Search Results (1,796)

The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, plays a crucial role in regulating immune homeostasis, inflammatory responses, and intestinal barrier function. Indole compounds and their derivatives are ligands of AHR, which can activate the AHR signal transduction pathway and show significant regulatory potential in various inflammatory and immune diseases. Cystic fibrosis (CF) is a life-threatening autosomal recessive genetic disorder. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction affects multiple systems throughout the body. The core of its pathological process is chronic infection, abnormal inflammation, and tissue damage caused by mucus accumulation. Exploring alternative or adjunctive therapeutic strategies targeting pathological pathways downstream of CFTR is of significant importance. The aim of the present study is to explore the multiple beneficial effects that indole compounds may exert in regulating pulmonary infection and inflammation, repairing intestinal barrier function, and regulating immune homeostasis in CF patients by activating the AHR signaling pathway. Additionally, this study discusses the risks and challenges associated with developing indole compounds as CF drugs, offering a novel research approach distinct from traditional CFTR modulators for creating new CF therapeutics. Full article

Intestinal bacterial dysbiosis develops in a number of immune-mediated disorders. Fecal microbiota transfer (FMT) is considered a potentially efficient tool for restoration of the patient’s gut microbiota. The aim of our study was to trace the time course of dominant bacterial populations and some Enterobacteria phages in patients with GVHD and Crohn’s disease after FMT procedure. Patients and methods: We observed 12 patients with intestinal graft-versus-host disease (GVHD), and 15 persons with Crohn’s disease after massive anti-infectious treatment. FMT was performed by a standard protocol using oral capsules administered for 2 days. Fecal bacteriome was assessed by 16S rRNA sequencing. Viral sequences were identified by NGS with a customized primer set. Plasma citrulline levels were measured in order to assess enterocyte damage in the patients. Results: Complete clinical response to FMT was observed in 5 of 12 GVHD patients and 10 of 15 Crohn’s disease cases. Before FMT, most anaerobic Bacillota were exhausted in both Crohn’s disease patients and GVHD. Following FMT, Akkermansia ratios tended to decrease within 30 days in Crohn’s disease, along with higher Faecalibacteria, Romboutsia, and Dialister ratios than in GVHD, thus suggesting lesser damage to anaerobic microbiota in Crohn’s disease. Increased contents of facultative anaerobes (Enterococcus and E. coli) was detected in GVHD patients after FMT. Fecal virome changes in Crohn’s disease after FMT included early transient decrease in Caudoviricetes with a rise in Lederbergvirus and Eganvirus ratios at later terms. In GVHD patients, reverse correlations were revealed between E. coli and E. coli-hosted Eganvirus species. Intestinal damage assessed by low plasma citrulline levels was associated with fecal Klebsiella expansion, being more pronounced in GVHD than in Crohn’s disease. Clinical response to FMT in GVHD patients correlated with increased plasma citrulline and lower Eganvirus abundance. Future studies will concern specific relations between fecal bacteriome and virome reconstitution following FMT in gut GVHD and other immune-mediated intestinal disorders. Full article

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus, Romboutsia, and Enterobacter. Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC. Full article

Coeliac disease (CD) is a chronic immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals carrying HLA-DQ2 or HLA-DQ8 haplotypes, characterized by small intestinal mucosal damage and systemic manifestations. This systematic review and meta-analysis aimed to compare the effectiveness of urine versus stool GIPS testing for monitoring gluten intake in coeliac patients, providing evidence-based recommendations for clinical practice. A comprehensive literature search was conducted in databases like PubMed and Embase. Studies evaluating urine or stool GIPS testing in coeliac patients were included, focusing on sensitivity, specificity, and patient adherence. The meta-analysis included six studies with a total of 572 participants. The stool GIPS testing demonstrated a pooled sensitivity of 85.1% (95% CI: 79.0–89.9%) and a specificity of 92.5% (95% CI: 88.3–95.6%), making it highly reliable for detecting gluten exposure and ruling out false positives. It also achieved an AUC of 0.9853, indicating excellent diagnostic performance. In contrast, the urine GIPS testing showed a pooled sensitivity of 55.4% (95% CI: 49.6–61.2%) and a specificity of 73.0% (95% CI: 67.4–78.1%), with an AUC of 0.7898. The heterogeneity across the studies was significant (I² > 80%), driven by variations in the population characteristics, sample handling, and testing protocols. These findings emphasize the need for standardized methodologies to enhance the reliability and comparability of results. Full article

Egg yolk IgY antibody has significant application potential in aquaculture as a form of passive immunotherapy against various bacterial infections owing to its capacity for large-scale and cost-effective production. In this research, laying hens were immunized with live or inactivated Aeromonas hydrophila to produce IgY antibodies. Following this, experiments were carried out to assess the passive immune protection rates of the two types of IgY antibodies when used to immunize goldfish (Carassius auratus), which were then infected with A. hydrophila or Aeromonas veronii. ELISA experiments were conducted to demonstrate the interaction between the IgY antibodies and the bacteria. The kidneys of C. auratus were coated on a Luria–Bertani (LB) medium to evaluate bacterial content. The leukocyte phagocytosis was detected by a cell phagocytosis assay. The serum of C. auratus was used to assess the expression of antioxidant factors, and a qRT-PCR was conducted to evaluate the mRNA expression of inflammatory factors in visceral tissue. Furthermore, histopathology and immunofluorescence analysis were performed to evaluate the structural integrity, apoptosis, and DNA damage of visceral tissues. The results indicated that the live or inactivated A. hydrophila IgY antibodies exhibited passive immune protection rates against A. hydrophila and A. veronii and could recognize these two bacteria in vitro. Additionally, these two IgY improved the phagocytic ability of leukocytes, diminished renal bacterial concentration, and decreased the levels of antioxidant factors and mRNA expression of inflammatory factors. Meanwhile, the two IgY antibodies did not cause any pathology of the kidney, spleen, and intestine, and decreased the levels of DNA damage factor (γH2A.X) and cell apoptosis factor (p53) in renal tissue. Therefore, live and inactivated A. hydrophila IgY antibodies can resist bacterial infections, with live bacteria IgY providing greater protection than inactivated bacteria IgY. Further, A. hydrophila is an aquatic pathogen that causes minimal damage to laying hens, and the immunity of live A. hydrophila conforms to animal welfare. Altogether, live A. hydrophila IgY antibody can serve as a polyvalent passive immune vaccine candidate in aquaculture. Full article

This study evaluated the protective effects of magnolol, rutin, and gallic acid in broilers fed oxidized soybean oil. Four hundred seven-day-old male Arbor Acre broilers were randomly assigned to five treatments with eight replicates each: CON (4% fresh oil), OOC (4% oxidized oil), and OOC supplemented with 200 mg/kg of magnolol (MAG), rutin (RUT), or gallic acid (GAA). OOC significantly reduced 42-day body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI), reduced serum antioxidant enzyme activities (T-SOD, GSH-Px) and elevated malondialdehyde and triglyceride levels. It also upregulated hepatic lipogenic (FASN, ACACA, SREBP-1) and inflammation (NF-κB1/2) genes, damaged intestinal morphology, reduced cecal Erysipelatoclostridium and Shuttleworthia abundances, and elevated oxidized lipids (9,10-DiHOME and prostaglandin G2) in breast muscle. All three polyphenols increased ADFI (22–42 d), ileal villus height and ZO-1 expression, while reducing serum triglycerides, ileal MDA, and hepatic NF-κB2 expression. Both magnolol and rutin further enhanced BW (42 d) and ADG (7–42 d), decreased ACACA expression, and elevated cecal Lachnoclostridium abundance. Additionally, magnolol significantly decreased the contents of 9,10-DiHOME and malondialdehyde, while rutin reduced prostaglandin G2 levels in the breast muscle. In conclusion, polyphenol supplementation alleviated oxidized oil-induced adverse effects, with magnolol and rutin being more effective. Full article

Aging is the result of the accumulation of a great variety of molecular and cellular damage over time. During aging, the brain undergoes changes and diseases such as depression, dementia, anxiety, Alzheimer’s, delirium, behavioral disorders and aggression, and prolonged mourning, among others, appear. The gut–brain axis suggests that the gut and the brain have a bidirectional communication, so it is important to maintain proper intestinal health to strengthen the neurological changes of this age group. The intestinal microbiota is a dynamic and highly complex ecosystem of microorganisms residing in the gastrointestinal tract. The bidirectional and dynamic communication between the homeostatic systems, such as the endocrine and immune systems, as well as the nervous system, allow us to face problems associated with several diseases. Probiotics are defined as non-pathogenic live microorganisms that provide beneficial effects to the organism and participate in the prevention and treatment of diseases, which is the reason why it is important to promote interventions that keep intestinal microbiota in eubiosis (microbiota balance). The concentration and balance of the intestinal microbiota depend on several conditions, such as diet, antibiotic consumption, and lifestyle, to mentioned a few. However, interventions with probiotics have shown improvements in both cognitive function and processes that promote neurodegeneration. It is such that the research has been directed on designing strategies that improve not only oral bioavailability but also intestinal adhesion and retention, to clarify the frequency and dosage that should be consumed. Full article

The present study aimed to evaluate the impact of varying dietary concentrations of calcium oxide nanoparticles (CaO-NPs) on important health regulators in Zebra fish (Danio rerio) using integrative physiological, histopathological, and computational approaches. The co-precipitation method was used to synthesize NPs and characterization was performed through DLS, XRD, FESEM, EDX, and FTIR depicting spherical-shaped CaO-NPs with a hydrodynamic diameter of 91.2 nm. Adult Danio rerio were administered with three different feed regimes enriched with 2.4 (T1), 1.6 (T2), and 0.8 (T3) mg CaO-NPs/kg for 30 days. Growth, survival, NP accumulation, and histological assessments, and bioinformatic studies, were performed to understand interactions of NPs with fish metabolic proteins. The T3 group demonstrated the highest survival (75%) and weight gain (+39.31%), and exhibited the lowest accumulation of CaO-NPs in the brain (0.133 mg/L), liver (0.642 mg/L), and intestine (0.773 mg/L) with no evident histological alterations, whereas T1 group exhibited major liver and intestinal damage. Molecular docking targeting the NRF-2 oxidative stress pathway revealed strong binding affinities of NPs with catalase (−3.7), keap1a (−3.5), keap1b (−3.3), and mafk (−2.4), highlighting potential modulation of redox homeostasis. Hence, a 0.8mg CaO-NPs/kg feed dose is recommended to promote potential health benefits in Danio rerio, which can be further applicable to commercial aquaculture for enhanced fish health while minimizing toxicity. Full article

Mycotoxins, toxic fungal secondary metabolites, exhibit a diverse array of toxicological effects, including hepatotoxicity, carcinogenicity, estrogenicity, immunotoxicity, and neurotoxicity. These toxins cause severe contamination in food, feed, and traditional Chinese medicines (TCMs), threatening global food security and imposing substantial economic burdens. Among over 400 distinct mycotoxins identified to date, aflatoxin B1 (AFB1), ochratoxin A (OTA), and zearalenone (ZEN) stand out for their pervasive contamination and grave toxicities. Upon absorption, these toxins undergo biotransformation into reactive metabolites that exert multifaceted toxicities via mechanisms such as carcinogenesis, estrogenic effects, oxidative stress, inflammation, and abnormal apoptosis, collectively threatening human and livestock health. The application of natural and engineered enterosorbents suppresses intestinal absorption and subsequent bioactivation of mycotoxins, while dietary small-molecule bioactive compounds neutralize post-absorption toxicity via biotransformation intervention and cytoprotective reinforcement, collectively preventing the onset and progression of related diseases. This paper reviews the biosynthetic routes of three representative mycotoxins (AFB1, OTA, and ZEN), along with their biotransformation and underlying pathogenic mechanisms. Furthermore, nutritional intervention approaches targeting the underlying mechanisms to ameliorate mycotoxin-induced damage are discussed. This review not only provides valuable insights for future research on mycotoxin toxicity, but also establishes a theoretical foundation for utilizing dietary strategies to counteract mycotoxin-induced physical damage. Full article

Polystyrene microplastic (PS-MP) particles disrupt aquatic biological systems due to their persistence and high bioaccumulation potential, causing structural damage and inflammatory responses. PS-MPs also act as metabolic disruptors, affecting glucose metabolism and insulin signaling, although the mechanisms underlying these effects remain unclear. In this study, grass carp were exposed to 100 μg/L and 400 μg/L of polystyrene MPs for 30 days. Histopathological analysis showed the shortening of intestinal villi, vacuolization, and inflammatory infiltration. Antioxidant enzyme activities (SOD and CAT) were reduced, while the presence of tissue damage markers (GPT and GOT) was elevated, suggesting a biphasic oxidative stress response. Transcriptomic analysis revealed downregulation of genes related to metabolism and insulin signaling, especially at 400 μg/L. Gene set enrichment analysis (GSEA) highlighted pathways related to insulin resistance and type 2 diabetes, indicating the disruption of glucose metabolism. Microbiome analysis showed reduced diversity, expansion of Proteobacteria (opportunistic pathogens), and a decrease in beneficial bacteria like Bacillus. These shifts correlated with changes in the expression of key insulin signaling genes, emphasizing the role of host–microbiota interactions in metabolic imbalances. This study revealed that PS-MPs disrupt glucose metabolism and insulin signaling in grass carp through a combination of histological damage, oxidative stress, and microbiota dysbiosis. Full article

Deoxynivalenol (DON), a mycotoxin from Fusarium that contaminates cereals, can also induce intestinal injury. However, the mechanisms underlying DON-induced jejunal barrier injury remain unclear. This study demonstrates that shikimic acid (SA) alleviates DON-induced jejunal barrier damage and dysbiosis via antioxidant pathways. Fifty 5-week-aged male KM mice were divided into control (CON), model (MOD, 2.4 mg/kg bw DON), and SA-treated groups (LDG/MDG/HDG: 25/50/100 mg/kg bw SA + DON). After SA treatment, notably MDG, reversed DON-induced weight loss and jejunal hyperemia; ameliorated villus atrophy, crypt deepening and goblet cell loss, increasing villus/crypt ratio; reduced gut permeability markers (D-LA/DAO) and pro-inflammatory cytokines (TNF-α/IL-6/IL-1β); and dose-dependently upregulated tight junction proteins (ZO-1/Occludin/Claudin1). Mechanistically, SA activated the Nrf2/HO-1/NQO1 pathway, elevating antioxidants (GSH/SOD/AOC) while reducing MDA, with MDG showing optimal efficacy. 16S rRNA sequencing revealed MDG counteracted DON-induced dysbiosis by enriching beneficial bacteria (e.g., Bacteroidota at phylum level; Muribaculaceae at family level) and suppressing pathogens (Staphylococcaceae) (LDA score > 4.0). Thus, SA mitigates DON toxicity via Nrf2-mediated barrier restoration, anti-inflammation, and microbiota modulation. This research provides new insights for the further development of Shikimic Acid and the treatment of DON-induced jejunal barrier injury. Full article

Celiac disease (CD) is an autoimmune disorder that affects genetically susceptible individuals, characterized by specific serological and histological features, and is triggered by the consumption of gluten. The current diagnosis is based on the demonstration of intestinal damage in small bowel biopsies, as well as the serological presence of CD-specific antibodies (usually IgA) against tissue transglutaminase (tTG), deamidated gliadin peptides (DGP), and endomysium (EMA). The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), in the 2020 updated guidelines, states that the diagnosis of CD in children and adolescents can be established without a biopsy if they have IgA tTG2 >10 ULN confirmed by positive IgA endomysial antibodies on two separate blood tests. Challenges, though, arise in serological and clinical diagnosis: in several cases false-positive results are observed. False-negative serological tests may also occur in children < 2 years of age, in patients adhering to a gluten-free diet, in individuals on immunosuppressive therapy, in cases of selective IgA deficiency, and finally due to potential laboratory errors. CD has a wide range of clinical manifestations, either gastrointestinal or extraintestinal. However, CD may be clinically silent and diagnosed through screening. Delayed diagnosis and treatment can lead to serious complications. Therefore, understanding and awareness of these challenges is imperative. Hence, the aim of this review is to highlight the diagnostic challenges of celiac disease in children and adolescents and stress the importance of prompt recognition in order to ensure appropriate management and prevention of complications. Full article

The prevalence of Ulcerative Colitis (UC) is continuously increasing globally, demanding the urgent search for new treatment agents due to the limitations of existing therapies. Premna puberula Pamp. (PP), a traditional medicinal and dietary plant, has anti-inflammatory properties. Its extracts’ therapeutic benefits for UC have not been documented, though. Therefore, we aim to investigate the therapeutic effects of PPEAC on UC, providing a reference for new UC therapies. In our study, we used UPLC-MS/MS to determine the composition of Premna puberula Pamp’s ethyl acetate extract (PPEAC). We assessed the effectiveness of PPEAC using a UC mouse model. The results demonstrated that PPEAC significantly reduced the Disease Activity Index (DAI) scores, lowered liver and spleen weight ratios, mitigated colonic shortening and histopathological damage, and alleviated oxidative stress. This research represented the first systematic investigation into the molecular mechanism of PPEAC ameliorating UC by modulating the intestinal flora-metabolism axis. PPEAC appeared to have a therapeutic impact on UC by boosting phosphatidylcholine (PC) analog levels and the number of Firmicutes and Muribaculaceae, as well as altering alpha-linolenic acid metabolism. Our research provided a new therapeutic approach for using PP as a traditional functional plant for food and medicine, as well as a new viewpoint for the creation of UC-targeted treatments based on conventional herbs. Full article

Static magnetic field (SMF) is an emerging food-processing technology that has been widely applied in areas such as processing and sterilization. However, its influence on sprout production or health-related attributes has not yet been investigated. Therefore, in this study, corn sprouts were used as the raw material to compare the differential health effects of SMF treatment in a mouse model of dextran sulfate sodium (DSS)-induced colitis. The in vivo anti-inflammatory effects of SMF-treated corn sprouts were assessed by analyzing changes in their active ingredients. Histological staining, qRT-PCR and 16s rDNA sequencing were performed in the DSS-induced colitis mouse model. The results indicated that dietary fiber and total phenol contents were significantly higher in SMF-treated corn sprouts (M-CSP) compared to SMF-untreated corn sprouts (C-CSP). M-CSP alleviated the symptoms of DSS-induced colitis, significantly reduced colonic epithelial damage, and suppressed the secretion of pro-inflammatory factors. In addition, M-CSP markedly improved the diversity and abundance of intestinal microbiota. These findings provide new insights for the development and application of SMF technology to functional food ingredients. Full article

Acute mesenteric ischemia (AMI) is a life-threatening condition characterised by oxidative stress, inflammation, apoptosis, and necrosis of intestinal epithelial cells. Different drugs with vasoactive, antioxidant, and anti-inflammatory properties have been used to treat AMI. Levosimendan is a drug with proven anti-ischemic effects used in the management of acute congestive heart failure. This study evaluated the protective effects of levosimendan pretreatment on intestinal, as well as lung, heart, and kidney tissue in a rat model of mesenteric artery ischemia/reperfusion (I/R) injury. Male Wistar rats (N = 24) were divided into four groups: control, I/R, levosimendan (LS) 1 mg/kg i.p, and LS + I/R (1 mg/kg i.p. 30 min before injury). I/R by itself caused elevation of oxidative markers (thyobarbituric acid reactive species (TBARS), hydrogen peroxide (H₂O₂), super oxide anjon radical (O₂⁻), and nitrogen dioxide (NO₂⁻)), induced inflammation (macrophage infiltration and Interleukin-6 (IL-6) production), and apoptosis (nuclear factor kappa light-chain enhancer of activated B cells (NF-κB), cleaved caspase-3 (CC3), and terminal deoxy-nucleotidyl transferase (TdT)-mediated dUTP nick end labelling (TUNEL)). Levosimendan pretreatment significantly reduced oxidative stress markers and enhanced antioxidant defences (catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD)). Histological analysis revealed reduced mucosal damage and preserved goblet cells in intestinal tissue. Similar protective effects of levosimendan were observed in other organs such as lung, heart, and kidney. Immunohistochemistry showed reduced epithelial apoptosis and upregulation of antioxidant and anti-inflammatory proteins. These findings highlight levosimendan’s ability to protect mesenteric I/R tissue injury and multi-organ damage by suppressing oxidative stress, inflammation, and apoptosis, emphasising its therapeutic potential in clinical settings. Full article