Intestinal Injury Research Articles

Single-cell transcriptomics predict novel potential regulators of acute epithelial restitution in the ischemia-injured intestine.

Intestinal ischemic injury damages the epithelial barrier predisposes patients to life-threatening sepsis unless that barrier is rapidly restored. There is an age-dependency of intestinal recovery in that neonates are the most susceptible to succumb to disease of the intestinal barrier versus older patients. We have developed a pig model that demonstrates age-dependent failure of intestinal barrier restitution in neonatal pigs which can be rescued by the direct application of juvenile pig mucosal tissue, but the mechanisms of rescue remain undefined. We hypothesized that by identifying a subpopulation of restituting enterocytes by their expression of cell migration transcriptional pathways, we can then predict novel upstream regulators of age-dependent restitution response programs. Superficial mucosal epithelial cells from recovering ischemic jejunum of juvenile pigs underwent single cell transcriptomics and predicted upstream regulator CSF-1 was interrogated in our model. A subcluster of absorptive enterocytes expressed several cell migration pathways key to restitution. Differentially expressed genes in this subcluster predicted their upstream regulation by colony stimulating factor-1 (CSF-1). We validated age-dependent induction of CSF-1 by ischemia and documented that CSF-1 and CSF1R co-localized in ischemic juvenile, but not neonatal, wound-adjacent epithelial cells and in the restituted epithelium of juveniles and rescued neonates. Further, the CSF-1 blockade reduced restitution in vitro, and CSF-1 improved barrier function in injured neonatal pig in preliminary ex vivo experiments. These studies validate an approach to inform potential novel therapeutic targets, such as CSF-1, to improve outcomes in neonates with intestinal injury in a unique pig model.

Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria.

We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl-1) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts. Hemolysis of infected red blood cells and impaired renal excretion of uric acid were the primary drivers of hyperuricemia in SM. Hyperuricemia was associated with multiple complications of SM, including acute kidney injury, acidosis, impaired perfusion, coma and intestinal injury with increases in the abundance of Gram-negative uricase-producing pathobionts (Escherichia and Shigella) in the stool. Clinical trials evaluating uric acid-lowering medications as adjunctive therapy for children with SM should be considered to improve survival and protect neurodevelopment.

Inflammation-Induced Th17 Cells Synergize with the Inflammation-Trained Microbiota to Mediate Host Resiliency Against Intestinal Injury.

Inflammation can generate pathogenic Th17 cells and cause an inflammatory dysbiosis. In the context of inflammatory bowel disease (IBD), these inflammatory Th17 cells and dysbiotic microbiota may perpetuate injury to intestinal epithelial cells. However, many models of IBD like T-cell transfer colitis and IL-10-/- mice rely on the absence of regulatory pathways, so it is difficult to tell if inflammation can also induce protective Th17 cells. We subjected C57BL6, RAG1-/-, or JH-/- mice to systemic or gastrointestinal (GI) Citrobacter rodentium (Cr). Mice were then subjected to 2.5% dextran sodium sulfate (DSS) to cause epithelial injury. Fecal microbiota transfer was performed by bedding transfer and co-housing. Flow cytometry, qPCR, and histology were used to assess mucosal and systemic immune responses, cytokines, and tissue inflammation. 16s sequencing was used to assess gut bacterial taxonomy. Transient inflammation with GI but not systemic Cr was protective against subsequent intestinal injury. This was replicated with sequential DSS collectively indicating that transient inflammation provides tissue-specific protection. Inflammatory Th17 cells that have a tissue-resident memory (TRM) signature expanded in the intestine. Experiments with reconstituted RAG1-/-, JH-/- mice, and cell trafficking inhibitors showed that inflammation-induced Th17 cells were required for protection. Fecal microbiota transfer showed that the inflammation-trained microbiota was necessary for protection, likely by maintaining protective Th17 cells in situ. Inflammation can generate protective Th17 cells that synergize with the inflammation-trained microbiota to provide host resiliency against subsequent injury, indicating that inflammation-induced Th17 TRM T cells are heterogenous and contain protective subsets.

Tetrahedral Framework Nucleic Acid Relieves Sepsis-Induced Intestinal Injury by Regulating M2 Macrophages.

This study aimed to clarify the role and mechanism of tetrahedral framework nucleic acids (tFNAs) in regulating M2 macrophages to reduce intestinal injury. An intestinal injury model was established by intraperitoneal injection of lipopolysaccharides (LPS) in mice to explore the alleviating effects of tFNAs on intestinal injury. Inflammatory factors were detected by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). The intestinal barrier and permeability were assessed using western blotting and immunohistochemistry. Macrophages in the gut were localised and quantified using immunofluorescence. Western blotting was used to investigate the role and mechanism of tFNAs in regulating macrophages and alleviating inflammation in the injured intestines. These results show that tFNAs attenuated sepsis-induced intestinal injury. tFNAs can also promote the intestinal barrier reconstruction and reduce intestinal permeability. Invivo, tFNAs accelerated the aggregation of M2 macrophages at an early stage of injury and reduced the number of M1 macrophages in the intestine. In addition, tFNAs enhanced the clearance ability of intestinal macrophages. They activated the signalling and transcription activating factor 1(STAT1) and cytokine signalling inhibitory factor 1/3 (SOCS1/3) pathways by increasing the expression of the phagocytic receptor Mertk. These findings indicated that tFNAs can alleviate sepsis-induced intestinal injury by regulating M2 macrophages, providing a new option for treating intestinal injury.

Geraniol modulates inflammatory and antioxidant pathways to mitigate intestinal ischemia-reperfusion injury in male rats.

Intestinal ischemia-reperfusion injury (IIR/I) significantly increases morbidity and mortality. This study examines the therapeutic effects of geraniol (GNL), which is noted for its anti-inflammatory and antioxidant properties, on intestinal I/R injury in rats. Forty-nine male Wistar-Albino rats were divided into seven groups. After 30min of ischemia and subsequent reperfusion for either 1 or 6h, intestinal and hepatic tissues were analyzed. Biochemical assessments measured malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), and nitric oxide (NO) activities. Inflammatory and apoptotic markers were evaluated using qRT-PCR and ELISA, and apoptotic cell rates were determined by flow cytometry. GNL treatment significantly protected intestinal and hepatic tissues, enhancing antioxidant enzyme activity and normalizing MDA and NO activities. It demonstrated notable anti-inflammatory effects at 100 and 200mg/kg doses, reducing TNF-α, IL-1β, and IL-6 levels while decreasing tissue MPO content. GNL also increased Bcl-2 levels and decreased Bax levels, indicating anti-apoptotic effects. Serum activities of ALT, AST, and creatine kinase were lower in GNL-treated rats, and flow cytometry showed a reduction in apoptotic cells. GNL effectively mitigated oxidative stress and histopathological damage from intestinal I/R injury by reducing pro-apoptotic markers and increasing anti-apoptotic markers, highlighting its protective effects.

Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition.

Sepsis is a severe systemic inflammatory syndrome characterized by a dysregulated immune response to infection, often leading to high mortality rates. The intestine, owing to its distinct structure and physiological environment, plays a pivotal role in the pathophysiology of sepsis. It functions as the "central organ" or "engine" in the progression of sepsis, with intestinal injury exacerbating the condition. Despite the availability of current therapies that offer partial symptom relief, they fall short of adequately protecting the intestinal barrier. In this study, an advanced nanodrug formulation (OLA@MΦ NPs) is developed by coating macrophage membranes onto polymeric organic nanoparticles encapsulating olaparib. When loaded into pH-responsive capsules, an intestine-decipher engineered capsule (cp-OLA@MΦ NPs) is successfully formulated. Upon oral administration in septic mice, these capsules withstand gastric acid and release their contents in the intestine, specifically targeting injured tissues. The released OLA@MΦ NPs effectively neutralize pro-inflammatory cytokines via macrophage membrane receptors, while olaparib inhibits intestinal epithelial parthanatos (a form of programmed cell death) by suppressing poly(ADP-ribose) polymerase 1 (PARP1) activation. This strategy significantly reduces bacterial translocation, slows the progression of sepsis, and enhances survival in septic mice, thus presenting a promising therapeutic approach for sepsis in clinical applications.

Adipose-derived stem cells promote the recovery of intestinal barrier function by inhibiting the p38 MAPK signaling pathway.

Intestinal barrier damage causes an imbalance in the intestinal flora and microbial environment, promoting a variety of gastrointestinal diseases. This study aimed to explore the mechanism by which adipose-derived stem cells (ADSCs) repair intestinal barrier damage. The human colon adenocarcinoma cell line Caco-2 and rats were treated with lipopolysaccharide (LPS) to establish in vitro and in vivo models, respectively, of intestinal barrier damage. The expression of inflammatory cytokines (TNF-α, HMGB1, IL-1β and IL-6), antioxidant enzymes (iNOS, SOD and CAT), and oxidative products (MDA and 8-iso-PGF2α) was detected using ELISA kits and related reagent kits. Apoptosis-related proteins (Bcl-2, Bax, Caspase-3 and Caspase-9), tight junction proteins (ZO-1, Occludin, E-cadherin, and Claudin-1) and p38 MAPK pathway-associated protein were detected by Western blotting. In addition, cell viability and apoptosis was determined by a CCK-8 kit and flow cytometry, respectively. Cell permeability was assayed by the transepithelial electrical resistance value and FITC-dextran concentration. The homing effect of ADSCs was detected by fluorescence labeling, and intestinal barrier tissue was observed by HE staining. After ADSC treatment, the level of phosphorylated p38 MAPK protein decreased, the expression of inflammatory factors, oxidative stress and cell apoptosis decreased, the expression of tight junction proteins increased, and cell permeability decreased in Caco-2 cells stimulated with LPS. In rats, ADSCs are directionally recruited to damaged intestinal tissue. ADSCs significantly decreased the levels of D-lactate, diamine oxidase (DAO) and FITC-dextran induced by LPS. ADSCs promoted tight junction proteins and inhibited oxidative stress in intestinal tissue. These effects were reversed after the use of a p38 MAPK activator. ADSCs can be directionally recruited to intestinal tissue, upregulate tight junction proteins, and reduce apoptosis and oxidative stress by inhibiting the p38MAPK signaling pathway. This study provides novel insights into the treatment of intestinal injury.

A retrospective Study on Intestinal Injury from Blunt Abdominal Trauma

Introduction: Blunt abdominal trauma is the primary cause of morbidity and mortality. Suppose there are no indications of external trauma or changes in the patient's vital signs; blunt abdominal injuries might be complicated to identify at first. It is possible to lose a significant amount of blood without the abdomen appearing significantly different. A direct blow from blunt trauma can result in visceral damage and solid organ rupture, which can cause hemorrhage, peritonitis, and related pelvic injuries. The liver, small bowel, and spleen are the most frequently injured organs. Objectives: To find out the etiology, manifestation, anatomical distribution, diagnostic method, management, and outcome of intestinal injuries from blunt abdominal trauma. Material and Methods: About 59 individuals who had laparotomies during a 3-year period to treat intestine damage from traumatic abdominal trauma were included in the research. In a retrospective analysis, the patients' causes, presentations, anatomical distributions, diagnostic techniques, related injuries, courses of therapy, and deaths were all examined. Results: About 59 individuals with 60 significant bowel and mesentery lesions from blunt abdominal trauma were conducted. The average age was 36.78 years, and the male-to-female ratio was 5.5: 1. About 60 people sustained severe injuries. Furthermore, there were 50 minor intestinal injuries, which included 48 perforations, 12 major seromuscular injuries, and seven mesenteric, eleven colonic, and one duodenal injury. Thirty-three individuals suffered injuries from automobile incidents. The most frequent damage was a perforation at the small bowel's antimesenteric boundary. For colonic perforations, treatment included protective colostomy after resection, anastomosis, and perforation repair. There were 2 (3.38%) documented fatalities, and 10 (16.9%) individuals experienced significant problems. Conclusion: Due to its enormous infectious potential, early detection of intestinal injuries following severe abdominal trauma is crucial, even if it might be challenging. Severe injuries are frequently linked to intestinal perforations and are likely the deciding factors in survival.

Inflammatory biomarkers and therapeutic potential of milk exosome-mediated CCL7 siRNA in murine intestinal ischemia-reperfusion injury

Inflammatory biomarkers and therapeutic potential of milk exosome-mediated CCL7 siRNA in murine intestinal ischemia-reperfusion injury

GSDMB modulates intestinal epithelial homeostasis via regulating hyperactive unfolded protein response in Crohn's disease.

Impaired intestinal epithelial barrier has been considered to be associated with an increasing variety of gastrointestinal diseases, especially inflammatory bowel disease (IBD) encompassing Crohn's disease (CD) and ulcerative colitis (UC). We aimed to investigate the role of Gasdermin B (GSDMB) in modulating intestinal epithelial barrier integrity and proposed a promising therapeutic strategy. GSDMB expression was evaluated in adult CD samples by molecular biology means and single-cell transcriptomes. We generated GSDMB (Rosa26-lsl/lsl-GSDMB;Villin-Cre) and one of its functional missense variant rs2305480 (Rosa26-lsl/lsl-GSDMB-MU;Villin-Cre) intestinal epithelial-specific knock in mice to observe the functions of GSDMB in intestinal epithelial barrier. RNA-seq analysis as well as human and murine intestine-derived organoids were used to determine the pathogenic mechanism of GSDMB. The expression of GSDMB was increased during active intestinal inflammation and principally localized in intestinal epithelial cells (IECs). Rosa26-lsl/lsl-GSDMB;Villin-Cre mice developed enterocolitis and exhibited aberrant intestinal barrier integrity. Mechanistically, epithelial GSDMB modulated hyperactive unfolded protein response of IECs by up-regulating BHLHA15 to mediate intestinal barrier injury. Rosa26-lsl/lsl-GSDMB-MU;Villin-Cre mice with the mutant rs2305480 of GSDMB aggravated such inflammatory effects. We have uncovered an important and a previously unrecognized role of GSDMB in intestinal homeostasis, which represents a potential therapeutic target for intestinal inflammation.

Betulinic acid mitigates lipopolysaccharide-induced intestinal injury of weaned piglets through modulation of the mitochondrial quality control.

Intestinal injury of weaned piglets often leads to reduced immunity, diarrhea and growth retardation, resulting in significant economic losses to agriculture. Betulinic acid (BA) is a natural plant-derived active ingredient with multiple pharmacological activities including immune modulation and anti-inflammatory. This study was aimed to investigate the potential mechanism that BA as a feed additive mitigated lipopolysaccharide (LPS)-induced intestinal injury in piglets. The results indicated that BA pretreatment improved the morphology and structure of the intestine, enhanced intestinal mucosal barrier function, and activated the PPAR signaling pathway to reduce the mRNA levels of intestinal CD40 and CXCL13. Meanwhile, BA pretreatment improved the LPS-induced disruption of intestinal microbiota by increasing the abundance of the Firmicutes and decreasing the abundance of the Bacteroidota and Proteobacteria. Furthermore, BA pretreatment activated the AMPK/SIRT1/PGC-1α signaling pathway to enhance mitochondrial biogenesis, restored a balance to mitochondrial dynamics, and modulated the PINK1/Parkin, BNIP3 and FUNDC1 signaling pathways to activate mitophagy, thereby alleviating LPS-induced intestinal injury. Overall, the present study elucidated that dietary supplementation with BA could alleviate LPS-induced intestinal injury in weaned piglets by regulating mitochondrial quality control, which provided a novel approach for alleviating intestinal stress in weaned piglets.

Cardiovascular protective effects of natural flavonoids on intestinal barrier injury.

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.

Reduced Glutathione Promoted Growth Performance by Improving the Jejunal Barrier, Antioxidant Function, and Altering Proteomics of Weaned Piglets.

Reduced glutathione (GSH) is a main nonenzymatic antioxidant, but its effects and underlying mechanisms on growth and intestinal health in weaned piglets still require further assessment. A total of 180 weaned piglets were randomly allotted to 5 groups: a basal diet (CON), and a basal diet supplemented with antibiotic chlortetracycline (ABX), 50 (GSH1), 65 (GSH2), or 100 mg/kg GSH (GSH3). Results revealed that dietary GSH1, GSH2, and ABX improved body weight and the average daily gain of weaned piglets, and ABX decreased albumin content but increased aspartate aminotransferase (AST) activity and the ratio of AST to alanine transaminase levels in plasma. GSH2 significantly decreased glucose content but increased the content of triglyceride and cholesterol in the plasma. Both GSH1 and GSH2 improved the jejunal mucosa architecture (villus height, crypt depth, and the ratio of villus height to crypt depth), tight junction protein (ZO-1 and Occludin), and antioxidant capacity (CAT and MDA), and the effects were superior to ABX. Dietary GSH improved the jejunal barrier by probably inhibiting the myosin light chain kinas pathway to up-regulate the transcript expression of tight junction protein (ZO-1 and Occludin) and Mucins. Through the proteomics analysis of the jejunal mucosa using 4D-DIA, the KEGG pathway enrichment analysis showed that differentiated proteins were significantly enriched in redox homeostasis-related pathways such as glutathione metabolism, cytochrome P450, the reactive oxygen species metabolic pathway, the oxidative phosphorylation pathway, and the phosphatidylinositol 3-kinase-serine/threonine kinase pathway in GSH2 vs. CON and in GSH2 vs. ABX. The results of proteomics and qRT-PCR showed that GSH supplementation might dose-dependently promote growth performance and that it alleviated the weaning stress-induced oxidative injury of the jejunal mucosa in piglets by activating SIRTI and Akt pathways to regulate GPX4, HSP70, FoxO1. Therefore, diets supplemented with 50-65 mg/kg GSH can promote the growth of and relieve intestinal oxidative injury in weaned piglets.

Rhamnogalacturonan promotes intestinal mucosal repair through increased cell migration.

Mucosal healing is the primary goal for Inflammatory Bowel Diseases (IBD) treatment. We previously showed the direct beneficial effects of rhamnogalacturonan (RGal) on intestinal epithelial barrier function. Here, we aimed to evaluate the effect of RGal in intestinal epithelial wound healing. Confluent cancer cell lines and colonoid monolayers were wounded, treated with RGal for 48 h and assessed using a live cell imaging system. Proliferation and apoptosis of cells were evaluated using EdU and TUNEL assays, respectively. Antagonists and inhibitors were used to determine the receptor and signaling pathways involved. Female and male mice with DSS-induced colitis were treated orally with RGal for 7 days during the recovery phase. RGal enhanced wound healing in Caco-2, T84 and primary cells by increasing cell migration. Inhibition of pre-transcriptional signaling pathways FAK, Src, PI3K, Rho family, and JNK reversed the RGal-induced wound healing. RNAseq data from Caco-2 and primary cells treated with RGal showed the upregulation of NF-κB pathway at 12 h. Actinomycin D, Bay 11-7082 or JSH-23, and NS-398 treatment significantly reversed the effect of RGal on wound healing, confirming that the response was also transcriptionally dependent and involved NF-κB signaling and downstream COX-2 protein activity. RGal treatment of male mice enhanced recovery from DSS colitis. RGal promoted wound healing in cancer and primary cells by increasing cell migration and accelerated epithelial mucosal healing in male mice. Our findings show a novel mechanism of action of RGal in wound healing that could help in mucosal healing and the resolution of intestinal inflammation.

Glyphosate-Based Herbicide Stress During Pregnancy Impairs Intestinal Development in Newborn Piglets by Modifying DNA Methylation.

Glyphosate-based herbicide (GBH), a feed contaminant, has been proven to impair the growth and development of humans and animals. Previous research has revealed that maternal toxin exposure during pregnancy could cause permanent fetal changes by epigenetic modulation. However, there was insufficient evidence of the involvement of DNA methylation in maternal GBH exposure-induced intestinal health of offspring. Here, we established pregnant sow exposure models to investigate the effects of GBH on the intestinal DNA methylation of newborn piglets. The results showed gestational exposure to GBH compromises the intestinal function of newborn piglets as well as decreases the mRNA expression of Dnmt1 and Dnmt3b jejunum. Further RRBS DNA methylation analysis revealed genomic hypomethylation in jejunum, and the differentially methylated regions were enriched in the pathways of intestinal development and food digestion and the related GO terms. Additionally, integrative analysis of methylome and transcriptome identified 23 genes showing inverse correlations and indicated the underlying injury mechanisms upon maternal GBH. These findings provide new insights and fundamental knowledge into the possible involvement of DNA methylation in the intestinal injury of offspring induced by maternal GBH exposure during pregnancy, which drives manufacturers to develop low-toxicity herbicide to ensure food safety and human health.

Exploring the Link Between Mucin 2 and Weaning Stress-Related Diarrhoea in Piglets.

To explore the relationship between intestinal mucin 2 (MUC2) and weaning-induced diarrhoea in piglets, we analysed Min and Landrace piglets. The piglets were divided into a healthy weaned group, a weaned diarrhoea group, and a healthy unweaned control group. Intestinal tissues were collected, and goblet cell numbers, sizes, and degrees of intestinal injury were observed and recorded. Intestinal tissue MUC2 mRNA and protein expression were analysed via quantitative real-time PCR (qRT-PCR) and Western blotting. Min pigs presented significantly lower diarrhoea rates and intestinal injury scores than Landrace pigs (p < 0.01). The intestinal injury scores in the weaned diarrhoea group were significantly greater than those in the unweaned groups (p < 0.05), with Min pigs consistently exhibiting lower injury scores than Landrace pigs. Specifically, unweaned Min pigs presented significantly greater duodenal MUC2 mRNA (p < 0.05), and weaned healthy Min pigs presented notably greater expression in both the duodenum and jejunum (p < 0.01). These findings reveal enhanced intestinal protection against weaning stress and diarrhoea in Min pigs, with elevated MUC2 levels likely contributing to lower injury scores and milder symptoms, thus highlighting the influence of genetic differences.

NVP-AUY922 relieves radiation-induced intestinal injury via regulating EPHX1.

As a common side effect of radiotherapy, radiation-induced intestinal injury (RIII) greatly affects the prognosis of patients and the efficacy of radiotherapy. Current therapeutic strategies for RIII are still very limited. Thus, the identification of effective radioprotective agents is of great importance. NVP-AUY922 is an HSP90 inhibitor with favorable anti-inflammatory and antioxidant activities. It has been proven to mitigate radiation-induced lung injury. However, its effects on the alleviation of RIII remain unclear. In this study, our data indicated that NVP-AUY922 remarkably increased the survival rate after radiation exposure. NVP-AUY922 treatment could enhance the viability of intestinal stem cells (ISCs) and promote the recovery of the small intestine. In addition, it also inhibited intestinal inflammation and reshaped the gut microbiota structure. We found that the radioprotective effect of NVP-AUY922 is partially dependent on EPHX1. In addition, NVP-AUY922 could attenuate dextran sulfate sodium (DSS)-induced colitis and promote intestinal barrier recovery. Thus, our results suggest that NVP-AUY922 contributes to the amelioration of intestinal injury after radiation exposure, which offers a new approach for the prevention of RIII.

Glycyrrhiza uralensis Polysaccharide Modulates Characteristic Bacteria and Metabolites, Improving the Immune Function of Healthy Mice.

Polysaccharides from Glycyrrhiza are known to have several bioactive effects. Previous studies have found that low-molecular-weight Glycyrrhiza polysaccharide (GP1) is degraded by Muribaculum_sp_H5 and promotes the production of beneficial bacteria and metabolites, which improves immune disorder and intestinal injury, and then enhances the body's immune regulation ability. However, the immune regulation effect of GP1 on a healthy body has not been studied. In this study, we aimed to reveal the immune enhancement effect and mechanism of GP1 on healthy mice. The cytotoxicity and immunomodulatory activity of GP1 were analyzed by cell experiment; the effects of GP1 on antioxidation, immune regulation and gut microbiota structure of healthy body were studied in vivo. In addition, the mechanism of GP1 enhancing immune response of healthy body was analyzed by multi-omics. The results show that GP1 enhanced the immune function of healthy mice by increasing the index of immune organs, improving the organizational structure of immune organs, and increasing the secretion of immune cytokines and immunoglobulin. GP1 also increased the contents of antioxidant factors such as total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in various organs and reduced the content of oxide malondialdehyde (MDA), thus enhancing the body's antioxidant capacity, promoting cell proliferation and prolonging life. Moreover, GP1 promoted the proliferation of beneficial bacteria, including Muribaculaceae_unclassified, Muribaculum, Prevotellaceae_UCG-001, and Paramuribaculum, and the production of characteristic metabolites (collectively referred to as postbiotics), including α-tocopherol, arachidonic acid, melibiose, taurine, and nicotinic acid. These beneficial bacteria and postbiotics have been proven to have health maintaining functions. GP1 promoted the proliferation of beneficial bacteria and increased the production of postbiotics, which should be the mechanism of its beneficial effect. It is expected to be a promising immune dietary supplement.

Sesamin Alleviates Allergen-Induced Diarrhea by Restoring Gut Microbiota Composition and Intestinal Barrier Function.

Food allergens are the key triggers of allergic diarrhea, causing damage to the immune-rich ileum. This weakens the mucosal barrier and tight junctions, increases intestinal permeability, and exacerbates allergen exposure, thereby worsening the condition. Sesamin, a natural lignan isolated from sesame seed, has shown potential in regulating immune responses, but its effects on intestinal health remain unclear. In this study, we constructed an ovalbumin (OVA)-induced allergic diarrhea mouse model, which demonstrated increased mast cell degranulation, reduced tight junction integrity, and impaired intestinal barrier function. Pro-inflammatory cytokines were significantly increased in the ileum, along with unbalanced cluster of differentiation 4 (CD4+) T-cell immunity, altered gut microbiota composition, and disrupted bacterial metabolism. Sesamin treatment significantly alleviated intestinal damage by modulating gut microbiota abundance, enhancing short-chain fatty acid (SCFA) production, and increasing SCFA receptor expression. This study suggests that sesamin may be a promising therapeutic candidate for allergic diarrhea and intestinal injury.

The major roles of intestinal microbiota and TRAF6/NF-κB signaling pathway in acute intestinal inflammation in mice, and the improvement effect by Hippophae rhamnoides polysaccharide.

Acute enteritis, an intestinal disease with intestinal inflammation and injury as the main pathological manifestations. Inhibiting the inflammatory response is critical to the treatment of acute enteritis. Previous studies have shown that the Hippophae rhamnoides polysaccharide (HRP) has strong immune-enhancing effects. However, their functions regarding the intestines and the underlying mechanism are still unclear. In this study, the role of HRP in lipopolysaccharide (LPS)-induced acute enteritis in mice and its related mechanisms are discussed from two aspects: intestinal inflammation and intestinal microbiota. Kunming mice were inoculated with LPS to establish animal models of acute enteritis. The results showed that HRP attenuated the histological damage and maintained the intestine mucosal barrier via up-regulating the expression of occludin, claudin-1, and zona occludens-1 (ZO-1), and suppressing the levels of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)). The relative mRNA and protein levels of nuclear factor-kappa B p65 (NF-κBp65) and tumor necrosis factor-receptor-associated factor 6 (TRAF6) in the intestine tissues of LPS-induced acute enteritis mice significantly increased, whereas these adverse changes were alleviated in the HRP intervention groups. Notably, HRP may regulate the expression of the TRAF6/NF-κB signaling pathway by affecting the diversity of the intestinal microbiota. Microbiota analysis showed that HRP promoted the proliferation of beneficial bacteria, including Clostridia_UCG-014, Candidatus_Saccharimonas, Lachnospiraceae_NK4A136_group, Bacteroidota, Deferribacterota, and reduced the abundance of Atopostipes, Corynebacterium, Actinobacteriota, and Desulfobacterota. The studies conformed that the gut microbiota is crucial in HRP-mediated immunity regulation. HRP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.