Search Results (3,632)

Background: Nutritional psychiatry increasingly links diet quality and specific bioactive nutrients to depression and anxiety outcomes. Mechanistic evidence implicates neuroimmune activation, inflammation, altered neurotransmitter synthesis, and microbiota-derived metabolites. Objective: The objective of this study is to synthesize evidence on omega-3 polyunsaturated fatty acids (n-3 PUFAs), the microbiota–gut–brain axis, and vitamins and minerals that influence neurotransmitter synthesis, inflammation, and brain function and to translate these findings into food-based strategies. Methods: This study consisted of a focused synthesis of randomized controlled trials (RCTs), meta-analyses, and systematic reviews indexed in PubMed, Scopus and Web of Science, selected for relevance to omega-3s, probiotics/prebiotics, dietary patterns, and micronutrients (folate/B-vitamins, vitamin D, magnesium, zinc, and vitamin C/copper pathways). Results: RCT and meta-analytic evidence suggest modest benefits of omega-3 supplementation for anxiety severity and depressive symptoms, with heterogeneity by dose, EPA: DHA composition, and baseline inflammatory status. The gut–brain axis literature supports bidirectional effects of stress and microbiota, and meta-analyses of probiotics/prebiotics show small improvements in depressive and anxiety symptoms, likely dependent on strain and host phenotype. Micronutrients serve as enzymatic cofactors for monoamine and GABA synthesis and modulate immune signaling; clinical effects are the most consistent when correcting insufficiency or in biomarker-defined subgroups. A whole-diet RCT demonstrates that structured dietary improvement can reduce depressive symptoms as adjunctive therapy. Conclusions: A food-first approach emphasizing Mediterranean-style dietary patterns, omega-3-rich seafood, a diverse array of fiber, and micronutrient density is the most defensible. Supplementation may be considered selectively, guided by clinical context and nutritional status. Full article

Metabolic diseases are strongly associated with chronic systemic inflammation and oxidative stress, which disrupt the microbiota–gut–brain (MGB) axis and promote neuroinflammation. Dysbiosis favors the release of proinflammatory metabolites, reactive oxygen species (ROS), and lipopolysaccharides (LPS), increasing intestinal permeability and triggering systemic immune responses that reach the central nervous system (CNS) through a weakened blood–brain barrier (BBB). This review summarizes current knowledge on the pathophysiological mechanisms linking the MGB axis, metabolic disorders, and neuroinflammation, as well as the therapeutic potential of antioxidants. A literature search was conducted in PubMed, Web of Science, Scopus, and ScienceDirect and included original research articles, reviews, clinical trials, and meta-analyses related to microbiota, neuroinflammation, oxidative stress, and antioxidant interventions. Evidence indicates that dysbiosis exacerbates metabolic dysfunction by activating the nuclear factor kappa B (NF-κB) and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathways, while excessive ROS production impairs mitochondrial function, neuronal survival, and cognitive processes. Antioxidant strategies, including polyphenols, omega-3 fatty acids, curcumin, vitamins C and E, and probiotics, can restore microbial diversity, reinforce intestinal and BBB integrity, and modulate oxidative and inflammatory signaling. In conclusion, supplements and bacteria with antioxidant properties show promising therapeutic effects by targeting oxidative stress mechanisms involved in metabolic diseases and their pathological consequences, such as dysbiosis and neuroinflammation. Full article

This study presents a comparative evaluation of solar cabinet drying and traditional open-air sun drying with respect to their influence on the retention of water-soluble vitamins and flavonoids in Plantago major L. leaves, aiming to identify an effective and sustainable drying strategy for functional food applications. Freshly harvested leaves were subjected to both drying methods under comparable environmental conditions. To account for possible structural heterogeneity, external and internal leaf tissues were analyzed separately. Qualitative and quantitative determination of bioactive compounds was performed using high-performance liquid chromatography with diode-array detection (HPLC-DAD). Flavonoids were analyzed at detection wavelengths of 254 and 276 nm, while water-soluble vitamins (C, B₂, B₃, B₆, and B₉) were determined at 250 nm. Quantification was carried out using external calibration, and results were expressed as concentrations (mg/g dry matter). The results demonstrate that solar cabinet drying provides superior preservation of oxidation- and light-sensitive bioactive compounds compared to open-air sun drying. In particular, vitamin C content in solar cabinet-dried samples reached 91.62 mg/g, which was more than three times higher than that observed after open-air drying (26.90 mg/g). Solar cabinet drying also enhanced the retention of key antioxidant flavonoids, notably dihydroquercetin (14.23 mg/g vs. 11.21 mg/g) and luteolin (0.38 mg/g vs. 0.26 mg/g). Although slightly higher concentrations of certain compounds, such as rutin and vitamins B₆ and B₉, were detected in open-air-dried samples, the overall nutraceutical profile favored solar cabinet drying. In conclusion, the controlled microclimate of the solar cabinet dryer significantly improves the stability and retention of critical water-soluble vitamins and antioxidant flavonoids in Plantago major L. leaves. These findings confirm that solar cabinet drying is a nutritionally advantageous, energy-efficient, and sustainable approach for producing high-quality plant-based ingredients suitable for functional food and nutraceutical applications. Full article

Peripheral nerve injuries often lead to incomplete recovery despite surgical repair. Vitamin B12 and folic acid have been implicated in nerve regeneration, but their comparative effects have not been systematically evaluated. Twenty-four male Wistar rats underwent femoral nerve transection and were assigned to three groups: control, vitamin B12 (2500 µg/kg weekly, subcutaneous), and folic acid (40 mg/L in drinking water). Functional recovery was assessed over eight weeks using foot-base angle (FBA) during beam walking. Histological analysis evaluated axon counts and myelination (g-ratio). Both treatments accelerated early gait recovery compared to controls, with significant FBA improvement at week 4 (p < 0.05). Vitamin B12 produced sustained functional benefits through week 8 and superior myelination (lower g-ratio, p < 0.0001), whereas folic acid increased axon numbers but did not enhance myelin thickness or late-phase recovery. High-dose vitamin B12 significantly improves structural and functional outcomes after femoral nerve injury, while folic acid primarily supports early axonal regrowth. Vitamin B12 represents a promising pharmacological adjunct for peripheral nerve repair. Further research should explore optimal dosing strategies and long-term effects in clinical settings. To our knowledge, no prior study has directly compared the effects of folic acid and vitamin B12 supplementation within the rat femoral-nerve model, providing the rationale for the present head-to-head design. Full article

Background: Nausea and vomiting in pregnancy affects up to 80% of pregnant women and may progress to hyperemesis gravidarum, leading to maternal morbidity and adverse pregnancy outcomes. Despite numerous pharmacological and non-pharmacological options, the comparative efficacy and safety of these interventions remain unclear. Methods: We conducted a systematic review and network meta-analysis of randomized controlled trials assessing pharmacological and non-pharmacological interventions for nausea and vomiting in pregnancy. The databases searched included CENTRAL, PubMed, and EMBASE (up to 28 May 2024). Eligible trials compared interventions with a placebo in pregnant women with nausea and vomiting in pregnancy. The primary outcomes were symptom severity, assessed using validated tools. Safety outcomes included adverse effects. Data were pooled using frequentist pairwise and network meta-analyses. The risk of bias was assessed using the RoB2 tool, and the certainty of evidence was evaluated using the CINeMA framework. Results: Of 9844 records screened, 24 randomized controlled trials (3017 participants) met the inclusion criteria, encompassing 16 intervention categories. Network analysis ranked quince, vitamin B6 with pomegranate and mint, acupressure P6, dimenhydrinate, and acupuncture combined with doxylamine–pyridoxine as the most effective interventions for reducing symptoms of nausea and vomiting in pregnancy, with considerable uncertainty and low-to-moderate quality of evidence. Reporting of adverse events was limited. Risk of bias was low to moderate. Discussion: Most interventions demonstrated significant benefit over a placebo. However, high heterogeneity and sparse reporting of adverse effects warrant caution when translating these results into clinical practice. Conclusions: This study indicates that both pharmacological (vitamin B6, metoclopramide, dimenhydrinate) and non-pharmacological (ginger, quince, acupressure, acupuncture) interventions might be effective in reducing symptoms of nausea and vomiting in pregnancy. Full article

Maternal nutrition during critical windows of development plays a pivotal role in shaping long-term disease susceptibility, including cancer risk. This study investigated whether maternal exposure to lipotropes (methyl donor nutrients) during pregnancy and lactation modulates gene expression in 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors in adult female offspring. Timed-pregnant Sprague-Dawley rats were fed with either a control or lipotrope-supplemented diet, with or without vitamin B6. Female offspring were exposed to DMBA at puberty, and mammary tumors were evaluated histologically and molecularly. DMBA-induced tumors displayed ductal carcinoma in situ-like morphology and significant upregulation of fetal mammary developmental genes (Tbx2 and Tbx3), the tumorigenesis-associated gene Tp53, and key epigenetic regulators (Hdac1, Dnmt1, and Mthfr). Estrogen receptor 1 (Esr1) mRNA expression also showed a significant increase. Maternal lipotropes supplementation significantly attenuated the expression of these genes in offspring tumors. Collectively, these findings demonstrate that maternal methyl donor nutrition modulates tumor-associated gene expression patterns, potentially by limiting the reactivation of developmental and epigenetic pathways in adulthood. This study highlights maternal nutrition as a modifiable early-life factor with important implications for long-term health programming. Full article

Background: Complex regional pain syndrome (CRPS) is a disabling post-traumatic pain condition that may occur after distal radius fracture (DRF), potentially impairing recovery and upper-limb function. Identifying effective preventive strategies after DRF is therefore clinically important. Objective: To synthesize and critically appraise interventions intended to prevent CRPS after DRF, including rehabilitation protocols and clinical prophylaxis strategies. Methods: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA and was registered in the International Prospective Register of Systematic Reviews PROSPERO (CRD42023408499). Five databases (PubMed, Web of Science, Scopus, ScienceDirect, and B-on) were searched for studies published from January 2013 to 22 September 2023 in English, Portuguese, or Spanish. The primary outcome was CRPS incidence after DRF. Findings were synthesized narratively due to heterogeneity in interventions and diagnostic criteria, and risk of bias was assessed using design-appropriate tools. Results: Nine studies were included (total N = 7075; CRPS cases n = 127). Interventions comprised vitamin C supplementation (2 studies), probiotics, aspirin, polarized/polychromatic light therapy plus conventional treatment, early rehabilitation/home-exercise programs, and general CRPS-prevention protocols after DRF. Probiotics and aspirin did not reduce CRPS incidence. Vitamin C showed mixed findings across the included studies and remains debated in the broader literature. Light therapy was associated with reduced CRPS occurrence in a single study, while early active home-exercise programs appeared promising but were supported by a limited number of studies. Study designs and CRPS diagnostic criteria varied, and risk of bias was moderate-to-serious in several non-randomized studies. Conclusions: Evidence remains insufficient to support a single standardized prevention protocol for CRPS after distal radius fracture. Early active rehabilitation and progressive mobilization appear promising, but the available evidence is still limited and heterogeneous. Adjunctive strategies such as vitamin C and light therapy should be interpreted with caution, as findings for vitamin C remain debated in the literature and the evidence for light therapy is currently based on a single study. Other approaches, including probiotics and aspirin, have shown inconclusive results. Full article

Background/Objectives: Mild cognitive impairment (MCI), the prodromal stage of Alzheimer’s disease, may be influenced by nutritional status and genetic susceptibility. This systematic review synthesised evidence on how nutritional biomarkers interact with genetic variants, particularly APOE ε4, to influence cognitive outcomes in individuals with MCI. Methods: Following PRISMA 2020 guidelines, seven studies were included (three longitudinal, two randomised controlled trials, and two cross-sectional) involving adults aged ≥55 years with MCI. Nutritional exposures comprised plasma or serum concentrations of vitamins A, D, E, the vitamin B group, lipids, selenium, and ketogenic medium-chain triglycerides. Genetic risk was assessed primarily through APOE ε4 status. Risk of bias was assessed using RoB 2 and ROBINS-I, and certainty of evidence using GRADE. Due to heterogeneity in biomarkers, cognitive tools, and study designs, findings were synthesised narratively. Results: Across nutrient categories, higher concentrations of vitamin D, selenium, and antioxidants were associated with better cognitive outcomes. kMCT supplementation improved episodic memory and brain energy metabolism. Evidence for nutrient–gene interactions was mixed: APOE ε4 modified responses to vitamin B group and selenium but showed limited influence on vitamin D, lipids, or kMCT effects. Heterogeneity in biomarker assays, cognitive tools, and genetic stratification limited comparability across studies. Conclusions: Nutritional biomarkers appear to influence cognitive trajectories in MCI, and some associations may differ by APOE ε4 status. However, small samples and limited genetic stratification constrain interpretation. Future research should prioritise standardised biomarker measurement, genetically stratified cohorts, and individual participant data meta-analyses to clarify nutrient–gene interactions in MCI. Full article

Plant foods have been the cornerstone of human diets since ancient times, fueling civilization and shaping cultures. Plants became central to sustainable food systems, offering diverse and nutritious options for the future. Sea buckthorn (Hippophae rhamnoides L.) has attracted growing scientific interest due to the presence of bioactive compounds, polyphenols, fatty acids, phytosterols, carotenoids, vitamins, and minerals in its fruit, seeds, and leaves. Moreover, sea buckthorn exhibit antioxidant, anti-inflammatory, antimicrobial, antidiabetic, antihyperlipidemic, anticancer, hepatoprotective, neuroprotective, and metabolic regulatory properties supported by in vitro and in vivo models. The biological activity of these phytochemical compounds plays a crucial role in regulating the AMP-activated protein kinase (AMPK) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathways, as well as pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), cell proliferation, and apoptosis. Furthermore, its potential against microbial growth, including S. aureus, S. epidermidis, S. intermedius, and S. pyogenes, among others, not only expands its applications in the pharmaceutical industry but also attracts researchers to incorporate it into food products. This could lead to the discovery of plant-based therapeutic products without significant adverse effects. However, further exploration of each component’s potential side effects is necessary to support the commercialization of formulated products in either the pharmaceutical or food industries, ensuring the highest safety standards for consumers. Including studies on bioavailability and pharmacodynamics could further strengthen the scientific evidence supporting the specific phytochemicals in sea buckthorn and their mechanistic interactions. Full article

Background and aim: Celiac disease (CD) is a systemic autoimmune disorder triggered by gluten ingestion, and the only effective treatment is strict adherence to a gluten-free diet (GFD). Many factors, including limited dietary diversity and poor adherence, are associated with an increased risk of specific micronutrient deficiencies and malnutrition. This study aims to evaluate the relationship between adherence to GFD, celiac antibody levels, micronutrient levels, and nutritional status in children with CD. Methods: This retrospective study was conducted on 402 children aged 2–18 years with a diagnosis of CD confirmed positive by anti-tTG IgA and duodenal biopsy, all of whom had been on GFD for at least six months. Demographic, anthropometric, clinical, serological, and biochemical data (including hemogram, serum iron, ferritin, vitamin D, folate, and B12 levels), and GFD adherence were collected from medical records. Results: Most individuals are girls (64.9%), with a mean age of 10.6 ± 4.20 years. Chronic malnutrition was observed in 29.4% of patients. Acute malnutrition was identified in 27.8% of children, and wasting was observed in 6.7%. Iron deficiency anemia was the most frequently encountered micronutrient deficiency among the patients (23.9%). The prevalence of stunting was significantly higher among individuals with positive tTG-IgA levels and poor adherence to the GFD. Conclusions: Poor adherence to the GFD and positive tTG-IgA levels were associated with higher rates of stunting, underlining the need for individualized dietary follow-up and regular monitoring of both nutritional status and serological response in children with CD. Full article

Background: Constipation is a common gastrointestinal (GI) state for which probiotics have shown promise as a relief. This study examined the laxative effects of the strain Bifidobacterium animalis subsp. lactis CECT 8145 (BPL1^®) in a loperamide-induced rat model of constipation. Methods: Fifty-nine rats were divided into control and loperamide-induced constipation groups. Animals received a 3-day intervention with either placebo or probiotic BPL1^® at two doses: 1.5 × 10⁸ CFU (colony-forming units) (low) and 3 × 10⁹ CFU (high). The study assessed several parameters to determine the probiotic’s effect, including: stool and gut characteristics, gastrointestinal transit time (GTT), gene expression and gut microbiome composition. Results: While loperamide significantly decreased stool number, weight and humidity, BPL1^® supplementation effectively restored these parameters, being more pronounced at a high dose. Microbiome analysis showed that BPL1^® at a low dose reduced the abundance of Muribaculaceae and Muribaculum gordoncarteri, associated with constipation. In addition, Muribaculaceae abundance was negatively correlated with stool humidity. Functional microbiome profiling indicated that BPL1^® suppressed pathways related to mucin degradation, vancomycin resistance and isoleucine biosynthesis while promoting L-lactate and pyridoxal-P (vitamin B6) biosynthesis, which may support gut motility and barrier integrity. Conclusions:Bifidobacterium animalis subsp. lactis BPL1^® exhibits potential as a functional probiotic for relieving constipation through improving stool excretion and consistency, inducing taxonomic changes and beneficial functional modulation of the intestinal microbiome. These findings justify further investigation into the mechanisms of BPL1^® as a probiotic for constipation management. Full article

Background/Objectives: Bordetella bronchiseptica is a Gram-negative bacterium that, either acting alone or in concert with other bacterial or viral pathogens, is a major cause of the canine infectious respiratory disease (CIRD) complex in dogs. Most currently available vaccines are given intranasally or orally and, whilst providing satisfactory reduction in disease severity, can be difficult to use especially in aggressive or anxious dogs. Whilst a small number of injectable B. bronchiseptica vaccines have been developed, little is known about their characteristics with regard to the age at first vaccination, the onset of immunity, duration of immunity, induction of antibody responses, concurrent use with the core vaccines used in most dogs, efficacy in the face of maternally derived antibodies (MDAs) or existing immunity and safety in pregnant animals. Here we describe the development of a safe and efficacious injectable B. bronchiseptica vaccine that utilises a novel process to purify fimbriae. Methods: The fimbrial antigen was formulated with a vitamin E-based oil-in-water adjuvant known to be safe in dogs (Nobivac^® Respira Bb). To evaluate dose response, thirty-nine naïve 5–6-week-old Beagle puppies were allocated to four groups and vaccinated subcutaneously with Nobivac^® Respira Bb at 69 U, 25 U, and 7 U (with a booster at two weeks). All groups were challenged with B. bronchiseptica two weeks after the booster. To evaluate the onset of immunity at 5–6 weeks of age, twenty-one naïve Beagle dogs were split into two groups: group 1 received Nobivac Respira Bb (88 U/dose) plus Nobivac DHPPi and Nobivac L4; group 2 received DHPPi and L4 only. Both groups were challenged with B. bronchiseptica two weeks after the second vaccination. Safety in pregnancy was evaluated by vaccinating pregnant dams and monitoring whelping outcomes and puppy health. Protection in puppies with maternally derived antibodies (MDAs) was studied in 28 pups (11 MDA-negative and 17 MDA-positive from vaccinated and unvaccinated dams). Pups were vaccinated at 5–6 weeks; one group remained unvaccinated to monitor MDA kinetics. All puppies were challenged with B. bronchiseptica at 19 weeks, after MDAs became undetectable. Serology was monitored throughout; daily clinical observations and nasal swabs post-challenge assessed protection and bacterial shedding. Results: Nobivac Respira Bb (MSD Animal Health), was safe for use in 5–6-week-old puppies alongside other Nobivac core canine vaccines without vaccine interference. The vaccine has an onset of immunity of two weeks and significantly reduces both the clinical signs of B. bronchiseptica-induced disease and bacterial excretion into the environment. Furthermore, the vaccine is equally efficacious in puppies with maternally derived antibodies derived from vaccinated dams and can be used safely in pregnant bitches. Conclusions: This vaccine represents a convenient, safe and efficacious alternative to vaccines delivered via the oral or intranasal routes and is a positive addition to the range of vaccines targeted at reducing disease induced by B. bronchiseptica. Full article

Background/Objectives: Periodontitis grade reflects differences in disease progression and risk, yet the underlying host-response signatures that distinguish grade B from grade C are not fully elucidated. Nuclear receptors involved in inflammation and tissue homeostasis may contribute to these biological differences. The present study aimed to evaluate the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), retinoid X receptor-α (RXR-α), and vitamin D receptor (VDR) in gingival tissues from periodontally healthy individuals and from patients with grade B and grade C periodontitis, with the primary comparison focusing on grade-related differences within the same disease stage (stage 3). Methods: Forty-five participants were allocated to three groups: Group 1, healthy controls; Group 2, stage 3 grade B periodontitis; and Group 3, stage 3 grade C periodontitis. Clinical parameters, including plaque index (PI), gingival index (GI), and clinical attachment loss (CAL), were recorded. Fibroblast and inflammatory cell density, and immunohistochemical expression levels of PPAR-γ, RXR-α, and VDR were assessed on histological sections. Results: Compared with healthy controls, both periodontitis groups showed lower fibroblast cell counts and higher inflammatory cell counts. PPAR-γ expression was significantly higher in Group 3 than in the other groups, whereas RXR-α and VDR expression were higher in Group 1 than in Groups 2 and 3. Conclusions: These findings suggest that increasing disease grade within stage 3 periodontitis is associated with increased PPAR-γ expression, whereas RXR-α and VDR expression primarily distinguish healthy from diseased gingival tissues. This nuclear receptor profile may help explain biological differences between healthy, grade B and grade C periodontitis and support future risk-stratified host-modulatory approaches. Full article

Background/Objective: Delaying muscle fatigue could alleviate economic and food security, and welfare concerns associated with transporting market-weight pigs to harvest. Previous research demonstrates barrow nicotinamide riboside (NR) supplementation at varying doses during the last 10 d of finishing shows to be a countermeasure to muscle fatigue by reducing muscle fiber recruitment and increasing mitochondrial DNA expression in a dose-dependent manner. Therefore, this study aims to determine if a greater NR dose further enhances barrow fatigue resistance and characterize muscle mitochondria content and efficiency. Methods: Barrows (N = 87) were assigned to one of two dietary NR supplementation doses (TRT): 0 (0NR) or 150 (150NR) mg/kg body weigh NR administered during the last 14 d of finishing. Muscle (MUS) biopsies were collected on supplementation d (DAY) 0, 7 and 14 from three hind-leg muscles for NAD+ quantification and mitochondrial DNA expression and efficiency. On days 15 and 16, barrows were subjected to a performance test until they were subjectively exhausted. Electromyography data collection during the performance test were divided into five periods (PER) and included normalized root mean square (nRMS) from the same muscles. Results: There were no three-way interaction for nRMS (p > 0.83), but there were MUS × TRT and PER × TRT interactions (p < 0.05). During performance testing, 150NR had greater nRMS than 0NR in the bicep femoris (BF) and tensor fasciae latae (TFL; p < 0.01), but there were no differences in the semitendinosus (ST; p = 0.77). Treatments did not differ during PER 1 and 2 (p > 0.14) but 150NR had greater nRMS than 0NR during PER 3, 4 and 5 (p < 0.01) across all muscles. There was no three-way interaction for normalized (nNAD+; p = 0.14), but there was a DAY × TRT interaction (p < 0.05). There were no differences between 0NR and 150NR at d 0 (p = 0.95); however, by d 7 and 14, 150NR muscles had greater nNAD+ than 0NR muscles (p < 0.01). There tended to be a three-way interaction for mitochondrial DNA expression (p = 0.09). At supplementation d 14, all 150NR muscles had greater mitochondrial DNA expression and electron transport chain complex I and II activities (p < 0.01). When normalized to citrate synthase activity, electron transport chain complex I and II activity did not differ (p > 0.05). Conclusions: Large-dose NR supplementation appears to support sustained muscle fiber recruitment during prolonged activity and enhance fatigue resilience, primarily through increased NAD+ and mitochondrial biomarkers abundance and not through mitochondrial efficiency. Full article

Background: Gut microbiome-derived metabolites, particularly short-chain fatty acids (SCFA) and tryptophan derivatives, are central mediators of the gut–brain axis. This ex vivo study assessed how nutritional interventions impact such metabolites during early life, a critical period for neurodevelopment. Methods: The effects of galacto-oligosaccharides (GOS), nutrient blends (vitamins, minerals and amino acids) and their combinations were evaluated in the gut microbiomes of infants (2–4 months, n = 6) and young children (2–3 years old, n = 6) using the ex vivo SIFR^® technology. Results: Baseline microbiome composition was age-dependent, with infants displaying lower α-diversity and greater interpersonal variability. After ex vivo incubation, nutrient blends increased the propionate/butyrate ratio and branched-chain fatty acids in young children and elevated several B-vitamins and amino acid-derived metabolites, including indole-3-carboxaldehyde, imidazoleacetic acid and pipecolinic acid. Combining nutrient blends with GOS exhibited potential synergistic effects on propionate (infants) and 2-hydroxyisocaproic acid (HICA, both age groups). GOS strongly stimulated Bifidobacteriaceae and increased metabolites linked to bifidobacterial metabolism like acetate, HICA, N-acetylated amino acids, aromatic lactic acids and acetylagmatine; in young children, butyrate and γ-aminobutyric acid (GABA) also increased. Conclusions: Combinations of GOS with nutrient blends impacted microbiome-derived metabolites associated with the gut–brain axis, with potential synergistic increases of metabolites with emerging roles in neurodevelopment, including GABA, acetylagmatine and HICA. Despite shared bifidogenic effects, differences between age groups indicate that microbiome maturity may influence responses to nutritional intervention. Future clinical studies are needed to determine whether these metabolite changes translate into neurodevelopmental benefits in vivo. Full article