Search Results (491)

Diet influences brain health through many connected metabolic and molecular pathways, and these effects are stronger in obesity. This review links diet quality with cognitive decline and dementia risk. Ultra-processed, high-fat, high-sugar diets drive weight gain, insulin resistance, and chronic inflammation. These changes trigger brain oxidative stress, reduce DNA repair, deplete NAD⁺, disturb sirtuin/PARP balance, and alter epigenetic marks. Gut dysbiosis and leaky gut add inflammatory signals, weaken the blood–brain barrier, and disrupt microglia. Mediterranean and MIND diets, rich in plants, fiber, polyphenols, and omega-3 fats, slow cognitive decline and lower dementia risk. Trials show extra benefit when diet improves alongside exercise and vascular risk control. Specific nutrients can help in certain settings. DHA and EPA support brain health in people with low omega-3 status or early disease. B-vitamins slow brain shrinkage in mild cognitive impairment when homocysteine is high. Vitamin D correction is beneficial when levels are low. A practical plan emphasizes healthy eating and good metabolic control. It includes screening for deficiencies and supporting the microbiome with fiber and fermented foods. Mechanism-based add-ons, such as NAD⁺ boosters, deserve testing in lifestyle-focused trials. Together, these measures may reduce diet-related brain risk across the life span. At the same time, artificial intelligence can integrate diet exposures, adiposity, metabolic markers, multi-omics, neuroimaging, and digital phenotyping. This can identify high-risk phenotypes, refine causal links along the diet–obesity–brain axis, and personalize nutrition-plus-lifestyle interventions. It can also highlight safety, equity, and privacy considerations. Translationally, a pattern-first strategy can support early screening and personalized risk reduction by integrating diet quality, adiposity, vascular risk, micronutrient status, and microbiome-responsive behaviors. AI can aid measurement and risk stratification when developed with privacy, equity, and interpretability safeguards, but clinical decisions should remain mechanism-aligned and trial-anchored. Full article

Background/Objectives: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by persistent social communication difficulties and restricted, repetitive behaviors, with prevalence estimates continuing to rise worldwide. The gut–brain axis has been proposed as a potential contributor to ASD, yet human studies yield inconsistent findings, partly due to confounding effects of diet and behavior. Methods: Here, we investigated the gut bacteriome and mycobiome of children with ASD (n = 17) compared with their non-ASD siblings (n = 9) and parents without ASD (n = 27), alongside detailed assessment of dietary intake (n = 79) using 7-day food diaries. Results: Multi-kingdom microbiome profiling revealed no significant differences in α- or β- diversity across ASD, sibling, and parental groups, with only minor taxonomic variation observed. Similarly, fungal community composition showed negligible group-level differences. By contrast, dietary patterns strongly differentiated ASD from non-ASD participants: children with ASD consumed higher levels of sweets and sugary foods, lower portions of vegetables, and exhibited reduced overall dietary diversity. Statistical analyses confirmed that dietary factors, rather than microbial composition, explained variation in ASD diagnosis. Conclusions: These findings suggest that selective and repetitive eating behaviors are characteristic of ASD shape dietary intake, which in turn influences gut microbial diversity. Thus, in humans, the directionality may run primarily from behavior to diet to microbiome, rather than from microbiome to behavior. Our results underscore the importance of incorporating dietary variables into microbiome research and highlight the need for targeted nutritional interventions to improve health outcomes in individuals with ASD. Full article

The gut-brain axis has emerged as a critical pathway influencing central nervous system (CNS) tumor biology through complex microbiome-mediated mechanisms. Understanding these interactions is essential for developing novel therapeutic strategies and biomarkers for CNS tumors. To systematically review and meta-analyze current evidence on gut microbiota interactions with CNS tumors, examining mechanisms, clinical correlations, therapeutic implications, and biomarker potential. We conducted a comprehensive systematic review following PRISMA guidelines, searching PubMed, EMBASE, Google Scholar, and Cochrane Library databases for studies published from 2010–2025. A random-effects meta-analysis of reported statistical outcomes was performed to quantify microbiome alterations using standardized mean differences (Cohen’s d) and diagnostic accuracy measures. Analyses were based on published summary statistics rather than reprocessed raw sequencing data, acknowledging cross-study heterogeneity. From 161 identified records, 12 studies met inclusion criteria (6 clinical studies, n = 387 participants; 6 preclinical studies). Meta-analysis revealed significant Shannon diversity reduction in CNS tumor patients (Cohen’s d = −1.237 [95% CI: −1.614, −0.860; 95% PI: −2.48, −0.12]) with moderate heterogeneity (I² = 60.5%). Evidence demonstrated significant gut microbiome alterations with reduced microbial diversity, increased pathogenic bacteria (Akkermansia muciniphila: 2.23-fold increase, Fusobacterium spp.: 2.04-fold increase), and decreased beneficial bacteria (Bifidobacterium spp.: 47% reduction, Lachnospira spp.: 56% reduction). Diagnostic performance showed fair discrimination (pooled AUC = 0.786 [95% CI: 0.781, 0.791]). Key mechanisms include bidirectional tumor-microbiota interactions through immune system modulation, metabolic pathway alterations involving short-chain fatty acids, and inflammatory response modifications within the altered CNS immune privilege environment. Preliminary evidence suggests gut microbiota alterations in CNS tumor patients, but findings require validation in large, standardized cohorts before clinical application. Current evidence quality is low (GRADE assessment), necessitating substantial additional research. Full article

COVID-19 can cause long-term symptoms, such as a post-infection syndrome, known as Long-COVID. Among the symptoms present during this period, the most reported are gastrointestinal symptoms. This study discusses the effects of changes in the gut microbiota of post-COVID-19 patients. SARS-CoV-2 infection is associated with significant alterations in gut microbial composition, disturbing its homeostasis and promoting a reduction in the abundance of beneficial symbiotic bacteria and an increase in the abundance of opportunistic pathogens. Furthermore, the composition of the gut microbiota may play a role in the prognosis of patients with post-COVID-19 infection. The microbiota of the intestinal tract and the respiratory tract influence each other; therefore, the gut–lung axis has attracted increasing interest in understanding COVID-19. Moreover, the brain–gut axis has been studied, since there have been reports of anxiety and depression along with post-COVID-19 gastrointestinal symptoms. Treatments options for intestinal dysbiosis in Long-COVID patients include probiotics, prebiotics, and fecal microbiota transplantation. These treatments may serve as an approach to improve gastrointestinal symptoms during Long-COVID, increasing microbiome diversity, strengthening the integrity of intestinal barrier functions, and consequently influencing the treatment of COVID-19. Full article

Treatment-resistant depression (TRD) affects 20–30% of patients with major depressive disorder and presents a significant clinical challenge due to its biological diversity. This review highlights standard mechanisms that contribute to treatment resistance beyond traditional monoaminergic models. Evidence supports serotonergic dysregulation, including 5-HT1A autoreceptor dysfunction and “serotonin flooding” as well as dopaminergic deficits linked to anhedonia and an imbalance between glutamate and GABA that impair synaptic plasticity. Changes in neurotrophic signaling, such as reduced BDNF and VEGF activity, complicate recovery by limiting neural repair and regeneration. Chronic inflammation and oxidative stress contribute to neuronal dysfunction, while HPA axis dysregulation may exacerbate depressive symptoms and resistance to antidepressants. Emerging evidence suggests that obesity and gut microbiota imbalance reduce the production of short-chain fatty acids by bacteria and increase intestinal permeability, thereby influencing neuroinflammatory and neurochemical processes in TRD. Neuroimaging studies reveal hyperconnectivity within the default mode network and impaired reward circuits, both of which are associated with persistent symptoms and a poor treatment response. By combining evidence on inflammation, oxidative stress, neuroendocrine disturbances, microbiome changes, and brain connectivity issues, this review develops a comprehensive framework for understanding TRD. It emphasizes the importance of biomarker-based subtyping to guide personalized future treatments. Full article

Irritable Bowel Syndrome (IBS) is one of the most prevalent gastrointestinal disorders, affecting about 11% of the global population and exerting a substantial burden on quality of life and healthcare systems. Despite the emerging interest in this disease, its pathophysiology remains elusive, reflecting the interplay between the brain–gut axis, neuroendocrine dysregulation, immune activation, barrier dysfunction, microbial imbalance, and environmental triggers. Disruptions in the hypothalamic–pituitary–adrenal axis, impaired serotonin signaling, bile acid malabsorption, and altered intestinal permeability collectively result in the emergence of abnormal motility, visceral hypersensitivity, and chronic inflammation. The gut microbiome further modulates these processes by influencing neurotransmitter metabolism, immune responses, and epithelial integrity, positioning it as both a driver of symptoms and a promising therapeutic target. The aim of this review is to synthesize current mechanistic insights into IBS, highlighting the interconnected roles of the brain–gut axis, immune modulation, and microbial dynamics, and to explore how these pathways may be translated into precision medicine approaches. This review integrates molecular, microbial, and neuroimmune perspectives to propose a systems-level understanding of IBS pathophysiology and its implications for precision medicine. By integrating host–microbe interactions, dietary influences, and genetic predispositions, we highlight the mechanistic complexity underlying IBS and the potential for translating these insights into personalized strategies for symptom control and improved quality of life. Full article

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

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 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

Globally, Parkinson’s disease (PD) is the neurodegenerative condition with the most rapidly increasing prevalence, and a growing body of evidence associates its pathology with impairments in the gut–brain axis. Traditionally viewed as a disease marked by the loss of dopaminergic neurons, emerging evidence emphasizes that chronic neuroinflammation is a driver of neurodegeneration, with gut-originating inflammation playing a crucial role. Increased intestinal permeability, often called “leaky gut,” allows harmful substances, toxins, and misfolded α-synuclein into the systemic circulation, potentially exacerbating neuroinflammation and spreading α-synuclein pathology to the brain through the vagus nerve or compromised blood–brain barrier (BBB). This review synthesizes current insights into the relationship between gut health and PD, emphasizing the importance of gut permeability in disrupting intestinal barrier function. This paper highlights innovative therapeutic approaches, particularly personalized therapies involving gut microbiome engineering, as promising strategies for restoring gut integrity and improving neurological outcomes. Modulating specific gut bacteria to enhance the synthesis of certain metabolites, notably short-chain fatty acids (SCFAs), represents a promising strategy for reducing inflammatory responses and decelerating neurodegeneration in Parkinson’s disease. 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

Methylphenidate (MPH) and its active enantiomer, dexmethylphenidate, are widely prescribed as first-line therapies for attention deficit hyperactivity disorder (ADHD), yet their increasing non-medical use highlights significant clinical and toxicological challenges. MPH blocks dopamine (DAT) and norepinephrine (NET) transporters, thereby elevating synaptic catecholamine levels. While this underpins therapeutic efficacy, prolonged or abusive exposure has been associated with mitochondrial impairment, disrupted bioenergetics, and excessive reactive oxygen species (ROS) production, which collectively contribute to neuronal stress and long-term neurotoxicity. Growing evidence suggests that the gut–brain axis may critically influence MPH outcomes: diet-induced shifts in microbiome composition appear to regulate oxidative stress, neuroinflammation, and drug metabolism, opening potential avenues for dietary or probiotic interventions. From a forensic perspective, the detection and monitoring of MPH misuse require advanced methodologies, including enantioselective LC–MS/MS and analysis of alternative matrices such as hair or oral fluids, which enable retrospective exposure assessment and improves abuse surveillance. Despite its established therapeutic profile, MPH remains a compound with a narrow balance between clinical benefit and toxicological risk. Future directions should prioritize longitudinal human studies, biomarker identification for abuse monitoring, and the development of mitochondria-targeted therapies to minimize adverse outcomes and enhance safety in long-term treatment. Full article