital for gingival health. The brain constantly receives information regarding microbial composition and inflammation status through afferent nerves and the bloodstream. It modulates immune responses via efferent nerves and hormonal systems to maintain homeostasis. This relationship determines whether the gingiva remains healthy or develops into gingivitis (non-destructive inflammation) or periodontitis (a destructive condition), collectively referred to as periodontal disease. Factors associated with severe periodontitis heighten the responsiveness of this homeostatic system, diminishing the adaptive immune system’s defence against symbiotic microorganisms with pathogenic properties, known as pathobionts. This leads to excessive innate immune system activation, effectively preventing infection but damaging the periodontium. Consequently, investigating the microbiota–brain axis is vital for understanding its impact on periodontal health and disease. Herein, we examine recent advancements in how the defence against pathobionts is organised within the brain, and how it regulates and adapts the pro-inflammatory and anti-inflammatory immune balance, controlling microbiota composition. It also discussed how pathobionts and emotional stress can trigger neurodegenerative diseases, and how inadequate coping strategies for managing daily stress and shift work can disrupt brain circuits linked to immune regulation, weakening the adaptive immune response against pathobionts. Full article

Pet humanization, particularly in dogs and cats, has transformed animal healthcare and highlighted the importance of nutrition in promoting human–pet social interaction, pet psychophysical well-being and, possibly, longevity. Nutraceuticals, such as omega-3 fatty acids, prebiotics, probiotics, plant extracts and dietary supplements, are endowed with antioxidant, anti-inflammatory, immune-modulating, cognitive-enhancing and gut-microbiota balancing properties. These effects have been shown to contribute to the possible prevention and management of bone and skin diseases, as well as gastrointestinal and behavioral disturbs. Moreover, the human–animal bond has been shown to play a pivotal role in reducing stress, improving sociability, and modulating pets’ emotional and physiological states. Evidence also suggests that nutrition and social interactions can influence the gut–brain axis, impacting the behavior, cognition, and resilience to stress-related disorders. Besides underlining the value of nutraceutical integration into pet nutrition strategies and offering a comprehensive, evidence-based perspective on their potential in improving animal welfare, literature reports about drawbacks of the use/misuse of such substances have been reported. Full article

Background/Objectives: Polygonatum sibiricum (PS), possessing both medicinal and edible dual functions, boasts a long history of application in Chinese traditional practices. As a component of its effectiveness, Polygonatum sibiricum polysaccharides (PSPs) have been reported to exert neuroprotective effects. However, the protective effects of PS on the cognitive deficits induced by simulated weightlessness remain unclear. This study evaluated the therapeutic potential of PSPs to counteract the cognitive deficits induced by simulated weightlessness using the Hindlimb Unloading (HU) method. Methods: Mice were subjected to HU to establish cognitive impairment, and PSP was administered for four weeks. The Morris water maze test (MWMT) and passive avoidance test (PAT) were used to evaluate the cognitive abilities of mice, followed by an analysis of molecular mechanisms. Results: PSP treatment increased learning and memory in mice. PSP treatment partially restored gut microbial diversity and composition towards beneficial taxa, including Lactobacillus and Firmicutes, while inhibiting proinflammatory genera, including Alistipes and Proteus. At the same time, PSP upregulated Claudin-5 and Zonula Occludens-1 (ZO-1) levels in the colon, suggesting improved intestinal barrier integrity, and decreased neuroinflammatory response by inhibiting NLRP3 inflammasome activation and NF-κB phosphorylation in the hippocampus. It also modulated neurotransmitter homeostasis along the microbiota–gut–brain (MGB) axis by increasing the levels of gamma-aminobutyric acid (GABA) and serotonin (5-HT) while reducing the levels of excitotoxic metabolites, including Glutamate (Glu) and 3-hydroxykynurenine (3-HK). Conclusions: These results indicate that PSP may have beneficial effects on HU-induced cognitive impairment by regulating gut microbiota, enhancing barrier function, suppressing neuroimmune signaling, and restoring neurotransmitter balance. Full article

Bone immunity represents a dynamic interface where skeletal homeostasis intersects with systemic immune regulation. We synthesize emerging paradigms by contrasting two functionally distinct microenvironments: the marrow cavity, a hematopoietic and immune cell reservoir, and cancellous bone, a metabolically active hub orchestrating osteoimmune interactions. The marrow cavity not only generates innate and adaptive immune cells but also preserves long-term immune memory through stromal-derived chemokines and survival factors, while cancellous bone regulates bone remodeling via macrophage-osteoclast crosstalk and cytokine gradients. Breakthroughs in lymphatic vasculature identification challenge traditional views, revealing cortical and lymphatic networks in cancellous bone that mediate immune surveillance and pathological processes such as cancer metastasis. Central to bone immunity is the neuro–immune–endocrine axis, where sympathetic and parasympathetic signaling bidirectionally modulate osteoclastogenesis and macrophage polarization. Gut microbiota-derived metabolites, including short-chain fatty acids and polyamines, reshape bone immunity through epigenetic and receptor-mediated pathways, bridging systemic metabolism with local immune responses. In disease contexts, dysregulated immune dynamics drive osteoporosis via RANKL/IL-17 hyperactivity and promote leukemic evasion through microenvironmental immunosuppression. We further propose the “brain–gut–bone axis” as a systemic regulatory framework, wherein vagus nerve-mediated gut signaling enhances osteogenic pathways, while leptin and adipokine circuits link marrow adiposity to inflammatory bone loss. These insights redefine bone as a multidimensional immunometabolic organ, integrating neural, endocrine, and microbial inputs to maintain homeostasis. By elucidating the mechanisms of immune-driven bone pathologies, this work highlights therapeutic opportunities through biomaterial-mediated immunomodulation and microbiota-targeted interventions, paving the way for next-generation treatments in osteoimmune disorders. Full article

Traumatic brain injury (TBI) remains a major global health problem, contributing significantly to morbidity and mortality worldwide. Despite advances in understanding its complex pathophysiology, current therapeutic strategies are insufficient in addressing the long-term cognitive, emotional, and neurological impairments. While the primary mechanical injury is immediate and unavoidable, the secondary phase involves a cascade of biological processes leading to neuroinflammation, blood–brain barrier (BBB) disruption, and systemic immune activation. The heterogeneity of patient responses underscores the urgent need for reliable biomarkers and targeted interventions. Emerging evidence highlights the gut–brain axis as a critical modulator of the secondary phase, with microbiota-derived extracellular vesicles (MEVs) representing a promising avenue for both diagnosis and therapy. MEVs can cross the intestinal barrier and BBB, carrying biomolecules that influence neuronal survival, synaptic plasticity, and inflammatory signaling. These properties make MEVs promising biomarkers for early detection, severity classification, and prognosis in TBI, while also offering therapeutic potential through modulation of neuroinflammation and promotion of neural repair. MEV-based strategies could enable tailored interventions based on the individual’s microbiome profile, immune status, and injury characteristics. The integration of multi-omics with artificial intelligence is expected to fully unlock the diagnostic and therapeutic potential of MEVs. These approaches can identify molecular subtypes, predict outcomes, and facilitate real-time clinical decision-making. By bridging microbiology, neuroscience, and precision medicine, MEVs hold transformative potential to advance TBI diagnosis, monitoring, and treatment. This review also identifies key research gaps and proposes future directions for MEVs in precision diagnostics and gut microbiota-based therapeutics in neurotrauma care. Full article

Functional bowel disorders (FBDs) are chronic gastrointestinal conditions characterized by recurrent symptoms associated with gut microbiota dysbiosis. Although accumulating evidence suggests that probiotics can improve symptoms in patients with FBD, the underlying mechanisms remain to be fully elucidated. In this randomized, double-blind, placebo-controlled clinical trial, 38 adults meeting the Rome IV diagnostic criteria of functional constipation (FC) and functional diarrhea (FD) received either a multi-strain probiotic complex or placebo for 8 weeks. Clinical outcomes were evaluated using the Irritable Bowel Syndrome Severity Scoring System (IBS-SSS), bowel habits questionnaire, and IBS Quality of Life (IBS-QoL) instrument. Fecal samples were collected at baseline and at week 8 for gut microbiota profiling via 16S rRNA gene sequencing and metabolomic analysis using gas chromatography–mass spectrometry. Probiotic supplementation significantly reduced the severity of abdominal bloating and its interference with quality of life, and improved the body image domain of the IBS-QoL. Beta diversity analysis showed significant temporal shifts in the probiotic group, while 16S rRNA sequencing revealed an increased relative abundance of Faecalibacterium prausnitzii and Blautia stercoris. Fecal metabolomic analysis further indicated elevated levels of metabolites implicated in the gut–brain axis. Multi-strain probiotic supplementation alleviated gastrointestinal symptoms and improved aspects of psychosocial well-being in adults with FBDs, potentially through modulation of the human gut microbiome. Full article

Background: Alterations of the gut microbiota have been increasingly implicated in the pathogenesis of dementia through mechanisms involving systemic inflammation, immune dysregulation, and gut–brain axis disruption. Clinical evidence, however, remains fragmented. Objectives: This systematic review aimed to characterize gut microbiota profiles in individuals with mild cognitive impairment (MCI) or Alzheimer’s dementia (AD), explore mechanistic associations with neurodegeneration, and evaluate the impact of microbiota-targeted interventions on cognitive outcomes. Methods: Following PRISMA 2020 guidelines and a registered protocol (PROSPERO CRD420251074832), PubMed/Medline was searched through May 2025. Eligible studies included randomized controlled trials (RCTs) and cohort and case–control studies assessing microbiota composition or interventions in participants with MCI or AD. Results: Twenty-one studies were included (1 RCT, 20 observational; sample size 22–302). Most used 16S rRNA sequencing; one used shotgun metagenomics. Across cohorts, MCI and AD patients consistently showed reduced short-chain fatty acid-producing bacteria (Faecalibacterium, Ruminococcaceae, Lachnospiraceae) and increased pro-inflammatory taxa (Escherichia/Shigella, Enterobacteriaceae, Bacteroides). Several studies reported reduced microbial diversity. Specific taxa, including Akkermansia muciniphila and Faecalibacterium, were associated with amyloid burden, hippocampal atrophy, and cognitive decline. Environmental and dietary factors influenced microbial composition and cognition. The RCT reported that probiotic supplementation improved inflammatory markers and BDNF levels, although changes in microbiota composition were inconsistent. Conclusions: Gut dysbiosis is strongly associated with cognitive impairment and markers of neurodegeneration. Modulation of the microbiota through diet and probiotics emerges as a promising avenue for dementia prevention and management, though robust longitudinal and interventional studies are needed to confirm causality and therapeutic efficacy. Full article