Search Results (253)

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

Background/Objectives: Emerging evidence suggests a role for oral microbiota in mood disorders, particularly bipolar disorder (BD), complementing established links between gut dysbiosis and psychiatric symptoms. This study investigates the composition of oral microbial taxa and the expression of inflammation-related pri-miRNAs (146a and 155) in individuals with BD, aiming to explore their potential as biomarkers in the oral–gut–brain axis. Methods: A matched case–control design was implemented, recruiting 25 BD patients and 46 controls matched by age and sex. Salivary samples were collected, and microbial profiling was conducted via real-time qPCR targeting major bacterial phyla and genera. Pri-miRNA 146a and 155 expression was evaluated through RT-qPCR using validated primers. Statistical comparisons between groups were performed using Fisher’s exact test and non-parametric tests for continuous variables. Results: Microbial analysis revealed significant reductions (p < 0.01) in α-Proteobacteria, γ-Proteobacteria, and Actinobacteria in BD patients versus controls. A shift toward a higher Firmicutes/Bacteroidetes ratio was observed in the BD cohort, suggesting differences in the oral biotic status between the two groups. However, pri-miRNA 146a and 155 expression levels did not differ significantly between the groups and exhibited high inter-individual variability. Conclusions: The findings indicate that oral microbiota composition differs in BD patients, potentially influencing systemic homeostasis through interactions with gut microbial communities and SCFA pathways. These findings should be interpreted as preliminary and hypothesis-generating given the modest sample size. While pri-miRNAs 146a and 155 did not distinguish BD status, the observed microbial taxa alterations should be regarded as exploratory and hypothesis-generating. Larger, longitudinal studies are required to clarify their potential role in BD pathogenesis and risk assessment. Full article

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders characterized by a number of dysfunctions in communication, social interactions and repetitive rigid patterns of behavior, interests, and activities. Despite much research, the causes of ASD remain elusive. In addition to genetic and epigenetic etiology, scientists have indicated inflammation, deregulation of cytokines, anti-brain autoantibodies, gut microbiota, and deregulated immunity as mechanisms possibly involved in the development of ASD phenotype. The aim of the study was to analyze the levels of IgA, IgE, and IgM immunoglobulins in the blood serum in patients with ASD to find out whether certain blood parameters are deregulated in that group of patients. The results suggest altered production of the immune cells in ASD patients which may be considered in the assessment of immune functions. Also, PCT% and LYMPH elevated values in patients with ASD might be of clinical relevance, possibly of predictive value for clinical preliminary diagnosis and therapy. Full article

Preterm birth remains a significant global health challenge and is strongly associated with heightened risks of long-term neurodevelopmental impairments, including cognitive delays, behavioural disorders, and emotional dysregulation. In recent years, accumulating evidence has underscored the critical role of the gut microbiota in early brain development through the gut–brain axis. In preterm infants, microbial colonisation is frequently delayed or disrupted due to caesarean delivery, perinatal antibiotic exposure, formula feeding, and prolonged stays in neonatal intensive care units (NICUs), all of which contribute to gut dysbiosis during critical periods of neurodevelopment. This review synthesises current knowledge on the sources, temporal patterns, and determinants of gut microbiota colonisation in preterm infants. This review focuses on the gut bacteriome and uses faecal-sample bacteriome sequencing as its primary method of characterisation. We detail five mechanistic pathways that link microbial disturbances to adverse neurodevelopmental outcomes: immune activation and white matter injury, short-chain fatty acids (SCFAs)-mediated neuroprotection, tryptophan–serotonin metabolic signalling, hypothalamic–pituitary–adrenal (HPA) axis modulation, and the integrity of intestinal and blood–brain barriers (BBB). We also critically examine emerging microbiota-targeted interventions—including probiotics, prebiotics, human milk oligosaccharides (HMOs), antibiotic stewardship strategies, skin-to-skin contact (SSC), and faecal microbiota transplantation (FMT)—focusing on their mechanisms of action, translational potential, and associated ethical concerns. Finally, we identify key research gaps, including the scarcity of longitudinal studies, limited functional modelling, and the absence of standardised protocols across clinical settings. A comprehensive understanding of microbial–neurodevelopmental interactions may provide a foundation for the development of targeted, timing-sensitive, and ethically sound interventions aimed at improving neurodevelopmental outcomes in this vulnerable population. Full article

Background/Objectives: Treatment for superior mesenteric artery (SMA) syndrome can include either weight restoration (conservative management) or surgical intervention, with the latter recommended when individuals fail conservative management. However, reasons for failure of conservative management are poorly understood. This systematic review seeks to better understand predictors of treatment outcomes for malnourished individuals with SMA syndrome, specifically regarding weight restoration and behavioral health intervention, and to better understand why individuals fail conservative management. Methods: Medline, Embase, and Web of Science were searched for articles that assessed treatment interventions for SMA syndrome in malnourished individuals. Results: Seventy-three articles (n = 189 malnourished individuals with SMA syndrome) were included in the final review. Most of the articles (n = 57) had an increased risk of bias as the amount of weight gain with treatment was not explicitly defined and thus the attribution of outcome for “failure” of conservative management could not be ascribed. Modest weight gain (mean 5.64 kg [12.1% body weight increase] or 1.3 kg/m² body mass index increase [9.4% increase in ideal body weight]) was associated with positive outcomes of conservative management. Psychological care also positively impacted treatment outcomes, especially for individuals with comorbid psychiatric conditions. Conclusions: Patients who achieve even modest weight gain have resolution of their SMA-related symptoms without a need for surgical intervention. Psychological treatment should be included for any patient struggling to achieve adequate weight restoration, with subsequent improved outcomes, given the high frequency of comorbid mental health illnesses, especially eating disorders. Full article

Autism spectrum disorder (ASD) involves complex genetic–environmental interactions. Prenatal valproic acid (VPA) exposure, a known environmental risk factor, induces ASD-like phenotypes in rodents, although the mechanisms linking gut microbiota dysbiosis to neurobehavioral deficits remain unclear. Evidence suggests gut–brain axis dysregulation via altered microbial diversity and reduced short-chain fatty acid (SCFA)-producing taxa contributes to ASD pathogenesis. This study investigated whether prenatal VPA exposure drives ASD-like behaviors through gut dysbiosis and SCFA-producer depletion (e.g., Clostridia, Lachnospiraceae), exploring neuroinflammation and oxidative stress as mechanisms. An ASD rat model was established by maternal VPA injection during specific gestational days. Behavioral tests assessed anxiety, sociability, repetitive behaviors, and cognition. Gut microbiota composition (16S rRNA sequencing), cytokine levels (ELISA), oxidative stress markers (biochemical assays), and microglial activation (Iba1 immunofluorescence) were analyzed. VPA-exposed offspring showed ASD-like behaviors accompanied by neurodevelopmental toxicity, manifesting as social deficits, repetitive grooming, and impaired memory. Concurrently, gut analysis revealed reduced alpha diversity and depleted SCFA-producers (e.g., Clostridia, Lachnospiraceae), alongside increased Bacteroidia and Enterobacteriaceae. Neuroinflammation (elevated IL-1β, IL-6, TNF-α, microglial activation) and oxidative stress (reduced GSH, SOD; elevated MDA, NO) were evident. Multivariate analyses linked dysbiosis to behavioral impairments. Prenatal VPA exposure induces gut microbiota dysbiosis, potentially exacerbating neuroinflammation and oxidative stress to drive ASD-like phenotypes. This establishes a mechanistic link between prenatal insults, gut–brain axis disruption, and neurodevelopmental abnormalities, highlighting microbial modulation and SCFA supplementation as potential ASD therapeutics. Furthermore, integrating behavioral, microbial, and molecular analyses advances understanding of gut–brain interactions in ASD and identifies microbiota–metabolite pathways as targets for neurodevelopmental disorders. Full article

Background: Disorders of gut–brain interaction (DGBI) have a significant impact on the quality of life of children and families. Forty percent of children with recurrent abdominal pain continue to have symptoms into adulthood. Specialized programs for the transition of adolescents with DGBI to adult care are scarce. There are no widely accepted guidelines for transition of care. Identifying risk factors for persistence of symptoms into adulthood is key to identifying the optimal population that should be part of such programs and guidelines design. Methods: A narrative comprehensive review was conducted using predefined keywords to identify risk factors for persistent DGBI in children/adolescents. Results: Female sex, psychological distress, family history of DGBI, and certain comorbidities had stronger evidence for persistence, whereas other risk factors rely on limited data. Conclusions: It is suggested that transition programs should focus on adolescents presenting with multiple coexisting risk factors. The program should at least include pediatric and adult neurogastroenterologists, dieticians, psychologists, and social workers. Tertiary prevention through psychological support, school-based programs, and management of anxiety and sleep disturbances may reduce the persistence of symptoms. Prospective studies should refine risk stratification and guide transition strategies. Full article

Recent studies increasingly highlight the complex interaction between gut microbiota and mental health, drawing attention to the role of the microbiota–gut–brain axis (MGBA) in the pathophysiology of mental and neurodevelopmental disorders. Changes in the composition of the gut microbiota—dysbiosis—are associated with conditions such as depression, schizophrenia, bipolar disorder (BD), autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and neurodegenerative diseases such as Parkinson’s and Alzheimer’s. These microbial imbalances can affect brain function through a variety of mechanisms, including activation of the immune system, alteration of intestinal permeability, modulation of the digestive and central nervous systems, and changes in the production of neuroactive metabolites such as short-chain fatty acids, serotonin, and tryptophan derivatives. The aim of this paper is to review the current state of knowledge on therapeutic strategies targeting the gut microbiome—including probiotics, prebiotics, synbiotics, personalized dietary interventions, and fecal microbiota transplantation (FMT)—which are becoming promising adjuncts or alternatives to conventional psychopharmacology, offering a forward-looking and individualized approach to mental health treatment. Understanding the bidirectional and multifactorial nature of MGBA may pave the way for new, integrative treatment paradigms in psychiatry and neurology, requiring further research and exploration of their scope of application. Full article

Background: Chronic ethanol consumption is a major global health concern traditionally associated with liver disease. Ethanol disrupts gut microbial communities, compromises intestinal barrier function, and contributes to hepatic, metabolic, and neurocognitive disorders. Methods: We conducted a systematic PubMed search and meta-analysis of 11 human and 19 animal studies evaluating ethanol-induced gut microbiota alterations. Studies were assessed for microbial diversity, taxonomic shifts, barrier integrity, and systemic effects. Effect sizes were calculated where possible, and interventional outcomes were examined. Results: Across species, ethanol exposure was consistently associated with reduced microbial diversity and depletion of beneficial commensals such as Faecalibacterium, Lactobacillus, Akkermansia, and Bifidobacterium, alongside an expansion of proinflammatory taxa (Proteobacteria, Enterococcus, Veillonella). Our analysis uniquely highlights discrepancies between human and animal studies, including opposite trends in specific genera (e.g., Akkermansia and Bifidobacterium) and the impact of confounders such as antibiotic exposure in human cohorts. We also demonstrate that microbiota-targeted interventions can partially restore diversity and improve clinical or behavioral outcomes. Conclusions: This meta-analysis highlights reproducible patterns of ethanol-induced gut dysbiosis across both human and animal studies. Full article

Background/Objectives: Recent evidence suggests that gut microbiota plays an important role in anxiety and stress-related disorders through interactions along the gut–brain axis. Our aim was to determine the microbiological diversity of intestinal microorganisms in individuals with acute and remission phases of PD when compared to healthy individuals. Another aim was also to analyze the differences in the metabolic pathways occurring in the intestinal microbiota of individuals from the three analyzed groups. Methods: A diagnosis was established using the Mini-International Neuropsychiatric Interview (M.I.N.I). The gut’s microbiota composition was analyzed through bacterial 16S rRNA gene sequencing (V1–V2 regions). The clinical evaluations included a BMI measurement, Short Form-36 Health Survey (SF-36), Hamilton Anxiety Scale (HAM-A), Montgomery–Åsberg Depression Rating Scale (MADRS), Columbia-Suicide Severity Rating Scale (C-SSRS), and State-Trait Anxiety Inventory (STAI). Results: We recruited 62 participants (31 PD and 31 controls). After conducting quality control filtering, data from 54 participants were analyzed (25 PD, 11 acute, 14 remission, and 29 controls). Observed richness was lower in the acute PD (63) group than in the control (74) and remission (66) (p = 0.038) groups, whereas the Shannon and Simpson indices and beta diversity (PERMANOVA) were not significantly different. The Ruminococcus gnavus group was enriched in acute PD; no other deconfounded differences in microbial composition were detected. Predicted functional differences were detected by edgeR only and included the pathways that are related to steroid biosynthesis and innate immune signaling. Conclusions: Distinct gut microbial signatures were associated with PD, implicating both the metabolic and inflammatory pathways in disease pathophysiology. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, and neuronal loss. Although amyloid-β plaques and neurofibrillary tangles have been the historical hallmarks of AD pathology, growing evidence highlights microglial-mediated neuroinflammation as a central driver of disease onset and progression. This review aims to provide an updated overview of the dual roles of microglia in AD, from their protective functions to their contribution to chronic inflammation and neurodegeneration. Methods: This review synthesizes findings from recent experimental and clinical studies to examine the molecular mechanisms underlying microglial activation and dysfunction in AD. Key areas of focus include microglial signaling pathways, gut–brain axis interactions, and immunometabolic regulation. The review also evaluates emerging immunomodulatory therapeutic strategies designed to restore microglial homeostasis. Results: Recent studies reveal that microglia undergo a dynamic transition from a homeostatic to a reactive state in AD, contributing to sustained neuroinflammation and impaired clearance of pathological aggregates. Molecular mechanisms such as TREM2 signaling, NLRP3 inflammasome activation, and metabolic reprogramming play critical roles in this process. Additionally, gut microbiota alterations and systemic inflammation have been shown to influence microglial function, further exacerbating disease pathology. Conclusions: Targeting microglial dysfunction through immunomodulatory strategies holds promise as a disease-modifying approach in AD. Therapeutic avenues under investigation include natural compounds, synthetic modulators, immunotherapies, and microbiota-based interventions. A deeper mechanistic understanding of microglial regulation may open new translational pathways for the development of effective treatments for AD. Full article

Alzheimer’s disease (AD), a prevalent neurodegenerative disorder in the aging population, remains without definitive therapeutic solutions. Emerging insights into the gut microbiota (GM) and its bidirectional communication with the central nervous system(CNS) through the microbiota–gut–brain axis (MGBA) have unveiled potential correlative mechanisms that may contribute to AD pathogenesis, though causal evidence remains limited. Dysregulation of GM composition (dysbiosis) exacerbates AD progression via neuroinflammation, amyloid-β (Aβ) deposition, and tau hyperphosphorylation (p-tau), while restoring microbial homeostasis presents a promising therapeutic strategy. Fecal microbiota transplantation (FMT), a technique to reconstitute gut ecology by transferring processed fecal matter from healthy donors, has demonstrated efficacy in ameliorating cognitive deficits and neuropathology in AD animal models. Preclinical studies reveal that FMT reduces Aβ plaques, normalizes tau phosphorylation, suppresses inflammasome activation, and restores microglial homeostasis through modulation of microbial metabolites and immune pathways. Although clinical evidence remains limited to case reports and small-scale trials showing potential therapeutic effect, safety concerns regarding long-term effects and protocol standardization necessitate further investigation. This review synthesizes current knowledge on GM–AD interactions, evaluates FMT’s mechanistic potential, and discusses challenges in translating this ancient practice into a cutting-edge AD therapy. Rigorous randomized controlled trials and personalized microbiota-based interventions are imperative to advance FMT from bench to bedside. Full article

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with behavioral and cognitive impairments. Increasing evidence also links ASD with systemic immune dysregulation, including abnormal cytokine profiles and chronic low-grade inflammation. Emerging evidence suggests that targeted dietary strategies and probiotic supplementation may modulate immune responses and gut–brain interactions in patients with ASD. This study aimed to evaluate the immunomodulatory effects of a structured anti-inflammatory diet (NeuroGutPlus) compared to multi-strain probiotics in children with ASD. NeuroGutPlus is a nutritionally complete anti-inflammatory dietary protocol that targets gut integrity, inflammation, and mitochondrial function. It includes a diet low in gluten, FODMAPs, casein, and artificial additives, and a high intake of omega-3 fatty acids, polyphenols, and fermentable fibers. Methods: A total of 30 children with ASD and 12 neurotypical controls were enrolled in a 12-week randomized controlled nutritional trial. Participants received either a NeuroGutPlus anti-inflammatory diet, probiotic supplementation (16 strains of Lactobacillus and Bifidobacterium), or no intervention. Plasma levels of 20 cytokines and chemokines were measured pre- and post-intervention using multiplex Luminex immunoassays. Principal component analysis (PCA) was used to explore shifts in the immune profile. Results: Patients treated with the NeuroGutPlus diet significantly reduced IFN-γ levels (p = 0.0090) and showed a stabilizing effect on immune profiles, as evidenced by PCA clustering. Probiotic supplementation led to a significant increase in IL-8 (+66.6 pg/mL; p = 0.0350) and MIP-1β (+74.5 pg/mL; p = 0.0100), along with a decrease in IFN-γ (p = 0.0070), suggesting reconfiguration of innate immune responses. Eight out of eleven biomarkers showed significant post-intervention differences between groups, indicating distinct immunological effects. Conclusions: This study provides evidence that anti-inflammatory diets exert broader and more consistent immunoregulatory effects than probiotics alone in children with ASD. These findings support the inclusion of precision dietary strategies as non-pharmacological interventions to mitigate immune-related dysfunction in patients with ASD. Full article

Oxytocin (OT), traditionally associated with reproduction and social bonding, has emerged as a key modulator of gastrointestinal (GI) physiology and appetite regulation behavior through its actions within the gut–brain axis. Central to this regulation are vagal oxytocin receptors (VORs), which are located along vagal afferent and efferent fibers and within brainstem nuclei such as the nucleus tractus solitarius and dorsal motor nucleus of the vagus. This review presents a comprehensive synthesis of current knowledge on the anatomical distribution, molecular signaling, developmental plasticity, and functional roles of VORs in the regulation of GI motility, satiety, and energy homeostasis. We highlight how VORs integrate hormonal, microbial, and stress-related cues and interact with other neuropeptidergic systems including GLP-1, CCK, and nesfatin-1. Recent advances in spatial transcriptomics, single-nucleus RNA sequencing, chemogenetics, and optogenetics are discussed as transformative tools for mapping and manipulating VOR-expressing circuits. Particular attention is given to sex differences, translational challenges, and the limited understanding of VOR function in humans. This article proposes VORs as promising therapeutic targets in dysphagia, obesity, and functional GI disorders. We outline future research priorities, emphasizing the need for integrative, cross-species approaches to clarify VOR signaling and guide the development of targeted, personalized interventions. Full article

The etiology of obsessive–compulsive disorder (OCD) remains incompletely understood, but it is widely recognized as the result of a complex interplay among multiple contributing mechanisms, often emerging during childhood. This narrative review synthesizes current evidence on the etiology of childhood-onset OCD, with particular focus on whether GM alterations are involved in the pathophysiological mechanisms underlying the disorder. Specifically, the review first examines both biological and psychosocial determinants of OCD, and then explores the role of the gut microbiome (GM), including the potential of psychobiotics as a novel therapeutic approach. OCD has a strong hereditary component, involving both common polygenic variants and rare mutations. Epigenetic mechanisms such as DNA methylation and microRNA play a role in mediating gene–environment interactions and influencing OCD risk. Dysfunction and hyperactivity within cortico-striato-thalamo-cortical circuits underlie one of the neurobiological bases of OCD. Infections and autoimmune reactions can trigger or exacerbate OCD, particularly in pediatric populations. A range of psychosocial factors have been implicated in the onset of OCD, often in interaction with underlying neurobiological vulnerabilities. Current evidence indicates that GM alterations may also contribute to OCD pathophysiology through immune-mediated neuroinflammation, disrupted gut–brain signaling, and neurotransmitter imbalance. Individuals with OCD present reduced microbial diversity and lower abundance of butyrate-producing taxa, as well as altered IgA levels and increased infection susceptibility. These shifts may affect dopaminergic, glutamatergic, and serotonergic pathways, particularly via tryptophan metabolism and compromised gut integrity. Thus, the GM plays a pivotal role in OCD, constituting a promising approach for understanding its etiology and highlighting the significant clinical potential of microbial-based treatments such as psychobiotics. Nevertheless, despite progress, gaps remain in understanding childhood-onset OCD determinants, including limited longitudinal studies, incomplete characterization of the GM, scarce psychobiotic trials, and a need for integrated multidisciplinary approaches. Moreover, epidemiological evidence is compromised by reliance on lay diagnoses, questionable assessment validity, and insufficient distinction from related disorders. Full article