Search Results (2,270)

Tryptophan (Trp) metabolism is involved in regulating various physiological and pathological processes, including neurological function, immune response, and gut homeostasis. This article focuses on autism spectrum disorder (ASD) and explores its relationship with abnormalities in the gut microbiota–Trp–brain axis. Studies have shown that ASD patients exhibit Trp metabolism disorders, with gut microbiota dysbiosis inducing systemic inflammation, activating indoleamine 2,3-dioxygenase 1 (IDO1), and promoting increased Trp entry into the kynurenine pathway (KP). This leads to a series of pathological changes, including the production of neurotoxic substances, serotonin system disorders, and impaired intestinal barrier function, which in turn exacerbate ASD symptoms through the gut–brain axis. Furthermore, based on preclinical and clinical studies, we have summarized that specific probiotic strains (such as Lactobacillus and Bifidobacterium) can alleviate the clinical manifestations of ASD by regulating the gut microbiota–Trp metabolic axis, improving immune responses, and enhancing intestinal barrier function. We emphasize that current probiotic interventions still face challenges such as insufficient long-term safety assessments and unclear molecular mechanisms. Future research should combine multi-omics technologies and multi-modal approaches to promote the development of personalized and precise intervention strategies. In summary, this review highlights the crucial role of tryptophan metabolism in ASD and the potential of probiotics as a novel adjunctive therapy targeting this metabolic pathway. Full article

The increasing and global distribution of microplastics and nanoplastics (MPs/NPs) in the environment has led to concern about their potential influence on human health, especially on the gastrointestinal tract, as well as the brain. MPs/NPs could traverse epithelial and endothelial barriers, disrupt the gut microbiota, and perturb the microbiota–gut–brain axis, leading to systemic inflammation and possibly extending neurodegenerative processes. Experimental models now demonstrate that MPs/NPs reprogram nuclear and mitochondrial epigenetics—DNA methylation, histone modifications, non-coding RNAs, and mitochondrial DNA regulation—in gut, immune, and neural cells with downstream effects on synaptic function, neuronal survival, and protein aggregation. This mechanistic narrative review integrates preclinical and emerging human evidence of how MPs/NPs compromise intestinal barrier integrity, modulate gut microbiota composition, affect the blood–brain barrier, and converge on oxidative stress, neuroinflammatory signaling, and cell death pathways within the central nervous system across key neurodegenerative diseases. Overall, the review offers an integrated model in which environmental exposure to chronic MPs/NPs disrupts the microbiota–gut–brain axis and drives concurrent nuclear and mitochondrial epigenetic remodeling, lowering the threshold for neurodegeneration in susceptible individuals, while outlining candidate mechanistic readouts that require exposure-specific validation in human-relevant models and longitudinal cohorts. Full article

The human gut microbiome is a complex ecosystem integral to host health, with butyrate-producing bacteria (BPB) playing a critical role in maintaining intestinal homeostasis. This scoping review explores the composition, function, and systemic influence of BPB, focusing on their metabolic product, butyrate, and its implications for gut integrity, immune modulation, and gut–brain axis (GBA) communication. Disruptions to BPB abundance, which is correlated with Western dietary patterns, food additives, and antibiotic exposure, are linked to gut dysbiosis and associated with a wide spectrum of chronic diseases, including inflammatory bowel disease (IBD), obesity, type 2 diabetes, neurodegenerative disorders, and psychiatric conditions. Butyrate supports colonocyte energy metabolism, reinforces epithelial barrier function, regulates goblet cell mucus production, and exerts anti-inflammatory effects via histone deacetylase inhibition and G-protein-coupled receptor signaling. The depletion of BPB and the resultant butyrate deficiency may represent a unifying pathophysiological mechanism underlying these conditions. Therapeutic strategies that restore BPB populations and butyrate levels, such as prebiotics, dietary fiber, and microbiota-targeted interventions, hold promise for mitigating inflammation and enhancing systemic health through microbiome modulation. Full article

Age-related neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and mild cognitive impairment, represent a growing global health challenge. The present medicines offer only symptomatic alleviation with poor disease-modifying efficacy. Increasing data suggests that the gut–brain axis and dietary health are measurable contributions to cognitive impairment as we age. This review first focused on the mechanistic link between gut dysbiosis and neurodegeneration. Furthermore, the review discusses preclinical and clinical research that show how probiotics and dietary supplements improve brain function in the elderly using supplemental therapy methods. It also indicates that randomized clinical studies and meta-analyses suggest that probiotics and particular nutritional supplements provide modest but consistent cognitive advantages, which are most noticeable when patients receive therapy at the initial stage of their disease development. These advantages might originate from the combined impact of gut microbiota, immunological signaling, and neuroprotective pathways, rather than specific targeted approaches. Thus, the current review highlights the reports, suggesting that probiotics and dietary supplements might be effective and safe therapies for age-related neurodegeneration. Full article

Background/Objectives: Irritable Bowel Syndrome (IBS) is a widely prevalent chronic disorder of brain–gut interaction which represents a clinical challenge due to its complex underlying causes and the lack of a standardized treatment approach. This cross-sectional research collected real-world data (RWD) on the effectiveness, safety, and usage pattern of a natural substance-based medical device, Colilen IBS, indicated for the treatment of IBS. Methods: Surveys were conducted both in Italy and Germany with 6101 participants, including 4425 patients, 1014 pharmacists, and 662 physicians using a structured GxP web platform that allows voluntary participants to share their experiences with the device. The validated platform was designed to comply with post-market surveillance requirements of EU Regulation 2017/745. Statistical analyses included descriptive evaluations of responses to gauge overall effectiveness and safety of the device. Results: The effectiveness reported with the medical device was judged extreme or great by 79.2% of patients, with 89.2% of whom observed symptom improvement within one month. Both safety and tolerability were rated extreme or great by 90.7% of patients. Healthcare professionals reported a similar rate on the overall effectiveness, with 94.9% of pharmacists and 95.9% of physicians indicating it extreme or great. Similarly, the safety profile was corroborated by nearly all pharmacists (97.0%) and physicians (98.2%) reporting extreme or great satisfaction with both safety and tolerability of the medical device. Conclusions: This research provides RWD supporting the effectiveness and safety of the product for treating IBS. The strong coherence among patients, pharmacists, and physicians in positively rating the device’s performance suggests that this medical device represents a therapeutic option that effectively addresses patient needs while minimizing safety concerns. Continuous RWD collection is essential, as it offers insights into real-world practice and ensures ongoing confirmation of the product’s safety and effectiveness. Ultimately, this will advance IBS patient care by integrating real-world evidence into clinical management. Full article

Mind–body practices integrating movement and meditation, such as Tai Chi and Aikido, have been proposed to influence the gut–brain axis through combined physiological and psychological pathways. However, evidence regarding their association with gut microbiota composition remains limited. This study explored gut microbiota diversity and taxonomic profiles in regular practitioners of Tai Chi and Aikido across different levels of meditation depth. Forty-two adults practicing Tai Chi or Aikido provided fecal samples for 16S rRNA sequencing, and meditation depth was assessed using the Meditation Depth Questionnaire (MEDEQ). Alpha diversity did not differ significantly between groups, although a descriptive trend toward higher diversity with increasing meditation depth was observed. Beta-diversity analyses suggested compositional differences associated with meditation level (ANOSIM R = 0.191, p = 0.035), along with an exploratory interaction signal between practice type and meditation depth (ANOSIM R = 0.296, p = 0.001). Taxonomic profiling highlighted distinct microbial patterns associated with both practice type and meditation depth. Short-chain fatty acid-associated genera, including Faecalibacterium and Roseburia, were relatively more abundant in Aikido practitioners with higher meditation scores, whereas Tai Chi practitioners showed higher relative abundances of Prevotella and Collinsella. Overall, these findings indicate that meditative movement practices are associated with distinct gut microbiota compositional patterns within this cohort. Given the exploratory and cross-sectional design, these results should be interpreted as hypothesis-generating. Future longitudinal studies incorporating functional and clinical outcomes are needed to clarify underlying mechanisms. Full article

Identifying probiotics that modulate the gut–brain axis is vital for non-pharmacological Alzheimer’s disease (AD) therapy. Through a staged screening from transgenic Drosophila to a D-galactose/AlCl₃-induced murine model, Lactobacillus acidophilus LA4 and Lacticaseibacillus paracasei F5 were prioritized for their ability to improve climbing indices and reduce Aβ deposition and AChE activity. In AD mice, LA4 and F5 significantly ameliorated cognitive deficits and anxiety-like behaviors. Mechanistically, both strains reduced hippocampal Aβ_1–42 and p-Tau levels, inhibited AChE, suppressed pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and enhanced antioxidant enzymes (SOD, GSH-Px). 16S rRNA analysis revealed restored Firmicutes/Bacteroidetes ratios and enrichment of SCFA-producers (Muribaculaceae, Dubosiella). Metabolomics highlighted remodeled purine and arginine pathways, with strain-specific effects on primary bile acid biosynthesis/sphingolipid metabolism (LA4) and butanoate metabolism/nicotinate and nicotinamide metabolism (F5). Consequently, LA4 and F5 alleviate AD pathology by restructuring microbial and metabolic profiles, thereby mitigating neuroinflammation and oxidative stress. These findings confirm the potential of specific probiotics as functional food ingredients for the prevention and adjuvant treatment of neurodegenerative diseases. Full article

Background/Objectives: Prebiotics, which are non-digestible compounds that selectively modulate gut microbiota, are recognized for their potential to promote host health. Although their bifidogenic effect is well documented, a systematic synthesis of how this microbial modulation translates into clinical gastrointestinal (GI) and metabolic outcomes across diverse populations is needed. This review aims to integrate mechanistic insights with clinical evidence to elucidate the pathway from prebiotic structures to tangible health benefits. Methods: This comprehensive narrative review details the structural properties of major prebiotics (e.g., inulin, FOS, and GOS) that govern their fermentation and the production of short-chain fatty acids (SCFAs). To evaluate clinical efficacy, an analysis of 22 randomized controlled trials from the past decade was conducted, focusing on human studies that utilized ISAPP-recognized prebiotics as the sole intervention. Results: The analysis confirms that prebiotic supplementation consistently increased the abundance of beneficial bacteria (e.g., Bifidobacterium and Lactobacillus) and SCFA production. These changes are associated with significant clinical improvements, including enhanced stool frequency and consistency, strengthened intestinal barrier function, and modulated immune responses. Benefits have been documented in healthy individuals, children, the elderly, and those with conditions such as constipation, metabolic syndrome, and antibiotic-associated dysbiosis. However, significant inter-individual variability in response was evident, and the study designs showed notable heterogeneity in prebiotic type, dosage, and duration. Conclusions: Prebiotics are effective modulators of gut health, driving clinical benefits through selective microbial fermentation and SCFA production. The documented heterogeneity and variability highlight the need for future research to focus on personalized nutritional strategies. Key priorities include standardizing intervention protocols, elucidating dose–response relationships, integrating multi-omics data to link taxonomy to function, and exploring novel applications such as synbiotic formulations and gut–brain axis modulation. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Compared with traditional two-dimensional (2D) models, patient-derived CRC organoids more faithfully preserve the genomic, transcriptomic, and architectural features of primary tumors, making them a powerful intermediate platform bridging basic discovery and clinical translation. Over the past several years, organoid systems have rapidly expanded beyond conventional epithelial-only cultures toward increasingly complex architectures, including immune-organoid co-culture models and mini-colon systems that enable long-term, spatially resolved tracking of tumor evolution. These advanced platforms, combined with high-throughput technologies and clustered regularly interspaced short palindromic repeats (CRISPR)-based functional genomics, have substantially enhanced our ability to dissect CRC mechanisms, identify therapeutic vulnerabilities, and evaluate drug responses in a physiologically relevant context. However, current models still face critical limitations, such as the lack of systemic physiology (e.g., gut–liver or gut–brain axes), limited standardization across platforms, and the need for large-scale, prospective clinical validation. These gaps highlight an urgent need for next-generation platforms and computational frameworks. The development of high-throughput multi-omics, CRISPR-based perturbation, drug screening technologies, and artificial intelligence-driven predictive approaches will offer a promising avenue to address these challenges, accelerating mechanistic studies of CRC, enabling personalized therapy, and facilitating clinical translation. In this perspective, we propose a roadmap for CRC organoid research centered on two major technical pillars: advanced organoid platforms, including immune co-culture and mini-colon systems, and mechanistic investigations leveraging multi-omics and CRISPR-based functional genomics. We then discuss translational applications, such as high-throughput drug screening, and highlight emerging computational and translational strategies that may support future clinical validation and precision medicine. Full article

Background: Irritable Bowel Syndrome (IBS) is a heterogeneous gastrointestinal disorder characterized by complex brain–gut interactions. Patient Similarity Networks (PSNs) offer a novel approach for exploring this heterogeneity and identifying clinically relevant patient subgroups. Methods: We analyzed data from 78 participants (49 IBS patients and 29 healthy controls) with 36 brain morphometric measures (FreeSurfer v7.4.1) and 6 measures of cognitive functions (5 RBANS domain indices plus a Total Scale score). PSNs were constructed using multiple similarity measures (Euclidean, cosine, correlation-based) with Gaussian kernel transformation. We performed community detection (Louvain algorithm), centrality analyses, feature importance analysis, and correlations with symptom severity. Statistical validation included bootstrap confidence intervals and permutation testing. Results: The PSN comprised 78 nodes connected by 469 edges, with four communities detected. These communities did not significantly correspond to diagnostic groups (Adjusted Rand Index = 0.011, permutation $p=0.212$), indicating IBS patients and healthy controls were intermixed. However, each community exhibited distinct neurobiological profiles: Community 1 (oldest, preserved cognition) showed elevated intracranial volume but reduced subcortical gray matter; Community 2 (youngest, most severe IBS symptoms) had elevated cortical volumes but reduced white matter; Community 3 (most balanced IBS/HC ratio, mildest IBS symptoms) showed the largest subcortical volumes; Community 4 (lowest cognitive performance across multiple domains) displayed the lowest RBANS scores alongside high IBS prevalence. Top network features included subcortical structures, corpus callosum, and cognitive indices (Language, Attention). Conclusions: PSN identifies brain–cognition communities that cut across diagnostic categories, with distinct feature profiles suggesting different hypothesis-generating neurobiological patterns within IBS that may inform personalized treatment strategies. Full article

This review highlights the anti-inflammatory and antioxidant effects of probiotics and their complex health-related impacts. The main health areas targeted are gastrointestinal inflammation, neuroinflammation, systemic metabolic disorders, and liver conditions. Probiotics work mechanistically to regulate key inflammatory pathways by suppressing nuclear factor (NF-κb) and mitogen-activated protein kinase (MAPK) pathways and activating antioxidant defenses through nuclear erythroid 2-related factor (Nrf2). They stimulate anti-inflammatory cytokines (including interleukin 10 (IL-10) and inhibit pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α), partly through the regulation of T cells. Probiotics also produce antioxidant metabolites (e.g., exopolysaccharides and short-chain fatty acids), which enhance the host’s resistance to oxidative stress. Supplementation with probiotics improves intestinal inflammation and oxidative injury in gut disorders. Clinical trials suggest that probiotic supplements may reduce neuroinflammation and oxidative stress, while improving cognitive or behavioral outcomes in neurodegenerative disorders. Overall, this review underscores that probiotics have potent anti-inflammatory and antioxidant effects within the gut–brain axis and across various organ systems, supporting their use as valuable adjunctive therapies for inflammatory and oxidative stress-related conditions. It further emphasizes that additional mechanistic research and controlled clinical trials are essential to translate these findings into the most effective therapeutic strategies. Full article

Background/Objectives: The milk fat globule membrane (MFGM) is a complex structure of polar lipids, gangliosides, and glycoproteins that has demonstrated anti-inflammatory, neuroprotective, and gut-modulatory effects in preclinical and human studies, but its effects on adult psychological outcomes have not been systematically synthesised. Methods: We conducted a systematic literature search across multiple databases using combined relevant keywords and Medical Subject Headings terms, with manual reference checks to ensure comprehensiveness. Of the 35 articles initially identified, 3 randomised controlled trials met the inclusion criteria: adult participants (≥20 years); bovine MFGM supplementation; a placebo or control group; and outcomes measuring stress, anxiety, or depression. A random-effects meta-analysis was performed, calculating standardised mean differences for stress, anxiety, and depression outcomes. Results: MFGM supplementation produced small but statistically significant reductions in stress and anxiety. Effects on depression were non-significant, though directionally favourable. Risk-of-bias assessments were conducted using Cochrane criteria and indicated low concerns across trials. Publication bias was not indicated, but interpretation was limited by the small number of studies. Conclusions: Whilst the evidence for depression is inconclusive, bovine MFGM supplementation may confer modest benefits for stress and anxiety in adults and could be part of a nutritional strategy to support overall mental well-being. Full article

Sweetener consumption has increased considerably in recent decades, driven by the growing demand from consumers of low-calorie products for weight control and, especially, from diabetic patients who require safe sweetener alternatives without affecting their glucose levels. However, the latest scientific evidence seems to indicate that the continued consumption of various sweeteners could significantly alter the gut microbiota, triggering consequences that go beyond metabolic health and could affect sleep quality. Among the most used non-caloric sweeteners in the food industry are sucralose and saccharin. Several studies have shown that prolonged consumption of these sweeteners can significantly alter the composition of the gut microbiota. In particular, its consumption might lead to a decrease in beneficial bacteria such as Lactobacillus and Bifidobacterium, along with an increase in potentially pathogenic microorganisms such as Clostridium difficile and Escherichia coli. This dysbiosis creates a chronic low-grade inflammatory environment and contributes to the deterioration of glucose metabolism, factors that negatively impact the regulation of the gut–brain axis. Consequently, these alterations could interfere with the neuroendocrine mechanisms involved in sleep, promoting the development of disorders such as insomnia, sleep fragmentation, and decreased subjective sleep quality. The aim of this narrative review is to synthesize the current scientific evidence on the impact of artificial sweeteners on the gut microbiota and their potential involvement in sleep disorders. The underlying biological mechanisms will be analyzed and the clinical relevance of these interactions discussed, laying the groundwork for future research that will contribute to the development of dietary recommendations and therapeutic strategies aimed at modulating the microbiota to improve sleep health. Full article

The gut microbiome produces thousands of metabolites with potential to modulate central nervous system function through peripheral or direct neural mechanisms. Tourette syndrome, attention-deficit/hyperactivity disorder, and autism spectrum disorder exhibit shared neurotransmitter dysregulation and microbiome alterations, yet mechanistic links between microbial metabolites and receptor-mediated neuromodulation remain unclear. We screened 27,642 microbiome SMILES metabolites for blood–brain barrier permeability using rule-based SwissADME classification and a PyTorch 2.0 neural network trained on 7807 experimental compounds (test accuracy 86.2%, AUC 0.912). SwissADME identified 1696 BBB-crossing metabolites following Lipinski’s criteria, while PyTorch classified 2484 metabolites with expanded physicochemical diversity. Following 3D conformational optimization (from SMILES) and curation based on ≤32 rotatable bonds, molecular docking was performed against five neurotransmitter receptors representing ionotropic (GABRA2, GRIA2, GRIN2B) and metabotropic (DRD4, HTR1A) receptor classes. The top 50 ligands across five receptors demonstrated method-specific BBB classification (44% SwissADME-only, 44% PyTorch-only, 12% overlap), validating complementary prediction approaches. Fungal metabolites from Ascomycota dominated high-affinity top ligands (66%) and menaquinone MK-7 showed broad phylogenetic conservation (71.4% of phylum). Our results establish detailed receptor–metabolite interaction maps, with fungal metabolites dominating high-affinity ligands, challenging the prevailing bacterial focus of the microbiome and providing a foundation for precision medicine and a framework for developing microbiome-targeted therapeutics to address clinical needs in neurodevelopmental disorders. Full article

In recent years, there has been increasing interest in the study of the gut–brain axis. Furthermore, there appears to be a relationship between abdominal pain, selective eating patterns, emotional instability, and intestinal disorders in Autism Spectrum Disorder (ASD). This work describes the development and accessibility evaluation of the INCE mobile app. This mobile app allows users to obtain levels of gut–brain interaction severity using two scientifically proven scales: The Gastrointestinal Symptom Severity Scale (GSSS) and the Pain and Sensitivity Reactivity Scale (PSRS). The validity of both instruments was established in previous studies in neurotypical and autistic populations. Statistically significant improvements were found following post-design changes in the use and accessibility of the INCE app (.NET Maui 9 Software) reported by professionals (p = 0.013), families (p = 0.011), and adolescents (p = 0.004). INCE represents an important contribution to evidence-based applications and clearly translates into society. Full article