Search Results (503)

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

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

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

Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent multi-systemic symptoms such as fatigue, cognitive impairment, and respiratory dysfunction. Accumulating evidence indicates that gut and oral microbiota play an important role in its pathogenesis. Patients with long COVID consistently exhibit reduced microbial diversity, depletion of beneficial short-chain fatty acid (SCFA)-producing species such as Faecalibacterium prausnitzii and Bifidobacterium spp. and enrichment of proinflammatory taxa including Ruminococcus gnavus, Bacteroides vulgatus, and Veillonella. These alterations may disrupt intestinal barrier integrity, sustain low-grade systemic inflammation, and influence host immune and neuroendocrine pathways through the gut–brain and gut–lung axes. Distinct microbial signatures have also been associated with symptom clusters, including neuropsychiatric, respiratory, and gastrointestinal manifestations. Proposed mechanisms linking dysbiosis to long COVID include impaired SCFA metabolism, tryptophan depletion, microbial translocation, and interactions with host immune and inflammatory responses, including autoantibody formation and viral antigen persistence. Preliminary interventional studies using probiotics, synbiotics, and fecal microbiota transplantation suggest that microbiome-targeted therapies may alleviate symptoms, although evidence remains limited and heterogeneous. This review synthesizes current literature on the role of gut and oral microbiota in long COVID, highlights emerging microbial biomarkers, and discusses therapeutic implications. While causality remains to be firmly established, restoring microbial balance represents a promising avenue for diagnosis, prevention, and management of long COVID. 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

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

Probiotics like Lactobacillus sp. are extensively studied for their beneficial host interactions, including the gut–brain axis, anti-inflammatory effects, immune system interactions, restoration of gut dysbiosis, and anti-aging effects. In the current study, pearl millet was fermented with Lactobacillus plantarum strains DHCU 70 and MCC 5231, which enhanced the nutritional, bioactive, and functional properties of derived probiotic beverages. Compared to unfermented controls, fermented beverages exhibited increased protein content and vitamins B₁, B_2, and B₃, with decreased carbohydrate and dietary fiber levels. The probiotics have maintained viability exceeding 12 log CFU/mL and showed resistance to harsh gastrointestinal conditions. Fermentation increased total phenolic content from 13.38 ± 0.40 mg GAE/100 g to 42.10 ± 2.65 mg GAE/100 g (LPDB) and 47.76 ± 1.37 mg GAE/100 g (LPMB) and total flavonoid content from 13.01 ± 1.18 mg QE/100 g to 23.12 ± 2.73 mg QE/100 g and 24.21 ± 0.98 mg QE/100 g, respectively. Antioxidant assays showed DPPH radical scavenging improved by 37%, ferrous ion chelation rose from 71.69 ± 0.09 mg TE/100 g to 91.45 ± 0.006 mg TE/100 g, ABTS scavenging increased from 71.62 mg TE/100 g to 82.51 ± 0.04 mg TE/100 g (LPDB) and 89.74 ± 0.04 mg TE/100 g (LPMB) and superoxide radical inhibition rose from 51.40 ± 0.98% to 81.77 ± 0.03% (LPDB) and 79.92 ± 0.02% (LPMB). In the in vivo model, Caenorhabditis elegans, fermented beverage treatments significantly improved health-span parameters like head-swing frequency (13.51% increase), body bend frequency (8.41% increase), pharyngeal pumping (8.15% increase) with reduced lipofuscin accumulation and intracellular reactive oxygen species while median lifespan extended beyond 24 days versus 14–16 days in controls (p < 0.05). Gompertz mortality modeling revealed a significant decrease in the aging rate parameter, indicating systemic mitigation of stress-induced physiological decline. These combined nutritional, bioactive, and in vivo longevity results underscore the potential of L. plantarum-fermented pearl millet beverages as functional nutraceuticals that target oxidative stress and promote healthy aging. 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

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

Alcohol-associated liver disease (ALD) includes a spectrum from steatosis and steatohepatitis to cirrhosis and hepatocellular carcinoma driven by oxidative stress, immune activation, and systemic inflammation. Ethanol metabolism through alcohol dehydrogenase, aldehyde dehydrogenase, and cytochrome P450 2E1 generates reactive oxygen and nitrogen species, leading to mitochondrial dysfunction, hepatocellular injury, and activation of inflammatory and fibrogenic pathways. Beyond hepatic effects, ALD engages the gut–liver–brain axis, where microbial dysbiosis, blood–brain barrier disruption, and neuroinflammation contribute to cognitive impairment and cerebrovascular risk. The emerging concept, metabolic dysfunction-associated steatotic liver disease and increased alcohol intake (MetALD), presents the synergistic impact of alcohol and metabolic comorbidities, enhancing oxidative injury and fibrosis. This review summarizes key mechanisms connecting oxidative stress to multisystem pathology and highlights the need for precision therapies targeting redox imbalance, immune dysregulation, and gut–brain–liver interactions to improve outcomes in ALD and MetALD. 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

Inter-organ communication plays a vital role in the pathogenesis of neurodegenerative diseases (ND), including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS). Emerging research highlights the involvement of the gut–brain axis, immune system, and peripheral metabolic systems in modulating neuroinflammation, protein misfolding, and neuronal dysfunction by releasing cytokines, adipokines, growth factors, and other soluble factors, which in turn affect neuronal health and systemic inflammation. This review explores the complex bidirectional interactions between the brain and peripheral organs, including the gut, adipose tissue, liver, muscle, bone and immune system. Notably, the gut microbiome’s role in neurodegenerative diseases through the gut–brain axis, the impact of adipose tissue in inflammation and metabolic regulation, and the muscle–brain axis with its neuroprotective myokines are also discussed. Additionally, we examine the neuro-immune axis, which mediates inflammatory responses and exacerbates neurodegeneration, and liver–brain axis that is implicated in regulating neuroinflammation and promoting disease progression. Dysregulation of inter-organ pathways contributes to the systemic manifestations of neurodegenerative diseases, offering insights into both potential biomarkers and therapeutic targets, and, in turn, promising strategies for preventing, diagnosing, and treating neurodegenerative diseases. 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