ID: 32673657
Title: Gut microbiome in neuroendocrine and neuroimmune interactions: The case of genistein.
Abstract: The healthy and diverse microbes living in our gut provide numerous benefits to our health. It is increasingly recognized that the gut microbiome affects the host's neurobehavioral state through production of metabolites, modulation of intestinal immunity (e.g., cytokines) and other mechanisms (e.g., gut neuropeptides). By sending the sensed information (e.g., metabolic and immunologic mediators) about the state of the inner organs to the brain via afferent fibers, the vagus nerve maintains one of the connections between the brain and GI tract, and oversees many critical bodily functions (e.g., mood, immune response, digestion and heart rate). The microbiota-gut-brain axis is a bidirectional communication between the gut, its microbiome, and the nervous system. In the present review, the roles of microbiome in neuroendocrine and neuroimmune interactions have been discussed using naturally occurring isoflavones, particularly the phytoestrogen genistein, as there are sex differences in the interactions among the microbiome, hormones, immunity and disease susceptibility. A deep understanding of the mechanisms underlying the interactions among the endocrine modulators, brain, endocrine glands, gut immune cells, vagus nerve, enteric nervous system and gut microbiome will provide important knowledges that may ultimately lead to treatment and prevention of debilitating disorders characterized by deficits of microbiome-neuroendocrine-neuroimmune relationships.

ID: 36444018
Title: Health benefits of proanthocyanidins linking with gastrointestinal modulation: An updated review.
Abstract: Proanthocyanidins (PACs) are the bioactive components naturally present in daily diet, especially in fruits and vegetables. Multiple pieces of evidence suggested that ingestion of PACs or diets full of PACs might contribute to physiological benefits, such as metabolic syndrome regulation, immune modulation, cancer prevention, and neuroprotection. Many studies stated that dysbiosis is closely linked with the abovementioned health conditions, and the extremely poor bioavailability of PACs, directly associated with the structural diversity, leads to extensively metabolized through gut microbiota (GM). GM transforms PACs into bioactive metabolites. Conversely, PACs also modulate the gut microbiome and the composition of GM. Thus, the complex bidirectional interactions between PACs and gut microbiota might help to understand the ambiguity between bioavailability and pleiotropic bioactivity. In this review, we summarize recent in vivo and in vitro studies from the aspect of intestinal function of PACs and its associated disease, as well as the underlying mechanisms.

ID: 39203783
Title: An Anti-Inflammatory Diet and Its Potential Benefit for Individuals with Mental Disorders and Neurodegenerative Diseases-A Narrative Review.
Abstract: This narrative review synthesizes current evidence regarding anti-inflammatory dietary patterns and their potential benefits for individuals with mental disorders and neurodegenerative diseases. Chronic low-grade inflammation is increasingly recognized as a key factor in the etiology and progression of these conditions. The review examines the evidence for the anti-inflammatory and neuroprotective properties of dietary components and food groups, focusing on whole foods rather than specific nutrients or supplements. Key dietary components showing potential benefits include fruits and vegetables (especially berries and leafy greens), whole grains, legumes, fatty fish rich in omega-3, nuts (particularly walnuts), olive oil, and fermented foods. These foods are generally rich in antioxidants, dietary fiber, and bioactive compounds that may help modulate inflammation, support gut health, and promote neuroprotection. Conversely, ultra-processed foods, red meat, and sugary beverages may be harmful. Based on this evidence, we designed the Brain Anti-Inflammatory Nutrition (BrAIN) diet. The mechanisms of this diet include the modulation of the gut microbiota and the gut-brain axis, the regulation of inflammatory pathways, a reduction in oxidative stress, and the promotion of neuroplasticity. The BrAIN diet shows promise as an aid to manage mental and neurodegenerative disorders.

ID: 40402417
Title: Fermented Vegetables as a Source of Psychobiotics: A Review of the Evidence for Mental Health Benefits.
Abstract: The human gut microbiome, comprised of trillions of microorganisms, plays a pivotal role in both physical and mental health. Recent research underscores the intriguing connection between gut bacteria and mental well-being, leading to the emergence of psychobiotics-microbes with mental health benefits. This review aims to explore fermented vegetables, a traditional dietary staple experiencing renewed interest, as a potential source of psychobiotics. Fermentation alters the microbial composition of vegetables, enriching them with beneficial bacteria such as Lactobacillus and Bifidobacterium. Various fermented vegetables, including kimchi, sauerkraut, and tempeh, host distinct bacterial communities. The review investigates how these psychobiotics may impact mental health through the gut-brain axis, a communication network between the gut and the central nervous system. Possible mechanisms encompass neurotransmitter modulation (e.g., serotonin, GABA), inflammation reduction and immunity modulation, and stress response enhancement through the hypothalamic-pituitary adrenal (HPA) axis. Clinical studies exploring the influence of fermented vegetables on mental health outcomes, including anxiety, depression, and cognitive function, are critically evaluated. The review assesses the efficacy of different fermented vegetables and probiotic strains while recognizing limitations in existing research and the necessity for further investigation.

ID: 41009418
Title: Plant-Derived Nutraceuticals in Mental Health and Brain Function: Mechanisms of Action and Therapeutic Potential.
Abstract: Considering the multiple benefits of nutraceuticals, and given the growing interest in exploring these effects, understanding their mechanisms and implications in mental well-being and neurological integrity is essential and requires further examination to clarify their therapeutic potential. This narrative review provides a comprehensive overview of recent advances in plant-derived nutraceuticals, particularly regarding their impact on mental health and brain function, by examining their bioactive components, their involvement in neuropsychiatric conditions, their role in neurodegeneration, emerging nutraceuticals with clinical relevance, and gut microbiome interactions with nutraceuticals and phytochemicals. Essential fatty acids, prebiotics, phytochemicals, and nutrients such as amino acids, vitamins, minerals, and omega-3 fatty acids contribute to mood regulation and cognitive function. Nutraceuticals can prevent or slow neurodegeneration by targeting misfolded proteins and modulating oxidative stress, neuroinflammation, mitochondrial dysfunction, and dysregulated signaling pathways. Phytochemicals act as phytopsychobiotics, influencing mental health through gut microbiome modulation and generation of bioactive metabolites. Hypericum and curcumin exert neuroprotective, anti-inflammatory, antioxidant, and antidepressant effects. Ginsenosides promote neuroprotection, partially via gut microbiome-mediated mechanisms. Administration of Ginkgo biloba polysaccharides and lavender essential oil improves neurotransmitter regulation, intestinal barrier integrity, and depressive-like behaviors in preclinical models. Omega-3 polyunsaturated fatty acids, anthocyanins, quercetin, catechins, and chlorogenic acid support neuroprotection and cognitive function via modulation of beneficial gut bacteria, short-chain fatty acid production, anti-inflammatory effects, and serotonin metabolism. The landscape of nutraceuticals offers a diverse range of dietary options with considerable potential to promote mental health and prevent neurodegeneration, but further research is required to elucidate how the gut microbiome may enhance these bioactivities.

ID: 41034120
Title: The Extraction Technologies, Nutritional Compositions, and Health Benefits of Camellia oleifera Seed Oil̶A Review.
Abstract: Camellia oleifera seed oil (COSO), a nutritionally rich oil from a key southern Chinese woody crop, has gained significance in food, cosmetic, and pharmaceutical fields. This review summarizes its high-value products, extraction technologies, chemical composition, and health benefits. High-value products include crude COSO and refined COSO, with by-products such as seed meal and shells that yield bioactive compounds for animal feed, fertilizers, and nutraceuticals. Extraction methods range from traditional mechanical pressing and solvent extraction to innovative approaches like supercritical CO2 extraction and enzyme/ultrasound/microwave-assisted techniques. Chemically, COSO features a balanced fatty acid profile dominated by oleic acid (52.13%-86.6%), along with abundant phytosterols, squalene, α-tocopherol, and phenolic compounds, which collectively enhance its oxidative stability and antioxidant activity. Health benefits include antioxidative and anti-inflammatory effects, cardiovascular protection, neuroprotection in Alzheimer's disease, anti-fatigue properties, antimicrobial activity, and osteoporosis prevention via mechanisms like NF-κB signaling modulation. In conclusion, COSO and its by-products offer nutritional, industrial, and therapeutic value, with innovative technologies promoting sustainability. Further research on large-scale optimization and by-product utilization is needed to fully exploit their potential in functional foods and healthcare.

ID: 41364932
Title: Dietary Fiber Deprivation Disrupts Colonic Homeostasis to Drive Anxiety-Like Behavior via the Gut-Brain Axis.
Abstract: Low-fiber diet poses a health risk, yet mechanisms linking dietary fiber deprivation to emotional disorders are unclear. Here, we demonstrate that dietary fiber deprivation (FD) induces pronounced anxiety-like behaviors in mice by disrupting the gut-brain axis. In the FD model, a 6-week intervention with mannan oligosaccharides (MOS, 500 mg/kg) ameliorated these deficits. Mechanistically, FD disrupted gut microbiota and impaired gut barrier integrity. FD triggered colonic inflammation, oxidative stress, and inhibited mitochondrial oxidative phosphorylation─a critical aspect of colonic energy metabolism. These intestinal insults were associated with hyperactivation of the HPA axis and neuroinflammation in the brain. MOS reversed these effects by reshaping the gut microbiota, promoting short-chain fatty acids (SCFAs), and restoring colonic energy homeostasis. Colonic energy metabolism is a critical node in the gut-brain axis, linking fiber intake to emotional regulation. Therefore, dietary fiber deprivation affects the HPA axis and emotions, making it an important nutritional intervention target.

ID: 41683715
Title: Butyrate-Producing Bacteria as a Keystone Species of the Gut Microbiome: A Systemic Review of Dietary Impact on Gut-Brain and Host Health.
Abstract: 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.

ID: 41711893
Title: Xylooligosaccharide in combination with Lactobacillus rhamnosus ameliorates disturbed circadian rhythm and associated neurological internal desynchronization by maintaining homeostasis of neuroactive molecules and gut microbiome.
Abstract: Disturbances in circadian rhythm and internal desynchronization are increasingly associated with various neurological health conditions, highlighting the need for effective therapeutic interventions. In the present study, we hypothesized a strong correlation between Prebiotics-Gut Microbiota-Circadian Rhythm, capable of influencing host neurochemical and physiological homeostasis. The effects of a synbiotic formulation comprising a well-characterized xylooligosaccharide (XOS) and Lactobacillus rhamnosus on circadian rhythm regulation in a Caco-2 cell model were investigated. The synbiotic treatment, effectively ameliorated disturbed circadian rhythm in Caco-2 cells and improved neurological internal synchronization through the modulation of neuroactive molecules, which was confirmed by the RT-PCR gene expression studies and transcriptome analysis. Among 73 circadian rhythm regulatory genes, 34 genes showed recovery toward normal expression levels, including PER1, PER2, CRY1, CRY2, and DBP. Furthermore, transcriptomic profiling revealed a significant recovery of neurotransmitter-related genes (DDC, TPH1, COMT, MAOA), suggesting a mechanistic link between circadian recovery and neurochemical pathways. Analysis of gut microbiota-derived metabolites demonstrated increased levels of serotonin, dopamine, and GABA in the treated Caco-2 cells, supporting the role of microbial metabolites in modulating host circadian rhythm. The findings indicate that XOS plays a central role not only as a prebiotic but also as a functional carbohydrate capable of influencing host chronobiology through gut microbiota interactions. These findings provide valuable insights into the complex interplay between circadian rhythm gene regulation and microbial metabolites. The results advance our understanding of the structure–function relationship of XOS in health applications and highlight its promise in developing targeted interventions for circadian rhythm-associated disorders.

ID: 41752066
Title: Reduced Neuroinflammation and Pain with a Functional Sourdough Bread Enriched with Legumes and Ancient Cereals in a Mouse Model of LPS-Induced Inflammation.
Abstract: Nutritional strategies based on sourdough fermented breads with wholemeal ancient grains and legumes are emerging as promising modulators of (neuro)immune processes. This study investigated whether prolonged consumption of a sourdough bread enriched with a mixture of ancient cereals and legumes, commercially available in Italy (Primus® bread, P®B), modulates neuroimmune systemic responses to repeated lipopolysaccharide (LPS) challenge in mice. For this study, male C57BL/6J mice were fed for 14 days with either a standard diet (SD) or P®B. Animals then received intraperitoneal LPS (3 mg/kg/day for 3 days) or vehicle. Body weight and food intake were monitored throughout. Pain-like behaviours were assessed by von Frey, plantar and tail flick tests, and plasma cytokine (32-plex panel), splenocyte and peritoneal macrophage cytokine expression, and expression of pro-inflammatory cytokines in sciatic nerves, dorsal root ganglia (DRG) and the spinal cord were analyzed by Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR). P®B prevented LPS-induced body weight loss and reduced splenomegaly. Unlike SD mice, which exhibited widespread plasmatic cytokine upregulation, P®B-fed mice displayed only limited increases Interleukin (IL)-1β, IL-12p40 and Tumor Necrosis Factor (TNF)α. Ex vivo cultures of splenocytes and macrophages confirmed attenuated cytokine overexpression. LPS-induced hypersensitivity to mechanical, thermal and nociceptive stimuli was significantly reduced in P®B mice. Molecular analyses revealed that the P®B diet blunted the pro-inflammatory cytokine expression present after LPS challenge in the sciatic nerves and DRG, with partial attenuation in the spinal cord. Our findings highlight the great potential of functional foods as affordable dietary strategies to mitigate systemic immune and neuroimmune dysregulation.

ID: 41813835
Title: Dietary patterns influence the in silico GABA production capacity of Bifidobacterium adolescentis HD17T2H and other human gut bacteria.
Abstract: Gamma-aminobutyric acid (GABA) is a neurotransmitter that inhibits neuronal excitability and also affects mucosal function and gut motility. Importantly, while the gut microbiome is a known source of GABA, little is known about the production capacities of its specific members. In our study, we investigated in silico how 11 predefined diets influence GABA production by Bifidobacterium adolescentis HD17T2H, an important GABA producer among bifidobacteria within the human gut microbiota. We show that the GABA production potential of B. adolescentis strain HD17T2H varies considerably across diets, with the vegetarian diet showing the highest potential and the ketogenic diet the lowest. Further, we analysed which specific compounds raised GABA production. Our in silico predictions revealed that carbohydrates and nitrogen-rich compounds, such as amino acids, strongly increase GABA production. We also analysed personalised nutritional data from a human cohort (Kiel cohort), in an in silico approach. In doing so, we found 87 potent GABA-producing strains across 47 bacterial genera, including Burkholderia, Pseudomonas, and Delftia, suggesting that not only commensals but also bacterial pathogens contribute to GABA production. Thus, our modelling approach highlights that nutrient availability is a central determinant of bacterial GABA production.

ID: 41931990
Title: Targeting astrocytic Nrf2 by Trilobatin alleviates lipopolysaccharide-induced depressive-like behaviors and cognitive impairment in mice: Mechanistic insights into gut microbiota and metabolites modulation.
Abstract: Clinical and preclinical evidence links major depressive disorder (MDD) and Alzheimer's disease (AD), suggesting MDD treatment could prevent some AD. Dysfunction within the microbiota-gut-brain axis contributes to MDD and AD pathogenesis via dysregulated microbial metabolites. Trilobatin (TLB) functions as a neuroprotective agent modulating gut microbiota. However, its capacity to alleviate depressive-like behavior and cognitive deficits through restoration of gut microbial ecology and metabolite profiles requires clarification. The present research was designed to examine the impact of TLB on depressive-like behavior and cognitive impairments, and the role of the gut microbiota and metabolites. Neuroprotective effects of TLB on MDD and AD were evaluated using an LPS mouse model exhibiting depressive-like behavior and memory impairment. The principal molecular target of TLB was identified through a combination of single-cell sequencing, surface plasmon resonance, and gene knockout approaches. Mechanistic insights into gut microbiota and metabolites were gained through 16S rRNA sequencing and fecal microbiota transplantation (FMT). TLB attenuated LPS-induced depressive-like behaviors manifested as lowered sucrose preference, extended immobility, and improved cognitive deficits as reflected by Y-maze and novel object recognition. Mechanistically, TLB directly bound Nrf2, enhanced Nrf2-ARE activity, and suppressed neuroinflammation and oxidative stress. TLB restored gut microbiota homeostasis, elevated Akkermansia muciniphila (AKK) abundance and short-chain fatty acids, and strengthened intestinal tight junction proteins. FMT from TLB-treated mice replicated these benefits in wild-type but not Nrf2-knockout mice. AKK supplementation similarly ameliorated behavioral and cognitive deficits via Nrf2 activation. Our findings reveal that TLB mitigates neuropsychiatric deficits by activating Nrf2, remodeling restructuring gut microbiota and fortifying intestinal barrier function. The Nrf2-mediated microbiota-gut-brain axis is suggested as a potential therapeutic target for MDD and AD, positioning TLB as a promising natural Nrf2 activator.

ID: 41987530
Title: The dietary intake and nutritional status of military veterans: a systematic literature review.
Abstract: Military veterans (ex-serving members of the Armed Services) experience unique physical and mental health challenges, with diet playing a critical role in chronic disease management and well-being. This review aimed to evaluate veterans' dietary intake against nutrient reference values (NRV) relevant to age and sex. A systematic search of CINAHL, MedLine, Scopus, PubMed and AMED (January 2024, updated March 2025) identified 1268 records; thirty-three studies (n 654 323) met inclusion criteria. Eligible designs included cross-sectional, cohort, quasi-experimental and randomised controlled trials. Data were extracted using the Joanna Briggs critical appraisal checklist, indicating low risk of bias. Across studies, veterans' intake of fibre, folate, vitamin D, Ca, potassium, fruits, vegetables, wholegrains and legumes was consistently inadequate, with overall diet quality rated poor to average. BMI ranged widely, and veterans reported high rates of mood disorders and low quality-of-life scores. These findings highlight key nutrients and dietary patterns that might be considered and targeted in dietary and lifestyle interventions for promoting the physical and mental health of veterans.

ID: 42193195
Title: Associations of Dietary Antioxidant and Phytochemical Indices with Cognitive Function: Mediating Roles of Basal Metabolic Rate and Systemic Inflammation.
Abstract: Dietary antioxidants and phytochemicals are believed to support cognitive health, but evidence on composite dietary indices remains limited. This cross-sectional study of 1845 community-dwelling older adults in China investigated the associations of the composite dietary antioxidant index (CDAI) and dietary phytochemical index (DPI) with cognitive function and mild cognitive impairment (MCI). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA; Beijing version). MCI was diagnosed through a two-stage procedure: MoCA-based preliminary screening (with education-stratified cutoffs: 13/14 for illiterate, 19/20 for 1-6 years, 24/25 for ≥7 years) followed by neurologist confirmation. CDAI was calculated as the sum of the standardized intakes of six antioxidants (selenium, zinc, carotenoids, vitamin A, vitamin C, vitamin E); DPI was defined as the percentage of the total energy intake from phytochemical-rich foods (fruits, vegetables excluding potatoes, legumes including soy products, nuts, seeds, and whole grains). Multivariable linear regression, logistic regression, and receiver operating characteristic (ROC) curve analyses were performed. The basal metabolic rate (BMR) and systemic immune-inflammation index (SII; platelets × neutrophils/lymphocytes) were tested as potential statistical mediators. Each one-unit increase in CDAI was associated with a 0.068-point higher MoCA score (95% CI: 0.012-0.123), and each one-unit increase in DPI was associated with a 0.029-point higher MoCA score (95% CI: 0.008-0.050). BMR and SII partially mediated the association between CDAI and MoCA score, but temporal ordering remains unclear due to the cross-sectional design. When both CDAI and DPI were in the highest quartile, participants had a 46.3% lower risk of MCI compared with those with both indices in the lowest quartile (OR = 0.537, 95% CI: 0.308-0.935). A predictive model incorporating CDAI, inflammatory markers, and red blood cell parameters showed moderate discriminatory ability in this study sample (apparent AUC = 0.731, bootstrap-corrected AUC = 0.728). These findings suggest that a higher combined dietary antioxidant and phytochemical intake may be jointly associated with better cognitive function, although the cross-sectional design precludes causal inference.

ID: 42266624
Title: Fiber-based vegetarian score and the risk of incident dementia among elderly Chinese adults: a prospective cohort study.
Abstract: With the acceleration of population aging, dementia has become a major public health challenge. Although vegetarian diets have been proven to be related to cognitive health in Western populations, there is a lack of longitudinal research evidence in the elderly population in China. This study aims to use data from the China Longitudinal Healthy Longevity Survey (CLHLS) to prospectively explore the association between vegetarian dietary patterns and the risk of dementia. This study included 1,948 elderly individuals aged ≥ 65 years at baseline and without dementia in the CLHLS 2008-2018 cohort. The frequency of intake of 10 types of foods was assessed using a food frequency questionnaire, and a vegetarian dietary score was constructed based on the intake frequency of vegetarian foods (grains, vegetables, fruits, nuts, fungi). During follow-ups in 2010, 2011, 2014, and 2018, dementia onset events were identified through Chinese version of the Mini-Mental State Examination (CMMSE), activities of daily living ability, and self-reported physician diagnoses. The Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI), with adjustment for confounding variables including sociodemographic characteristics, lifestyle, and health status. Subgroup analyses and sensitivity analyses were conducted to evaluate effect modification and the robustness of the results. During the 10-year follow-up period, a total of 53 incident dementia cases (2.7%) were documented. After multivariate adjustment, each 1-point increase in the vegetarian dietary score was associated with a 17% reduction in dementia risk (HR = 0.83, 95% CI: 0.70-0.98, p = 0.031). Compared with participants in the lowest tertile of vegetarian score, those in the intermediate tertile (HR = 0.49, 95% CI: 0.26-0.93, p = 0.028) and the highest tertile (HR = 0.50, 95% CI: 0.23-0.99, p = 0.048) had significantly lower risks of dementia. Subgroup analyses revealed that the protective effect of a vegetarian diet was more pronounced among participants aged < 80 years (HR = 0.62, 95% CI: 0.48-0.80), non-drinkers (HR = 0.81, 95% CI: 0.67-0.97), those without formal education (HR = 0.79, 95% CI: 0.63-0.98), those engaged in physical labor (HR = 0.66, 95% CI: 0.49-0.89), and those married/cohabiting (HR = 0.70, 95% CI: 0.54-0.90). After excluding cases with early onset during follow-up and extreme age values, sensitivity analyses confirmed the robustness of the findings. A vegetarian dietary pattern is significantly associated with a lower risk of dementia in Chinese elderly individuals, and this protective effect varies across demographic and lifestyle subgroups. This study supports the inclusion of vegetarian diets patterns in primary prevention strategies for dementia and highlights their particular application value in specific vulnerable populations.

ID: 42280422
Title: Brain Foods: A Narrative Review of Food Items and Their Impact on Cognition over the Life Course.
Abstract: Background/Objectives: Cognitive function is fundamental to daily life, and nutrition is a key modifiable determinant of brain health across the lifespan. While plant-based "brain foods" have been emphasized, the contributions of animal-sourced foods (ASF) to neurodevelopment and cognitive performance remain underexplored. This review synthesizes current evidence on the effects of both plant- and animal-derived foods on cognitive outcomes from early development through older adulthood. Methods: A narrative review was conducted focusing on eight major categories of brain-supportive foods-dairy, eggs, seafood, lean meat, berries, leafy green vegetables, nuts, and whole grains. Evidence was evaluated across life stages, considering nutrient bioavailability, dietary patterns, and the interplay between structural, socioeconomic, and environmental factors that influence access to these foods. Results: Nutrient-dense foods, including ASF and plant-based sources, support cognitive outcomes across the life course. In early childhood, eggs, meat, and nuts were linked to improved neurodevelopment and reductions in developmental delays, while evidence for seafood and dairy was more mixed. During adolescence and adulthood, berries, walnuts, vegetables, and whole grains were associated with improvements in executive function, verbal reasoning, and mood, with adequate bioavailable protein from ASF remaining important. Among older adults, higher intake of leafy greens, nuts, berries, and moderate seafood consumption correlated with slower cognitive decline and improved memory. Findings were limited by heterogeneous study designs, dietary assessments, and underrepresentation of adolescents and populations in low- and middle-income countries. Conclusions: Both animal-sourced and plant-based brain foods uniquely support cognitive development, maintenance, and resilience. While nutritional needs vary across the life course, strong evidence supporting distinct food-based dietary recommendations for cognitive outcomes at different ages, particularly adolescents, remains limited. Current findings suggest stage-specific associations, particularly during early development, but more longitudinal and experimental research is needed. Expanding rigorous, inclusive research will be critical for informing nutrition policies that support lifelong cognitive health.

ID: 42325523
Title: Dietary polyphenols in pediatric obesity and cardiometabolic risk: mechanisms and clinical evidence.
Abstract: Pediatric obesity is a major global health concern and is associated with early cardiometabolic alterations, including insulin resistance, dyslipidemia, hypertension, endothelial dysfunction, and chronic low-grade inflammation. Dietary polyphenols, naturally present in fruits, vegetables, legumes, cocoa, and tea, have emerged as potential nutritional modulators of these pathways because of their antioxidant, anti-inflammatory, metabolic, and microbiota-related effects. This narrative overview summarizes current evidence on the role of dietary polyphenols in pediatric obesity and cardiometabolic risk. It examines the main biological mechanisms through which polyphenols may influence oxidative stress, inflammation, glucose and lipid metabolism, vascular function, and gut microbiota composition. It also reviews the available observational and clinical evidence in children and adolescents, with particular attention to polyphenol-rich dietary patterns. Available evidence suggests that polyphenols may influence key mechanisms involved in pediatric obesity, including oxidative stress, inflammation, glucose and lipid metabolism, endothelial function, and gut microbiota balance. Observational studies indicate that polyphenol-rich dietary patterns, especially Mediterranean-style diets, are associated with more favorable adiposity and cardiometabolic profiles in children and adolescents. However, pediatric clinical trials remain limited and heterogeneous, preventing firm conclusions on efficacy and long-term safety. Polyphenols are biologically plausible contributors to cardiometabolic health in pediatric obesity, but current evidence mainly supports food-based dietary patterns rather than isolated supplementation. Larger pediatric-specific trials are needed to clarify their clinical relevance and long-term benefits.

ID: 42354056
Title: Lactiplantibacillus plantarum P133, a Folate-Producing Probiotic, Ameliorates Cardiac Injury in Hyperhomocysteinemia Mice by Modulating Gut Microbiota and Serum Metabolome.
Abstract: Hyperhomocysteinemia (HHcy) constitutes a significant risk factor for cardiovascular disease. The present study examined the cardioprotective effects and underlying mechanisms of the folate-producing strain Lactiplantibacillus plantarum (L. plantarum) P133, isolated from traditional fermented pickled vegetables, in a murine model of HHcy induced by a methionine-choline-deficient diet. The findings revealed that administration of P133 significantly reduced serum homocysteine concentrations and improved cardiac function, as evidenced by decreased serum cardiac enzymes (AST, LDH, Ctnt, Ctni), mitigated myocardial histopathological damage, and lowered oxidative stress levels (e.g., decreased MDA). Mechanistically, P133 appears to provide dual protective effects: firstly, it functions as an intrinsic source of folate, thereby mitigating disturbances in one-carbon metabolism; secondly, it influences the composition of the gut microbiota, significantly enhancing the prevalence of beneficial taxa such as Muribaculaceae, and modifies the serum metabolomic profile by increasing favorable metabolites like indoleacetic acid, which correlate strongly with attenuated cardiac injury. These synergistic effects are associated with attenuated cardiac injury. Therefore, L. plantarum P133 emerges as a promising probiotic candidate for the prevention and treatment of cardiac damage related to HHcy via a multifaceted intervention approach.

ID: 42354068
Title: Dietary Plant-Derived Phenolic Acids and Phenolamides as Natural Preservatives: Antibacterial, Antioxidant and Food Preservation Applications.
Abstract: Food spoilage from microbial contamination and oxidation drives the search for natural preservatives. Phenolic acids (PAs) and phenolamides are plant-sourced metabolites with broad-spectrum antimicrobial and antioxidant activities. This review comprehensively examines their sources, classification, structure-activity relationships, and multi-target mechanisms. PA antimicrobial action involves membrane disruption, intracellular acidification, and oxygen species generation, while antioxidant effects rely on hydrogen donation and metal chelation. For phenolamides, antimicrobial evidence is largely indirect, based on computational docking and one non-food nucleotide biosynthesis study, and direct validation of these mechanisms in food matrices against common foodborne pathogens is lacking. Delivery strategies (direct incorporation, encapsulation, edible coatings, active packaging) are critically evaluated, with emphasis on PA-grafted chitosan systems. Applications of PAs in fruits, vegetables, meat, aquatic products, and lipid-rich emulsions are summarized. Phenolamide applications are limited by low natural abundance, high purification costs, poor aqueous solubility, and a historical bias toward pharmacology. Safety assessments confirm favorable profiles for many PAs and select phenolamides, though chronic toxicity data for phenolamides remain limited. This review provides a theoretical framework for leveraging PAs and emerging phenolamides as natural preservatives and identifies critical knowledge gaps requiring future investigation.

ID: 42354073
Title: High-Value Utilization of Coconut Kernel Fiber By-Products: The Insulin-Sensitizing Effect of Novel α-Glucosidase-Inhibiting Peptides Derived from Coconut Kernel Fiber on T2DM Mice.
Abstract: Coconut kernel fiber (CKF) is a by-product of coconut oil processing; it is rich in protein and serves as a potential source of bioactive peptides. In this study, from the enzymatic hydrolysis products of CKF (CKFH), a low-molecular-weight CKFH component (LW-CKFH, 1-3 kDa), exhibiting 74.49% α-glucosidase inhibition and restoring glucose metabolism in IR-HepG2 cells to 71.37% of normal levels. In a type 2 diabetes (T2DM) mouse model, LW-CKFH alleviated insulin resistance and enhanced insulin sensitivity by repairing liver damage, thereby improving glucose and lipid metabolism and reducing inflammation; its effects on improving insulin resistance and sensitivity reached 75.43% and 75.47% of the efficacy of metformin, respectively. Molecular docking analysis identified FDLPAR, LPFPRPAGPR, and ANVFNPR as key active peptides responsible for inhibiting α-glucosidase activity. Furthermore, LW-CKFH exhibited good gastrointestinal digestibility and processing stability, while significantly reducing the glucose release rate from bread (>50%), indicating its suitability for the development of hypoglycemic or low-GI functional foods. LW-CKFH was particularly suitable as a functional ingredient for fruits, vegetables, grains, and dairy products to develop low-GI or hypoglycemic foods. This study provides new insights into the high-value utilization of the coconut processing by-product CKF.

ID: 42354121
Title: A Comprehensive Review of Bioactive Constituents, Health-Promoting Effects, Processing Technologies, and Industrial Applications of Sparassis crispa Sensu Lato.
Abstract: Sparassis crispa sensu lato (S. crispa) is a highly valued medicinal and culinary fungus rich in nutritional and bioactive compounds. Polysaccharides, particularly β-glucans, are its most extensively studied constituents, accounting for up to 43.6% of its dry weight-the highest concentration reported among edible fungi. Alongside proteins, terpenoids, phenolics, and ergosterol, these biomolecules confer diverse physiological benefits, including immunomodulatory, antitumor, antioxidant, anti-inflammatory, and neuroprotective effects, as well as the capacity to modulate gut microbiota. Consequently, S. crispa exhibits substantial market potential and is increasingly incorporated into functional foods, nutraceuticals, pharmaceuticals, and cosmetics. This review systematically summarizes the primary bioactive components of S. crispa sensu lato and their associated health benefits, with emphasis on recent advances in immunomodulatory, antitumor, and antioxidant activities. Furthermore, it critically compares the retention of active ingredients, product quality, and bioavailability of key processing technologies. These technologies include various drying methods, grinding techniques, extraction methods, and formulation systems. Despite significant research progress, challenges persist regarding optimal cultivation conditions and standardized industrial processing. Future perspectives highlight the necessity for intelligent cultivation strategies, the adoption of advanced processing technologies, and robust policy support to drive the sustainable development and commercial exploitation of the S. crispa industry.

ID: 42356261
Title: A Single-Food Substitution Strategy (SFSS) Improves Fat Mass and Metabolic Parameters in MASLD: A Prospective Pilot Study.
Abstract: Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with obesity, insulin resistance, and altered body composition. Although dietary intervention is a cornerstone of treatment, complex or calorie-restricted regimens may reduce long-term adherence. This study evaluated the effects of a pragmatic, short-term intervention that involved replacing one daily carbohydrate serving with cruciferous vegetables on body composition and metabolic parameters in individuals with obesity and MASLD. Associations between changes in fat mass and vitamin D and follistatin levels were also explored. Methods: In this prospective pilot study, 44 adults with obesity and MASLD followed a two-month intervention, substituting one daily serving of carbohydrate-rich foods with 200 g of cruciferous vegetables, without prescribed caloric restriction. Anthropometric, bioimpedance, biochemical, and FibroScan assessments were performed at baseline and post-intervention. Changes were analyzed using the Wilcoxon signed-rank test, Spearman's correlation analysis, and generalized estimating equation (GEE) models adjusted for confounding factors. Results: The intervention was associated with a significant reduction in fat mass (-4.86 kg, p < 0.001), corresponding to an average relative decrease of approximately 12% along with improvements in metabolic and hepatic parameters. Changes in fat mass were inversely correlated with changes in vitamin D (rho = -0.33, p = 0.035), fat-free mass (rho = -0.37, p = 0.018), and follistatin (rho = -0.24, p = 0.143). In multivariate GEE models, the intervention remained independently associated with fat mass reduction (β = -5.190, p < 0.001). Conclusions: A simple carbohydrate-to-vegetable substitution without prescribed caloric restriction was associated with improvements in body composition and metabolic health. These exploratory findings suggest that pragmatic dietary modifications may provide clinically meaningful metabolic benefits and support the feasibility of minimal dietary substitution strategies in this population. However, causal inferences remain limited by a single-arm pilot design and require confirmation in larger randomized controlled trials.

ID: 42356356
Title: Mediterranean Diet Adherence, Dietary Components, and Vision-Related Quality of Life in Type 2 Diabetes: A Cross-Sectional Study According to Diabetic Retinopathy Status.
Abstract: Background/Objectives: Diabetic retinopathy (DR) is a major microvascular complication of type 2 diabetes (T2D) and a leading cause of visual impairment. The relationships among Mediterranean diet adherence, dietary components, DR, and vision-related quality of life remain incompletely defined. This cross-sectional study evaluated Mediterranean Diet Score (MDS) as the primary dietary endpoint, individual MDS components as secondary endpoints, and micronutrient intakes as exploratory endpoints. Methods: In this single-centre study, 129 subjects with long-standing T2D were classified as no DR (NDR; n = 85), non-proliferative DR (NPDR; n = 36), or proliferative DR (PDR; n = 8). Dietary intake was assessed using a food frequency questionnaire and vision-related quality of life using the NEI-VFQ-25. Results: Subjects with DR had longer diabetes duration than those without DR (18 vs. 16 years, p < 0.01). Overall MDS did not differ by DR status, indicating a null finding for the primary dietary endpoint. In secondary analyses, lower legume consumption was observed among participants with DR and was associated with higher odds of DR in multivariable models. Participants with PDR showed poorer vision-related quality of life, although this finding was limited by the small PDR subgroup and high NEI-VFQ-25 scores in other groups. Exploratory analyses suggested associations between selected micronutrient intakes and NEI-VFQ-25 domains. Conclusions: Overall Mediterranean diet adherence was not associated with DR status. Secondary and exploratory findings should be considered hypothesis-generating and require confirmation in prospective studies.

ID: 42356376
Title: Multi-Axis Functional Mechanisms of the Milpa Diet in Obesity: A Scoping Review.
Abstract: Background: Obesity is a multifactorial metabolic disorder characterized by chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, lipotoxicity, dysregulated adipogenesis, and alterations in the gut microbiota, which collectively contribute to insulin resistance and cardiometabolic complications. In this context, dietary patterns rich in bioactive compounds have gained relevance as potential strategies to modulate these interconnected pathways. Objective: To assess the potential of the Milpa Diet (a sustainable, plant-dominant Mesoamerican eating pattern centered on the ancient three sisters' polyculture of maize, beans, and squash, along with chili) as a culturally relevant, multi-axis functional dietary pattern, and to evaluate the molecular mechanisms underlying obesity-associated with metabolic dysfunction. Methods: A scoping review of preclinical and clinical studies was conducted using Medline via PubMed, Scopus, and Web of Science databases. The ChEMBL database was also used to identify chemical structures. The search focused on evidence related to inflammation, oxidative stress, adipogenesis, lipotoxicity, mitochondrial function, and gut microbiota modulation in the context of the main foods of the Milpa Diet, including maize, legumes, chili peppers, nopal, and quelites. Studies were selected based on peer-review status and their relevance to molecular, metabolic, and functional outcomes. Results: The current evidence shows that the core components of the Milpa Diet provide dietary fiber and a broad range of bioactive compounds, such as flavonoids, carotenoids, capsaicinoids, phenolic acids, pigments, and vitamins, which exhibit antioxidant and anti-inflammatory effects. These compounds have been associated with modulation of adipogenesis and lipotoxicity, preservation of mitochondrial function, and favorable regulation of gut microbiota composition and activity, collectively influencing metabolic pathways relevant to obesity. Conclusions: Overall, mechanistic and emerging clinical evidence suggests that the Milpa Diet represents a multi-axis nutritional strategy with potential to mitigate obesity-related metabolic dysfunction through coordinated effects on inflammation, oxidative stress, adipogenesis, lipotoxicity, mitochondrial function, and gut microbiota regulation. Although comprehensive clinical trials evaluating this dietary pattern as an integrated intervention remain limited, current evidence supports its relevance for future translational research, public health strategies, and the development of sustainable dietary models aimed at improving metabolic health.

ID: 42357432
Title: Cereal-Legume Food Matrices as Functional Systems: Processing-Driven Synergies in Nutrition, Bioactive Compounds and Sensory Acceptability.
Abstract: As global trends continue to embrace environmentally friendly, plant-based diets, food systems that are nutrient-dense, climate-resilient, and economically viable in addressing protein-energy malnutrition, micronutrient deficiencies, and food insecurity have increased. Although cereal-legume combinations are widely recognised to be highly nutritious, most studies have focused primarily on enhancing compositional efficiency and have overlooked their interactions with the food matrix and the processing-mediated transformations they undergo. This review combines recent findings examining cereal-legume food matrices as functional systems, with particular emphasis on nutritional complementarity, bioactive interactions, processing-induced modifications, and sensory acceptability. Studies indicate that cereals and legumes provide complementary amino acid profiles, dietary fibre, essential micronutrients, and phytochemicals within these composite matrices that influence digestibility, bioavailability, antioxidant activity, and glycaemic response. Processing methods, including fermentation, germination, roasting, and extrusion, modulate these interactions by releasing bound phenolics, reducing antinutritional factors, and altering starch-protein-phenolic complexes, thereby affecting health functionality and sensory quality. However, inadequately optimised processing can affect nutrient retention and consumer acceptability. Overall, this review emphasises the relevance of integrating food matrix science and processing optimisation for the production of functional, acceptable, and sustainable cereal-legume foods that promote product innovation, public health improvement, and the utilisation of underutilised crops for sustainable food systems.

ID: 42358231
Title: Spermidine in Alzheimer's Disease: Evidence from Animal Models and Human Studies.
Abstract: Spermidine is a naturally occurring polyamine involved in multiple cellular processes, including growth regulation, protein translation, and autophagy. Increasing attention has been devoted to its potential neuroprotective effects, particularly in Alzheimer's disease (AD), a neurodegenerative disorder characterized by β-amyloid and phosphorylated tau accumulation, synaptic dysfunction, and progressive neuronal loss. In this narrative review, we examine potential mechanisms through which spermidine may influence AD pathophysiology and summarize available preclinical and clinical evidence. Preclinical studies indicate that spermidine induces autophagy, a key cellular clearance pathway responsible for removing damaged organelles and aggregated proteins. Because impaired neuronal autophagy contributes to the accumulation of β-amyloid and tau in AD, increasing intracellular spermidine levels may enhance the degradation of these toxic species. In addition, spermidine exhibits anti-inflammatory and antioxidant properties, attenuates microglial activation, and supports mitochondrial function. In animal models of AD and brain aging, spermidine administration has been associated with improvements in cognitive performance and synaptic function. However, human clinical evidence remains limited and largely inconclusive. Observational studies suggest associations between higher dietary spermidine intake and better cognitive outcomes, but do not establish causality. Randomized clinical trials to date are few, include small and heterogeneous populations, and have not demonstrated consistent effects on primary cognitive endpoints. Overall, spermidine represents a biologically plausible modulator of pathways relevant to neurodegeneration, but translation of preclinical findings into clinical benefit remains uncertain. Current evidence is insufficient to support its use as a therapeutic or preventive intervention in AD, and further well-designed clinical studies are required to clarify its efficacy and mechanisms of action. Alzheimer’s disease is one of the most common causes of memory loss in older adults. Researchers are searching for ways to protect brain cells and slow the biological processes that lead to this disease. One molecule that has recently attracted attention is spermidine, a natural compound found in all living cells and in many foods, including whole grains, legumes, mushrooms, and aged cheeses. Spermidine plays several roles in the body. One of its most important effects is activation of autophagy, a natural cellular process that removes damaged proteins and other cellular waste. This process is relevant to Alzheimer’s disease because the condition is associated with the accumulation of abnormal proteins in the brain. Experimental studies also suggest that spermidine may influence inflammation in the brain, support mitochondrial function (the energy system of cells), and help maintain communication between nerve cells. In this review, we summarized evidence from laboratory experiments, animal studies, and available human research. In animal models of brain aging and Alzheimer’s disease, spermidine consistently shows neuroprotective effects and can improve memory performance. Human evidence is more limited. Observational studies suggest that higher dietary spermidine intake may be associated with better cognitive performance, while clinical trials investigating supplementation have produced mixed results. Spermidine is naturally present in many foods and is increasingly studied in the context of aging and brain health. Overall, current evidence suggests that spermidine may play a role in brain aging. Larger and well-designed clinical studies are needed to clarify its potential relevance for Alzheimer’s disease.

ID: 42373816
Title: Ketogenic diet alleviates acute radiation-induced intestinal injury through JAK2/STAT3/RORγt/IL-17A signaling pathway via gut microbiome.
Abstract: Emerging evidence suggests dietary interventions regulate inflammatory signaling through gut microbiome modulation, yet their therapeutic potential in radiation-induced intestinal injury (RIII) remains underexplored. This study demonstrates that ketogenic diet (KD), a high-fat and low-carbohydrate dietary regimen, exerts protective effects against RIII through dual mechanisms involving microbial regulation and inflammatory pathway inhibition. Using high-salt diet (HSD) as a dietary control, KD significantly attenuated intestinal inflammation by downregulating pro-inflammatory cytokines while enhancing barrier integrity through tight junction protein upregulation in radiation-exposed murine model. 16S rDNA sequencing showed KD enriched Akkermansia and reduced Enterobacteriaceae, whereas HSD exhibited inverse patterns. Mechanistically, RNA sequencing revealed that KD uniquely suppressed the JAK2/STAT3 pathway in RIII mice. In vitro studies demonstrated that β-hydroxybutyrate, a key ketone metabolite, effectively suppressed RORγt expression and subsequent downregulation of IL-17A gene transcription via the inhibition of JAK2/STAT3 pathway, thus mitigate inflammatory damage. Fecal microbiota transplantation validated that KD-modified microbiome directly inhibited JAK2/STAT3 signaling activation, as well as the downregulation of RORγt and IL-17A. These findings establish KD as a promising dietary strategy mitigate acute RIII through synergistic modulation of gut microbiota and inflammatory signaling, providing novel insights into nutritional approaches targeting microbial-host crosstalk in radiation injury.

ID: 42374551
Title: Food is the Best Medicine (FBM): design and baseline findings from a multi-arm randomized controlled trial among food-insecure postpartum mothers in Texas.
Abstract: Food is Medicine (FIM) interventions, which connect health-supporting food programs with healthcare systems, demonstrate substantial clinical and economic benefits. However, few FIM studies have focused on the health of postpartum mothers, a population facing unique vulnerabilities during a critical period. Food is the Best Medicine (FBM) is an 8-week, home-delivery-based FIM intervention targeting postpartum mothers experiencing food insecurity. Developed through partnerships between healthcare providers and community-based organizations, the FBM intervention integrates food delivery with supportive services. Here, we describe the research design and present baseline findings of a study evaluating the impacts of supplementing the FBM intervention with different sustainability-enhancing modalities. The Food is the Best Medicine (FBM) study was a three-arm randomized controlled trial conducted in Central Texas. Food-insecure postpartum mothers (n = 150) were randomized to receive: (1) FBM-Standard (8-week food delivery), (2) FBM-CHW (standard delivery plus Community Health Worker (CHW) support), or (3) FBM-Virtual (standard delivery plus online educational platform). Primary planned outcome measures included food security and fruit, vegetables, and whole grain intake. Secondary planned outcome measures included nutrition security, breastfeeding rates, mental health, financial stress, and cooking behaviors. Baseline data were collected via telephone or online surveys prior to randomization. Participants were predominantly Hispanic (71%) and Spanish-speaking (79%), with a mean household income of $20,620 (SD = $18,190). Most lived in households with multiple children (74%), in which the number of children and adults ranged from 1 to 15 and 1 to 9, respectively, and had limited formal education (38% without a high school diploma). Marital status was not collected. At baseline, 89% were food insecure. Depression screening indicated mental health concerns in 13% of participants. The 10-item Dietary Screener Questionnaire was used to assess fruit and vegetable intake. Mean fruit and vegetable consumption was 3.9 cups daily, but consumption of whole-grain bread and cooked whole grains was low, at about once a week. The FBM study uses a multi-component, randomized design to evaluate variations of a FIM intervention among food-insecure postpartum mothers. The intervention incorporates food delivery, CHW support, and virtual education components. Ongoing analyses will assess the potential of these approaches to improve food security and related maternal health outcomes in the postpartum period. ClinicalTrials.gov NCT06428578 (registered May 20, 2024).

ID: 42377735
Title: The interplay between gut microbiota and Alzheimer's disease: mechanistic insights from dysbiosis to disease modulation.
Abstract: Alzheimer's disease (AD) is a chronic, progressive, neurodegenerative condition marked by memory loss and cognitive decline. It is characterized by neuropathological features such as amyloid plaque accumulation, neurofibrillary tangles of tau protein, and inflammatory changes in the brain. Recent research emphasizes how gut microbes influence the onset and progression of AD primarily through the gut-brain connection, a bidirectional communication system. The human gastrointestinal tract (GI) contains trillions of bacteria, primarily Bacteroidetes, Firmicutes, and Actinobacteria, which play vital roles in digestion, metabolic regulation, and immune modulation. However, factors such as diet, lifestyle, and environmental exposure can disrupt microbial balance, weaken intestinal barrier function, and initiate systemic inflammation. Such dysbiosis has been linked to defective regulation of the amyloid precursor protein (APP), leading to increased deposition of amyloidogenic peptides (Aβ). Moreover, the enteric nervous system, which expresses APP, may serve as an initial site of amyloid deposition, affecting gastrointestinal motility and inflammatory susceptibility. The gut microbiota also produces key bioactive compounds, including neurotransmitters such as serotonin, dopamine, acetylcholine, histamine, and gamma-aminobutyric acid (GABA), which influence the central nervous system (CNS) through neural, immune, and endocrine pathways. An imbalance in these neuroactive molecules may disrupt synaptic signaling and contribute to Alzheimer's-related cognitive dysfunction. Therefore, improving our understanding of gut-brain communication may advance knowledge of AD development and support the creation of new therapies. This review highlights the strong association between intestinal microbes and Alzheimer's pathogenesis, emphasizing microbiota modulation through probiotics, prebiotics, postbiotics, synbiotics, and antibiotics as potential therapeutic approaches, supported by emerging clinical trial evidence.

ID: 42381725
Title: Precision prebiotics: Engineering food-derived polysaccharides to target specific SCFA-producing taxa for neuroprotection via the microbiota-gut-brain axis.
Abstract: Neurodegenerative and neuropsychiatric disorders lack disease-modifying therapies. The microbiota-gut-brain (MGB) axis, particularly short-chain fatty acid (SCFA)-producing microbiota dysbiosis, has emerged as a conserved driver of neuroinjury pathogenesis. Natural food-derived polysaccharides have been explored as prebiotic substrates, but their clinical translation is hindered by poor target specificity, high interindividual heterogeneity, and low bioavailability. Engineered food-derived polysaccharides, as a next-generation precision prebiotic platform, enable rational tailoring of molecular fine structures via targeted physical, chemical, biological, and combinatorial modification technologies, aiming for strain-specific directional modulation of intestinal SCFA-producing microbiota and multi-pathway neuroprotection through the MGB axis. In this review, we systematically delineate the bidirectional regulatory mechanisms between SCFA-producing microbiota and neural homeostasis, dissect disease-specific pathological cascades driven by SCFA-producing microbiota dysbiosis, and discuss conflicting findings on the dual effects of SCFAs. We further propose a full-chain framework of the structure-activity relationship of engineered polysaccharides, dissecting core modification strategies, strain-specific targeting mechanisms, and a multi-dimensional efficacy evaluation system for these precision prebiotics. Additionally, we assess safety evaluation status, major global regulatory differences, and core clinical translation bottlenecks. Finally, we outline key unresolved challenges and propose a conceptual roadmap for AI-assisted rational design of precision prebiotics, personalized microbiota-adapted intervention strategies, and multicenter clinical translation directions. This review provides a mechanism-driven theoretical framework and practical guidance for developing engineered food-derived polysaccharides as precision nutrition interventions for neuroinjury-related disorders.

ID: 42383946
Title: AGA Clinical Practice Update on Management of Clostridioides difficile Infection in Adults: Expert Review.
Abstract: Clostridioides difficile infection is a common cause of clinically significant diarrhea, often becomes recurrent, and can be fatal when severe or fulminant. The purpose of this America Gastroenterological Association (AGA) Clinical Practice Update Expert Review is to provide best practice advice for C difficile infection management. This expert review was commissioned by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The review was developed from expert opinion and a review of the published literature. Because systematic reviews were not performed, these best practice advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. The review underwent internal peer review by the Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. BEST PRACTICE ADVICE STATEMENTS BEST PRACTICE ADVICE 1: Prevention of C difficile infection should include proper barrier protection and disinfection with United States Environmental Protection Agency-approved sporicidal agents in health care settings. Patients should be counseled on the importance of handwashing and to consider disinfecting areas of the home potentially contaminated with C difficile spores, to prevent reinfection. Reassurance should be provided that C difficile infection transmission to unaffected family members is uncommon. BEST PRACTICE ADVICE 2: C difficile infection is a clinical diagnosis that requires compatible symptoms (typically acute diarrhea, following antibiotics) in combination with supportive laboratory testing. Multistep testing is preferred for best diagnostic accuracy; however, patients with discordant testing who have a high clinical suspicion for C difficile infection should be treated. BEST PRACTICE ADVICE 3: Clinicians should classify hospitalized patients with C difficile infection as having nonsevere, severe, or fulminant disease at diagnosis. White blood cell count >15,000 cells/uL and/or creatinine >1.5 × baseline are indicative of severe C difficile infection and increased risk for recurrence and poor outcomes. Patients with additional findings of shock, ileus, or megacolon have fulminant C difficile infection, which can be fatal. BEST PRACTICE ADVICE 4: Fidaxomicin (200 mg twice daily oral for 10 days) is a narrower spectrum agent, and given lower recurrence rates, is favored as first-line therapy for nonfulminant C difficile infection. However, given practical considerations, vancomycin (125 mg 4 times daily oral for 10 days) is also acceptable therapy. Metronidazole should not be used outside of fulminant disease. BEST PRACTICE ADVICE 5: Cholestyramine and other bile acid-binding agents should not be used as monotherapy or concurrently with oral vancomycin or fidaxomicin. Psyllium fiber can be used to bulk stools in patients who have recovered from the infection. BEST PRACTICE ADVICE 6: Following treatment of C difficile infection, clinicians should not perform routine test of cure. Stool testing should only be performed for persistent worsening of diarrheal symptoms. BEST PRACTICE ADVICE 7: First C difficile infection recurrence (second episode) within 8 weeks of completing anti-C difficile infection therapy should be treated with either a tapering course of vancomycin or fidaxomicin. Treatment of C difficile infection should include a risk assessment for C difficile infection recurrence and consideration of microbiota restoration therapy to prevent recurrence. BEST PRACTICE ADVICE 8: Fecal microbiota-based therapies (fecal microbiota spores, live-brpk, fecal microbiota, live-jslm, or conventional fecal microbiota transplant) should be offered after treatment of a second recurrence (third C difficile infection episode). Microbiota restoration therapy may be considered after treatment of an initial infection or first recurrence in patients who are at high risk for further recurrence or in patients whose initial C difficile infection episode was particularly morbid or difficult to treat. BEST PRACTICE ADVICE 9: Prolonged, low dose, suppressive vancomycin regimen (125 mg daily) for secondary prophylaxis may be considered in patients with multiple recurrent episodes who are not candidates for fecal microbiota-based therapies due to ongoing comorbidities, limited life expectancy, or ongoing/frequent systemic antibiotics or who have failed multiple courses of fecal microbiota-based therapy. BEST PRACTICE ADVICE 10: Fulminant C difficile infection should be managed by a multidisciplinary team (gastroenterology/infectious disease, surgery, medicine/critical care) and treated with high-dose vancomycin 500 mg every 6 hours (oral or enteral), with metronidazole 500 mg intravenously every 8 hours, and if ileus is present, rectal vancomycin 500 mg every 6 hours should be added. BEST PRACTICE ADVICE 11: Multi-dose fecal microbiota transplantation (fresh-directed donors, or institutional stool banks) delivered via lower endoscopy, should be considered in individuals with fulminant C difficile infection. Fecal microbiota, live-jslm (Rebyota), and fecal microbiota spores, live-brpk (Vowst) have not been studied and are not approved for treatment of severe and/or fulminant C difficile infection. Due to high risk of C difficile infection recurrence, patients who recover from severe or fulminant C difficile infection should be maintained on a suppressive vancomycin regimen until a final fecal microbiota transplantation can be administered as an outpatient. BEST PRACTICE ADVICE 12: Use of vancomycin is not advised during systemic antibiotic administration to prevent C difficile infection. Probiotics are not advised to prevent an initial or recurrent C difficile infection. To promote restoration of healthy gut microbiota, patients should be instructed to consume a healthy diet including a variety of fruits and vegetables, rich in both soluble and insoluble fiber. BEST PRACTICE ADVICE 13: During the treatment of C difficile infection or the prevention of its recurrence, the use of proton pump inhibitors should be evaluated. If a legitimate indication exists for their use, proton pump inhibitor discontinuation is not necessary. BEST PRACTICE ADVICE 14: Individuals with a history of C difficile infection should be specifically counseled to avoid unnecessary antibiotic therapy.

ID: 42385432
Title: Polyphenols extracted from Lycium barbarum seeds regulate gut microbiota to improve type 2 diabetes mellitus in db/db mice.
Abstract: Mounting evidence positions the gut microbiota as a pivotal player in the onset and progression of type 2 diabetes mellitus (T2DM). Lycium barbarum seed polyphenols (LBSPs), a byproduct of Lycium barbarum processing, have shown antioxidant and anti-inflammatory bioactivities, but potential anti-T2DM effects remain unclear. To evaluate the preventive effects of LBSPs against T2DM and the associated gut microbiota mechanisms. The effects of LBSPs on fasting blood glucose, insulin sensitivity, liver lipid accumulation, intestinal barrier, gut microbiota composition, and microbial metabolites were investigated in db/db mice. LBSPs significantly reduced fasting blood glucose, improved insulin sensitivity, and alleviated dyslipidemia and hepatic steatosis in db/db mice. Furthermore, LBSPs restored intestinal barrier integrity by up-regulating tight junction proteins Claudin-1, Occludin, and Zonula Occludens-1 (ZO-1). 16S rRNA analysis revealed that LBSPs reversed gut microbiota dysbiosis, enriching Lactobacillus, Ligilactobacillus, Rikenella, Lachnospiraceae_NK4A136_group, while decreasing Escherichia-Shigella and Klebsiella. Mechanically, LBSPs can modulate aromatic amino acid metabolism, lipid metabolism, and bile acid biosynthesis by metabolomics. Mediation analysis indicated that specific gut microbiota influenced host metabolic parameters through metabolites such as 7-megastigmene-3,6,9-triol 9-glucoside. Our findings reveal that LBSPs can be used as a potential microbiota-targeted nutraceutical that reverses gut microbiota dysbiosis and diabetes-associated metabolic disorders during T2DM progression.

ID: 42387948
Title: Changes in food patterns over a 10-year period in the UK adult population; findings from the National Diet and Nutrition Survey.
Abstract: The prevalence of overweight and obesity in adults is increasing worldwide. Food portion size (PS) is an important environmental determinant of energy intake (EI) and may contribute to the obesity epidemic. However, UK evidence on the typical PS of commonly consumed foods in adults and how these may have changed over time is limited. Using combined data from Years 1-4 (2008/9-2011/12) and Years 9-11 (2016/17-2018/19) of the National Diet and Nutrition Survey (NDNS), this study examined trends in the PS of commonly consumed food groups over the last decade among UK adults. Significant increases in both consumption frequency and PS were observed for pasta, rice & pizza, eggs, oils & spreads, vegetables, fruits, nuts & seeds, and low-calorie carbonated/soft drinks (all p≤0.005). In contrast, bread, potato & potato products, condiments, and fruit juice & smoothies showed significant decreases in both frequency and PS (all p≤0.032). Divergent patterns were also evident: red meat showed increased frequency but reduced PS, while white meat and fish increased in frequency without significant changes in PS. Changes in PS alone were identified for milk and milk products, processed meat, alcoholic drinks, and total beverages.Although fibre intake increased, recommendations are still not being met. There was no clear evidence that overweight or obese individuals consumed greater PS than those with normal weight. These findings highlight changes in food patterns among UK adults over the past decade and the importance of continued monitoring.

ID: 42390065
Title: Indole-3-carbinol attenuates DNCB-induced atopic dermatitis in mice by reducing inflammation and IL-4/IL-13 expression.
Abstract: Atopic dermatitis (AD), commonly known as atopic eczema, is a chronic inflammatory skin disease. Indole-3-carbinol (I3C), a phytochemical naturally occurring in Brassica vegetables, has been traditionally used in folk medicine for inflammatory and metabolic disorders. This study investigated the immunomodulatory and anti-inflammatory effects of I3C in a mouse model of 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis. Atopic dermatitis was induced by DNCB sensitization on days 0 and 3. Following disease confirmation on day 7, mice received daily oral or topical administrations of I3C or prednisolone from day 7 to day 19. Macroscopic evaluations included dorsal skin and ear thickness measurements. Histopathological changes were assessed using hematoxylin and eosin staining, and hematological parameters were also analyzed. Gene expression of interleukin (IL)-4 and IL-13 in ear tissue was quantified by real-time polymerase chain reaction (RT-qPCR). Computational molecular docking was performed to determine I3C's affinity for both cytokines. The data indicated that I3C attenuated DNCB-induced AD-like symptoms following both oral and topical administration. Treatment with I3C also resulted in reduced ear thickness. Hematological analysis revealed significantly decreased total leukocyte counts (TLC) and a general downward numerical trend in differential leukocyte count (DLC) parameters in I3C-treated groups. Histopathological evaluation confirmed that I3C ameliorated skin thickening and reduced inflammatory cell infiltration. Furthermore, IL-4 and IL-13 expression levels were decreased in I3C-treated groups. Molecular docking analysis demonstrated moderate binding affinities of -5.1 kcal/mol and -5.3 kcal/mol with IL-4 and IL-13, respectively. In conclusion, findings from this exploratory study suggest that I3C treatment ameliorated DNCB-induced atopic dermatitis in mice, evidenced by reductions in ear thickness and IL-4/IL-13 mRNA expression. Molecular docking analysis demonstrated moderate binding affinities of I3C toward IL-4 and IL-13, providing supportive evidence of potential ligand-protein interactions.

ID: 42390483
Title: Psychological stress and (poly)phenol intake in free-living healthy adults: an ecological momentary assessment study.
Abstract: Stress can impact physical and psychological health, partially driven by a deterioration in dietary choices during periods of stress. Crucially, the nutritional composition of food choices made in the context of stress may protect from or exacerbate its impact on health. Dietary (poly)phenols can be cardioprotective during stress but whether individuals tend to consume (poly)phenol-rich foods during stressful periods is unknown. This study aimed to investigate within- and between-person associations between daily stress and (poly)phenol intake in a free-living environment. Daily levels of perceived stress and psychological wellbeing (anxiety, depression, positivity, energy, fatigue), (poly)phenol intake (including flavonoids and phenolic acids sub-groups), (poly)phenol-rich food intake (fruit and vegetables, tea and coffee, red wine), and diet composition (fat, saturated fat, sugar, fibre) were measured using ecological momentary assessment (EMA) in 67 young healthy participants over 7 days. Multilevel linear mixed models examined within- and between-person associations between daily perceived stress, psychological wellbeing and (poly)phenol intake, (poly)phenol-rich food intake and dietary composition. Higher stress at the within-person level and symptoms of depression at the between-person level were associated with more consumption of tea and coffee. This was paralleled by a tendency to increase polyphenol (p = 0.070) and phenolic acid (p = 0.064) intake during stress. Furthermore, the association between stress and tea and coffee consumption was stronger in participants with higher habitual stress. A lower perception of feeling positive at the within-person level was associated with higher saturated fat and sugar consumption, and higher fatigue at the between-person level was associated with increased fat intake. Our findings suggest that when perceived stress is higher, individuals show preference for consumption of (poly)phenol-rich beverages such as tea and coffee. Future research should investigate whether tea and/or coffee are a viable strategy to deliver (poly)phenols during stressful periods with the ultimate goal of protecting cardiovascular health.

ID: 42392735
Title: [Modulatory effects of raw and honey-processed Astragali Radix fractions on intestinal microbiota, short-chain fatty acid metabolism and immune activity in rats with spleen deficiency].
Abstract: This study aimed to investigate the effects of total saponins, total flavonoids, and total polysaccharides from raw and honey-processed Astragali Radix on intestinal microbiota, short-chain fatty acid metabolism, and immune activity in rats with spleen deficiency. A spleen deficiency model was established using a combination of irregular diet, bitter-cold purgative administration and excessive fatigue. High-throughput 16S rRNA sequencing was employed to analyze the modulatory effects of different fractions from raw and honey-processed Astragali Radix on the structural diversity of intestinal microbiota in spleen-deficient rats. Headspace gas chromatography-mass spectrometry was used to determine the modulatory effects of these fractions on the metabolism of short-chain fatty acids. ELISA was employed to assess the effects of raw and honey-processed Astragali Radix on specific and non-specific immune activities of spleen-deficient rats. The results demonstrated that the total flavonoids, total saponins, and total polysaccharides from raw and honey-processed Astragali Radix significantly restored the abundance of the harmful bacterial genus Helicobacter in the intestines of spleen-deficient rats. Moreover, except for the total polysaccharides from both raw and honey-processed Astragali Radix, all other treatment groups also significantly reduced the abundance of the harmful bacterial genus Sutterella(P<0.05). The fractions from raw and honey-processed Astragali Radix were able to restore the levels of various short-chain fatty acids in the colon of spleen-deficient rats. Notably, the total polysaccharides from honey-processed Astragali Radix significantly outperformed those from raw Astragali Radix in increasing acetic acid content(P<0.05). The total polysaccharides of both raw and honey-processed Astragali Radix significantly restored the levels of IL-4, IL-6, IL-10, IL-18, IgA, and IgG in the serum and colon, as well as the level of IL-2 in the serum of spleen-deficient rats(P<0.05 or P<0.01). The restorative effects of the processed product were superior to those of the raw product. In summary, the specific and non-specific immunomodulatory effects of the components from raw Astragali Radix increased after honey-processing, thereby potentiating its efficacy in ameliorating spleen deficiency. These findings may provide a scientific basis for elucidating the mechanism by which honey-processing enhances the qi-tonifying and middle-strengthening effects of Astragali Radix.

ID: 42393879
Title: Herbal Medicine and Metabolic Syndrome: Phytochemicals Targeting the Molecular Causes of Insulin Resistance and Related Comorbidities.
Abstract: Metabolic Syndrome (MetS) is a global health concern characterized by a cluster of interrelated metabolic abnormalities, including insulin resistance, central obesity, dyslipidemia, hypertension, and chronic low-grade inflammation. These factors significantly increase the risk of developing Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD), and other complications. In recent years, plant-derived natural products and herbal medicines have garnered increasing attention for their potential to modulate the underlying mechanisms of Metabolic Syndrome (MetS) safely and cost-effectively. This review explores the therapeutic role and molecular mechanisms of several key botanicals, including berberine, Cinnamomum cassia (Cinnamon), Zingiber officinale (ginger), Trigonella foenum-graecum (Fenugreek), Nigella sativa (black seed), Curcuma longa (Curcumin), Artemisia dracunculus (Russian tarragon), Momordica charantia (bitter melon), and Vaccinium angustifolium (lowbush blueberry). These agents exert multifaceted effects, including the activation of AMPK, enhancement of insulin receptor signaling, increased GLUT4 translocation, anti-inflammatory and antioxidant activities, and modulation of lipid metabolism and gut microbiota. While preclinical data strongly support their efficacy, human clinical trials have shown mixed results due to factors such as inconsistent formulations, poor bioavailability, and individual variability. Despite these challenges, the evidence suggests that plant-based therapies may serve as effective adjuncts to conventional treatment, particularly in the early or preventive stages of MetS. The review highlights the importance of standardized formulations, enhanced delivery systems, and well-controlled clinical trials to validate their efficacy and integrate them into evidence-based therapeutic protocols. These findings support the growing role of natural products in the holistic management of metabolic syndrome.

ID: 42399703
Title: Reduced meat and dairy consumption improves health, environmental and most nutritional outcomes without increasing diet costs among Scottish adults.
Abstract: Shifting diets away from high levels of meat and dairy is increasingly considered an important part of climate mitigation, yet the best pathways for achieving these reductions without compromising nutrition, health or affordability remain unclear. Here, in a representative sample of Scottish adults, we evaluate 33 pathways to meeting the UK Climate Change Committee's recommendations to reduce meat and dairy consumption by 20% by 2030, increasing to a 35% reduction in meat by 2050. The pathways incorporate existing dietary guidance, and modelled outcomes include intakes of 54 nutrients, obesity, type 2 diabetes, cardiovascular disease, all-cause mortality, diet costs, greenhouse gas emissions, freshwater use, land use and eutrophication. Nearly all pathways were estimated to benefit most nutritional, health and environmental outcomes without increasing diet costs. Benefits were greater when reductions targeted high consumers of red meat and when meat and dairy were replaced gram for gram with foods such as vegetables, beans, eggs and plant-based dairy alternatives.

ID: 42402300
Title: Lotus seed resistant starch alleviates OVA-induced food allergy in rats by promoting a Bifidobacterium-enriched gut microbiota and enhancing acetic acid production.
Abstract: This study established a rat model of ovalbumin (OVA)-induced food allergy. By systematically comparing allergic phenotypes, gut microbiota remodeling, and short-chain fatty acids (SCFAs) profiles among groups receiving single interventions-Type 3 lotus seed resistant starch (LRS3), sodium acetate (AC), Bifidobacterium animalis subsp. lactis DSM 10140 (BA)-and combined interventions (LRS3-AC, LRS3-BA), a multi-level correlation network of "gut microbiota-SCFAs-immune markers" was constructed. This study found that single interventions with LRS3, AC, and BA, as well as combined interventions with LRS3-AC and LRS3-BA, all improved allergy-related symptoms and immune dysregulation, with the LRS3-BA group showing the best intervention effect; all intervention groups shifted the gut microbiota structure away from the allergic state. LRS3 promoted the proliferation of Bifidobacterium, and when combined with BA, further promoted Bifidobacterium to become a core indicator bacterium. All intervention groups significantly increased fecal acetic acid concentration, the acetic acid level in the LRS3-BA group reached 2.15 μg/mg. As a common downstream effector molecule, acetic acid showed a strong positive correlation with Bifidobacterium and exhibited a stronger association with allergy markers than propionate and butyrate. The study proposed a potential "LRS3-Bifidobacterium-acetic acid" axis for regulating the gut microbiota and alleviating food allergies, providing a theoretical basis for developing food allergy intervention strategies targeting the gut microbiota.

ID: 42409523
Title: How drying technologies shape digestive fate of polyphenols in fruits and vegetables: A critical evaluation.
Abstract: Drying is widely applied to fruits and vegetables to extend shelf life, reduce post-harvest losses, and produce stable, bioactive-rich ingredients. However, the nutritional value of dried products is still often assessed solely based on polyphenol retention, despite the fact that drying-induced changes in tissue architecture, oxygen exposure, enzyme activity, and matrix integrity can strongly affect gastrointestinal release and bioaccessibility. This critical evaluation synthesizes 17 studies examining how different drying technologies influence the release behaviour, bioaccessibility, and antioxidant activity of polyphenols in dried fruits, vegetables, and herbs using in vitro gastrointestinal digestion models. Across matrices, the oral phase contributed minimally to polyphenol release, whereas the gastric phase generally represented the main liberation step. The intestinal phase displayed compound-dependent behaviour, acting either as a secondary release stage for bound or matrix-associated phenolics or as a stage of degradation and reduced recovery for anthocyanins and other labile flavonoids. Phenolic acids were generally the most digestion-recoverable polyphenols, while flavan-3-ols, flavonols, and anthocyanin derivatives showed greater dependence on matrix structure, oxidation, glycosylation/acylation, and pH stability. Drying methods that balanced moderate structural disruption with low oxygen exposure, such as vacuum, microwave-vacuum, ultrasound-assisted vacuum, infrared, and low-temperature vacuum drying, often improved bioaccessibility compared with conventional hot-air or freeze-drying methods, although matrix-specific exceptions occurred. Measured antioxidant activity reflects not only total polyphenol release but also compound transformations, degradation products, and the inherent sensitivity of the analytical assay. Overall, the review highlights the need to move beyond retention-based evaluation toward bioaccessibility- and bioavailability-oriented process design, supported by harmonized digestion protocols and compound-specific profiling.

ID: 42409865
Title: High adherence to a Mediterranean diet is associated with a diverse faecal microbiome and reduced systemic inflammation in a cohort of pregnant women.
Abstract: The Mediterranean diet (MD), known for its high intake of fruits, vegetables, whole grains, legumes, and healthy unsaturated fats, has been linked to a diverse and beneficial gut microbiome. However, its effect on the gut microbiome during pregnancy remains understudied. This study aimed to investigate the impact of high adherence to a Mediterranean diet on gut microbiome composition and function in pregnant women by analysing their metabolic profiles and faecal microbiome composition. Stool, serum, and urine samples were collected from 48 pregnant women at weeks 20/28 and at week 36. Participants were stratified based on MD adherence using a validated questionnaire. Stool samples underwent 16 S rRNA gene amplicon sequencing, and serum short-chain fatty acids (SCFAs) were measured using UPLC-MS. Women with high MD adherence showed significantly higher α-diversity in their faecal microbiomes at both time points. Significant differences in microbiome composition were observed between low and high adherence groups at weeks 20/28, but not at week 36. No significant differences in serum short-chain fatty acid concentrations were found between the groups. Our findings suggest that adherence to the Mediterranean diet during pregnancy is associated with changes in gut microbiome diversity and function. These results contribute to a better understanding of how dietary patterns during pregnancy may influence gut microbiome ecology.

ID: 42413643
Title: Gut microbiome-mediated modulation of the glioblastoma tumor microenvironment for enhanced immunotherapy response: Mechanistic insights and future perspectives.
Abstract: Glioblastoma (GBM) is known to be one of the most aggressive and deadly brain tumors in adults, with a very poor prognosis. An immunosuppressive tumor microenvironment, the blood-brain barrier's (BBB's) protective nature, and genetic heterogeneity mediate resistance to conventional treatments, such as immune checkpoint inhibitors. Recent studies have shed light on the important role of the gut-brain axis in regulating GBM pathogenesis. Studies have demonstrated that patients with GBM frequently exhibit gut dysbiosis, with limited beneficial microbial populations, thereby enhancing immunosuppression and reducing the effectiveness of immune checkpoint inhibitors. This is mediated by SCFAs derived from the gut microbiota, such as acetate, propionate, and butyrate, which influence CNS immunity through direct effects on immune cells and processes, including HDAC inhibition. SCFAs can enhance the proliferation of anti-inflammatory T regulatory cells, promote pro-inflammatory responses from microglia and tumor-associated macrophages, and fortify the integrity of the BBB. Also, certain bacteria belonging to the genera Blautia and Bifidobacterium have been found to enhance the recruitment of anti-tumor CD8+ cytotoxic T lymphocytes. Thus, FMT, probiotics, prebiotics, and high-fiber diets are very promising adjuvant strategies to overcome GBM resistance by therapeutically enhancing the gut microbiome. This will aid in restoring microbial resilience, optimizing SCFA production, and potentiating anti-tumor immune responses. To validate microbial biomarkers and causative pathways, future advances in this field will integrate multi-omics data with robust clinical trials. Moreover, to examine how the gut microbiome influences the glioblastoma tumor microenvironment and the response to immunotherapy, this narrative review synthesizes existing data from studies of GBM patients, experimental models, and neuroimmunology research.

ID: 42413654
Title: Temporal response patterns of swine gut microbiota to arabinoxylan.
Abstract: Arabinoxylan (AX) is a major dietary fiber that is depolymerized and fermented by gut microbiota to produce short-chain fatty acids (SCFAs), thereby influencing host energy harvest and gut homeostasis. However, it remains unclear how baseline differences in the gut microbiota among individuals shape the temporal dynamics and metabolic outcomes of AX fermentation. This study aimed to investigate how preexisting variation in swine gut microbial ecosystems affects the utilization of AX. We employed an in vitro fermentation model inoculated with fecal microbiota from two genetically divergent pig breeds: Jinhua (JH, a native breed) and Duroc × Landrace × Yorkshire (DLY, a commercial crossbred). Microbial succession was characterized by 16S rRNA gene amplicon sequencing coupled with time-series clustering, co-occurrence network reconstruction, and co-abundance response groups (CARGs) analysis. We used PICRUSt2 to predict the functional potential of the microbial communities and assessed fermentation outputs by measuring pH, SCFA concentrations, and key enzyme activities. JH and DLY maintained distinct baseline community structures and displayed pronounced, stage-dependent succession during AX fermentation, with most structural changes occurring within 24  h. The JH microbiota consistently exhibited higher α-diversity than DLY, driven by enrichment of fiber-degrading bacteria. Functional prediction identified the pentose and glucuronate interconversion pathways as key functional differences between the two microbial ecosystems. CARG analysis revealed a consortium of Limosilactobacillus species (L. mucosae, L. balticus, L. agrestimuris) and Lactobacillus delbrueckii subsp. jakobsenii as keystone taxa positively correlated with acetate production. Our findings elucidate temporal ecological principles governing AX metabolism by distinct swine gut microbial communities and identify key microbial players, offering a basis for developing microbiome-targeted nutritional strategies.