Search Results (1,842)

Given the limited efficacy of current interventions and the complexity of chronic pain, identifying perpetuating factors is crucial for uncovering new mechanistic pathways and treatment targets. The oral and gut microbiome has emerged as a potential modulator of pain through immune, metabolic, and neural mechanisms. Contemporary evidence indicates that chronic pain populations exhibit altered oral and gut microbiota, characterized by reduced short-chain fatty acid (SCFA)-producing taxa and an overrepresentation of pro-inflammatory species. These compositional changes affect metabolites such as SCFAs, bile acids, and microbial cell wall components, which interact with host receptors to promote peripheral and central sensitization. Microbiota-derived metabolites modulate peripheral sensitization by altering nociceptive neuron excitability and stimulating immune cells to release pro-inflammatory cytokines that increase blood–brain barrier permeability, activate microglia, and amplify neuroinflammation. Activated microglia further disrupt the balance between excitatory and inhibitory neurotransmission by enhancing glutamatergic activity and weakening GABAergic signaling, thereby contributing to the induction and maintenance of central sensitization. While observational studies establish associations between dysbiosis and chronic pain, animal models and early human fecal microbiota transplantation studies suggest a potential causal role of dysbiosis in pain, although human evidence remains preliminary and influenced by diet, lifestyle, and comorbidities. Overall, microbiota appears to regulate pain via peripheral and central mechanisms, and targeting it through specific interventions, such as dietary modulation to enhance SCFA production, alongside broader lifestyle measures like sleep, physical activity, stress management, and oral hygiene, may represent a new therapeutic strategy for the management of chronic pain. Full article

Black rice has gained increasing attention due to its abundant phenolic compounds and gut microbiota modulation potential, but its health benefits are highly dependent on processing methods. In the present study, the effects of extrusion, traditional cooking, and their combinations with solid-state fermentation (SSF) on phenolic bioaccessibility and the gut microbiota modulation potential of black rice were compared. Results indicated that extrusion combined with SSF (E-SSF) was the most prominent in improving the bioaccessibility of phenolics, flavonoids, and antioxidant activities of black rice during in vitro gastrointestinal digestion. In addition, black rice after SSF induced significantly lower gas production and higher pH during in vitro fecal fermentation. Particularly, black rice after E-SSF showed great advantages in the yield of propionic acid, butyric acid, and total short-chain fatty acids. Consequently, black rice after SSF increased alpha diversity and Bacteroidetes abundance but decreased Firmicute abundance of gut microbiota, while black rice after E-SSF induced the highest alpha diversity and Bacteroide abundance. These results suggested that SSF was beneficial to improve the gut microbiota modulation potential of black rice, and E-SSF was the most preferred. In conclusion, E-SSF was the most suitable to improve the phenolic bioaccessibility and gut microbiota modulation potential of black rice. Full article

Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk and play crucial roles in shaping the gut microbiome and promoting infant health. Although their functions during infancy are well established, emerging evidence suggests that HMOs exert region-specific effects throughout the gastrointestinal tract, extending their benefits beyond early life. This review summarizes current findings on HMO activity in the oral cavity, stomach, small intestine, and large intestine, focusing on their microbiota-modulating, barrier-enhancing, and immunoregulatory effects. In the oral cavity, HMOs inhibit pathogen adhesion and biofilm formation, maintaining oral homeostasis. In the stomach, fucosylated and sialylated HMOs act as soluble decoy receptors, preventing Helicobacter pylori infection. In the small intestine, HMOs strengthen epithelial integrity, regulate inflammation, and promote nutrient absorption. In the large intestine, they serve as selective prebiotics for beneficial microbes, enhancing short-chain fatty acid production and improving barrier function. Although preclinical and clinical studies demonstrate their safety and efficacy, further research is required to elucidate their mechanisms in adults. Overall, HMOs represent multifunctional bioactive glycans with promising applications for gastrointestinal health across all ages. Full article

Background/Objectives: The over 100-year-old practice of using ketogenic diet (KD) in the treatment of epilepsy has consolidated its position as an effective therapeutic tool. The available publications suggest a significant influence of KD on gut microbiome and metabolome and, on the other hand, a correlation between microbiome and metabolome changes and the course of epilepsy. The conclusion is therefore justified that KD can exert a therapeutic effect in epilepsy through the mechanism of gut microbiome and metabolome modulation. Methods:This article is a narrative review aimed at a comprehensive analysis of the literature to gather existing evidence on the relationship between ketogenic diet, its antiepileptic effects and modulation of gut microbiome and metabolome. Results: It has been demonstrated that a ketogenic diet exerts a significant effect on intestinal bacteria and their metabolites, among other actions, increasing the Bacteroides to Firmicutes (B/F) ratio, alleviating dysbiosis, reducing the inflammatory condition in the gut and whole body, increasing the number of specific strains associated with antiepileptic effect, mediating the production of neurotransmitters (GABA, serotonin), exerting influence on the dopaminergic system, on a number of metabolic pathways, on inhibition of genotoxicity and production of short-chain fatty acids (SCFA) in the intestine. Conclusions: Further studies are needed, since the effect of KD on gut microbiome and metabolome modulation in the treatment of epilepsy is an extremely promising and trendsetting direction of research. Full article

The microbiota–gut–organ axis is widely recognized as a pivotal mediator of systemic health, primarily through gut-derived immune, metabolic, and inflammatory signaling. Fucoidans, a class of fucose-containing sulfated polysaccharides predominantly composed of L-fucose and exclusively found in brown seaweeds, have been demonstrated to modulate gut microbiota composition and function, resulting in the enrichment of beneficial bacteria and the suppression of harmful species. They enhance the production of beneficial metabolites, such as short-chain fatty acids and specific bile acids, while suppressing harmful metabolites, including lipopolysaccharide, thereby ameliorating organ damage via key mechanisms such as the mitigation of oxidative stress and inhibition of inflammatory responses. Furthermore, fucoidan supplementation was found to restore intestinal barrier integrity. Using disease models including Parkinson’s disease, alcoholic liver disease, diabetic kidney disease, and obesity, the mechanisms through which fucoidans ameliorate extraintestinal diseases via the microbiota–gut–organ axis were elucidated. Microbiota-dependent mechanisms have been confirmed via experimental approaches such as fecal microbiota transplantation and specific bacterial strain supplementation. Fucoidans represent promising prebiotic agents for the restoration of microbial ecology and the treatment of extraintestinal diseases, highlighting the need for further clinical investigation. Full article

Peptides are short amino acid chains that can be released from proteins through hydrolysis or fermentation, exhibiting various biological activities, including antioxidant, antihypertensive, anti-inflammatory, and anticancer effects. Generally, these compounds are extracted from food products. However, to maximize resource utilization under the premise of sustainability in favor of a circular economy, there is an interesting approach to obtaining peptides from sub-utilized parts and non-food products of food production and processing, based on the grade at which they can be valued. These by-products may contain large quantities of protein that can be utilized. Although some may have a low protein content, they stand out for the quality and proportion of their amino acids, which provide properties with functional applications. This revision approaches some of the most recent reports on isolated peptides from residues, by-products, or underutilized parts from plant, animal, or sea origin; the conventional methods and alternative technologies to isolate them from the origin matrixes; the methods to purify and identify them, the biological activities they perform, as well as a brief description of the application fields of these compounds and the challenges that their application faces in biomedicine and the food industry. Full article

Background: Short-chain fatty acids (SCFAs), the main microbial fermentation products in the colon, have immunometabolic and anti-neoplastic properties. Alterations in fecal SCFA profiles have been proposed as potential non-invasive biomarkers for colorectal cancer (CRC), but previous findings remain inconsistent. This systematic review and meta-analysis aimed to determine whether fecal acetate, propionate, and butyrate concentrations differ between patients with CRC and healthy individuals. Methods: A comprehensive search of PubMed, Web of Science and Cochrane Library was conducted on 18 September 2025. Eligible studies were observational, included adults with histologically confirmed CRC and healthy controls, and reported fecal concentrations of at least one SCFA quantified using validated analytical methods. Two independent reviewers performed study screening, data extraction, and risk-of-bias assessment. Random-effects models were applied to calculate pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Thirteen studies met inclusion criteria for qualitative synthesis, and four (141 CRC cases, 98 controls) were eligible for meta-analysis. Compared with healthy controls, patients with CRC had significantly lower fecal acetate (pooled SMD −0.37; 95% CI −0.63 to −0.10; p = 0.006; I² = 0%) and butyrate (pooled SMD −0.59; 95% CI −1.10 to −0.07; p = 0.026; I² = 64.4%), whereas propionate did not differ significantly (pooled SMD −0.02; 95% CI −0.85 to 0.82; p = 0.971; I² = 89%). Conclusions: CRC is associated with reduced fecal butyrate and, to a lesser extent, acetate, suggesting impaired microbial fermentation. Propionate shows no consistent difference. SCFA profiling currently lacks sufficient standardization and validation for clinical application. Future harmonized, longitudinal studies integrating diet, microbiome, and metabolomic data are warranted to confirm SCFAs as reproducible biomarkers of CRC. Full article

The search for natural alternatives that improve the productive efficiency and metabolic state of dairy cows has driven the use of phytogenic compounds such as silymarin, a flavonolignan extracted from Silybum marianum L. Gaertn with recognized antioxidant, anti-inflammatory, and hepatoprotective properties. This study evaluated the effects of silymarin supplementation on the productive performance; milk composition; and ruminal, hematological, biochemical, and oxidative parameters of lactating Jersey cows kept in a confined system with robotic milking. Twelve cows (230 ± 30 days in lactation; 22 ± 3.5 kg/day of milk) were distributed in a crossover design, receiving a control diet (GCON) or a diet supplemented with 5 g/cow/day of silymarin (GSIL) for 28 days in each stage. Silymarin intake did not alter dry matter intake, feed efficiency, or average milk production (p > 0.05), but it increased milk fat content (4.27 × 4.02%; p = 0.05) and, consequently, milk production corrected for 4% fat (24.4 × 23.2 kg/day; p = 0.05). In the rumen environment, cows in the GSIL group showed higher concentrations of acetic acid (57.4 × 48.4 nmol/L), and total short-chain fatty acids (100.2 × 89.4 nmol/L; p = 0.01). Regarding the biochemical profile, silymarin reduced gamma-glutamyltransferase and aspartate aminotransferase activities, as well as haptoglobin levels, indicating a hepatoprotective effect, combined with a lower inflammatory response in the liver. Oxidative status was improved by decreased levels of TBARS (lipid peroxidation) and reactive oxygen species, as well as myeloperoxidase activity in the serum of cows fed silymarin (p ≤ 0.05), but there was no difference between groups for superoxide dismutase activity and glutathione levels. The inclusion of silymarin in the diet of lactating Jersey cows improved the antioxidant and hepatic profile, increased milk fat content, and favored ruminal fermentation, suggesting metabolic and productive benefits in confined systems with high physiological demands. Full article

Traditional product demand forecasting has typically been modeled as a single time series problem relying exclusively on temporal information. However, temporal features alone are insufficient to capture complex demand dynamics in modern, interconnected markets. To address this limitation, we propose a product demand forecasting method based on a Spatiotemporal Hypergraph Attention Network (STHA), which jointly models temporal dependencies and higher-order spatial interactions among multiple market entities to enhance forecasting accuracy and robustness. STHA integrates a Long Short-Term Memory (LSTM) network with a Hawkes attention mechanism to capture temporal patterns and constructs a hypergraph to represent multi-entity relationships. It further incorporates hypergraph convolution and a hypergraph attention mechanism to dynamically aggregate higher-order spatial information and weight relational importance. Experiments on the Corporación Favorita sales dataset demonstrate that STHA substantially outperforms single time series benchmarks (ARIMA, LSTM, TCN, Transformer, and PatchTST), achieving notable reductions in MAE, RMSE, and MAPE—with improvements in MAPE exceeding 15 percentage points for certain stores. Compared with the graph-based STGCN model, STHA also exhibits superior robustness. These results demonstrate the effectiveness of STHA for complex multi-market-entity demand forecasting and highlight its potential as a reliable framework for improving inventory management and supply chain decision-making. Full article

Resveratrol (RES), a natural polyphenol, and β-hydroxy-β-methylbutyric acid (HMB), a key metabolite of leucine, are emerging as potent feed additives in animal production. This study investigated the individual and combined effects of dietary RES and HMB on gut microbiota, metabolic profiles, and meat quality in Tibetan sheep. A total of 120 two-month-old male lambs were randomly assigned to four experimental groups: control (C, basal diet, n = 6), RES (basal diet + 1.5 g/d RES, n = 6), HMB (basal diet + 1.25 g/d HMB, n = 6), and RES-HMB (basal diet + 1.5 g/d RES + 1.25 g/d HMB, n = 6), with 16S rDNA sequencing and LC-MS/MS analyses performed on rumen fluid and longissimus lumborum (LL). Meat quality improved significantly in all supplemented groups, the RES-HMB co-administration exhibited the most pronounced effects, suggesting a synergistic interaction. These improvements were linked to the activation of amino acid (AA) and unsaturated fatty acid biosynthesis pathways, leading to increased levels of AAs and polyunsaturated fatty acids (PUFAs). Concurrently, dietary RES and HMB supplementation enriched the relative abundance of beneficial gut microbiota, notably Christensenellaceae_R-7_group and Solibacillus, which further promoted the production of short-chain fatty acids, AAs, and PUFAs. The study highlights the role of rumen microbiota in regulating muscle metabolism and meat quality, offering a new scientific basis of strategies for using green feed additives in Tibetan sheep. Full article

This study aimed to investigate the effects of pineapple pomace as a functional feed additive on growth performance, fecal microbiota composition, short-chain fatty acids (SCFAs), and odor substance emissions in weaned piglets. The experiment utilized 90 weaned three-way crossbred piglets (Duroc–Yorkshire–Guoshou Black Pig) at 28 days of age, randomly divided into three groups of 10 pigs each: the control group (CON, basal diet), the fish meal group (FM, basal diet + 2% imported fish meal), and the pineapple pomace group (PPC, basal diet + 2% pineapple pomace compound). The results indicated the PPC group exhibited significantly higher average daily gain (ADG) (p < 0.05) and significantly lower feed conversion ratio (FCR) (p < 0.05) than the CON group. 16S rRNA sequencing analysis revealed that the PPC group significantly increased fecal microbiota species richness and diversity (p < 0.01) while enriching beneficial bacteria including Lactobacillus, Bifidobacterium, and butyrate-producing bacteria such as Blautia. Concurrently, acetic acid and butyric acid levels in feces were significantly elevated in the PPC group (p < 0.05), with butyric acid production markedly higher than in the FM group (p < 0.05). However, no significant differences were observed in the levels of branched-chain fatty acids (BCFAs), such as isobutyric acid and isovaleric acid (p < 0.05). Moreover, PPC supplementation led to a significant decrease in fecal levels of indole and 3-methylindole (skatole) (p < 0.05). In summary, dietary inclusion of 2% pineapple pomace improves growth performance and intestinal health in weaned piglets by modulating the fecal microbiota, promoting beneficial SCFA production, and inhibiting protein putrefaction. These findings support PPC as an effective and sustainable alternative to fish meal, contributing to the development of environmentally friendly feeding strategies in pig production. Full article

Background: Gut dysbiosis is implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH) caused by diets rich in advanced glycation end products (AGEs). European bilberry extract (EBE) exerts a regulatory effect on gut microbiota. Nevertheless, it is still unknown whether EBE influences NASH via gut microbiota and their metabolites. This study aimed to investigate the effects and underlying mechanisms of EBE on NASH caused by a long-term AGEs diet. Methods: Rats fed with a high-AGE diet were orally administered with EBE for 80 weeks, and NASH was measured. 16S rRNA analysis and targeted metabolomics were used to detect gut microbiota and SCFA, respectively. The hepatic expression of SCFA receptors and that of the HMGB1/RAGE/NF-κB signaling pathway were detected to investigate the possible molecular mechanism. Results: EBE reduced the accumulation of AGEs in the circulation and liver of high-AGE diet-fed rats. EBE also ameliorated impaired glucose tolerance and insulin sensitivity, liver inflammation, steatosis, fibrosis, and dysfunction in high-AGE-fed rats. EBE reshaped high-AGE diet-induced gut dysbiosis by increasing short-chain fatty acid (SCFA)-producing bacteria and SCFA levels and reducing deleterious bacteria. Mechanistically, EBE promoted the activation of GPR43 and inhibited the activation of downstream HDAC3 and HMGB1/RAGE/NF-κB signaling pathway in the liver of high-AGE diet-fed rats. Additionally, EBE decreased the levels of TNF-α, IL-1β, and IL-6 and increased the level of IL-10 in the liver of high-AGE diet-fed rats. Conclusions: EBE promoted the production of SCFA, which might engage with the GPR43 receptor and inhibited the activation of HDAC3 and HMGB1/RAGE/NF-κB signaling pathway, ultimately alleviating NASH caused by a high-AGE diet. Full article

Edible trees, such as Bordão-de-velho (BVP; Samanea tubulosa), are being studied for their nutritional potential and the presence of bioactive compounds that influence ruminal fermentation. This study aimed to evaluate, using an in vitro assay, the effects of increasing the inclusion of BVP pods in dairy cow diets formulated with different energy levels. The experiment was conducted with eight treatments obtained from a 4 × 2 factorial arrangement, containing four levels of pod inclusion (0, 100, 200, and 300 g/kg dry matter) and two dietary energy levels (high and low). Increasing BVP levels resulted in a linear reduction in gas production from digestible organic matter in low-energy diets, without altering dry matter and organic matter digestibility or methane production. There was an increase in pH and in the acetate/propionate ratio, along with a reduction in the concentrations of short-chain fatty acids and isoacids. In conclusion, Samanea tubulosa pods improve fermentation efficiency and reduce gas production, making them a promising forage source for low-productivity animal diets. Full article

Background/Objectives: Short-chain fatty acids (SCFAs) produced by gut microbiota from dietary fiber fermentation play crucial roles in health and disease. While most research focuses on individual fibers, this study investigated whether a fiber mixture could synergistically increase SCFAs, exceeding the expected average production of individual contributions and microbial signatures associated with this phenomenon. Methods: We quantified synergistic SCFA production using secondary analysis of in vitro fecal fermentation data from 33 participants across four health conditions (healthy controls, Crohn’s disease, ulcerative colitis, and Parkinson’s disease), by comparing observed fiber mixture output to expected additive contributions from individual components and identified microbial signatures associated with synergistic SCFA production through differential abundance and network analyses. Results: The fiber mixture consistently outperformed most individual fibers and demonstrated synergistic SCFA production, yielding 32.8 ± 20.1% more total SCFAs than expected. This synergistic effect was observed across all four health conditions studied, with many individuals showing >50% synergy and some exceeding 80%. Differential abundance analysis revealed that individuals exhibiting synergistic responses were enriched in taxa from Lachnospiraceae and Ruminococcaceae families, key butyrate-producing groups that likely facilitate cooperative interactions. Network analysis confirmed these families as central hubs in synergy-associated microbial interactions. Conclusions: These findings suggest that fiber mixtures can harness cooperative microbial interactions to synergistically enhance SCFA production regardless of health status, offering potential for developing more effective prebiotics for superior therapeutic outcomes. Full article

Background/Objectives: Lactoferrin, a key bioactive component in human milk, may bridge functional gaps in infant formula; however, its long-term effects on growth and the gut microbiota in term infants remain underexplored, particularly in real-world settings. Methods: This real-world evidence (RWE) study assessed the impact of lactoferrin-fortified formula (LF) on infant growth, the gut microbiota, and feeding tolerance compared with control formula (CF) and exclusive breastfeeding (BF). After propensity score matching (PSM) for maternal education level and infant age, 111 matched Chinese infants (37 per group: LF, CF, and BF; age: 6–12 months) were analyzed. Growth was evaluated using WHO Z-scores (WAZ, LAZ, WLZ, and zBMI). The gut microbiota was profiled via 16S rRNA sequencing (n = 81). Feeding challenges were quantified using the Montreal Children’s Hospital Feeding Scale (MCH-FS). Results: The LF group exhibited significantly higher length-for-age Z-scores (LAZ) compared with both the BF and CF groups (p < 0.001), indicating superior linear growth. LF infants also showed reduced MCH-FS scores (18.0 vs. 36.2 in CF; p < 0.001), signifying fewer feeding difficulties. Gut microbiota analysis revealed enrichment of Bifidobacterium breve and butyrate-producing taxa (e.g., Faecalibacterium and Ruminococcaceae), higher alpha diversity, and metabolic divergence, involving enhanced lysine fermentation to acetate/butyrate in LF infants, suggesting a higher level of short-chain fatty acid (SCFA) production. Beta diversity analysis demonstrated that the LF microbiota clustered close to BF. Conclusions: Lactoferrin-fortified formula was associated with improved linear growth and feeding tolerance while shaping a healthy gut microbiota, showing similarities to breastfed infants’ microbiota. These findings support LF fortification as a strategy to improve functional outcomes in formula-fed infants. Full article