Search Results (1,486)

Background/Objectives: The gut microbiome is increasingly recognized as a key modulator of central nervous system function through the gut–brain axis. Dysbiosis has been associated with neuropsychiatric disorders such as depression, anxiety, impulsivity, cognitive decline, and addiction. This review aims to synthesize mechanistic insights and therapeutic perspectives on how gut microbiota influence mood regulation, decision-making, and cognitive processes. Methods: A comprehensive narrative review was conducted using peer-reviewed articles retrieved from PubMed, Scopus, and Web of Science up to August 2025. Studies were included if they explored microbiota-related effects on behavior, mood, cognition, or decision-making using human or animal models. Emphasis was placed on molecular mechanisms, microbiome-targeted therapies, and multi-omics approaches. Results: Evidence indicates that gut microbiota modulate neurochemical pathways involving serotonin, dopamine, GABA, and glutamate, as well as immune and endocrine axes. Microbial imbalance contributes to low-grade systemic inflammation, impaired neuroplasticity, and altered stress responses, all of which are linked to mood and cognitive disturbances. Specific microbial taxa, dietary patterns, and interventions such as probiotics, prebiotics, psychobiotics, and fecal microbiota transplantation (FMT) have shown promise in modulating these outcomes. The review highlights methodological advances including germ-free models, metagenomic profiling, and neuroimaging studies that clarify causal pathways. Conclusions: Gut microbiota play a foundational role in shaping emotional and cognitive functions through complex neuroimmune and neuroendocrine mechanisms. Microbiome-based interventions represent a promising frontier in neuropsychiatric care, although further translational research is needed to define optimal therapeutic strategies and address individual variability. Full article

Background/Objectives: Disorders of gut–brain interaction (DGBI) include a spectrum of disorders with chronic/recurrent gastrointestinal symptoms, caused by dysregulation of microbiota–gut–brain interaction. Early-life events have been suggested as the main factors influencing the microbiota–gut–brain axis. We aimed to evaluate the prevalence of DGBI in 3-year-old children and its relationship with early-life events. Methods: The parents of children aged 3 years, who had been followed up in a well-baby clinic since they were 2 months old, were asked about any GI symptoms their child had experienced during the check-up visits between September 2023 and June 2024. The final diagnosis of DGBI was based on ROME IV criteria. Demographic data, including early-life factors, were collected. Results: Overall, 568 children (48.6% boys) were included, of whom 139 (24.5%) had symptoms consistent with at least one DGBI diagnosis. The most prevalent DGBI was functional constipation (20.4%), followed by colic (4.6%), infant regurgitation (2.8%), and dyschezia (1.6%). Approximately 48% of the children were breastfed for ≥6 months, and 21% were exposed to ≥1 antibiotic/antiviral drugs in the first year of life. DGBI prevalence was significantly higher in girls than in boys (28.1% vs. 20.7%; p = 0.041). Exclusive breastfeeding was the most significant protective factor against DGBI, particularly if performed for ≥3 months. Conclusions: Sex was the most significant factor affecting DGBI prevalence in children aged ≤3 years; breastfeeding offers the most effective protection against DGBI development. Full article

Background: Alzheimer’s disease (AD) lacks effective therapeutic strategies. Electroacupuncture (EA) offers promising neuroprotective effects, but its underlying mechanisms remain unclear. Objective: To explore the mechanisms of EA’s neuroprotective effects on AD via microbiome and metabolome integration. Methods: Utilizing a well-established model of AD, Senescence-Accelerated Mouse Prone 8 (SAMP8), EA intervention was performed. 16S ribosomal RNA (rRNA) sequencing and serum metabolomics were conducted on SAMP8 mice, SAMP8 mice after EA intervention, and their normal control group Senescence-Accelerated Mouse Resistant 1 (SAMR1) mice. Results: SAMP8 mice were subjected to electroacupuncture (EA) treatment at the Baihui (GV20) and Shenshu (BL23) acupoints for 15 min daily over a period of four weeks. EA enhanced cognitive function and reduced neuronal damage in AD models. The treatment lowered pro-inflammatory cytokines (TNF-α, IL-1β) and AD-related pathologies (tau, Aβ_1-42). EA also rebalanced gut microbiota by increasing beneficial Gastranaerophilales while decreasing harmful Proteobacteria. Additionally, it restored purine and phenylpropanoid metabolism by regulating key metabolites. Importantly, EA reduced levels of specific metabolites linked to pro-inflammatory bacteria (Sphingomonas, Massilia, Escherichia-Shigella), simultaneously decreasing their abundance. These findings highlight EA’s multi-target effects on neuroinflammation, gut microbiota, and metabolic pathways in AD. Notably, the interactions between EA-regulated key metabolites and AD-related targets, predicted via PubChem and ChEMBL databases, remain computational and have not been validated by experimental studies. Conclusions: EA exerts neuroprotective effects in AD via modulation of gut microbiota and metabolic pathways, representing a novel non-pharmacological therapeutic strategy. Full article

Background: Modulation of the gut–brain axis using probiotics present a promising approach for enhancing cognitive function in mild cognitive impairment (MCI). In prior non-clinical research, Lactobacillus delbrueckii subsp. lactis CKDB001 (LL) exhibited potential to enhance cognitive function. We therefore conducted a clinical trial to assess the efficacy and safety of LL supplementation in MCI. Methods: A 12-week, randomized, double-blind, placebo-controlled, multi-center trial was performed in 100 participants aged 55–80 years. Subjects were randomly assigned to receive LL (n = 50, 5.0 × 10⁹ CFU/day) or placebo (n = 50). Efficacy and safety were evaluated at baseline and after 12 weeks. Results: LL supplementation resulted in significantly greater improvements than placebo in the Alzheimer’s Disease Assessment Scale–Cognition 13 total score, the memory sub-score, reaction time for Part A of the Trail Making Test, and word/color reaction times on the Stroop test. Taxonomic and metabolomic profiling of fecal samples showed significantly greater changes in the relative abundance of beneficial microorganisms in the LL group, with the most pronounced shifts at the family (Lactobacillaceae, Bifidobacteriaceae) and genus (Lactobacillus) levels. In addition, the LL group exhibited significantly higher fecal levels of indole-derived metabolites, including 5-hydroxyindole-3-acetic acid, indole-3-lactic acid, and indole-3-glycol. Safety assessments indicated LL was safe and well-tolerated, with no clinically relevant changes in laboratory findings or adverse events. Conclusions: These findings suggest that LL supplementation may enhance cognitive function in MCI by modulating the gut–brain axis through effects on gut microbiota and related metabolites, and could serve as a safe functional food to support cognitive health. Full article

Artificial sweeteners, or non-caloric sweeteners (NCSs), are widely consumed as sugar substitutes to reduce energy intake and manage obesity. Once considered inert, accumulating evidence now shows that NCSs interact with host physiology, altering gut microbiota composition and neural circuits that regulate feeding. This review synthesizes current knowledge on how NCSs disrupt the gut–brain axis (GBA), with particular focus on microbiota-mediated effects and neural reward processing. In homeostatic regulation, NCS-induced dysbiosis reduces beneficial taxa such as Akkermansia muciniphila and Faecalibacterium prausnitzii, diminishes short-chain fatty acid production, impairs gut barrier integrity, and promotes systemic inflammation. These changes blunt satiety signaling and favor appetite-promoting pathways. Beyond homeostasis, NCSs also rewire hedonic circuits: unlike caloric sugars, which couple sweet taste with caloric reinforcement to robustly activate dopaminergic and hypothalamic pathways, NCSs provide sensory sweetness without energy, weakening reward prediction error signaling and altering neuropeptidergic modulation by orexin, neurotensin, and oxytocin. Microbial disruption further exacerbates dopaminergic instability by reducing precursors and metabolites critical for reward regulation. Together, these top-down (neural) and bottom-up (microbial) mechanisms converge to foster maladaptive food seeking, metabolic dysregulation, and increased vulnerability to overeating. Identifying whether microbiome-targeted interventions can counteract these effects is a key research priority for mitigating the impact of NCSs on human health. Full article

Background: Postoperative cognitive dysfunction (POCD) is a common postoperative condition after neurosurgery, and in patients of advancing age, with far-reaching implications for recovery and quality of life. Current evidence points to the gut–brain axis as the main mechanism for the regulation of perioperative neuroinflammation and cognition. Objective: The aim of this review is to consolidate the existing evidence for perioperative gut microbiome dysbiosis in POCD, specifically in neurosurgical patients. Methods: A review of preclinical and clinical evidence on the gut microbiome, surgical stress, and cognitive recovery was conducted. Both mechanistic and therapeutic evidence were examined. Results: Surgery and anesthesia enhance gut microbial diversity, intestinal permeability, and systemic inflammation, thereby compromising neuroplasticity and the integrity of blood–brain barriers. Preclinical models show that interventions to reestablish microbial homeostasis with probiotics, prebiotics, or fecal microbiota transplantation decrease postoperative cognition. Clinical studies offer evidence supporting the associations between decreased short-chain fatty acid-producing bacteria and POCD risk. Randomized controlled trials have demonstrated that perioperative probiotics lower the incidence and markers of POCD. Multi-omic approaches to integrating microbiome, metabolome, and neuroimaging signatures are being engineered to discern recovery phenotypes prior to surgery. Conclusions: Perioperative gut microbiota are a modifiable target for the optimization of cognitive recovery from neurosurgery. The inclusion of microbiome treatments and diagnostics into standard surgical care pathways is one potential pathway to POCD minimization, but large randomized trials will be necessary to establish this. Full article

This study explored the potential therapeutic effect and possible mechanism of Atractylodes macrocephala Koidz. Polysaccharide (AP) on pirarubicin chemotherapy-induced depression (CID) in breast cancer mice. This study utilized a variety of techniques to explore the potential of AP in mitigating behavioral abnormalities and elucidate the role of gut microbiota regulation in its therapeutic effects on chemotherapy in breast cancer mice. These included a chemotherapy mouse model, behavioral assessments, histological analysis using hematoxylin and eosin staining, ultrastructural examination, enzyme-linked immunosorbent assays, 16S rDNA sequencing, metabolomic profiling, Western blot analysis, and a pseudo-germ-free animal model. Oral administration of AP significantly improved depression-like behaviors in breast cancer chemotherapy mice while also reducing neuronal damage and inflammation in the hippocampus. AP prevented ferroptosis of intestinal tissues caused by chemotherapy and had a repairing effect on the intestinal barrier damage of chemotherapy-induced mice. Additionally, AP enhanced gut microbiota composition and altered intestinal metabolites in chemotherapy-treated mice. It notably decreased the abundance of certain microbes, such as Bacteroidaceae, Lachnospiraceae, Oscillospiraceae, and Clostridium, while significantly increasing the abundance of Alistipes. Moreover, AP efficiently modulated intestinal metabolites, including glycocholic acid, L-Phenylalanine, and palmitoylcarnitine. More importantly, depletion of gut microbiota through antibiotics diminished the effectiveness of AP. Our results suggest that AP alleviates depression-like behaviors in chemotherapy-treated mice by regulating the gut microbiota and microbial metabolism, as well as suppressing ferroptosis in intestinal tissues. Full article

Post-COVID-19 syndrome, also known as long-COVID, is characterized by a wide spectrum of persistent symptoms involving multiple body organs and systems, including fatigue, gastrointestinal disorders, and neurocognitive dysfunction. Emerging evidence suggests that gut microbiota dysbiosis and disruption of the gut–brain axis play a central role in the pathophysiology of this condition. Probiotics and their metabolites (postbiotics) have gained increasing attention as potential therapeutic agents given their immunomodulatory, anti-inflammatory, and antiviral properties. In this review, we discuss the current understanding of the antiviral mechanisms of probiotics, including reinforcement of intestinal epithelial barrier function, direct virus inhibition, receptor competition, and immune system modulation. Special emphasis is placed on short-chain fatty acids (SCFAs), lactic acid, hydrogen peroxide, and bacteriocins as key factors that contribute to these effects. SCFAs appear to be essential postbiotic compounds during post-COVID recovery. We also highlight recent clinical trials involving specific probiotic species, such as Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Bifidobacterium longum, and their potential role in alleviating long-term COVID symptoms. Although the current results are promising, further research is needed to clarify the most effective strains, dosages, and mechanisms of action in post-COVID therapeutic strategies. Full article

Background/Objectives: Psychological stress is a main factor in the pathophysiology of irritable bowel syndrome (IBS) and contributes to changes in gastrointestinal motility and inflammatory responses. We investigated the effects of three probiotic strains, Lactobacillus brevis N1, L. brevis N2, and Bacillus amyloliquefaciens S1, isolated from Korean fermented foods, on stress-induced colonic hypermotility and inflammatory signaling in a rat model. Methods: Thirty female Wistar rats were divided into five groups: Control (sham), Stress (water avoidance stress, WAS), Treatment A (WAS + L. brevis N1), Treatment B (WAS + L. brevis N2), and Treatment C (WAS + B. amyloliquefaciens S1) (n = 6 per group). Rats were exposed to WAS for 1 h daily for nine consecutive days. Furthermore, before stress exposure, probiotics were administered by oral gavage. The fecal pellet output (FPO), body weight, and food intake were recorded daily. Colon tissues were harvested for protein extraction, and inflammatory signaling was evaluated by Western blotting for NF-κB and IκBα, with β-actin as loading control. Immunoreactive bands were visualized by enhanced chemiluminescence (ECL) and quantified using ImageJ software version 1.54k. Results: The WAS group showed significantly higher FPO than the sham group (p < 0.01). FPO was significantly decreased in rats treated with L. brevis N2 compared to that in the WAS-only group (p < 0.05). Additionally, immunohistochemical analysis revealed that NF-κB expression was suppressed in all the probiotic groups. Conclusions: Therefore, probiotics are suggested to have elevated anti-inflammatory effects through the downregulation of the NF-κB signaling pathway by restoring IκBα expression and can be utilized as potential therapeutics for stress-induced gastrointestinal dysfunction. Full article

Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), arises from complex genetic and environmental interactions. Here, we integrate genome-wide association study (GWAS) meta-analyses with tissue-specific expression data from GTEx to map the polygenic architecture of IBD and its systemic implications. We identified 69 genome-wide significant single-nucleotide polymorphisms (SNPs) across 26 genes shared by CD and UC, revealing an almost equal partition of subtype-specific (50.7%) and shared (49.3%) risk variants. IL23R exhibited the highest allelic heterogeneity—three UC-specific, one CD-specific, and three shared SNPs—while ATG16L1′s four CD-specific variants underscored autophagy’s pivotal role in CD. Chromosomal mapping revealed distinct regulatory hotspots: UC-only loci on chromosomes 1 and 6, CD-only loci on chromosomes 10 and 16, and shared loci on chromosomes 7 and 19. Pathway enrichment emphasized IL-23/IL-17, Th17 differentiation, NF-κB, and JAK–STAT signaling as central to IBD pathogenesis. GTEx analyses showed uniformly high expression of IBD genes in gastrointestinal tissues, but pronounced heterogeneity across brain regions, including the cerebellum, frontal cortex, and hippocampus. This neuro-expression, together with enrichment of neurotrophin and neurodegeneration pathways and a nearly two-fold gene overlap with autism spectrum disorder, schizophrenia, and depression (FDR < 0.05), provides integrative evidence for gut–brain axis involvement in IBD. These findings consolidate prior work while extending perspectives on systemic disease implications. This study consolidates and systematizes dispersed genetic and transcriptomic findings into a unified reference framework. Our results highlight recurrent immune-regulatory and neuro-inflammatory pathways shared between gut and brain, offering a resource to guide future mechanistic, clinical, and translational investigations in IBD and related disorders. Full article

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