Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection.

Nociceptive pain is a hallmark of many chronic inflammatory conditions including inflammatory bowel diseases (IBDs); however, whether pain-sensing neurons influence intestinal inflammation remains poorly defined. Employing chemogenetic silencing, adenoviral-mediated colon-specific silencing, and pharmacological ablation of TRPV1+ nociceptors, we observed more severe inflammation and defective tissue-protective reparative processes in a murine model of intestinal damage and inflammation. Disrupted nociception led to significant alterations in the intestinal microbiota and a transmissible dysbiosis, while mono-colonization of germ-free mice with Gram+Clostridium spp. promoted intestinal tissue protection through a nociceptor-dependent pathway. Mechanistically, disruption of nociception resulted in decreased levels of substance P, and therapeutic delivery of substance P promoted tissue-protective effects exerted by TRPV1+ nociceptors in a microbiota-dependent manner. Finally, dysregulated nociceptor gene expression was observed in intestinal biopsies from IBD patients. Collectively, these findings indicate an evolutionarily conserved functional link between nociception, the intestinal microbiota, and the restoration of intestinal homeostasis.

Carrageenan oligosaccharide alleviates intestinal damage via gut microflora through activating IMD/relish pathway in female Drosophila melanogaster.

Recent evidence suggests the anti-inflammatory effect of carrageenan oligosaccharides (COS). The effects of COS on intestinal injury induced by 0.6% sodium dodecyl sulfate (SDS) and the molecular mechanisms involved were investigated in this study. 0.625, 1.25, and 2.5 mg/mL COS in diet had no toxic effect in flies, and they could all prolong SDS-treated female flies' survival rate. 1.25 mg/mL COS prevented the development of inflammation by improving the intestinal barrier integrity and maintaining the intestinal morphology stability, inhibited the proliferation of intestine stem cells (ISCs), and the production of lysosomes induced by SDS, accompanied by a decrease in the expression of autophagy-related genes. Moreover, COS decreased the active oxygen species (ROS) content in gut and increased the antioxidant activity in SDS-induced female flies, while COS still played a role in increasing survival rate and decreasing intestinal leakage in CncC-RNAi flies. The improvement of anti-inflammation capacity may be associated with the regulation of intestinal microflora with COS supplementation for Drosophila melanogaster. COS changed the gut microbiota composition, and COS had no effect on germ-free (GF) flies. It is highlighted that COS could not work in Relish-RNAi flies, indicating relish is required for COS to perform beneficial effects. These results provide insights into the study of gut microbiota interacting with COS to modulate intestinal inflammation in specific hosts.

Dietary α-Ketoglutarate Alleviates Escherichia coli LPS-Induced Intestinal Barrier Injury by Modulating the Endoplasmic Reticulum-Mitochondrial System Pathway in Piglets.

BACKGROUND: α-Ketoglutarate (AKG) plays a pivotal role in mitigating inflammation and enhancing intestinal health. OBJECTIVES: This study aimed to investigate whether AKG could protect against lipopolysaccharide (LPS)-induced intestinal injury by alleviating disorders in mitochondria-associated endoplasmic reticulum (MAM) membranes, dysfunctional mitochondrial dynamics, and endoplasmic reticulum (ER) stress in a piglet model. METHODS: Twenty-four piglets were subjected to a 2 × 2 factorial design with dietary factors (basal diet or 1% AKG diet) and LPS treatment (LPS or saline). After 21 d of consuming either the basal diet or AKG diet, piglets received injections of LPS or saline. The experiment was divided into 4 treatment groups [control (CON) group: basal diet + saline; LPS group: basal diet +LPS; AKG group: AKG diet + saline; and AKG_LPS group: AKG + LPS], each consisting of 6 piglets. RESULTS: The results demonstrated that compared with the CON group, AKG enhanced jejunal morphology, antioxidant capacity, and the messenger RNA and protein expression of tight junction proteins. Moreover, it has shown a reduction in serum diamine oxidase activity and D-lactic acid content in piglets. In addition, fewer disorders in the ER-mitochondrial system were reflected by AKG, as evidenced by AKG regulating the expression of key molecules of mitochondrial dynamics (mitochondrial calcium uniporter, optic atrophy 1, fission 1, and dynamin-related protein 1), ER stress [activating transcription factor (ATF) 4, ATF 6, CCAAT/enhancer binding protein homologous protein, eukaryotic initiation factor 2α, glucose-regulated protein (GRP) 78, and protein kinase R-like ER kinase], and MAM membranes [mitofusin (Mfn)-1, Mfn-2, GRP 75, and voltage-dependent anion channel-1]. CONCLUSIONS: Dietary AKG can prevent mitochondrial dynamic dysfunction, ER stress, and MAM membrane disorder, ultimately alleviating LPS-induced intestinal damage in piglets.

Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway.

Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.

Environmentally Relevant Concentrations of Microplastic Exposure Cause Cholestasis and Bile Acid Metabolism Dysregulation through a Gut-Liver Loop in Mice.

The massive production of plastics causes the ubiquitous existence of microplastics (MPs) in the biota, therefore, posing exposure risks and potential health concerns to human beings. However, the exact mechanisms of MPs-induced toxicities and abnormalities are largely unknown. In this study, we developed a mouse model of gavage polystyrene microplastics (PS MPs) for 30 days. We found that PS MPs can damage the intestinal barrier, accumulate in the liver tissue, and cause injury. The liver and intestine are both highly associated with bile acid (BA) metabolism. Indeed, we found that PS MPs dysregulate BA synthesis and efflux-related gene expression in the liver, causing cholestasis. Tandemly, PS MPs alter the ratio of primary to secondary BA in the feces by affecting the composition of the intestinal flora. At last, PS MPs alter mice's fecal BA profile, which affects normal BA metabolism. Taken together, the present study provides robust data on the mechanism of toxicity of MPs causing the disturbance of BA metabolism via a 4-step gut-liver loop.

Neutrophil extracellular trap formation and its implications in nonsteroidal anti-inflammatory drug-induced small intestinal injury.

BACKGROUND AND AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs) damage the small intestine via neutrophil infiltration driven by the mucosal invasion of enterobacteria. The antimicrobial function of neutrophils is partially dependent on neutrophil extracellular traps (NETs). Excessive NET formation has been associated with several inflammatory diseases. Here, we aimed to investigate the role of NETs in NSAID-induced small intestinal damage using human samples and an experimental mouse model. METHODS: Human small intestine specimens were obtained from NSAID users during double-balloon enteroscopy. Wild-type, protein arginine deiminase 4 (PAD4) knockout, and antibiotic-treated mice were administered indomethacin to induce small intestinal injury. The expression of NET-associated proteins, including PAD4, citrullinated histone H3 (CitH3), cell-free DNA, and myeloperoxidase (MPO), was evaluated. RESULTS: The double-positive stained area with CitH3 and MPO, which is specific for neutrophil-derived extracellular traps, was significantly high in the injured small intestinal mucosa of NSAID users. In a mouse model, small intestinal damage developed at 6 h after indomethacin administration, accompanied by increased mRNA levels of interleukin-1ß and keratinocyte chemoattractant and elevated NET-associated protein levels of PAD4, CitH3, and MPO in small intestine and serum levels of cell-free DNA. Both genetic deletion and pharmacological inhibition of PAD4 attenuated this damage by reducing the mRNA expression of inflammatory cytokines and NET-associated proteins. Furthermore, mice pretreated with antibiotics showed resistance to indomethacin-induced small intestinal damage, with less NET formation. CONCLUSION: These results suggest that NETs aggravate NSAID-induced small intestinal injury. Therefore, NET inhibition could be a potential treatment for NSAID-induced small intestinal injury.

Epigallocatechin gallate alleviated the in vivo toxicity of ZnO nanoparticles to mouse intestine.

To evaluate the oral toxicity of nanoparticles (NPs), it is necessary to consider the interactions between NPs and nutrient molecules. Recently, we reported that epigallocatechin gallate (EGCG), a healthy component in green tea, alleviated the toxicity of ZnO NPs to 3D Caco-2 spheroids in vitro. The present study investigated the combined effects of EGCG and ZnO NPs to mice in vivo. Mice were administrated with 35 or 105 mg/kg bodyweight ZnO NPs with or without the presence of 80 mg/kg bodyweight EGCG via gastric route, once a day, for 21 days, and the influences of EGCG on the toxicity of ZnO NPs to intestine were investigated. We found that EGCG altered the colloidal properties of ZnO NPs both in water and artificial intestine juice. As expected, ZnO NPs induced toxicological effects, such as decreased bodyweight, higher Chiu's scores, and ultrastructural changes in intestine, whereas EGCG alleviated these effects. Combined exposure to EGCG and ZnO NPs also changed trace element levels in mouse intestine. For example, the levels of Ti, Co, and Ni were only significantly elevated after co-exposure to EGCG and ZnO NPs, and Fe levels were only significantly decreased by ZnO NPs. Western blot analysis suggested that tight junction (TJ) and endoplasmic reticulum (ER) proteins were elevated by ZnO NPs, but EGCG inhibited this trend. Combined, these data suggested that gastric exposure to ZnO NPs induced intestinal damage, trace element imbalance, and TJ/ER protein expression in mouse intestine, whereas EGCG alleviated these effects of ZnO NPs.

The crosstalk between gut barrier impairment, mitochondrial dysfunction, and microbiota alterations in people living with HIV.

Functional and structural damage of the intestinal mucosal barrier significantly contribute to translocation of gut microbial products into the bloodstream and are largely involved in HIV-1 associated chronic immune activation. This microbial translocation is largely due to a progressive exhaustion of intestinal macrophage phagocytic function, which leads to extracellular accumulation of microbial derived components and results in HIV-1 disease progression. This study aims to better understand whether the modulation of gut microbiota promotes an intestinal immune restoration in people living with HIV (PLWH). Long-term virologically suppressed PLWH underwent blood, colonic, and fecal sampling before (T0) and after 6 months (T6) of oral bacteriotherapy. Age- and gender-matched uninfected controls (UC) were also included. 16S rRNA gene sequencing was applied to all participants' fecal microbiota. Apoptosis machinery, mitochondria, and apical junctional complex (AJC) morphology and physiological functions were analyzed in gut biopsies. At T0, PLWH showed a different pattern of gut microbial flora composition, lower levels of occludin (p = 0.002) and zonulin (p = 0.01), higher claudin-2 levels (p = 0.002), a reduction of mitochondria number (p = 0.002), and diameter (p = 0.002), as well as increased levels of lipopolysaccharide (LPS) (p = 0.018) and cCK18 (p = 0.011), compared to UC. At T6, an increase in size (p = 0.005) and number (p = 0.008) of mitochondria, as well as amelioration in AJC structures (p < 0.0001) were observed. Restoration of bacterial richness (Simpson index) and biodiversity (Shannon index) was observed in all PLWH receiving oral bacteriotherapy (p < 0.05). Increased mitochondria size (p = 0.005) and number (p = 0.008) and amelioration of AJC structure (p < 0.0001) were found at T6 compared to T0. Moreover, increased occludin and zonulin concentration were observed in PLWH intestinal tracts and decreased levels of claudin-2, LPS, and cCK18 were found after oral bacteriotherapy (T0 vs. T6, p < 0.05 for all these measures). Oral bacteriotherapy supplementation might restore the balance of intestinal flora and support the structural and functional recovery of the gut mucosa in antiretroviral therapy treated PLWH.

Understanding the Connection between Gut Homeostasis and Psychological Stress.

Long-term exposure to adverse life events that provoke acute or chronic psychological stress (hereinafter "stress") can negatively affect physical health and even increase susceptibility to psychological illnesses, such as anxiety and depression. As a part of the hypothalamic-pituitary-adrenal axis, corticotropin-releasing factor (CRF) released from the hypothalamus is primarily responsible for the stress response. Typically, CRF disrupts the gastrointestinal system and leads to gut microbiota dysbiosis, thereby increasing risk of functional gastrointestinal diseases, such as irritable bowel syndrome. Furthermore, CRF increases oxidative damage to the colon and triggers immune responses involving mast cells, neutrophils, and monocytes. CRF even affects the differentiation of intestinal stem cells (ISCs), causing enterochromaffin cells to secrete excessive amounts of 5-hydroxytryptamine (5-HT). Therefore, stress is often accompanied by damage to the intestinal epithelial barrier function, followed by increased intestinal permeability and bacterial translocation. There are multi-network interactions between the gut microbiota and stress, and gut microbiota may relieve the effects of stress on the body. Dietary intake of probiotics can provide energy for ISCs through glycolysis, thereby alleviating the disruption to homeostasis caused by stress, and it significantly bolsters the intestinal barrier, alleviates intestinal inflammation, and maintains endocrine homeostasis. Gut microbiota also directly affect the synthesis of hormones and neurotransmitters, such as CRF, 5-HT, dopamine, and norepinephrine. Moreover, the Mediterranean diet enhances the stress resistance to some extent by regulating the intestinal flora. This article reviews recent research on how stress damages the gut and microbiota, how the gut microbiota can improve gut health by modulating injury due to stress, and how the diet relieves stress injury by interfering with intestinal microflora. This review gives insight into the potential role of the gut and its microbiota in relieving the effects of stress via the gut-brain axis.

Lafutidine Ameliorates Indomethacin-Induced Small Intestinal Damage in Rats by Modifying the Intestinal Mucosal Barrier, Inflammation, and Microbiota.

INTRODUCTION: Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage is a serious and escalating clinical problem without effective treatment. Lafutidine (LAF) is a novel histamine H2 receptor antagonist with a mucosal protective action. This study aimed to investigate the protective effect of LAF on indomethacin (IND)-induced enteropathy in rats. METHODS: Rats were treated with LAF for 10 days with concomitant IND treatment on the final 5 days. Changes in metabolism and hematological and biochemical parameters were measured, and intestinal damage was blindly scored. Intestinal mucosal tissue and luminal contents were collected for transcriptome and microbiota sequencing. Intestinal inflammation and barrier function were also evaluated. RESULTS: LAF treatment prevented anorexia and weight loss in rats and ameliorated reductions in hemoglobin, hematocrit, total protein, and albumin levels. LAF reduced the severity of IND-induced intestinal damage including macroscopic and histopathological damage score. Transcriptome sequencing results indicated that LAF might have positive effects on intestinal inflammation and the intestinal mucosal barrier. Further research revealed that LAF decreased neutrophil infiltration, and IL-1ß and TNF-α expression in intestinal tissue. Besides, the treatment increased mucus secretion, MUC2, Occludin, and ZO-1 expression, and decreased serum D-lactate levels. LAF treatment also ameliorates microbial dysbiosis in small intestine induced by IND and increased the abundance of Lactobacillus acidophilus. CONCLUSION: LAF may protect against NSAID enteropathy via enhancing the intestinal mucosal barrier, inhibiting inflammation, and regulating microbiota.

Calcium-sensing receptor protects intestinal integrity and alleviates the inflammatory response via the Rac1/PLCγ1 signaling pathway.

This study aimed to test the hypothesis that the calcium-sensing receptor (CaSR) can protect intestinal epithelial barrier integrity and decrease inflammatory response mediated by the Ras-related C3 botulinum toxin substrate 1 (Rac1)/phospholipase Cγ1 (PLC-γ1) signaling pathway. IPEC-J2 monolayers were treated without or with TNF-α in the absence or presence of CaSR antagonist (NPS 2143), CaSR overexpression, and Rac1 silencing, PLCγ1 silencing or spermine. Results showed that spermine increased transepithelial electrical resistance (TER), tight junction protein levels, the protein concentration of Rac1/PLC-γ1 signaling pathway, and decreased paracellular permeability in the presence of TNF-α. NPS2143 inhibited spermine-induced change in above-mentioned parameters. CaSR overexpression increased TER, the levels of tight junction proteins and the protein concentration of CaSR, phosphorylated PLCγ1, Rac1, and IP3, and decreased paracellular permeability and contents of interleukin-8 (IL-8) and TNF-α after TNF-α challenge. Rac1 and PLCγ1 silencing inhibited CaSR-induced increase in barrier function and the protein concentration of phosphorylated PLCγ1, Rac1, and IP3, and decrease in contents of IL-8 and TNF-α after TNF-α challenge. These results suggest that CaSR activation protects intestinal integrity and alleviates the inflammatory response by activating Rac1 and PLCγ1 signaling after TNF-α challenge, and spermine can maintain barrier function via CaSR/Rac1/PLC-γ1 pathway.

Characterization of Early and Late Damage in a Mouse Model of Pelvic Radiation Disease.

Pelvic radiation disease (PRD), a frequent side effect in patients with abdominal/pelvic cancers treated with radiotherapy, remains an unmet medical need. Currently available preclinical models have limited applications for the investigation of PRD pathogenesis and possible therapeutic strategies. In order to select the most effective irradiation protocol for PRD induction in mice, we evaluated the efficacy of three different locally and fractionated X-ray exposures. Using the selected protocol (10 Gy/day × 4 days), we assessed PRD through tissue (number and length of colon crypts) and molecular (expression of genes involved in oxidative stress, cell damage, inflammation, and stem cell markers) analyses at short (3 h or 3 days after X-ray) and long (38 days after X-rays) post-irradiation times. The results show that a primary damage response in term of apoptosis, inflammation, and surrogate markers of oxidative stress was found, thus determining a consequent impairment of cell crypts differentiation and proliferation as well as a local inflammation and a bacterial translocation to mesenteric lymph nodes after several weeks post-irradiation. Changes were also found in microbiota composition, particularly in the relative abundance of dominant phyla, related families, and in alpha diversity indices, as an indication of dysbiotic conditions induced by irradiation. Fecal markers of intestinal inflammation, measured during the experimental timeline, identified lactoferrin, along with elastase, as useful non-invasive tools to monitor disease progression. Thus, our preclinical model may be useful to develop new therapeutic strategies for PRD treatment.

Chitosan nanoparticles attenuate intestinal damage and inflammatory responses in LPS-challenged weaned piglets via prevention of IκB degradation.

Chitosan nanoparticles (CNP), widely applied as oral drug/gene/vaccine carrier, were found to have anti-inflammatory properties. In this study, the effects of CNP on lipopolysaccharide (LPS)-induced intestinal damage in weaned piglets and the related mechanisms were investigated. Twenty-four weaned piglets (Duroc × Landrace × Yorkshire, 21 ± 2 day of age, initial mass: 8.58 ± 0.59 kg) were randomly assigned into four groups: control, LPS, CNP and CNP + LPS. The control and LPS groups were fed a corn-soybean meal-based control diet, whereas the CNP and CNP + LPS groups were fed a control diet supplemented with 400 mg/kg CNP. After 28 days of feeding, piglets in LPS and CNP + LPS groups were injected with LPS (100 µg/kg); meanwhile, the piglets in control and CNP groups were injected with sterile saline. After 4 h from the LPS challenge, pigs were sacrificed to collect the intestinal samples for analysis. The results showed that CNP could attenuate the intestinal damages and inflammatory response stimulated by LPS treatment. LPS induced dramatically higher levels of CD177+ neutrophils invasion in jejunum mucosa (p < 0.01), which accompanied by increased secretion of marks of inflammation (p < 0.01) compared with the control, whereas CNP administration obviously inhibited LPS-induced CD177+ neutrophils invasion (p < 0.01) and secretion of marks of inflammation, such as interleukin-8 (p < 0.05), intercellular adhesion molecule-1 (p < 0.05) secretion in jejunum mucosa compared with LPS group. Moreover, CNP was shown to inhibit IκB-α degradation in cytoplasm, which resulted in reduced nuclear translocation of NF-κB p65 in LPS-challenged piglets. These findings suggest that CNP attenuates intestinal damage and inflammatory responses in LPS-challenged weaned piglets by impairing the NF-κB signalling pathway.

Synergistic synbiotic containing fructooligosaccharides and Lactobacillus delbrueckii CIDCA 133 alleviates chemotherapy-induced intestinal mucositis in mice.

Intestinal mucositis is a commonly reported side effect in oncology patients undergoing chemotherapy and radiotherapy. Probiotics, prebiotics, and synbiotics have been investigated as alternative therapeutic approaches against intestinal mucositis due to their well-known anti-inflammatory properties and health benefits to the host. Previous studies showed that the potential probiotic Lactobacillus delbrueckii CIDCA 133 and the prebiotic Fructooligosaccharides (FOS) alleviated the 5-Fluorouracil (5-FU) chemotherapy-induced intestinal mucosa damage. Based on these previous beneficial effects, this work evaluated the anti-inflammatory property of the synbiotic formulation containing L. delbrueckii CIDCA 133 and FOS in mice intestinal mucosa inflammation induced by 5-FU. This work showed that the synbiotic formulation was able to modulate inflammatory parameters, including reduction of cellular inflammatory infiltration, gene expression downregulation of Tlr2, Nfkb1, and Tnf, and upregulation of the immunoregulatory Il10 cytokine, thus protecting the intestinal mucosa from epithelial damage caused by the 5-FU. The synbiotic also improved the epithelial barrier function by upregulating mRNA transcript levels of the short chain fatty acid (SCFA)-associated GPR43 receptor and the occludin tight junction protein, with the subsequent reduction of paracellular intestinal permeability. The data obtained showed that this synbiotic formulation could be a promising adjuvant treatment to be explored against inflammatory damage caused by 5-FU chemotherapy.

Bacillus thuringiensis toxins with nematocidal activity against the pinewood nematode Bursaphelenchus xylophilus.

The pine wilt disease is caused by the pinewood nematode Bursaphelenchus xylophilus and it results in serious ecological and economic losses. Therefore, effective prevention and control methods for the pinewood nematode are urgently required. Bacillus thuringiensis (Bt), a widely used microbial insecticide, produces toxins that are toxic to several species of parasitic nematodes, however, its effects on B. xylophilus have not been determined. In this study, Cry5Ba3, App6Aa2, Cry12Aa1, Cry13Aa1, Cry14Aa1, Cry21Aa3, Cry21Fa1, Xpp55Aa1, and Cyt8Aa1 toxins' nematocidal activity against B. xylophilus was evaluated, six toxins with high toxicity were identified: App6Aa2 (LC50 = 49.71 µg/mL), Cry13Aa1 (LC50 = 53.17 µg/mL), Cry12Aa1 (LC50 = 58.88 µg/mL), Cry5Ba3 (LC50 = 63.99 µg/mL), Xpp55Aa1 (LC50 = 65.14 µg/mL), and Cyt8Aa1 (LC50 = 96.50 µg/mL). The six toxins caused shrinkage and thinning of the intestinal cells, contraction of the intestine from the body wall, vacuolization, and degenerated appearance of the pinewood nematodes. The results of this study provide basic information to study the action mechanism of nematocidal toxins on the pinewood nematode and direction for the use of nematocidal toxins in the biological control of B. xylophilus.

Potential role of gut microbiota and its metabolites in radiation-induced intestinal damage.

Radiation-induced intestinal damage (RIID) is a serious disease with limited effective treatment. Nuclear explosion, nuclear release, nuclear application and especially radiation therapy are all highly likely to cause radioactive intestinal damage. The intestinal microecology is an organic whole with a symbiotic relationship formed by the interaction between a relatively stable microbial community living in the intestinal tract and the host. Imbalance and disorders of intestinal microecology are related to the occurrence and development of multiple systemic diseases, especially intestinal diseases. Increasing evidence indicates that the gut microbiota and its metabolites play an important role in the pathogenesis and prevention of RIID. Radiation leads to gut microbiota imbalance, including a decrease in the number of beneficial bacteria and an increase in the number of harmful bacteria that cause RIID. In this review, we describe the pathological mechanisms of RIID, the changes in intestinal microbiota, the metabolites induced by radiation, and their mechanism in RIID. Finally, the mechanisms of various methods for regulating the microbiota in the treatment of RIID are summarized.

Effects of Avenanthramide on the Small Intestinal Damage through Hsp70-NF-κB Signaling in an Ovalbumin-Induced Food Allergy Model.

A food allergy is caused by an abnormal immune reaction and can induce serious intestinal inflammation and tissue damage. Currently, the avoidance of food allergens is still the most effective way to prevent or reduce allergic symptoms, so the development of new strategies to treat allergies is important. Avenanthramide (AVA) is a bioactive polyphenol derived from oats with a wide range of biological activities; however, it is still not clear whether or how AVA alleviates intestinal damage under allergic situations. The aim of this study was to explore the effect of AVA on the small intestinal damage in an ovalbumin (OVA)-induced food allergy model and its mechanism. In experiment 1, 10 mg/kg bw and 20 mg/kg bw doses of AVA both decreased the serum levels of OVA-specific IgE, histamine, and prostaglandin D induced by OVA. The AVA administration relieved inflammation indicated by the lower serum concentrations of pro-inflammatory cytokines including interleukin-1ß, IL-6, and tumor necrosis factor-α. The levels of tight junction proteins including Claudin-1, ZO-1, and Occludin in the jejunum were elevated after AVA administration, accompanied by the improved intestinal morphology. Furthermore, AVA elevated the protein expression of heat shock protein 70 (Hsp70) and inhibited the phosphorylation of nuclear factor kappa-B (NF-κB), thus the apoptozole, which a Hsp70 inhibitor, was applied in experiment 2 to assess the contribution of Hsp70-NF-κB signaling to the effects of AVA. In the experiment 2, the inhibition of Hsp70 signaling treatment abolished the beneficial effects of AVA on the small intestinal damage and other allergic symptoms in mice challenged with OVA. Taken together, our results indicated that AVA exerted an intestinal protection role in the OVA-induced allergy, the mechanism of which was partly mediated by the Hsp70-NF-κB signaling.

Effects of Dietary Glycinin on Oxidative Damage, Apoptosis and Tight Junction in the Intestine of Juvenile Hybrid Yellow Catfish, Pelteobagrus fulvidraco ♀ × Pelteobaggrus vachelli ♂.

The objective of this study was to examine the influences of glycinin for growth and intestinal structural integrity related to oxidative damage, apoptosis and tight junction of juvenile hybrid yellow catfish (Pelteobagrus fulvidraco ♀ × Pelteobaggrus vachelli ♂). Fish (initial weight, 1.02 ± 0.01 g) were fed diets containing five different levels of glycinin at 0%, 2%, 4%, 6%, and 8% for 8 weeks. The results demonstrated that dietary glycinin levels had a negative correlation with final weight, feed intake, protein efficiency ratio and survival rate of the experiment fish. When the level of dietary glycinin exceeded 4%, the structural integrity of the posterior intestine was observably impaired, characterized by disordered and exfoliated margin of intestinal villi, blurred and broken boundaries of tight junctions, damaged organelles and cell vacuolation. Levels of 4-8% dietary glycinin depressed the total antioxidant capacity and total superoxide dismutase activities of posterior intestine. Furthermore, a high level of dietary glycinin linearly and quadratically down-regulated the mRNA expressions of Claudin-1, Occludin and ZO-1, while it linearly and significantly up-regulated the mRNA expressions of Bax, Cyt C, Caspase 3, Caspase 9 and p53 in the posterior intestine. In conclusion, dietary 4-8% glycinin impaired the morphological structure of the posterior intestine by inducing oxidative stress and cell apoptosis, and eventually impeded the growth performance of juvenile hybrid yellow catfish.

Gastrointestinal Dysfunction and HIV Comorbidities.

PURPOSE OF REVIEW: Gut dysfunction and resulting chronic low-grade inflammation have been linked to metabolic and chronic diseases in the general population. In this review, we present recently published studies of HIV-associated gut dysfunction and comorbidities including obesity, diabetes, cardiovascular disease, liver disease, and neurocognitive disease. RECENT FINDINGS: Biomarkers of microbial translocation, dysbiosis, or intestinal epithelial integrity have been used to investigate relationships between HIV-associated gut dysfunction and metabolic, cardiovascular, and neurologic complications. Many studies point to worsened comorbidities associated with gut dysfunction in people with HIV (PWH), but some studies show mixed results, and thus, the data are still inconclusive and limited to surrogate biomarkers rather than direct intestinal assessments. Inflammation and immune activation stemming from changes in intestinal epithelial integrity and dysbiosis are present in PWH and relate to metabolic, cardiovascular, and neurologic complications of HIV. However, future investigations, especially future studies that directly assess intestinal pathology, are needed to investigate the direct contributory role of gastrointestinal dysfunction to comorbidities of HIV.

Cell death induction (extrinsic versus intrinsic apoptotic pathway) by intestinal ischemia-reperfusion injury in rats is time-depended.

PURPOSE: We investigate the mechanism of intestinal cell apoptosis and its relation to the time of reperfusion in a rat model of intestinal ischemia-reperfusion (IR). METHODS: Rats were divided into 4 groups: Sham-24 and Sham-48 rats underwent laparotomy without an intentional ischemic intervention and were sacrificed 24 or 48 h hours later; IR-24 and IR-48 rats underwent occlusion of SMA and portal vein for 20 min followed by 24 or 48 h of reperfusion, respectively. Park's injury score, cell proliferation and apoptosis were determined at sacrifice. Proliferation and apoptosis-related gene and protein expression were determined using Real-Time PCR, Western Blot and Immunohistochemistry. RESULTS: IR-24 rats demonstrated a strong increase in cell apoptosis along with an elevated Bax and decreased Bcl-2 expression and a decrease in cell proliferation (vs Sham-24). IR-48 group showed an increase in cell proliferation and a decrease in cell apoptosis compared to IR-24 animals. IR-48 rats demonstrated an increase in apoptotic rate that was accompanied by greater TNF-α mRNA, Fas mRNA and FasL mRNA compared to Sham-48 animals. CONCLUSION: While cell apoptosis in IR-24 rats is regulated mainly by intrinsic apoptotic pathway, 48 h followed ischemia extrinsic apoptotic pathway is responsible for pro-apoptotic effects of IR injury.