Zinc and several physiologically relevant ligands of the aryl hydrocarbon receptor (AHR) are nutrients that promote intestinal barrier function. We have identified that AHR activation upregulates the expression of zinc importers in the intestinal epithelium to increase intracellular zinc concentrations, which leads to improved epithelial barrier function. Here, we investigated if an amino acid chelate of zinc, in cooperation with AHR activation, can improve the barrier function of a differentiated Caco-2 cell epithelium. Functional assays of the Caco-2 cell epithelium demonstrate that both ZnSO4 and a lysine and glutamic acid chelate of Zn, in combination with the physiological AHR agonist 6-formylindolo[3,2-b]carbazole (FICZ), increase expression of tight junction proteins at the mRNA and protein levels. FICZ increases uptake of zinc into the epithelium in the presence of ZnSO4 or the amino acid Zn chelate in the medium to equal extents. We conclude that the lysine and glutamic acid chelate of Zn is as efficacious as ZnSO4 in reducing permeability of the Caco-2 cell epithelium in the presence of FICZ. The results suggest that dietary supplementation with bioavailable forms of zinc together with nutritional AHR agonists may be beneficial in improving gut barrier function and help prevent inflammatory bowel disease (IBD).

While the prolonged consumption of sucrose-containing beverages is known to impact many organs, their specific effects on the small intestine remain elusive. This study aimed to evaluate how regular intake of sucrose, in amounts typically consumed, affects goblet cells, which play a critical role in regulating the mucosal barrier and innate immune defenses in the small intestine. Ten-week-old male ddY mice, a model of diet-induced obesity, were given a regular diet with either plain water or 7% sucrose water. Caloric intake was monitored weekly through food and drink measurements. After 8 weeks, glucose and insulin responses were evaluated following an oral gavage of glucose or sucrose. At 14 weeks, plasma, whole small intestine, and liver samples were collected. Despite achieving an isocaloric state, mice drinking sucrose water showed approximately a 1.5-fold increase in body weight and impaired glucose tolerance. In the small intestine, genes involved in sucrose digestion and absorption (Sis, Sglt1, Glut2, and Glut5) were upregulated, while genes essential for maintaining the intestinal barrier and function (Epcam, Fabp2, Cldn1, Ocln, and Tjp1) were downregulated. Serum levels and mRNA expression of the inflammatory cytokine, interleukin-18 were elevated. Genes responsible for goblet cell differentiation and function (Hes1, Gfi1, Spdef, and Klf4) were downregulated, leading to an increase in immature goblet cells and a decrease in mucin-producing markers (Muc2, Muc4, and Muc13) in the jejunum. The findings underscore that besides obesity, long-term intake of sucrose-containing drinks provokes localized inflammation and disrupts small intestinal barrier function by impairing goblet cell differentiation and activity.

Over the past 3 years, there has been a growing interest in clinical research regarding the potential involvement of intestinal flora in thyroid cancer (TC). This review delves into the intricate connection between intestinal flora and TC, focusing on the particular intestinal flora that is directly linked to the disease and identifying which may be able to predict potential microbial markers of TC. In order to shed light on the inflammatory pathways connected to the onset of TC, we investigated the impact of intestinal flora on immune modulation and the connection between chronic inflammation when investigating the role of intestinal flora in the pathogenesis of TC. Furthermore, the potential role of intestinal flora metabolites in the regulation of thyroid function was clarified by exploring the effects of short-chain fatty acids and lipopolysaccharide on thyroid hormone synthesis and metabolism. Based on these findings, we further explore the effects of probiotics, prebiotics, postbiotics, vitamins, and trace elements.

Natural flavonoids may be utilized as an important therapy for cardiovascular diseases (CVDs) caused by intestinal barrier damage. More research is being conducted on the protective properties of natural flavonoids against intestinal barrier injury, although the underlying processes remain unknown. Thus, the purpose of this article is to present current research on natural flavonoids to reduce the incidence of CVDs by protecting intestinal barrier injury, with a particular emphasis on intestinal epithelial barrier integrity (inhibiting oxidative stress, regulating inflammatory cytokine expression, and increasing tight junction protein expression). Furthermore, the mechanisms driving intestinal barrier injury development are briefly explored, as well as natural flavonoids having CVD-protective actions on the intestinal barrier. In addition, natural flavonoids with myocardial protective effects were docked with ZO-1 targets to find natural products with higher activity. These natural flavonoids can improve intestinal mechanical barrier function through anti-oxidant or anti-inflammatory mechanism, and then prevent the occurrence and development of CVDs.

Ulcerative colitis is an idiopathic and chronic inflammatory bowel disease, characterized by inflammation of the mucosa of the colon and rectum. Clinical manifestations commonly include abdominal pain, diarrhea (with or without hematochezia), and weight loss. The pathogenesis of ulcerative colitis is multifactorial, involving a combination of genetic predispositions and lifestyle factors. High consumption of processed food, sedentary habits, alcohol intake, and stress are among the lifestyle factors implicated in disease onset and progression. Current treatment strategies focus on managing symptoms and inducing remission, however, the chronic nature of the disease, along with the adverse effects of conventional therapies, often compromises patient's quality of life. Therefore, exploring alternative therapies that can prolong remission and reduce symptom burden is important. Experimental evidence suggests that probiotics may extend remission duration in ulcerative colitis. Moreover, probiotics exhibit efficacy in amelioration clinical symptoms by reducing inflammation markers, preserving, and restoring intestinal epithelial. This review explores the advantages of the administration of probiotics in the treatment of ulcerative colitis, elucidating their mechanism of action.

Oral administration has long been considered the most convenient method of drug delivery, requiring minimal expertise and invasiveness. Unlike injections, it avoids discomfort, wound infections, and complications, leading to higher patient compliance. However, the effectiveness of oral delivery is often hindered by the harsh biological barriers of the gastrointestinal tract, which limit the bioaccessibility and bioavailability of drugs. The development of oral drug delivery systems (ODDSs) represents a critical area for the advancement of pharmacotherapy. This review highlights the characteristics and precise targeting mechanisms of ODDSs. It first examines the unique properties of each gastrointestinal compartment, including the stomach, small intestine, intestinal mucus, intestinal epithelial barrier, and colon. Based on these features, it outlines the targeting strategies and design principles for ODDSs aimed at overcoming gastrointestinal barriers to enhance disease treatment. Lastly, the review discusses the challenges and potential future directions for ODDS development, emphasizing their importance for advancing drug delivery technologies and accelerating their future growth.

This study explored the in vitro alleviation of the soluble and non-digestible Chinese yam polysaccharides (YP) with covalent selenite-grafting on the nonylphenol-induced cytotoxicity and barrier damage in rat intestinal epithelial (IEC-6) cells. Two grafted products YPSe-I and particularly YPSe-II possessed much higher Se contents than YP (0.803 and 1.486 versus 0.037 g/kg), could alleviate the cytotoxicity of nonylphenol by causing higher cell viability but lower lactate dehydrogenase release and ROS production, and were capable of repairing the induced barrier damage through increasing transepithelial electrical resistance, reducing paracellular permeability, promoting the production and distribution of cytoskeleton F-actin, and up-regulating the expression levels of three tight junction proteins namely zonula occludens-1, occludin, and claudin-1. Meanwhile, the expression levels of two proteins namely p-p38 and p-JNK in the cells, which are crucial to the activation of the MAPK signaling pathway, were up-regulated by nonylphenol but down-regulated by YPSe-I and YPSe-II. The results consistently confirmed that YP and YPSe-II exhibited the respective lowest and highest activities in the cells to alleviate the nonylphenol-induced cytotoxicity and barrier damage, declaring that both YP selenization and higher selenite-grafting extent were the critical factors controlling the measured activities of YPSe-I and YPSe-II. Collectively, this selenite-grafting of YP endowed the selenized products with higher activity in the cells to reduce nonylphenol-induced cytotoxicity, especially to alleviate the induced barrier damage by inactivating the MAPK signaling pathway.

The well-being and development of fish are affected to varying degrees under the intensive aquaculture model, and the use of Chinese herbs for aquaculture disease control and feed additives has received increasing attention. This study examined fraxetin supplementation in juvenile grass carp to investigate its effects on growth and intestinal structure. There were 1080 grass carp (11.58 ± 0.01 g) assigned to 6 treatments, fed with fraxetin (0, 3.9, 7.9, 15.8, 31.5, and 63.1 mg/kg) for 60 days in each treatment. In our study, appropriate fraxetin significantly increased final body weight (FBW), percent weight gain (PWG), and specific growth rate (SGR) compared to the unadded group (P < 0.05), but did not affect feed efficiency (FE) (P > 0.05). The administration of 7.9 mg/kg of fraxetin significantly improved fish intestinal development and body composition. Appropriate dietary fraxetin significantly enhanced intestinal digestive enzymes and brush border enzyme activity (P < 0.05), decreased serum diamine oxidase (DAO) levels (P < 0.05), and decreased intestinal cell apoptosis (P < 0.05). Appropriate levels of fraxetin inhibited the RhoA/ROCK signaling pathway while upregulating both mRNA and protein expression of tight junction (TJ) and adherens junction (AJ) (P < 0.05). These changes significantly improved apical junction complex (AJC) integrity. In conclusion, dietary supplementation with appropriate levels of fraxetin added to the diets had a facilitating effect on digestion and absorption, improved intestinal structure, and promoted fish growth performance in juvenile grass carp. In addition, the optimal dietary fraxetin levels were evaluated to be 6.06 and 7.79 mg/kg based on linear regression analysis of PWG and DAO, respectively.

Recent reports have shown that metabolites derived from gut microbiota play a vital role in intestinal diseases, immune regulation, and neuroinflammation. Nowadays, calycosin has been revealed the protective mechanism from different perspectives on cerebral ischemia-reperfusion injury (CIRI), while the effect of gut microbiota-bile acid-farnesoid X receptor (FXR) axis on the inflammatory protection of CIRI has not been explored. To this end, we established a middle cerebral artery occlusion (MCAO) model firstly to assess the protection of calycosin in CIRI through neurological deficit scoring, TTC staining, and HE staining. Secondly, 16s RNA sequencing, ELISA, real-time qPCR, Western blot, and total bile acid (TBA) detection kit were utilized to detect the pharmacology of calycosin on MCAO rats. Our data indicated that calycosin could significantly improve nerve function scores, reduce cerebral infarction volume, lower serum levels of IL-10, IL-17 inflammatory factors, and TBA, increase mRNA and protein levels of ZO-1 and Occludin in brain, as well as FXR, ZO-1 and Occludin levels in colon. In summary, calycosin can exert a neuroinflammatory protective effect on CIRI in rats via regulating the gut microbiota to improve bile acid metabolism.

This study investigated the effects of astaxanthin (AST) supplementation in drinking water on the growth performance, intestinal barrier function, and cecal microbiota of broilers challenged with Salmonella Enteritidis. During the 20-day experiment, two hundred and forty 1-day-old male Arbor Acres birds were randomly assigned into a 2 × 2 factorial design with four groups: a non-challenged control (CON), an S. Enteritidis-challenged group (SA), a group receiving AST treatment (AST), and an S. Enteritidis-challenged group receiving AST treatment (SA+AST). Each treatment comprised six replicate groups, and challenged groups were inoculated with S. Enteritidis from day 2 to day 4. The results indicated that S. Enteritidis infection significantly reduced the average daily feed intake (ADFI) in broilers and adversely affected average daily gain (ADG) and feed conversion ratio (FCR) by day 20. AST supplementation significantly improved FCR. While S. Enteritidis infection did not significantly affect ileal mucosa antioxidation, it significantly decreased villus height and the villus height-to-crypt depth ratio (VCR), and significantly downregulated mRNA expression of ZO-1 and Occludin. However, AST supplementation significantly enhanced antioxidant capacity (T-AOC), increased villus height and VCR in the ileum, and notably upregulated ZO-1 and MUC2 expression levels, particularly mitigating the adverse effects of S. Enteritidis infection on ileal crypt depth. Furthermore, S. Enteritidis infection significantly affected both the α- and β-diversity of cecal microbiota. Infection with S. Enteritidis was associated with changes at the phylum level, including significant increases in Alistipes, unclassified_f__Lachnospiraceae, and bacteria of the Clostridia UCG-014 grouping, alongside notable decreases in Bacteroides, Akkermansia, Blautia, and Butyricicoccus. AST supplementation significantly decreased the abundance of norank_f__Ruminococcaceae and increased the abundance of Lachnoclostridium and unclassified_f__Lachnospiraceae in the challenged group. In conclusion, AST supplementation in drinking water could improve growth performance and intestinal health in broilers challenged with S. Enteritidis.

The starch-polyphenol complex, identified as RS5-resistant starch, has been shown to regulate the gut environment and inhibit metabolic diseases, including obesity. In a study with C57BL/6 obese mice fed LSE, potential anti-obesity effects were demonstrated through physiological and biochemical assessments, gut microbiota analysis, and mechanistic insights. The study showed that LSE reduced mice body weight, serum total cholesterol, and triglycerides (P < 0.05). Serum inflammatory markers (TNF-α, IL-6, IL-1β) and LPS levels were significantly decreased, while glucose tolerance (AUC reduced by 29.29 %) and insulin sensitivity (AUC reduced by 31.79 %) were improved. Histological analysis indicated reduction in adipocyte size and attenuation of hepatic steatosis. Gut microbiota profiling demonstrated LSE increased beneficial bacteria genera Faecalibacterium, Bifidobacterium, and Akkermansia. This correlated with enhanced SCFA production (acetate 41.53 %, propionate 45.52 %, butyrate 57.49 % increase). These findings demonstrate that LSE exerts anti-obesity effects through modulation of the gut microbiota-SCFA-metabolic axis, supporting starch-polyphenol complexes as functional food candidates.

Ochratoxin A (OTA) is a toxic fungal secondary metabolite that triggers liver inflammation in animals. OTA could disrupt intestinal microbiota balance by promoting Gram-negative bacteria growth and activating the Toll-like receptor 4 (TLR4)/Nuclear factor-kappa B (NF-κB) signaling pathway, thereby inducing liver inflammation. Ginsenoside Rg1 (Rg1) is an active component of ginseng, exhibits anti-inflammatory, antibacterial, and antioxidative properties, particularly against gram-negative bacteria. Rg1 has been shown to maintain intestinal microbiota homeostasis and inhibit the TLR4 signaling pathway to alleviate liver inflammation. Given these established mechanisms, the aim of this study was to explore the preventive effect of Rg1 in countering OTA-induced liver inflammation through modulation of intestinal microbiota and the TLR4/NF-κB signaling pathway. The results revealed that Rg1 reduced OTA residues in the cecum and enhanced intestinal barrier function. Moreover, Rg1 ameliorated the intestinal microbiota composition in OTA-treated ducklings by decreasing the relative abundance of lipopolysaccharide (LPS)-related bacteria. Rg1 also increases the abundance of short-chain fatty acid (SCFA)-producing bacteria. Additionally, Rg1 supplementation with OTA decreased the accumulation of LPS in tissues and inhibited the TLR4/NF-κB signaling pathway. Intriguingly, Rg1 maintained its beneficial effects in OTA-treated ducklings even after antibiotic treatment by inhibiting the TLR4/NF-κB pathway. These findings emphasized the importance of intestinal microbiota homeostasis and TLR4/NF-κB pathway suppression in the anti-inflammatory action of Rg1 during OTA-induced liver inflammation.

Inflammatory Bowel Disease (IBD) is a chronic, idiopathic inflammatory disorder of the intestines. Oxymatrine (OMT) is a naturally active substance found in the desiccated roots of Sophora flavescens. It possesses anti-tumor, antiviral, and anti-inflammatory properties. In recent years, its therapeutic role in IBD has gradually been discovered. This review aims to explore the impact of OMT on inflammatory bowel disease by animal models.

Conduct a systematic search in the PubMed, Embase, Web of Science, Cochrane, and Medline databases. Using SYRCLE's risk of bias tool to assess the bias risk and quality of the included studies. For some data presented as figures, Web Plot Digitizer 4.2 software was used to extract it. STATA 16.0 was selected for the final meta-analysis.

After rigorous literature screening, 12 studies were included. The data analysis results indicated that the disease activity index (DAI), histopathological score (HS), interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB), and myeloperoxidase (MPO) activity in the IBD animal models significantly decreased following intervention with oxymatrine. Furthermore, OMT also extended the colon length in the animal models and improved the expression level of zonula occludens-1(ZO-1) and occludin. These results suggested that OMT may improve the condition of IBD through anti-inflammatory, antioxidative stress and protecting the intestinal barrier.

Meta-analysis suggests oxymatrine positively affects IBD animal models. This provides new insights for the clinical treatment of inflammatory bowel disease.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024570580, identifier [CRD42024570580].

Functional dyspepsia (FD) is a chronic gastrointestinal disorder without a readily identifiable organic cause, resulting in bothersome upper abdominal symptoms. It is a highly prevalent disorder of which the pathophysiology remains mostly elusive, despite intensive research efforts. However, recent studies have found alterations in the microenvironment of the duodenum in patients with FD. In this review we summarize the duodenal microenvironment in homeostatic conditions and the alterations found in patients with FD, highlighting the similarities and discrepancies between different studies. The most consistent findings, being an impaired duodenal barrier and duodenal immune activation, are reviewed. We discuss the potential triggers for these observed alterations, including psychological comorbidities, luminal alterations and food related triggers. In summary, this review presents the evidence of molecular and cellular changes in patients with FD, with an impaired duodenal barrier and activated mucosal eosinophils and mast cells, challenging the notion that FD is purely functional, and offering different targets for potential future treatments.

Inflammatory bowel diseases (IBD) are chronic, relapsing gastrointestinal disorders with complex pathological mechanisms and limited treatment options, caused by various uncertain factors. Zinc plays a crucial role in wound healing, tissue regeneration, and immune responses. While zinc deficiency is common among patients with IBD, the effects of dietary zinc supplementation on the disease course remain unclear. In this study, 125 male C57BL/6 J mice were randomly divided into five groups: a control group (Con), a 2,4,6-trinitrobenzenesulfonic acid (TNBS) induction group, and three zinc supplementation groups receiving 160 ppm, 400 ppm, and 1000 ppm of zinc oxide nanoparticles ( ZnO NPs), respectively. The results showed that dietary supplementation with ZnO NPs significantly alleviated damage to the colonic mucosal epithelial cells and crypts in IBD mice, while effectively reducing the inflammatory response. Furthermore, ZnO NPs helps maintain the quantity and secretion function of goblet cells, restores normal expression levels of tight junction proteins (ZO-1, occludin), and proliferating cell nuclear antigen (PCNA), and preserves the diversity of gut microbiota. Notably, a significant protective effect was observed with dietary zinc supplementation at 160 ppm. These findings suggest that ZnO NPs significantly improves TNBS-induced intestinal inflammatory damage by modulating the gut microbiota, mucus, and mechanical barriers.

Polysaccharides have garnered increasing attention in recent years for their potential in oral drug delivery within biomaterials and pharmaceuticals, owing to their excellent physicochemical properties, bioactivity, and low toxicity. However, the absorption of polysaccharides encounters multiple challenges posed by the biological, chemical, mechanical, and immune barriers of the intestinal mucosa. Therefore, elucidating the mechanisms by which polysaccharides traverse the intestinal mucosa for oral absorption is essential for their further development and application. Current studies have identified several polysaccharide absorption pathways, including transcellular transport, paracellular transport, M cell and Peyer's patches mediated transport, and intestinal flora mediated transport. Furthermore, numerous studies have demonstrated that polysaccharides can enhance the solubility, gastrointestinal stability, and permeability of small molecule components, which significantly improves their bioavailability. More importantly, nano-delivery systems utilizing polysaccharides as carriers have shown great promise in enhancing the targeting of small molecule components, thereby opening new avenues for drug delivery applications. We hope this review will provide theoretical support and inspiration for a deeper understanding of oral absorption mechanisms and the potential of polysaccharides in the development of nano-delivery systems.

Sargassum fusiforme, widely consumed in Asian countries, has been proven to have various biological activities. However, the impacts and mechanisms of Sargassum fusiforme polysaccharides (SFPs) on intestinal bacterial infection are not yet fully understood. Our findings indicate that SFPs pretreatment ameliorates intestinal inflammation by reducing C. rodentium colonization, increasing colon length and levels of IL-10 and IL-22, decreasing IL-1β, IL-6, TNF-α, and IL-17 levels, inhibiting colonic crypt elongation and hyperplasia, and enhancing the intestinal mucosal barrier. The protective effects against intestinal bacterial infection are linked to enhanced clearance of C. rodentium and improvements in the intestinal mucosal barrier and C. rodentium-induced intestinal microbiota dysbiosis. Fecal microbiota transplantation experiments were conducted to evaluate the functional impact of microbiota induced by SFPs. The results suggest that intestinal microbiota modified by SFPs effectively countered C. rodentium infection. In addition, our study identified that miRNA-92a-3p is partially complementary to the 3'-UTR of the Notch1 gene, thereby repressing the Notch1-Hes1 signaling pathway and enhancing Muc2 secretion. Taken together, these findings reveal that SFPs protect mice from C. rodentium infection by activating the miR-92a-3p/Notch1-Hes1 regulatory axis driven by the intestinal microbiota, which stimulates Muc2 production to maintain intestinal barrier homeostasis.

This study investigates the effects of the red macroalgae Galaxaura oblongata diet supplementation on roach (Rutilus rutilus) fingerlings growth and gene expression related to immunity, the intestinal barrier, and antioxidant status. Roach fingerlings (2.26 ± 0.04 g) were fed a basic diet supplemented with three different percentages of G. oblongata powder: 0.25 % (G1), 0.50 % (G2), and 1.0 % (G3) over 8 weeks, with a control group (C) receiving no supplementation. The study found that growth parameters significantly increased in the G1 and G2 groups compared to the C and G3 groups (P < 0.05). Immune responses, measured by total immunoglobulin (Ig) and lysozyme activity, showed a significant increase in the whole-body extract of the G2 group (P < 0.05) and the skin mucus of all treated groups compared to the control (P < 0.05). G. oblongata supplementation did not significantly affect catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in the whole-body extract, although GPx activity in skin mucus was significantly higher in the supplemented groups. Additionally, the gene expression of interleukin 1-beta (il-1β), occludin, gpx and sod, but not Toll-like receptor increased in G. oblongata treated groups. These results suggest that G. oblongata can serve as a beneficial feed additive in the culture of roach fingerlings, enhancing growth and immune function.

Deoxynivalenol (DON) is a pervasive ribotoxic stressor that induces intestinal epithelial barrier disruption by impairing tight junctions (TJs) and causing cellular damage. Curcumin (CUR), known for its enteroprotective properties and low toxicity, has been shown to attenuate DON-induced intestinal epithelial barrier injury. However, the underlying mechanisms are still unclear. In this study, we established in vivo and in vitro models using 30 male Kunming mice and IPEC-J2 cells to investigate the mechanisms by which CUR alleviates DON-induced intestinal epithelial barrier injury. The results showed that CUR markedly reduced DON-induced increases in intestinal permeability by restoring TJ protein expression (Claudin-4 and occludin) and preventing fiber-shaped actin (F-actin) contraction. CUR also attenuated DON-induced apoptosis by downregulating p53 and caspase activation and alleviated the G1 cell cycle arrest by reducing p21 expression. Mechanistically, CUR inhibited the activation of the ribosomal stress response (RSR)-associated p38 pathway, evidenced by decreased phosphorylation of p38, GSK3β, and ATF-2. The p38 activator dehydrocorydaline reversed CUR's protective effects. In conclusion, CUR alleviates DON-induced intestinal epithelial barrier disruption by improving RSR-associated p38 pathway-mediated TJ injury, apoptosis, and cell cycle arrest. These findings highlight the potential of CUR as a therapeutic agent for mitigating mycotoxin-induced intestinal dysfunction and suggest new avenues for drug target discovery.

Turpiniae folium extract (TFE) has shown anti-inflammatory and immunomodulatory effects in broilers. However, its mechanisms remain unclear. The aim of this study is to investigate the underlying mechanisms by which TFE influences growth performance, jejunal morphology, immune function, antioxidant capacity and barrier integrity in broilers challenged with Lipopolysaccharide (LPS). A total of 240 one-day-old female broilers were randomly divided into four groups with six replicates of ten birds each. A 2 × 2 factorial design with TFE (basal diets supplemented with 0 or 500 mg/kg TFE) and LPS challenge (intraperitoneal injection of 1 mg/kg body weight of sterile saline or LPS at 21, 23 and 25 days of age). The trial lasted for 26 days. The results showed that: Prior to the LPS challenge, dietary supplementation with TFE for 21 days increased both average daily gain (ADG) (P = 0.037) and average daily feed intake (ADFI) (P = 0.045) in broilers. During the LPS challenge period, LPS challenge led to a decline in growth performance and a negative impact on intestinal morphology, while TFE supplementation significantly reversed these adverse effects, as evidenced by increases in ADG (P = 0.004), ADFI (P = 0.046), jejunal villus height (VH) (P = 0.035), the villus height to crypt depth ratio (VH/CD) (P = 0.007) and decreases in the feed-to-gain ratio (F/G) (P = 0.025), jejunal crypt depth (CD) (P = 0.049). LPS induced inflammatory responses and oxidative stress in the jejunum, leading to a significant upregulation of pro-inflammatory factor gene and protein expression, and a marked downregulation of anti-inflammatory and antioxidant gene and protein expression. TFE supplementation mitigated these effects by yielding completely opposite results except for the expression of toll-like receptor 4 (TLR4) protein (P = 0.916). LPS negatively regulates the expression of genes and proteins involved in intestinal mucosal barrier function. In contrast, TFE supplementation significantly upregulated the expression of zonula occludens-1 (ZO-1) (P < 0.001) gene and ZO-1 (P < 0.001), occludin (OCLN) (P < 0.001), claudin (CLDN) (P < 0.001) proteins. In conclusion, dietary supplementation with TFE effectively counteracts the intestinal immune and oxidative stress induced by LPS challenge in broilers, improves intestinal mucosal barrier integrity and tissue morphology, and ultimately mitigates the negative impact of LPS on broiler growth performance. This effect may involve the modulation of the Nrf2 and nuclear factor kappa B (NF-κB) signaling pathways.

To construct a model of intestinal injury induced by radiotherapy for lung cancer and to study the protective effect and mechanism of isoliquiritigenin. The lungs of mice were irradiated with 0, 2, 4, 6, 8 Gy X-rays to screen the optimal radiation dose. A mouse model of lung cancer was established, and the tumor was irradiated once. At 3, 7, and 10 days after irradiation, H&E was used to detect the pathological manifestations of colon tissue in mice, and WB was used to detect the expression level of tight junction protein in colon tissue, so as to screen the best time point and study its possible mechanism. Molecular docking was used to study the tightness of isoliquiritigenin binding to TNF-α. Isoliquiritigenin (40 mg/kg) was given on the next day after 4 Gy X-ray irradiation. The levels of TNF-α and apoptosis, intestinal mucosal barrier function, MUC2 protein expression, and colon stem cell proliferation were detected. 4Gy X-ray local irradiation induced obvious colon injury in mice, and the injury was obvious on the 7th day. Isoliquiritigenin significantly improved the general condition, colonic histopathological changes, intestinal stem cell proliferation, and colonic tight junction function of lung cancer-bearing mice after radiotherapy. Further studies have found that isoliquiritigenin can downregulate the activation of TNF-α/Caspase-3 signaling pathway by inhibiting the expression of pro-inflammatory factor TNF-α, alleviate the apoptosis of colonic epithelial cells, improve the upregulation of colonic tight junction function, regulate the expression of MUC2, and promote the proliferation of intestinal stem cells, which may be related to the stable binding of isoliquiritigenin to TNF-α. Radiotherapy-induced bystander effect of lung cancer may be related to the abnormal expression of TNF-α. Isoliquiritigenin may downregulate the expression of TNF-α by binding to TNF-α, inhibit the apoptosis of colon cells, promote the proliferation of intestinal stem cells, and maintain the intestinal mucosal barrier to alleviate the colon injury induced by radiation bystander effect.

(1) Background: Glucuronolactone (GLU) is a glucose metabolite with antioxidant activity. At present, the exact role of it in regulating the intestinal health of piglets under weaning stress is not clear. The purpose of this study is to investigate the effects of GLU on the growth performance and intestinal health of piglets under weaning stress and to explore potential mechanisms. (2) Methods: Twenty-four weaned piglets were randomly assigned into two groups, with one group receiving a basal diet and the other group receiving an experimental diet supplemented with 200 mg/kg of GLU. (3) Results: GLU increased the ADG, ADFI, and final body weight of piglets, while reducing the diarrhea rate. Mechanistically, GLU alleviates weaning stress-induced intestinal oxidative stress and inflammatory responses in piglets partly through activating the Nrf2-Akt signaling pathway to suppress the transcriptional activity of FOXO1, while also inhibiting the activation of the TLR4-MAPK signaling pathway to reduce the secretion of pro-inflammatory cytokines. Moreover, GLU increased the relative abundance of Lactobacillus reuteri in the ileum of piglets and improved the composition of the gut microbiota. (4) Conclusions: GLU reduced inflammation and oxidative stress through the Nrf2/Akt/FOXO1 signaling pathway and improved intestinal health, resulting in improved growth performance of the piglets.

Obesity is a prominent global health concern associated with chronic inflammation and metabolic disorders, such as insulin resistance, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Excessive consumption of saturated fats exacerbates these conditions by increasing intestinal barrier permeability and circulating endotoxins. This study aims to investigate, in a murine model of high-fat diet (HFD)-induced obesity, the potential beneficial effects of a grape pomace extract (GPE), rich in phenolic compounds, at mitigating endotoxemia, and liver steatosis. Underlying mechanisms were characterized in an in vitro model of intestinal inflammation and permeabilization, as induced by tumor necrosis factor alpha (TNFα) in Caco-2 cell monolayers. Consumption of a HFD (60% calories from fat) for 13 weeks induced obesity, insulin resistance, and liver damage, evidenced by higher levels of plasma alanine aminotransferase (ALT), hepatic triglycerides content, and steatosis. In addition, HFD caused metabolic endotoxemia, hepatic toll-like receptor 4 (TLR4) upregulation and inflammation. GPE supplementation significantly reduced body weight and subcutaneous and visceral adipose tissue weight, and attenuated metabolic dysregulation. Furthermore, GPE decreased circulating LPS levels and mitigated HFD-mediated hepatic TLR4 upregulation, nuclear factor kappa B (NF-κB) activation, and downstream expression of proteins involved in oxidative stress and inflammation (NOX4, TNFα, and F4/80). In Caco-2 cells, GPE mitigated TNFα-induced monolayer permeabilization, decreased tight junction (TJ) protein levels, enhanced cellular oxidant production, activated redox-sensitive signaling, i.e., NF-κB and ERK1/2, and increased NOX1 and MLCK mRNA levels, the latter being a key regulator of monolayer permeability. The above findings suggest that GPE may protect against HFD-induced obesity and associated metabolic dysfunction (insulin resistance and NAFLD) by modulating intestinal barrier integrity and related endotoxemia.

The extraction of polysaccharides from wood by-products is recognized as a green re-utilization approach to shape a recycling-oriented society. In this research, we identified the structural properties of arabinogalactan (AG) extracted from Larix sibirica Ledeb wood chips and verified its efficacy as an additive in broiler framing. Results showed that the molecular weight of AG is 19.805 KDa. Methylation analysis and NMR spectra indicate that AG has a 1,6-linked Galp backbone, side residues mainly branched at C-1,3,6 on β-D-Galp. The Ara residues were substituted at C-3 of 1,6-linked Galp consisting of α-L-Araf-(1→3)-α-L-Araf-(1 → 3)-α-L-Araf (1→ and α-L-Araf-(1 → 4) β-D-Galp-(1 → 3)-β-D-Galp-(1→. As a dietary supplement in broiler model, AG treatment improved the body weight of broilers especially breast and leg muscle weight. Furthermore, AG could regulate host immune response, gut microbiota composition, and metabolic activity, especially promoting lipid metabolism. By means of serum non-targeted metabolomics analysis, enrichment of pantothenate and CoA biosynthesis and beta-alanine metabolism pathways could be determined. AG treatment led to a rise in bacteria that produce SCFAs, with elevated concentrations of acetic and butyric acids. In conclusion, AG can be considered as a potential dietary supplement to beneficially affect host's health status.

Current in vitro methods for intestinal barrier assessment predominantly utilize two-dimensional (2D) membrane inserts in standard culture plates, which are widely recognized for their inability to replicate the microenvironment critical to intestinal barrier functionality. Our study focuses on creating an alternative method for intestinal barrier function by integrating a 3D-printed transwell device with a paper-based membrane. Caco-2 cells were grown on a Matrigel-modified paper membrane, in which the tight junction formation was evaluated using TEER measurements. Neutrophil-like dHL-60 cells were employed for neutrophil extracellular trap (NET) formation experiments. Furthermore, intestinal barrier dysfunction was demonstrated using NET-isolated and Staurosporine interventions. Intestinal barrier characteristics were investigated through immunofluorescence staining of specific proteins and scanning electron microscopy (SEM). Our paper-based intestinal barrier exhibited an increased resistance in a time-dependent manner, consistent with immunofluorescence images of Zonulin Occludens-1 (ZO-1) expression. Interestingly, immunofluorescence analysis revealed changes in the morphology of the intestinal barrier and the formation of surface villi. These disruptions were found to alter the localization of tight junctions, impacting epithelial polarization and surface functionality. Moreover, we successfully demonstrated the permeability of a paper-based intestinal barrier using FITC-dextran assay. Hence, the 3D-printed transwell device integrated with a paper membrane insert presents a straightforward, cost-effective, and sustainable platform for an in vitro cell model to evaluate intestinal barrier function.

Although rare, the ability to produce surface S-layer proteins is beneficially associated with particular Lactobacillus strains being investigated as probiotics. Therefore, this work aimed to study specific probiotic functionalities of selected Levilactobacillus brevis strains MB1, MB2, MB13 and MB20, isolated from human milk microbiota, and to assess the contribution of S-proteins. Firstly, Rapid Annotation using Subsystem Technology revealed that cell wall-related genes were abundant in analysed L. brevis genomes. Furthermore, the results demonstrated that S-proteins mediate aggregation capacity and competitive exclusion of selected pathogens by L. brevis strains. The improvement of Caco-2 epithelial monolayer barrier function was demonstrated by the increase in JAM-A and occludin expressions when L. brevis strains or S-proteins were added, with the effect being most pronounced after treatment with MB2 and S-proteins of MB1. L. brevis strains, especially MB20, exerted the potential to adhere to recombinant human ZG16. Strain MB2 and MB20-S-proteins improved the barrier function of HT29 epithelial monolayer, as evidenced by increased ZG16 expression. Analysed L. brevis strains and S-proteins differentially affected the protein expression of IL-1β, IL-6 and IL-8, and IL-10 cytokines. The most prominent effect was observed by S-proteins of MB20, since IL-1β production was decreased while IL-10 production was significantly increased.

A 12-week aquaculture trial was conducted to evaluate the effects of vitamin B6 on the intestinal health of largemouth bass (Micropterus salmoides). Six feeds with a vitamin B6 content of 2.03 (control group), 2.91, 3.30, 6.03, 9.53, and 21.79 mg/kg were prepared. The results were as follows. Regarding digestive efficiency, the 9.53 mg/kg group showed significantly higher activities of AMY, LPS, and TRY compared to the control group; the 6.03 mg/kg group exhibited increased AKP and Na+/K+ ATPase activities. Regarding immunity, the 6.03 mg/kg group had markedly higher relative expressions of zo-1 and occ than the control group; the 9.53 mg/kg group showed significantly higher relative expressions of il-10, tgf-β, igm, and cd83, while il-8 and tnf-α were notably lower, and nf-κb was noticeably decreased in 21.79 mg/kg group. For antioxidant capacity, the 6.03 mg/kg group had markedly higher activities of CAT, SOD, GSH-Px, and T-AOC levels, compared to the control group; the MDA level in the control group was markedly higher than in the other groups. The relative expressions of nrf2, cat, Cu-Zn sod, and gpx were highest in 9.53 mg/kg group and significantly higher than in the control group. In conclusion, an appropriate level of vitamin B6 in the feed is vital for protecting the intestinal health of largemouth bass.

The intestinal epithelium represents a critical interface between the host and external environment, serving as the second largest surface area in the human body after the lungs. This dynamic barrier is sustained by specialized epithelial cell types and their complex interactions with the gut microbiota. This review comprehensively examines the recent advances in understanding the bidirectional communication between intestinal epithelial cells and the microbiome. We briefly highlight the role of various intestinal epithelial cell types, such as Paneth cells, goblet cells, and enteroendocrine cells, in maintaining intestinal homeostasis and barrier function. Gut microbiota-derived metabolites, particularly short-chain fatty acids and bile acids, influence epithelial cell function and intestinal barrier integrity. Additionally, we highlight emerging evidence of the sophisticated cooperation between different epithelial cell types, with special emphasis on the interaction between tuft cells and Paneth cells in maintaining microbial balance. Understanding these complex interactions has important implications for developing targeted therapeutic strategies for various gastrointestinal disorders, including inflammatory bowel disease, metabolic disorders, and colorectal cancer.

Significance: Hydrogen sulfide (H2S), a ubiquitous small gaseous signaling molecule, plays a critical role in various diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), ischemic stroke, and myocardial infarction (MI) via reducing inflammation, inhibiting oxidative stress, and cell apoptosis. Recent Advances: Uncontrolled inflammation is closely related to pathological process of ischemic stroke, RA, MI, and IBD. Solid evidence has revealed the axes between gut and other organs like joint, brain, and heart, and indicated that H2S-mediated anti-inflammatory effect against IBD, RA, MI, and ischemic stroke might be related to regulating the functions of axes between gut and other organs. Critical Issues: We reviewed endogenous H2S biogenesis and the H2S-releasing donors, and revealed the anti-inflammatory effects of H2S in IBD, ischemic stroke, RA, and MI. Importantly, this review outlined the potential role of H2S in the gut-joint axis, gut-brain axis, and gut-heart axis as a gasotransmitter. Future Direction: The rate, location, and timing of H2S release from its donors determine its potential success or failure as a useful therapeutic agent and should be focused on in the future research. Therefore, there is still a need to explore internal and external sources monitoring and controlling H2S concentration. Moreover, more efficient H2S-releasing compounds are needed; a better understanding of their chemistry and properties should be further developed. Antioxid. Redox Signal. 42, 341-360.

Increasing research has indicated that circular RNAs (circRNAs) are crucial for the development of ulcerative colitis (UC). Thus, we attempted to identify the role of hsa_circ_0004662 in UC progression. Hsa_circ_0004662 expression was determined via qRT-PCR. Lipopolysaccharide (LPS)-induced inflammation in normal colonic epithelial cells (ECs). The hsa_circ_0004662 content was then assessed in a mucosal inflammatory bowel disease (IBD) model. Cell proliferation was examined via CCK-8 and EdU uptake assays. Apoptotic rates were analysed via flow cytometry. The protein content was quantified via Western blotting. Enzyme-linked immunosorbent assay kits were used to detect IL-1β, TNF-α and IL-6, and dual-luciferase reporter (DLR) assays were used to identify interactions between miR-532 and circ_0004662 or HMGB3. An animal model of UC was also developed for confirmation. In this study, we identified the function of hsa_circ_0004662 in promoting UC progression. Hsa_circ_0004662 was upregulated in clinical UC tissues and LPS-induced colonic ECs, and its knockdown inhibited apoptosis, reduced inflammatory cytokine release and promoted cell proliferation in vitro. Mechanistically, hsa_circ_0004662 acted as a molecular sponge for miR-532, which targets HMGB3. The hsa_circ_0004662/miR-532/HMGB3 axis was further validated in a DSS-induced colitis mouse model, where hsa_circ_0004662 knockdown attenuated inflammation and tissue damage. These findings suggested that hsa_circ_0004662 contributes to UC progression through the miR-532/HMGB3 signalling pathway, offering potential targets for UC therapy.

In 2023, the World Obesity Atlas Federation concluded that more than 50% of the world's population would be overweight or obese within the next 12 years. At the heart of this epidemic lies the gut microbiota, a complex ecosystem that profoundly influences obesity-related metabolic health. Its multifaced role encompasses energy harvesting, inflammation, satiety signaling, gut barrier function, gut-brain communication, and adipose tissue homeostasis. Recognizing the complexities of the cross-talk between host physiology and gut microbiota is crucial for developing cutting-edge, microbiome-targeted therapies to address the global obesity crisis and its alarming health and economic repercussions. This narrative review analyzed the current state of knowledge, illuminating emerging research areas and their implications for leveraging gut microbial manipulations as therapeutic strategies to prevent and treat obesity and related disorders in humans. By elucidating the complex relationship between gut microflora and obesity, we aim to contribute to the growing body of knowledge underpinning this critical field, potentially paving the way for novel interventions to combat the worldwide obesity epidemic.

Pyraclostrobin (PY) is highly toxic to aquatic organisms, and its increased residues in aquatic environments may have harmful effects on the intestine of aquatic creatures. Previous research demonstrated that vitamin E (VE) alleviated the acute toxicity of PY to zebrafish. This study further explored the mitigation effect of VE on PY-induced intestinal toxicity in fish and the underlying mechanisms by exposing adult zebrafish to PY (10, 20 μg/L) with or without 4 μM VE supplementation for 21 days. The results showed that VE alleviated the gut histopathological lesions caused by PY. VE co-exposure also improved PY-induced intestinal inflammation and restored the expression level of genes encoding intestinal tight junction protein. Furthermore, VE restored the anti-oxidation level inhibited by PY and reduced pro-apoptotic cytokine level and apoptotic enzyme activity increased by PY. 16S rRNA high-throughput sequencing showed that VE improved the zebrafish intestinal flora imbalance caused by 20 μg/L PY, increased the relative abundance of beneficial bacterium Cetobacterium, and reduced the relative abundance of pathogenic bacteria. In conclusion, VE alleviated PY-induced intestinal toxicity via repairing the damaged intestinal mucosal barrier, inhibiting inflammation, reducing oxidative stress and apoptosis, and improving the intestinal microbial disorder in zebrafish.

Parkinson's disease is recognized as the second most prevalent neurodegenerative disorder globally, with its incidence rate projected to increase alongside ongoing population growth. However, the precise etiology of Parkinson's disease remains elusive. This article explores the inflammatory mechanisms linking gut microbiota to Parkinson's disease, emphasizing alterations in gut microbiota and their metabolites that influence the disease's progression through the bidirectional transmission of inflammatory signals along the gut-brain axis. Building on this mechanistic framework, this article further discusses research methodologies and treatment strategies focused on gut microbiota metabolites, including metabolomics detection techniques, animal model investigations, and therapeutic approaches such as dietary interventions, probiotic treatments, and fecal transplantation. Ultimately, this article aims to elucidate the relationship between gut microbiota metabolites and the inflammatory mechanisms underlying Parkinson's disease, thereby paving the way for novel avenues in the research and treatment of this condition.

With the exacerbation of global population aging, sarcopenia has become an increasingly recognized public health issue. Sarcopenia, characterized by a progressive decline in skeletal muscle mass, strength, and function, significantly impacts the quality of life in the elderly. Herein, we explore the role of chroniclow-gradeinflammation in the development of sarcopenia and its underlying molecular mechanisms, including chronic inflammation-associated signaling pathways, immunosenescence, obesity and lipid infiltration, gut microbiota dysbiosis and intestinal barrier disruption, and the decline of satellite cells. The interplay and interaction of these molecular mechanisms provide new perspectives on the complexity of the pathogenesis of sarcopenia and offer a theoretical foundation for the development of future therapeutic strategies.

The purpose of this study was to investigate the effects of Bacillus subtilis supplementation on the health of weaned piglets and whether B. subtilis supplementation can reduce the damage of piglets induced by ETEC K88.

The experiment was designed with a 2 × 2 factorial arrangement, comprising the control group, B. subtilis (PRO) group, Escherichia coli K88 (ETEC) group, and B. subtilis + ETEC (PRO + ETEC) group. Regardless of the presence of ETEC, the addition of PRO increased the piglets' final body weight, average daily gain, and daily feed intake. Additionally, PRO primarily achieves a reduction in heat-stable enterotoxin (ST) levels, suppresses the expression of NF-κB, TLR4, and MyD88 mRNA in the jejunum and ileum, lowers pro-inflammatory factors in the blood and small intestine, enhances the expression of tight junction proteins in the small intestine, improves the composition of the colonic microbiota, increases colonic short-chain fatty acid contents, thereby alleviating diarrhea and mitigating bodily damage caused by ETEC K88 infection.

The addition of B. subtilis MZ-01 alleviated ETEC K88-induced piglet diarrhea by reducing ST levels, decreasing pro-inflammatory factors in the blood and intestine, and enhancing the intestinal barrier and tight junction proteins.

Sanguinarine constitutes the main components of Macleaya cordata, and exhibits diverse biological and pharmacological activities. This study investigated the effects of sanguinarine chloride hydrate (SGCH) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. Five groups were designed to investigate the effects of SGCH on the pathological symptoms, the mRNA expression levels of inflammatory cytokines, colonic mucosal barrier damage, microbiota composition, and SCFAs metabolism in UC mice. The administration of SGCH in DSS-induced UC mice resulted in the amelioration of pathological symptoms, as evidenced by an increase in body weight, a decrease in disease activity index score, elongation of colon length, reduction in spleen index, and improvement in colon injury. SGCH can regulate the expression of inflammatory cytokines (IL-6, TNF-α, IL-1β and IL-10) and tight junction proteins (ZO-1 and Occludin) associated with UC. SGCH exhibited a significant decrease in NF-κB P65 mRNA expression levels, accompanied by a significantly reduced protein level of NF-κB P-P65/P65. Further studies revealed SGCH effectively reversed the decrease in intestinal microbiota diversity induced by UC, thereby promoting the growth of beneficial bacteria such as Akkermansia, Alistipes, and norank_o_Clostridia_UCG-014. Correlation analysis demonstrated a positive association between butanoic acid, propanoic acid, isobutyric acid, isovaleric acid, valeric acid, hexanoic acid with Colidextribacter, while Coriobacteriaceae_UCG-002 exhibited a negative correlation with butanoic acid, acetic acid and propanoic acid. In conclusion, the administration of SGCH can ameliorate clinical symptoms in UC mice, regulate the expression of inflammatory cytokines and tight junction proteins, modulate intestinal microbiota metabolism and SCFAs production.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition with increasing global prevalence. Current therapies are limited, leading to exploration of novel treatments like Pu-erh tea, a fermented tea recognized for its health benefits. This study shows that long-term consumption of Pu-erh tea significantly reduces IBD symptoms in DSS-induced mice by moderating inflammation and enhancing oxidative responses in the colon. Pu-erh tea notably increases the abundance of specific gut microbiota, particularly enhancing Firmicutes, Bacteroidota, and Proteobacteria phyla, and raising levels of Lactobacillus and Muribaculaceae genera. Key species such as Lactobacillus johnsonii, Lactobacillus reuteri, and Lactobacillus murinus also showed increased abundance. Additionally, Pu-erh tea helps restore the integrity of the intestinal barrier. These findings highlight the potential of Pu-erh tea as a complementary dietary strategy for IBD, potentially improving disease management and patient outcomes through its effects on the intestinal microbiota and mucosal barrier.

The online version contains supplementary material available at 10.1007/s10068-024-01696-9.

The vascular response following injury is pivotal for successful bone-defect repair but constitutes a major hurdle in the field of regenerative medicine. Throughout this process, vessel stabilization is crucial to provide an adequate nutrient supply and facilitate efficient waste removal. Therefore, this study investigated whether promoting vascular stabilization improves bone defect repair outcomes. The findings show that insulin-like growth factor-binding protein (IGFBP) 7 exhibits a novel biological function in attenuating vascular permeability and enhancing vascular wall integrity. The potential underlying mechanism involves the up-regulation of insulin-like growth factor 1 receptor (IGF1R) expression by IGFBP7 on endothelial cell membrane, followed by activation of the downstream PI3K/AKT signaling pathway and upregulated expression of the tight junction protein zonula occludens-1 (ZO-1). IGFBP7 delayed administration in mice with cranial defects significantly improved bone defect healing by increasing ZO-1 and CD31 co-localization within vessel walls and optimizing the perfusion function of the final vascular network. Furthermore, the application of the typical tight junction regulator AT1001 effectively promoted ZO-1-dependent vascular stabilization and facilitated bone defect repair. This study presents a new approach to enhance bone defect healing via vascular stabilization-targeted interventions and significantly advances the understanding of the complex interplay between osteogenesis and angiogenesis in bone defect healing.