Search Results (1,670)

Early weaning of piglets elicits weaning stress, which in turn induces oxidative stress and consequently impairs growth and development. Hydrogen-rich water (HRW), characterized by selective antioxidant properties, mitigates oxidative stress damage and serves as an ideal intervention. This study aimed to evaluate the effects of HRW on weaned piglets, specifically investigating its impact on growth performance, diarrhea incidence, antioxidant function, intestinal morphology, gut microbiota, and hepatic metabolites. The results demonstrate that HRW significantly increased the average daily feed intake and significantly reduced the diarrhea rate in weaned piglets. Analysis of serum oxidative stress indicators revealed that HRW significantly elevated the activities of total antioxidant capacity and total superoxide dismutase while significantly decreasing malondialdehyde concentration. Assessment of intestinal morphology showed that HRW significantly increased the villus height to crypt depth ratio in the duodenum, jejunum, and ileum. Microbial analysis indicated that HRW significantly increased the abundance of Prevotella in the colon. Furthermore, HRW increased the abundance of beneficial bacteria, such as Akkermansia, in the jejunum and cecum, while concurrently reducing the abundance of harmful bacteria like Escherichia. Hepatic metabolite profiling revealed that HRW significantly altered the metabolite composition in the liver of weaned piglets. Differentially abundant metabolites were enriched in oxidative stress-related KEGG pathways, including ABC transporters; pyruvate metabolism; autophagy; FoxO signaling pathway; glutathione metabolism; ferroptosis; and AMPK signaling pathways. In conclusion, HRW alleviates diarrhea and promotes growth in weaned piglets by enhancing antioxidant capacity. These findings provide a scientific foundation for the application of HRW in swine production and serve as a reference for further exploration into the mechanisms underlying HRW’s effects on animal health and productivity. Full article

Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution. Full article

Postbiotics, defined as metabolites produced by probiotics, encompass both bacterial cells and their metabolic byproducts, and offer significant health benefits to the host. However, there are relatively few reports on their effects on intestinal microbiota. In this study, we investigated the components, total antioxidant capacity of Lactobacillus helveticus postbiotics (LHPs) and their impact on intestinal flora using the Simulator for Human Intestinal Microecology Simulation (SHIME). The results indicate that the primary components of postbiotics include polysaccharides, proteins, and organic acids. Furthermore, LHPs have a strong ability to inhibit the growth of harmful bacteria while promoting the growth of probiotics. Additionally, LHPs significantly increased the total antioxidant capacity in the intestine and regulated the balance of intestinal microbiota. Notably, there was also a significant increase in the content of short-chain fatty acids (SCFAs) in the intestine. Overall, LHPs have the potential to aid in the prevention and treatment of diseases by enhancing gut microbiology. Full article

Background/Objectives: Selective serotonin reuptake inhibitors (SSRIs), widely prescribed for anxiety disorders, may negatively impact the gut microbiota, contributing to dysbiosis. Considering the gut–brain axis’s importance in mental health, probiotics could represent an effective adjunctive strategy. This study evaluated the effects of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on microbiota composition, metabolic activity, and immune markers in fecal samples from patients with anxiety on SSRIs, using the SHIME^® (Simulator of the Human Intestinal Microbial Ecosystem) model. Methods: The fecal microbiotas of four patients using sertraline or escitalopram were inoculated in SHIME^® reactors simulating the ascending colon. After stabilization, a 14-day probiotic intervention was performed. Microbial composition was assessed by 16S rRNA sequencing. Short-chain fatty acids (SCFAs), ammonia, and GABA were measured, along with the prebiotic index (PI). Intestinal barrier integrity was evaluated via transepithelial electrical resistance (TEER), and cytokine levels (IL-6, IL-8, IL-10, TNF-α) were analyzed using a Caco-2/THP-1 co-culture system. The statistical design employed in this study for the analysis of prebiotic index, metabolites, intestinal barrier integrity and cytokines levels was a repeated measures ANOVA, complemented by post hoc Tukey’s tests to assess differences across treatment groups. For the 16S rRNA sequencing data, alpha diversity was assessed using multiple metrics, including the Shannon, Simpson, and Fisher indices to evaluate species diversity, and the Chao1 and ACE indices to estimate species richness. Beta diversity, which measures microbiota similarity across groups, was analyzed using weighted and unweighted UniFrac distances. To assess significant differences in beta diversity between groups, a permutational multivariate analysis of variance (PERMANOVA) was performed using the Adonis test. Results: Probiotic supplementation increased Bifidobacterium and Lactobacillus, and decreased Klebsiella and Bacteroides. Beta diversity was significantly altered, while alpha diversity remained unchanged. SCFA levels increased after 7 days. Ammonia levels dropped, and PI values rose. TEER values indicated enhanced barrier integrity. IL-8 and TNF-α decreased, while IL-6 increased. GABA levels remained unchanged. Conclusions: The probiotic combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 modulated gut microbiota composition, metabolic activity, and inflammatory responses in samples from individuals with anxiety on SSRIs, supporting its potential as an adjunctive strategy to mitigate antidepressant-associated dysbiosis. However, limitations—including the small pooled-donor sample, the absence of a healthy control group, and a lack of significant GABA modulation—should be considered when interpreting the findings. Although the SHIME^® model is considered a gold standard for microbiota studies, further clinical trials are necessary to confirm these promising results. Full article

Background: Myeloproliferative neoplasms (MPN), a group of chronic hematologic neoplasms, are driven by inflammatory mechanisms that influence disease initiation and progression. Emerging evidence highlights the gut microbiome and plasma metabolome as pivotal immunomodulators, yet their causal roles in MPN pathogenesis remain uncharacterized. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to systematically evaluate causal relationships between 196 gut microbial taxa, 526 plasma metabolites, and MPN risk. Instrumental variables were derived from genome-wide association studies (GWASs) of microbial/metabolite traits. Validation utilized 16S rRNA sequencing data from NCBI Bioproject PRJNA376506. Mediation and multivariable MR analyses elucidated metabolite-mediated pathways linking microbial taxa to MPN. Results: Our MR analysis revealed that 7 intestinal taxa and 17 plasma metabolites are causally linked to MPN. External validation confirmed the three taxa’s differential abundance in MPN cohorts. Mediation analysis revealed two mediated relationships, of which succinylcarnitine mediated 14.5% of the effect, and lysine 27.9%, linking the Eubacterium xylanophilum group to MPN. Multivariate MR analysis showed that both succinylcarnitine (p = 0.004) and lysine (p = 0.040) had a significant causal effect on MPN. Conclusions: This study identifies novel gut microbiota–metabolite axes driving MPN pathogenesis through immunometabolic mechanisms. The validated biomarkers provide potential therapeutic targets for modulating inflammation in myeloproliferative disorders. Full article

This study investigated the effects of dietary capsaicinoid (CAP) supplementation on broiler chickens subjected to an inflammatory challenge induced by lipopolysaccharide (LPS). A total of 144 Cobb500™ male broilers (Rivelli Alimentos SA, Matheus Leme, Brazil), raised from 1 to 21 days, were randomly assigned to three treatments, with eight replicates of six birds. Treatments were a control diet (CON), a control diet with LPS administration (CON+LPS), and a control diet supplemented with 1 mg CAP/kg feed and LPS (CAP+LPS). LPS was administered intraperitoneally on days 14, 16, 18, and 20. Performance, intestinal morphometry, serum metabolites, and jejunal gene expression related to oxidative and inflammatory responses were evaluated. Slaughter was at 20 days. Data were subjected to ANOVA and means compared by Tukey’s test at 0.05 significance. CON broilers exhibited the highest feed intake and a better feed conversion ratio (p < 0.05) compared to CON+LPS. CAP+LPS broilers showed higher body weight gain than CON+LPS but lower than CON broilers (p < 0.001). CON+LPS broilers had the highest crypt depth (p = 0.002). Higher mRNA expression of superoxide dismutase and catalase (p > 0.05) was observed in CON broilers. In conclusion, supplementation with a 1 mg CAP/kg diet improves the growth performance and intestinal morphometry of LPS-challenged broiler chickens. Full article

Mycotoxins represent a group of highly toxic secondary metabolites produced by diverse fungal pathogens. Mycotoxin contaminations frequently occur in foods and feed and pose significant risks to human and animal health due to their carcinogenic, mutagenic, and immunosuppressive properties. Notably, deoxynivalenol, zearalenone, fumonisins (mainly including fumonisins B1, B2, and FB3), aflatoxin B1 (AFB1), and T-2/HT-2 toxins are the major mycotoxin contaminants in foods and feed. Undoubtedly, exposure to these mycotoxins can disrupt gut health, particularly damaging the intestinal epithelium in humans and animals. In this review, we summarized the detrimental effects caused by these mycotoxins on the intestinal health of humans and animals. The fundamental molecular mechanisms, which cover the induction of inflammatory reaction and immune dysfunction, the breakdown of the intestinal barrier, the triggering of oxidative stress, and the intestinal microbiota imbalance, were explored. These signaling pathways, such as MAPK, Akt/mTOR, TNF, TGF-β, Wnt/β-catenin, PKA, NF-kB, NLRP3, AHR, TLR2, TLR4, IRE1/XBP1, Nrf2, and MLCK pathways, are implicated. The abnormal expression of micro-RNA also plays a critical role. Finally, we anticipate that this review can offer new perspectives and theoretical foundations for controlling intestinal health issues caused by mycotoxin contamination and promote the development of prevention and control products. Full article

Cardiac surgery, particularly procedures involving cardiopulmonary bypass (CPB), is associated with a high risk of postoperative complications, including systemic inflammatory response syndrome (SIRS), postoperative atrial fibrillation (POAF), and infection. Growing evidence suggests that the gut–heart axis, through mechanisms involving intestinal barrier integrity and gut microbiota homeostasis, may influence these outcomes. This review summarizes the relationship between gut microbiota composition and the inflammatory response in patients undergoing cardiac surgery and the extent to which these alterations impact clinical outcomes. The reviewed studies consistently show that cardiac surgery induces notable alterations in microbial diversity and composition during the perioperative period. These changes, indicative of dysbiosis, are characterized by a reduction in health-associated bacteria such as Blautia, Faecalibacterium, and Bifidobacterium and an increase in opportunistic pathogens. Inflammatory biomarkers were frequently elevated postoperatively, even in patients without evident complications. Key microbial metabolites and biomarkers, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and bile acids (BAs), were implicated in modulating inflammation and clinical outcomes. Additionally, vitamin D deficiency emerged as a contributing factor, correlating with increased systemic inflammation and a higher incidence of POAF. The findings suggest that gut microbiota composition prior to surgery may influence the severity of the postoperative inflammatory response and that perioperative modulation of the gut microbiota could represent a novel approach to improving surgical outcomes. However, the relationship between dysbiosis and acute illness in surgical patients is confounded by factors such as antibiotic use and other perioperative interventions. Large-scale, standardized clinical studies are needed to better define these interactions and guide future therapeutic strategies in cardiac surgery. Full article

Plastic pollution has recently become a serious environmental problem, since the continuous increase in plastic production and use has generated enormous amounts of plastic waste that decomposes to form micro- and nanoparticles (MPs/NPs). Recent evidence suggests that nanoplastics may be potent toxins because they are able to freely cross biological barriers, posing health risks, particularly to developing organisms. Therefore, the aim of the current study was to investigate the toxic potential of polystyrene nanoparticles (PS-NPs) on the jejunum of immature rats. Two-week-old animals were orally exposed to environmentally relevant dose of small PS-NPs (1 mg/kg b.w.; 25 nm) for 3 weeks. We detected a significant accumulation of PS-NPs in the epithelium and subepithelial layer of the intestine, which resulted in significant changes in the expression of genes related to gut barrier integrity, nutrient absorption, and endocrine function. Moreover, increased expression of proinflammatory cytokines was observed together with decreased antioxidant capacity and increased markers of oxidative damage to proteins. Additionally, in the jejunal extracts of exposed rats, we also noted changes in the metabolite profile, mainly amino acids involved in molecular pathways related to cellular energy, inflammation, the intestinal barrier, and protein synthesis, which were consistent with the observed molecular markers of inflammation and oxidative stress. Taken together, the results of the metabolomic, molecular, and biochemical analyses indicate that prolonged exposure to PS-NPs may disrupt the proper function of the intestine of developing organisms. Full article

Oxidative stress (OS) is a major concern in young poultry and livestock, prompting extensive research on OS models. This study aimed to systematically investigate the dynamic effects and temporal trends of OS induced with lipopolysaccharide (LPS) over time. Twenty-eight piglets were randomly divided into four groups and equally intraperitoneally injected with LPS at doses of 0 μg/kg (control), 50 μg/kg (L-LPS), 100 μg/kg (M-LPS) and 150 μg/kg (H-LPS) body weight, respectively. The results showed that total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and catalase (CAT) were decreased, while malondialdehyde (MDA), nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), diamine oxidase (DAO) and D-lactic acid (D-LA) were increased in the M-LPS and H-LPS group on day 1 in comparison with the control group, but no differences were found among treatments on day 7. However, LPS treatments gave rise to varying degrees of pathological injury in the intestines, livers and spleens on day 7. Metabolomics analysis indicated that compared with the control group, glycyl-valine, histamine and lepidine F were decreased in the M-LPS group. Most differentially expressed metabolites were enriched in amino acid-related metabolism pathways on both day 1 and day 7. Microbiome analysis identified that Oscillibacter_sp._CAG:241 was decreased in the M-LPS group compared with the control group on day 1, while Bacteroides_thetaiotaomicron and Lactobacillus_amylovorus were reduced in the M-LPS group on day 7. Collectively, an LPS dose of 100 μg/kg body weight is optimal for inducing acute inflammation in Wuzhishan miniature pigs. These findings highlight the importance of considering both the duration of OS induction and the specific research objectives when establishing OS models. Full article

Konjac glucomannan (KGM) is a natural polysaccharide polymer. It is degraded by gut microbiota-derived β-mannanase into small-molecule nutrients, which exert diverse physiological regulatory effects. As a prebiotic, KGM modulates gut microbiota composition. It selectively fosters the proliferation of beneficial commensals and suppresses potential pathogens, thereby alleviating microbiota-related disorders. Moreover, microbiota fermentation of KGM produces metabolites. Short-chain fatty acids (SCFAs) are particularly notable among these metabolites. They exert multifaceted beneficial effects, including metabolic regulation, intestinal barrier strengthening, and neuroprotective functions. These effects are mediated through inhibition of inflammatory pathways (e.g., NF-κB, MAPK), modulation of lipid metabolism genes (e.g., CD36), and regulation of neurotransmitters (e.g., GABA, 5-HT). This highlights KGM’s therapeutic potential for metabolic, inflammatory, and neurodegenerative diseases. Current clinical use is limited by dose-dependent adverse effects and interindividual response variability, which stem from different microbial communities. This necessitates personalized dosage strategies. Despite these limitations, KGM as a prebiotic polysaccharide exhibits multifaceted bioactivity. Current evidence suggests its potential to synergistically modulate metabolic pathways, gut microbiota composition, immune cell signaling, and neuroendocrine interactions. This highlights its promise for developing novel therapeutic interventions. Full article

Enteroendocrine cells (EECs) are specialized secretory cells in the gut epithelium that differentiate from intestinal stem cells (ISCs). Mature EECs secrete incretin hormones that stimulate pancreatic insulin secretion and regulate appetite. Decreased EEC numbers and impaired secretion of the incretin glucagon-like peptide-1 (GLP1) have been implicated in obesity-associated metabolic complications. Gut microbial metabolites of dietary tryptophan (TRP) were recently shown to modulate ISC proliferation and differentiation. However, their specific effects on EEC differentiation are not known. We hypothesized that the gut microbial metabolites of dietary tryptophan counteract impaired GLP1 production and function in obesity by stimulating EEC differentiation from ISCs. We utilized complementary models of human and rat intestines to determine the effects of obesity or TRP metabolites on EEC differentiation. EEC differentiation was assessed by the EEC marker chromogranin A (CHGA) levels in the intestinal mucosa of normal versus obese rats. The effects of TRP metabolites on EEC differentiation were determined in human intestinal organoids treated with indole, a primary TRP metabolite, or the culture supernatant of Lactobacillus acidophilus grown in TRP media (LA-CS-TRP). Our results showed that the mRNA and protein levels of CHGA, the EEC marker, were significantly decreased (~60%) in the intestinal mucosa of high-fat-diet-induced obese rat intestines. The expression of the transcription factors that direct the ISC differentiation towards the EEC lineage was also decreased in obesity. In human organoids, treatment with indole or LA-CS-TRP significantly increased (more than 2-fold) CHGA levels, which were blocked by the aryl hydrocarbon receptor (AhR) antagonist CH-223191. Thus, the stimulation of EEC differentiation by colonic microbial metabolites highlights a novel therapeutic role of TRP metabolites in obesity and associated metabolic disorders. Full article

Colorectal cancer (CRC) is associated with factors such as an unhealthy diet, physical inactivity, obesity, diabetes, and chronic inflammatory conditions like inflammatory bowel disease (IBD), as well as TP53 mutations, which are observed in a broad spectrum of CRC. Additionally, alteration in the composition of the gut microbiome community and metabolism plays a significant role in the development of colorectal cancer and its therapeutic effects. It is well known that treatment with sodium butyrate (NaB), an intestinal microbial metabolite, can induce apoptosis by activating histone deacetylase (HDAC) in cancer cells. Therefore, this study examined the relationship between NaB-induced apoptosis and p53 protein level in colorectal cancer cells. Treatment with NaB triggered cell death in the HCT116 cell line. Furthermore, a notable elevation in p53 protein level was detected following treatment with a high concentration of NaB, compared to both the control group and the low concentration NaB. Furthermore, apoptotic cell death was diminished in a p53-deficient cell line (HCT 116 p53^−/−) and p53 protein expression was more stabilized. Although p53 mRNA expression was not affected, acetylation of p53 protein was clearly observed by high concentration NaB treatment. To demonstrate the relationship between p53 acetylation and cell death, HT29 cells were treated with a high concentration of NaB. In HT29 cells with a mutation in the p53 gene, increased cell viability, overproduction p53 protein, and hyperacetylation of p53 were observed compared to the control. The results of this study suggest that p53 protein expression plays an important role in the effectiveness of therapy utilizing gut microbiota metabolites. Full article

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is increasingly recognized as a systemic condition with cardiovascular implications. Among these, heart failure has emerged as a significant complication. The aim of this narrative review was to explore the cellular and molecular pathways that link IBD and heart failure. Drawing upon findings from epidemiologic studies, experimental models, and clinical research, we examined the pathways through which IBD may promote cardiac dysfunction. Chronic systemic inflammation in IBD, driven by cytokines such as TNF-α and IL-1β, can impair myocardial structure and function. Furthermore, intestinal barrier dysfunction and gut dysbiosis can facilitate the translocation of proinflammatory microbial metabolites, including lipopolysaccharide and phenylacetylglutamine, and deplete cardioprotective metabolites like short-chain fatty acids, thereby exacerbating heart failure risk. Additional contributing factors include endothelial and microvascular dysfunction, autonomic dysregulation, nutritional deficiencies, shared genetic susceptibility, and adverse pharmacologic effects. IBD contributes to heart failure pathogenesis through multifactorial and interrelated mechanisms. Recognizing the role of the gut–heart axis in IBD is crucial for the early identification of cardiovascular risk, providing guidance for integrating care and developing targeted therapies to reduce the risk of heart failure in this vulnerable population. Full article

In this study, we established a mouse colitis model using DSS to investigate the impact of curcumin on gut injury, the intestinal microbiota, and fecal metabolites. The findings indicated that curcumin effectively mitigated weight loss and colon shortening caused by colitis, enhanced the expression of anti-inflammatory factor IL-10 mRNA (p < 0.05), and suppressed the expression of pro-inflammatory factors (IL-1β, IL-6, and TNF-α mRNA; p < 0.05). 16S rDNA sequencing analysis showed that in the CUR group, compared to the NC and DSS groups, the abundances of Bacteroides, Lachnospiraceae NK4A136, and Ruminococcaceae UGC 014 significantly increased, while that of Lactobacillus markedly decreased. Additionally, compared with the DSS group, the CUR group demonstrated a significant decrease in levels of metabolites associated with nucleic acid and fat metabolism, including xanthosine, isocitric acid, and D-xylose. Conversely, levels of metabolites of curcumin, such as demethoxycurcumin and tetrahydrocurcumin, were significantly elevated in the CUR group. Curcumin appears to offer protection against mouse colitis by potentially enhancing the composition of the gut microbiota and regulating metabolic and inflammatory processes through its metabolites. Full article