Intestinal Mucosa Research Articles

Dual bacteriocin and extracellular vesicle-mediated inhibition of Campylobacter jejuni by the potential probiotic candidate Ligilactobacillus salivarius UO.C249.

Campylobacter jejuni (C. jejuni) is a major cause of gastroenteritis and a global public health concern. The increasing antibiotic resistance and lack of effective alternatives in livestock production pose serious challenges for controlling C. jejuni infections. Therefore, alternative strategies are needed to control this pathogen, especially in the poultry industry where it is prevalent and can be transmitted to humans through contaminated food products. In this study, Ligilactobacillus salivarius UO.C249 isolated from broiler intestinal mucosa inhibited C. jejuni and exhibited important probiotic features. Beyond bacteriocins, Lg. salivarius UO.C249 secretes antimicrobial extracellular vesicles (EVs) with a unique protein set distinct from bacteriocins that are involved in transmembrane transport and peptidoglycan degradation. Our findings suggest that beyond bacteriocins, EV production is also a distinct inhibitory signaling mechanism used by Lg. salivarius UO.C249 to control C. jejuni. These findings hold promise for the application of probiotic EVs for pathogen control.

Dietary Nitrosamines from Processed Meat Intake as Drivers of the Fecal Excretion of Nitrosocompounds.

Diet is one of the main exogenous sources of potentially carcinogenic nitrosamines (NAs) along with tobacco and cosmetics. Several factors can affect endogenous N-nitroso compounds (NOCs) formation and therefore the potential damage of the intestinal mucosa at initial colorectal cancer stages. To address this issue, 49 volunteers were recruited and classified according to histopathological analyses. Lifestyle and dietary information were registered after colonoscopy. The mutagenicity of fecal supernatants was assayed by a modified Ames test. Fecal heme-derived NOCs and total NOC concentrations were determined by selective denitrosation and chemiluminescence-based detection. Results revealed processed meats as the main source of dietary nitrites and NAs, identifying some of them as predictors of the fecal concentration of heme-derived and total NOCs. Furthermore, increased fecal NOC concentrations were found as the severity of colonic mucosal damage increased from the control to the adenocarcinoma group, these concentrations being strongly correlated with the intake of the NAs N-nitrosodimethylamine, N-nitrosopiperidine, and N-nitrosopyrrolidine. Higher fecal NOC concentrations were also noted in higher fecal mutagenicity samples. These results could contribute to a better understanding of the importance of modulating dietary derived xenobiotics as related with their impact on the intestinal environment and colonic mucosa damage.

Effect of oregano essential oil on intestinal immunoglobulin G in Holstein dairy bulls.

Immunoglobulin G (IgG) is important in mediating humoral immunity and in the maintenance of immune homeostasis in the intestinal mucosa. Oregano essential oil (OEO) is a natural herbal extract that possesses antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory properties. As the effects of OEO on intestinal mucosal immunity in Holstein dairy bulls remained unclear, we investigated the effect of dietary supplementation of OEO on IgG levels and IgG+ cells residing in the intestinal tract in Holstein dairy bulls. Twelve Holstein bulls in good health of approximately 10 months of age were selected for the experiment and randomly equally divided into two groups. The control (CK) group was fed a basal ration, and in the OEO group, the basal ration was supplemented with OEO (20 g/head/day). After 300 days of feeding, tissue samples of the jejunum, ileum, and colon of the bulls in each group were collected for histopathological analysis, immunohistochemistry, and enzyme-linked immunosorbent assays, respectively. The jejunum, ileum, and colon of bulls in the CK group had obvious pathological damage, whereas the structure of each intestinal segment was clear and intact. In the OEO group, pathological damage was significantly reduced. IgG+ plasma cells were diffusely distributed in the lamina propria of the jejunum, ileum, and colon in the CK and OEO groups, with no significant difference between the groups. OEO supplementation significantly reduced the number of IgG+ plasma cells in each intestinal segment, with the highest decrease rate being noted for the ileum (22.87%), followed by the colon (19.45%) and jejunum (8.52%). ELISA test results and immunohistochemical results were mutually verified. The change in IgG content was consistent with the trend of change in the number of IgG+ plasma cells. Our findings suggest that OEO supplementation does not alter the diffuse spatial distribution of IgG+ plasma cells in the intestines of Holstein dairy bulls, but lowers immunoglobulin levels to normal levels, significantly reduces intestinal damage, and may enhance mucosal immune defence barrier function by inhibiting inflammatory reactions.

Discordant effects of Janus kinases inhibition ex-vivo on inflammatory responses in colonic compared to ileal mucosa.

Janus kinase (JAK) inhibitors are used for treating inflammatory bowel diseases (IBD). We aimed to identify molecular effects of JAK inhibition in human intestinal mucosa, considering IBD location and phenotype. Colonic and ileal explants from patients with ulcerative colitis (UC), Crohn's disease (CD), and non-IBD controls (NC) were assessed for phosphorylated signal transducers and activators of transcription (p-STAT) levels and Inflammatory genes expression panel in response to ex-vivo JAK inhibitor (tofacitinib). Cytokine production by lamina propria lymphocytes in response to tofacitinib was assessed. Human intestinal organoids were used to investigate JAK inhibitors' effects on iNOS expression. Explants were collected from 68 patients (UC=20; CD=20; NC=28). p-STAT1\3\5 inhibition rates varied, being higher in colonic compared to ileal explants. p-STAT1\3 inhibition rates negatively correlated with CRP levels. While significant alterations in 120 of 255 inflammatory genes were observed in colonic explants, only 30 were observed in ileal NC explants. In colonic explants from UC, significant alterations were observed in 5 genes, including NOS2. JAK inhibition significantly decreased Th1\Th2\Th17-related cytokine production from lamina propria lymphocytes. Various JAK inhibitors reduced IFN-γ-induced increase in iNOS expression in organoids. Site-specific anti-inflammatory effect of JAK inhibition by tofacitinib was noticed, whereby the colon was more robustly affected than the ileum. Ex-vivo response to tofacitinib is individual. JAK inhibition may attenuate inflammation by decreasing iNOS expression. Ex-vivo mucosal platforms may be a valuable resource for studying personalized drug effects in patients with IBD.

Effect of probiotics on hematology and histopathology of organs associated with immune system in male and female Wistar rats

In the present study, potential probiotics were isolated from dairy products and characterized on a molecular basis. Male and female (16 + 16, n = 4) Wistar rats were randomly assigned to 5 groups to revise the effects of isolated potential probiotics on the gut immune system: 0-day, negative control, positive control (commercial product Lactobacillus acidophilus-14), laboratory isolated strains Pro-3 (Weissella confusa MZ735961), and Pro-4 (Lactiplantibacillus plantarum MZ727611). Aspartate-aminotransferase, Interleukin-6, bilirubin, and Alanine-transaminase values in both genders were expected but AST and creatinine values had a minor increase in the female group compared to the male probiotic-treated group. Cellular blood count level of mean corpuscular hemoglobin in male groups showed no considerable differences (p = 0.95), while there were decreased differences (p = 0.00) in female groups. The level of mean corpuscular hemoglobin concentration (MCHC) showed distinct variations (p = 0.02) in male groups, while these values were insignificant changes (p > 0.05) among female groups. No damage to the liver, thymus, or colon was ascertained based on morphological findings. The colon wall thickness, external muscle, crypt depth, and mucosa were significantly (p = 0.03) improved in rats given potential probiotics. In conclusion, probiotic supplementation stimulates the immune system. It may protect the intestinal mucosa by strengthening the gut’s immune system and promoting intestinal efficiency (nutrient absorption and number of goblet cells). L. plantarum can therefore offer a reliable, affordable, and safe treatment for functional gastrointestinal illnesses.

The potential of enteroids derived from children and adults to study age-dependent differences in intestinal CYP3A4/5 metabolism

Drug metabolism in the intestinal wall affects bioavailability of orally administered drugs and is influenced by age. Hence, it is important to fully understand the drug metabolizing capacity of the gut to predict systemic exposure. The aim of this study was to investigate the potential of enteroids as a tool to study CYP3A4/5 -mediated metabolism in both children and adults.Bioconversion of midazolam, a CYP3A4/5 model substrate, was studied using enteroid monolayers as well as tissue explants in the Ussing chamber, both derived from pediatric [median (range age): 54 weeks (2 days – 13 years), n = 21] and adult (n = 5) tissue. Caco-2 cellular monolayers were employed as controls. In addition, mRNA expression of CYP3A4 was determined in enteroid monolayers (n = 11), tissue (n = 23) and Caco-2 using RT-qPCR.Midazolam metabolism was successfully detected in all enteroid monolayers, as well as in all tissue explants studied in the Ussing chamber, whereas Caco-2 showed no significant metabolite formation. The extracted fraction of midazolam was similar between enteroid monolayers and tissue. The fraction of midazolam extracted increased with age in enteroid monolayers derived from 0 to 70 week old donors. No statistically significant correlation was observed in tissue likely due to high variability observed and the smaller donor numbers included in the study. At the level of gene expression, CYP3A4 increased with age in tissues (n = 32), while this was not reflected in enteroid monolayers (n = 16). Notably, asymmetric metabolite formation was observed in enteroids and tissue, with higher metabolite formation on the luminal side of the barrier.In summary, we demonstrated that enteroids can be used to measure CYP3A4/5 midazolam metabolism, which we show is similar as observed in fresh isolated tissue. This was the case both in children and adults, indicating the potential of enteroids to predict intestinal metabolism. This study provides promising data to further develop enteroids to study drug metabolism in vitro and potentially predict oral absorption for special populations as an alternative to using fresh tissue.

Impact of <i>Tritrichomonas</i> spp. on the immune system of Muc2<sup>–/–</sup> mice after antibiotic therapy

While pathogenic protists inhabiting the reproductive tract are well studied, the gastrointestinal (GI) tract contains a constitutive protist microbiota that is an integral part of the vertebrate microbiome. Currently, the effect of protozoan infections on the host immune system and their potential contribution to disruption of mucosal immune homeostasis are not well understood. Protists, along with bacteria and viruses, are permanent representatives of the human microbiota. The main attention of researchers is focused on studying their pathogenic role in gastrointestinal diseases. However, their role in symbiotic relationships with hosts is relatively little studied. It was previously shown that the closest human ortholog of mouse Trichomonas (Tritrichomonas spp.) is Trichomonas Dientamoeba fragilis, which can cause symptoms of inflammatory bowel disease. It is currently unclear whether Dientamoeba fragilis and other protist species such as Enteromonas spp., Entamoeba dispar are commensals, pathobionts, or pathogens of the human intestinal tract. Thus, information about the mutualistic relationships between protists, the gastrointestinal microbiota, and the immune system of mice can be used to understand host-protozoan relationships in humans. The data obtained allow us to evaluate the potential contribution of commensal protozoa in the formation of protective mechanisms of the mucous membrane of animals and humans. We have previously shown that antibiotic therapy leads to an increase in the number of Tritrichomonas spp. along with a reduction in bacteria in the gut of mice with a mutation in the Muc2 gene. A mutation in this gene leads to impaired formation of the intestinal mucosa in mice. Mice with a mutation in the Muc2 gene can be used as model to study human inflammatory bowel diseases (IBDs). In this work, we conducted a comparative study of the immunological status of Muc2–/– mice harboring Tritrichomonas spp. after antibiotic therapy for 2 weeks followed by gavage of Lactobacillus johnsonii into mice and mice without introduction of probiotic microorganisms (self-recovery). Analysis of the main populations of lymphocytes in the blood, spleen and lymph nodes showed that the introduction of Lactobacillus johnsonii after antibiotic therapy leads to a significant increase in the population of T-lymphocytes in the blood and spleen, and an increase in the number of helper T cells in the lymph nodes of Muc2–/– mice compared to mice without the addition of probiotic microorganisms.

Fecal IgE Analyses Reveal a Role for Stratifying Peanut-Allergic Patients.

Peanut allergy (PA) is an IgE-mediated food allergy with variable clinical outcomes. Mild-to-severe symptoms affect various organs and, often, the gastrointestinal tract. The role of intestine-derived IgE antibodies in astrointestinal PA symptoms is poorly understood. This study aimed to examine fecal IgE responses in PA as a novel approach to patient endotyping. Feces and serum samples were collected from peanut-allergic and healthy children (n=26) to identify IgE and cytokines using multiplex assays. Shotgun metagenomics DNA sequencing and allergen database comparisons made it possible to identify microbial peptides with homology to known allergens. Compared to controls, fecal IgE signatures showed broad diversity and increased levels for 13 allergens, including food, venom, contact, and respiratory allergens (P<.01-.0001). Overall, fecal IgE patterns were negatively correlated compared to sera IgE patterns in PA patients, with the greatest differences recorded for peanut allergens (P<.0001). For 83% of the allergens recognized by fecal IgE, we found bacterial homologs from PA patients' gut microbiome (eg, thaumatin-like protein Acinetobacter baumannii vs Act d 2, 109/124 aa identical). Compared to controls, PA patients had higher levels of fecal IgA, IL-22, and auto-IgE binding to their own fecal proteins (P<.001). Finally, levels of fecal IgE correlated with abdominal pain scores (P<.0001), suggesting a link between local IgE production and clinical outcomes. Fecal IgE release from the intestinal mucosa could be an underlying mechanism of severe abdominal pain through the association between leaky gut epithelia and anticommensal TH2 responses in PA.

Review of Process and Extraction Effects on the Bioavailability of Anthocyanins in Grapes

Grapes are widely consumed worldwide in various forms, including fresh and dried, or processed into products like juice, vinegar, wine, and so on. Anthocyanins, mainly found in grapes, are responsible for various health-promoting effects and contribute to their colours such as red, purple, and blue. Although grapes contain a high quantity of anthocyanins, their bioavailability is considered limited. Anthocyanins may be absorbed by the gastrointestinal wall, undergo intensive first-pass metabolism, and emerge as metabolites in systemic circulation. A significant percentage of some anthocyanins can enter the large intestine and undergo breakdown induced by digestive system microorganisms. Several factors, such as pH, temperature, light, and solvents, can affect anthocyanin bioavailability, and processing grapes into products may impact their bioavailability. Considering the high market share of grapes and grape products, it is important to understand the effects of processing on anthocyanin bioavailability. This review discusses changes in the bioavailability of anthocyanins found in grapes and grape products during food processing, the effect of extraction conditions on bioavailability, as well as the health-promoting effects of grapes and grape products.

Polystyrene nanoplastics-induced intestinal barrier disruption via inflammation and apoptosis in zebrafish larvae (Danio Rerio)

Plastics are one of the most pervasive materials on Earth, to which humans are exposed daily. Polystyrene (PS) is a common plastic packaging material. However, the impact of PS on human health remains poorly understood. Therefore, this study aimed to identify intestinal damage induced by PS nanoplastics (PS-NPs) in zebrafish larvae which have a high homology with humans. Four days post fertilization (dpf), zebrafish larvae were exposed to 0-, 10-, and 50-ppm PS-NPs for 48 h Initially, to ascertain if 100 nm PS-NPs could accumulate in the gastrointestinal (GI) tract of zebrafish larvae, the larvae were exposed to red fluorescence-labeled PS-NPs, and at 6 dpf, the larvae were examined using a fluorescence microscope. Analysis of the fluorescence intensity revealed that the GI tract of larvae exposed to 50-ppm exhibited a significantly stronger fluorescence intensity than the other groups. Nonfluorescent PS-NPs were then used in further studies. Scanning electron microscopy (SEM) confirmed the spherical shape of the PS-NPs. Fourier-transform infrared spectroscopy (FT-IR) analysis revealed chemical alterations in the PS-NPs before and after exposure to larvae. The polydispersity index (PDI) value derived using a Zetasizer indicated a stable dispersion of PS-NPs in egg water. Whole-mount apoptotic signal analysis via TUNEL assay showed increased apoptosis in zebrafish larval intestines exposed to 50-ppm PS-NPs. Damage to the intestinal tissue was assessed by Alcian blue (AB) and hematoxylin and eosin (H&E) staining. AB staining revealed increased mucin levels in the zebrafish larval intestines. Thin larval intestinal walls with a decrease in the density of intestinal epithelial cells were revealed by H&E staining. The differentially expressed genes (DEGs) induced by PS-NPs were identified and analyzed. In conclusion, exposure to PS-NPs may damage the intestinal barrier of zebrafish larvae due to increased intestinal permeability, and the in vivo gene network may change in larvae exposed to PS-NPs.

Mechanisms of enteric neuropathy in diverse contexts of gastrointestinal dysfunction.

The enteric nervous system (ENS) commands moment-to-moment gut functions through integrative neurocircuitry housed in the gut wall. The functional continuity of ENS networks is disrupted in enteric neuropathies and contributes to major disturbances in normal gut activities including abnormal gut motility, secretions, pain, immune dysregulation, and disrupted signaling along the gut-brain axis. The conditions under which enteric neuropathy occurs are diverse and the mechanistic underpinnings are incompletely understood. The purpose of this brief review is to summarize the current understanding of the cell types involved, the conditions in which neuropathy occurs, and the mechanisms implicated in enteric neuropathy such as oxidative stress, toll like receptor signaling, purines, and pre-programmed cell death.

Effects of sand substrate removal on the intestinal antioxidant and metabolism in Marsupenaeus japonicus

M. japonicus is an important specie for factory farming, and factory farming requires an environment with sand at the bottom of the pond. However, the physiological responses as well as survival in the process of factory farming without laying sand are currently unknown. In the present study, we explored the effect of sand substrate removal on the intestinal histomorphology, antioxidant enzyme activity, and metabolic profile of M. japonicus. Our results indicate a gradual increase in the mortality rate of kuruma shrimp in ponds lacking sand substrate. The intestinal mucosa exhibited necrosis and the presence of vacuoles, with their number gradually increasing over time. The intestinal villi showed significant erosion, accompanied by a decrease in intestinal superoxide dismutase (SOD) activity and catalase (CAT) activity, and consistent with an upregulation in the expression of apoptosis-related genes such as caspase-3, indicating an adaptive response to the adverse environmental conditions. Additionally, the metabolomic analysis revealed that most significantly differential metabolites were linked to amino acid and lipid metabolism. These findings enhance our understanding of the sand substrate removal on the intestinal health of kuruma shrimp, which provides a basis for the factory farming.

Evaluation of Salvia officinalis in the Treatment of Acetic Acid-induced Ulcerative Colitis in a Rat Model

Abstract Introduction Ulcerative colitis (UC) is an inflammatory bowel disease that causes long-lasting inflammation and ulcers within the digestive tract. This study aims to determine the histochemical alteration of Salvia officinalis (sage), an anti-inflammatory and antioxidant herbal agent on UC. Materials and Methods The disease was induced in 37 Sprague-Dawley rats with 2 mL of 3% acetic-acid (AA) enema. The rats were divided into five groups: a control group (AA), two 5-aminosalicylic (5-ASA) groups treated either orally (AO) or rectally (AR) with a dose of 100 mg/kg, and two salvia groups treated with 300mg/kg salvia orally (SO) or rectally (SR). Histopathological analyses of the colon were done on day 7, and markers such as C-reactive protein (CRP), superoxide dismutase (SOD), and complete blood count were measured. Result In macroscopic evaluation, the AO group demonstrated the lowest involvement, followed by the SO, SR, AR, and AA groups, respectively (p = 0.01). There was no significant difference between the SO and AO groups (p = 0.10), and the SR and AR groups (p = 0.58). Regarding microscopic histopathological findings, the AO and SO group demonstrated the most satisfactory results, with no significant difference between the AO versus SO, and AR versus SR groups. Inflammation was resolved in all of the AO and SO subjects. Conclusion Salvia can be beneficial in the treatment course of UC by inhibiting inflammatory responses, increasing the growth and viability of intestinal mucosa, and its antioxidant effects. Therefore, we propose the prescription of salvia as an adds-on or alternative therapy in the management of UC.

Lactobacillus rhamnosus GG and Tannic Acid Synergistically Promote the Gut Barrier Integrity in a Rat Model of Experimental Diarrhea via Selective Immunomodulatory Cytokine Targeting.

Diarrhea is a common health issue that contributes to a significant annual death rate among children and the elderly worldwide. The anti-diarrheal activity of Lactobacillus rhamnosus GG (LGG) and tannic acid (TA), alone or combined, is examined, in addition to their effect on intestinal barrier integrity. Fifty-six adult male Wistar rats are randomly assigned into seven groups: control, LGG alone, TA alone, diarrhea model, diarrhea+LGG, diarrhea+TA, and diarrhea+LGG+TA-treated groups. Diarrhea is induced by high-lactose diet (HLD) consumption. LGG (1x109 CFU/rat) and TA (100 mg Kg-1 d-1) were given orally 4 days after HLD feeding and continued for 10 days. Ileum specimens are processed for biochemical analysis of the local intestinal cytokines, polymerase chain reaction (PCR), and histological study. Also, immunohistochemistry-based identification of Proliferating Cell Nuclear Antigen (PCNA) and zonula occludens 1 (ZO-1) is performed. Compared to the diarrhea model group, both treatments maintain the intestinal mucosal structure and proliferative activity and preserve ZO-1 expression, with the combination group showing the maximal effect. However, LGG-treated diarrheic rats show a remarkable decrease in the intestinal tissue concentrations of tumor necrosis factor-alpha (TNF-α) and nuclear factor Kappa beta (NF-κB); meanwhile, TA treatment leads to a selective decrease of interferon-gamma (INF-γ) and transforming growth factor-beta (TGF-β1). Individual LGG and TA treatments significantly alleviate diarrhea, probably through a selective immunomodulatory cytokine-dependent mechanism, while the combination of both synergistically maintains the intestinal mucosa by keeping the intestinal epithelial barrier function and regenerative capability.

Gone but not forgotten: expanding the spectrum of ORISE (submucosal lifting agent) associated diagnostic pitfalls and complications

AimsA synthetic lifting agent, ORISE, used for endoscopic mucosal resections, has been recalled from the market since November 2022 due to clinical complications. Despite this, the impact of ORISE-associated complications...

Investigation of copper-induced intestinal damage and proteome alterations in Takifugu rubripes: Potential health risks and environmental toxicology detection

Copper is one of the predominant water pollutants. Excessive exposure to copper can cause harm to animal health, affecting the central nervous system and causing blood abnormalities. Cuproptosis is a novel form of cell death that differs from previous programmed cell death methods. However, the impact of copper on the intestines remains unclear. Therefore, we investigated the effects of different concentrations of copper exposure on the intestinal proteome of Takifugu rubripes (T. rubripes). Relevant biomarkers were used to detect cuproptosis. We revealed the crosstalk relationship between cuproptosis and self-rescue at different concentrations, and discussed the feasibility of using potential cuproptosis indicators as anti-infection factors. We observed intestinal damage in the three copper exposure groups, especially in T. rubripes treated with 100 and 500 μg/L copper, with shedding and breakage of intestinal villus and fuzzy and loose structure of intestinal mucosa. The presence of copper stress not only causes cuproptosis but also oxidative damage caused by reactive oxygen species (ROS). The results of quantitative proteomics by TMT showed that compared to the 50 and 100 μg/L copper exposure groups, the expression of glutaminase, pyruvate kinase, and skin mucus lectin in the 500 μg/L group was significantly increased. The positive mediators COX5A and CTNNB1, as well as the negative mediators CD4 and FDXR, were found to be differentially expressed. Using the protein expression trends of cuproptosis indicator factors FDX1 and DLAT to indicate the concentration of copper ions in the environment. In addition, we found a new effect of promoting ferroptosis: providing additional copper ions can activate the phenomenon of ferroptosis. Our results expand our understanding of the potential health risks of copper in T. rubripes. At the same time, it is of great significance for the process of copper poisoning and the development of new environmental toxicology detection reagents.

Dietary Citrus Flavonoids Improved Growth Performance and Intestinal Microbiota of Weaned Piglets via Immune Function Mediated by TLR2/NF-κB Signaling Pathway.

This study investigated the effects of citrus flavonoids (CF) and compared to antibiotics on piglet growth and gut health. Weaned piglets were fed either a basal diet (CON) or a basal diet supplemented with 75 mg/kg chlortetracycline (CTC), 20 mg/kg CF (CF1), 40 mg/kg CF (CF2), or 80 mg/kg CF (CF3). The CF group, especially CF3, exhibited improved growth performance; reduced diarrhea; significantly higher levels of serum growth factors, immunoglobulins, and anti-inflammatory cytokines; and significantly lower levels of pro-inflammatory factors and markers of intestinal barrier damage (P < 0.05). The intestinal mucosa proteins ZO-1 and occludin increased, while NF-κB and TLR2 decreased, correlating with CF dosage (P < 0.05). Furthermore, CF promoted a favorable balance in the gut microbiota, with an increased relative abundance of Bacteroidetes and Prevotella and decreased taxa Tenericutes and Clostridiales. Overall, CF enhanced piglet growth and gut health by modulating the TLR2/NF-κB pathway, offering a natural antibiotic alternative. The optimal dose of CF was 80 mg/kg.

Protective effect and mechanism of Xiaoyu Xiezhuo decoction on ischemia–reperfusion induced acute kidney injury based on gut–kidney crosstalk

This study aimed to explore the mechanism of Xiaoyu Xiezhuo decoction (XXD) on ischemia–reperfusion-induced acute kidney injury (IRI-AKI) using network pharmacology methods and gut microbiota analysis. A total of 1778 AKI-related targets were obtained, including 140 targets possibly regulated by AKI in XXD, indicating that the core targets were mainly enriched in inflammatory-related pathways, such as the IL-17 signaling pathway and TNF signaling pathway. The unilateral IRI-AKI animal model was established and randomly divided into four groups: the sham group, the AKI group, the sham + XXD group, and the AKI + XXD group. Compared with the rats in the AKI group, XXD improved not only renal function, urinary enzymes, and biomarkers of renal damage such as Kim-1, cystatin C, and serum inflammatory factors such as IL-17, TNF-α, IL-6, and IL 1-β, but also intestinal metabolites including lipopolysaccharides, d-lactic acid, indoxyl sulfate, p-cresyl sulfate, and short-chain fatty acids. XXD ameliorated renal and colonic pathological injury as well as inflammation and chemokine gene abundance, such as IL-17, TNF-α, IL-6, IL-1β, ICAM-1, and MCP-1, in AKI rats via the TLR4/NF-κB/NLRP3 pathway, reducing the AKI score, renal pathological damage, and improving the intestinal mucosa’s inflammatory infiltration. It also repaired markers of the mucosal barrier, including claudin-1, occludin, and ZO-1. Compared with the rats in the AKI group, the α diversity was significantly increased, and the Chao1 index was significantly enhanced after XXD treatment in both the sham group and the AKI group. The treatment group significantly reversed this change in microbiota.

A Comprehensive Multidisciplinary Approach to Diagnosing Chronic Inflammatory Bowel Diseases: Integration of Clinical, Endoscopic, and Imaging Modalities.

Chronic inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, present diagnostic challenges due to their complex and heterogeneous nature. While histology remains fundamental for accurate diagnosis, a multidisciplinary approach incorporating clinical, endoscopic, and imaging modalities is increasingly recognized as essential for comprehensive evaluation. This article delves into the importance of integrating various diagnostic techniques in the assessment of IBD. Colonoscopy and histology, with its ability to directly visualize the intestinal mucosa, play a central role in the diagnostic process. However, histological analysis alone may not suffice, necessitating the inclusion of advanced imaging techniques, such as magnetic resonance enterography (MRE), computed tomography enterography (CTE), and intestinal ultrasound (IUS). These techniques provide valuable insights into the disease's extent, severity, and complications, and should be used in conjunction with biochemical parameters. These modalities complement traditional endoscopic and histological findings, offering a more holistic understanding of the disease process. A multidisciplinary approach that incorporates clinical, endoscopic, histological, serological, and imaging assessments enables clinicians to achieve a more accurate and timely diagnosis of IBD. Moreover, this integrated approach facilitates personalized treatment strategies tailored to individual patient needs, ultimately improving clinical outcomes and quality of life for those affected by chronic inflammatory bowel diseases.

Unlocking the potential of microfold cells for enhanced permeation of nanocarriers in oral drug delivery

The therapeutic effects of orally administered nanocarriers depend on their ability to effectively permeate the intestinal mucosa, which is one of the major challenges in oral drug delivery. Microfold cells are specialized enterocytes in the intestinal epithelium known for their high transcytosis abilities. This study aimed to compare and evaluate two targeting approaches using surface modifications of polymer-based nanocarriers, whereas one generally addresses enterocytes, and one is directed explicitly to microfold cells via targeting the sialyl LewisA motif on their surface. We characterized the resulting carriers in terms of size and charge, supplemented by scanning electron microscopy to confirm their structural properties. For predictive biological testing and to assess the intended targeting effect, we implemented two human intestinal in vitro models containing microfold-like cells. Both models were thoroughly characterized prior to permeation studies with the different nanocarriers. Our results demonstrated improved transport for both targeted formulations compared to undecorated carriers in the in vitro models. Notably, there was an enhanced uptake in the presence of microfold-like cells, particularly for the nanocarriers directed by the anti-sialyl LewisA antibody. These findings highlight the potential of microfold cell targeting to improve oral administration of drugs and emphasize the importance of using suitable and well-characterized in vitro models for testing novel drug delivery strategies.