Intestinal Inflammatory Response Research Articles

AhR Activation Ameliorates Intestinal Barrier Damage in Immunostressed Piglets by Regulating Intestinal Flora and Its Metabolism.

The primary factor leading to elevated rates of diarrhea and decreased performance in piglets is immunological stress. The regulation of immune stress through the intestinal flora is a crucial mechanism to consider. In total, 30 weaned piglets were randomly allocated to five groups: the basal diet group (Control), basal diet + lipopolysaccharides group (LPS), basal diet + 250 μg/kg 6-Formylindolo [3,2-b] carbazole + LPS group (FICZ), basal diet + 3mg/kg Cardamonin + LPS group (LCDN), and basal diet + 6mg/kg Cardamonin + LPS group (HCDN/CDN). The results showed that compared with those of the LPS group, the expression of tight junction proteins (occludin; claudin-1) in the FICZ group was significantly increased, and the mRNA levels of IL-1β and TNF-α were significantly reduced (p < 0.05). HCDN treatment had a better effect on LPS-induced intestinal barrier damage in this group than it did in the LCDN group. HCDN treatment leads to a higher villus height (VH), a higher ratio of villi height to crypt depth (V/C), higher tight junction proteins (ZO-1; occludin), and higher short-chain fatty acids (SCFAs). In addition, correlation analyses showed that Succinivibrio was positively correlated with several SCFAs and negatively correlated with prostaglandin-related derivatives in the FICZ group and CDN group (p < 0.05). In summary, Cardamonin alleviates intestinal mucosal barrier damage and inflammatory responses by regulating the intestinal microbiota and its metabolism.

ETS translocation variant 5 (ETV5) promotes CD4+ T cell–mediated intestinal inflammation and fibrosis in inflammatory bowel diseases

ETS translocation variant 5 (ETV5) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the exact roles of ETV5 in regulating CD4+ T cell-mediated intestinal inflammation and fibrosis formation remain unclear. Here, we reveal that ETV5 overexpression induced IL-9 and its transcription factor IRF4 expression in naïve IBD CD4+ T cells under Th9-polarizing conditions. Silencing of IRF4 inhibited ETV5-induced IL-9 expression. CD4+ T cell-specific ETV5 deletion (CKO) ameliorated intestinal inflammation and fibrosis in TNBS-induced experimental colitis and CD4+ T cell-transferred Rag1-/- colitis mice, characterized by less CD4+ T cell infiltration, lower fibroblast activation and collagen deposition in the colonic tissues. Furthermore, IL-9 treatment aggressive TNBS-induced intestinal fibrosis in CKO and wild type (WT) control mice. In vitro, human intestinal fibroblasts cocultured with ETV5 overexpressed-Th9 cells expressed higher levels of collagen I and III, whereas an inclusion of anti-IL-9 antibody could reverse this effect. RNA sequencing analysis demonstrated that IL-9 upregulated TAF1 expression in human intestinal fibroblasts. Clinic data showed that number of α-SMA+TAF1+ fibroblasts are higher in inflamed mucosa of IBD patients. Importantly, TAF1 siRNA treatment suppressed IL-9-mediated profibrotic effect in vitro. These findings reveal that CD4+ T cell-derived ETV5 promotes intestinal inflammation and fibrosis through upregulating IL-9-mediated intestinal inflammatory and fibrotic response in IBD. Thus, the ETV5/IL-9 signal pathway in T cells might represent a novel therapeutic target for intestinal inflammation and fibrosis in IBD.

Dietary bile acids inclusion improves dietary carbohydrate utilization, antioxidant capacity and intestinal microbiota and inflammation of largemouth bass (Micropterus salmoides)

The study explored the role of dietary bile acids inclusion in improving dietary carbohydrate utilization, antioxidant capacity and intestinal microbiota and inflammation of largemouth bass (Micropterus salmoides). Two isonitrogenous (50.40%) and isolipidic (12.00%) diets were formulated, containing a positive control with 5% α-starch and a negative control with 10% α-starch, respectively. The other three diets were supplemented with 200 mg, 500 mg, or 1000 mg bile acids kg−1 based on 10% α-starch diet. Different experiment diets were fed to cultured fish twice daily for 8 weeks. The results showed that the growth of cultured fish was inhibited by high carbohydrate diet and hepatic glycogen and lipid inordinate accumulation were induced. Meanwhile, high carbohydrate diet caused liver oxidative damage, but supplementation of bile acids significantly improved the antioxidant capacity. Compared with the negative control group, dietary bile acids supplementation didn't affect the growth of largemouth bass, but significantly reduced hepatic glycogen and lipid inordinate accumulation and the viscerosomatic index and hepatosomatic index. In addition, the increase of dietary carbohydrate increased liver bile acids content, and dietary bile acids inclusion could linearly increase liver bile acids content. Results showed that bile acids supplementation regulated liver bile acid synthesis and metabolism of largemouth bass through activating FXR-FGFR4-CYP7A1 pathway. Meanwhile, bile acids inclusion inhibited the expression of foxo1 and genes related to gluconeogenesis, including g6pc, fbp1 and gs, enhanced the expression of genes related to glycolysis, including pfkl and gk through activating insulin pathway. Moreover, high carbohydrate diet with bile acids supplementation also increased gut microbial diversity, and changed the relative abundance of some phyla and genera related to carbohydrate utilization and energy balance, and improved the intestinal inflammatory response. Those findings indicated that dietary bile acids inclusion improved carbohydrate utilization, antioxidant capacity and intestinal microbiota and inflammation of largemouth bass.

Exposure to nanopolystyrene and phoxim at ambient concentrations causes oxidative stress and inflammation in the intestines of the Chinese mitten crab (Eriocheir sinensis)

Nanopolystyrene (NP) and phoxim (PHO) are common environmental pollutants in aquatic systems. We evaluated the toxic effects of exposure to ambient concentrations of NP and/or PHO in the intestines of the Chinese mitten crab (Eriocheir sinensis). Our study showed that histopathological changes were observed in the intestines. Specifically, NP and/or PHO exposure increased intraepithelial lymphocytes. Furthermore, NP and/or PHO exposure induced oxidative stress, as evidenced by a significant decrease in superoxide dismutase activity (SOD), peroxidase activity (POD), and total antioxidant capacity (T-AOC). Pro-inflammatory gene expression and transcriptome analysis demonstrated that NP and/or PHO exposure induced the intestinal inflammatory response. Transcriptome results showed that NP and/or PHO exposure upregulated the NF-κB signaling pathway, which is considered a key pathway in the inflammatory response. Additionally, the expression of pro-inflammatory genes significantly increased after a single exposure to NP or PHO, but it exhibited a significant decrease after the co-exposure. The downregulation of these genes in the co-exposure group likely suggested that the co-exposure mitigated intestinal inflammation response in E. sinensis. Collectively, our findings mainly showed that NP and/or PHO exposure at ambient concentrations induces oxidative stress and inflammatory response in the intestines of E. sinensis.

Effects of different concentrations and particle sizes of nanoplastics on gut microbiology, metabolism, and immunity in Chiromantes dehaani

This study investigated the effects of nanoplastics (NPs) of varying particle sizes (75, 500, and 1000 nm) and concentrations (2.5 and 10 mg/L) on the gut health of Chiromantes dehaani. The experimental groups included a control (Cg0), and varying combinations of particle size and concentration. Our results showed that 75 nm NPs were more likely to enhance pathogenic bacterial growth than other sized NPs. Compared with CK, Low NPs concentrations (2.5 mg/L) raised total cholesterol (T-CHO) levels in the gut, while high concentrations significantly decreased both triglyceride (TG) and T-CHO levels (p < 0.05). The enzymatic activities of intestinal lipase and amylase were inhibited by NPs exposure, with greater inhibition at higher NPs concentrations. The 500 nm NPs exhibited a notably higher inhibitory effect than the 75 and 1000 nm NPs (P < 0.05). In terms of apoptosis, NPs exposure led to reduced mRNA expression of Bcl2 and increased expression of Caspase-3, Caspase-8, and Caspase-9, indicating an induction of apoptosis. This effect was more pronounced at higher NPs concentrations, with 75 nm NPs more likely to induce apoptosis in intestinal cells than 500 nm and 1000 nm NPs. Moreover, NPs triggered intestinal inflammatory responses, evidenced by the increased mRNA expression of TNF-β, TNF-α, IL1β, IL6, and IL8, and the decreased expression of IL10. High NPs concentrations were more likely to induce intestinal inflammation, with 500 nm NPs imparting the strongest effect. In summary, the study demonstrated that NPs, and particularly those at higher concentrations, disrupted the gut environment of C. dehaani by altering the microflora, reducing microbial diversity, inhibiting digestion and metabolism, inducing apoptosis, and triggering inflammation. Among the sizes of NPs tested, 500 nm NPs had the most significant adverse impact on digestion, metabolism, and inflammation, while 75 nm NPs most strongly induced apoptosis in C. dehaani's intestinal cells.

All-trans retinoic acid alleviates transmissible gastroenteritis virus-induced intestinal inflammation and barrier dysfunction in weaned piglets

BackgroundTransmissible gastroenteritis virus (TGEV) is one of the main pathogens causing severe diarrhea of piglets. The pathogenesis of TGEV is closely related to intestinal inflammation. All-trans retinoic acid (ATRA) is the main active metabolite of vitamin A, which has immunomodulatory and anti-inflammatory properties. However, it is unclear whether ATRA can alleviate TGEV-induced intestinal inflammation and barrier dysfunction in piglets. This study aimed to investigate the effects of ATRA on growth performance, diarrhea, intestinal inflammation and intestinal barrier integrity of TGEV-challenged piglets.MethodsIn a 19-d study, 32 weaned piglets were randomly divided into 4 treatments: Control group (basal diet), TGEV group (basal diet + TGEV challenge), TGEV + ATRA5 group (basal diet + 5 mg/d ATRA + TGEV challenge) and TGEV + ATRA15 group (basal diet + 15 mg/d ATRA + TGEV challenge). On d 14, piglets were orally administered TGEV or the sterile medium.ResultsFeeding piglets with 5 and 15 mg/d ATRA alleviated the growth inhibition and diarrhea induced by TGEV (P < 0.05). Feeding piglets with 5 and 15 mg/d ATRA also inhibited the increase of serum diamine oxidase (DAO) activity and the decrease of occludin and claudin-1 protein levels in jejunal mucosa induced by TGEV, and maintained intestinal barrier integrity (P < 0.05). Meanwhile, 5 mg/d ATRA feeding increased the sucrase activity and the expressions of nutrient transporter related genes (GLUT2 and SLC7A1) in jejunal mucosa of TGEV-challenged piglets (P < 0.05). Furthermore, 5 mg/d ATRA feeding attenuated TGEV-induced intestinal inflammatory response by inhibiting the release of interleukin (IL)-1β, IL-8 and tumor necrosis factor-α (TNF-α), and promoting the secretion of IL-10 and secretory immunoglobulin A (sIgA) (P < 0.05). Feeding 5 mg/d ATRA also down-regulated the expressions of Toll-like receptors and RIG-I like receptors signaling pathway related genes (TLR3, TLR4, RIG-I, MyD88, TRIF and MAVS) and the phosphorylation level of nuclear factor-κB-p65 (NF-κB p65), and up-regulated the inhibitor kappa B alpha (IκBα) protein level in jejunal mucosa of TGEV-challenged piglets (P < 0.05).ConclusionsATRA alleviated TGEV-induced intestinal barrier damage by inhibiting inflammatory response, thus improving the growth performance and inhibiting diarrhea of piglets. The mechanism was associated with the inhibition of NF-κB signaling pathway mediated by TLR3, TLR4 and RIG-I.Graphical

Sodium butyrate alleviates heat stress-induced damage to morphology, anti-oxidant status, inflammatory response and barrier integrity in jejunum of broilers

To evaluate the protective effects of sodium butyrate (SB) on intestinal morphology, anti-oxidant status, inflammatory response and barrier integrity in male broilers under heat stress. A total of 180 21-d-old male Arbour Acres broilers with similar body weight were used for this 21-d experiment. Broilers were randomly allocated to three groups: CON group, basal diet and raised under 24 °C; HS group, basal diet and raised under heat stress condition (34 °C from 10:00 to 18:00 and 24 °C for the rest time); HS-SB group, basal diet with 1200 mg/kg SB and raised under heat stress condition. Compared to the HS group, SB supplementation increased average daily gain (ADG), villus height: crypt depth ratio (VH: CD), VH, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity, and interleukin-10 (IL-10) level, decreased feed conversion ratio (FCR), CD, reactive oxygen species (ROS), IL-1β and tumour necrosis factor-alpha (TNF-α) level, up-regulated the mRNA expression of nuclear factor erythroid 2-related factor 2, haem oxygenase 1, GSH 1 (GPX1), SOD and CAT, down-regulated the mRNA expression of toll-like receptor 4 (TLR4), nuclear transcription factors, IL-1β, and TNF-α in jejunum of heat-stressed broilers. Furthermore, SB supplementation up-regulated the mRNA expression of occluding, claudin-1 and zona occludens-1 (ZO-1) in jejunum of heat-stressed broilers, accompanied with decreasing serum endotoxin and D-lactic acid concentration, and diamine oxidase (DAO) activity. There results suggested that SB supplementation could alleviate heat stress-induced jejunal tight junction structure dysfunction by up-regulated the expression of occluding, claudin-1 and ZO-1, presumably through alleviating oxidative stress and inflammatory response. HIGHLIGHTS Sodium butyrate alleviated heat stress-induced jejunal morphology damage. Sodium butyrate alleviated heat stress-induced jejunal oxidative damage. Sodium butyrate alleviated heat stress-induced jejunal inflammatory response. Sodium butyrate alleviated heat stress-induced tight junction structure dysfunction.

Taurine Regulates the Expression of Interleukin -17/10 and Intestinal Flora and Protects the Liver and Intestinal Mucosa in a Nonalcoholic Fatty Liver Disease Rat Model.

To investigate the intestinal inflammatory response and the abundance of intestinal bacteria in rats with high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and assess the intervention effects of taurine (TAU). Forty male Sprague-Dawley rats were randomly divided into five groups: group I, normal diet and normal saline gavage; group II, normal diet and TAU gavage; group III, HFD and normal saline gavage; group IV, HFD and TAU gavage (from the 1st week); group V, HFD and TAU gavage (from the 10th week). At the end of the 16th week, all the animals were sacrificed. Body weight, liver weight, liver function, and serum lipid levels were measured. The histopathologies of the liver and ileum were observed. The mRNA and protein expression levels of interleukin 17 (IL-17) and IL-10 in the ileum were detected by reverse transcription quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Three types of bacteria were detected in intestinal feces using the 16S rDNA qPCR method. The ileal IL-17 level in group III was significantly higher than those in the other four groups (P < 0.01). The ileal IL-10 mRNA levels in group IV was significantly higher than those in groups III and V (P < 0.05), and IL-10 protein MOD levels in group III was significantly lower than those in the other four groups (P < 0.01). The numbers of Lactobacillus in group III were significantly lower than those in the other four groups (P < 0.01 or P < 0.05). The numbers of Bifidobacteria in groups IV and V were significantly increased compared with that in group III (P < 0.05). TAU may down-regulate the expression of IL-17, up-regulate the expression of IL-10 and regulate the intestinal flora, and alleviate the liver and intestinal damage in rats with HFD-induced NAFLD.

M6A Methylated Long Noncoding RNA LOC339803 Regulates Intestinal Inflammatory Response.

Cytokine mediated sustained inflammation increases the risk to develop different complex chronic inflammatory diseases, but the implicated mechanisms remain unclear. Increasing evidence shows that long noncoding RNAs (lncRNAs) play key roles in the pathogenesis of inflammatory disorders, while inflammation associated variants are described to affect their function or essential RNA modifications as N6-methyladenosine (m6A) methylation, increasing predisposition to inflammatory diseases. Here, the functional implication of the intestinal inflammation associated lncRNA LOC339803 in the production of cytokines by intestinal epithelial cells is described. Allele-specific m6A methylation is found to affect YTHDC1 mediated protein binding affinity. LOC339803-YTHDC1 interaction dictates chromatin localization of LOC339803 ultimately inducing the expression of NFκB mediated proinflammatory cytokines and contributing to the development of intestinal inflammation. These findings are confirmed using human intestinal biopsy samples from different intestinal inflammatory conditions and controls. Additionally, it is demonstrated that LOC339803 targeting can be a useful strategy for the amelioration of intestinal inflammation in vitro and ex vivo. Overall, the results support the importance of the methylated LOC339803 lncRNA as a mediator of intestinal inflammation, explaining genetic susceptibility and presenting this lncRNA as a potential novel therapeutic target for the treatment of inflammatory intestinal disorders.

P150 Ulcerative Colitis Patients’ Luminal Zinc Induces Clostridioides difficile Virulence and Exacerbates Inflammatory Responses

Abstract Background The refractory acute severe UC patients are often complicated by C. difficile infection (CDI), resulting in higher surgery and mortality rates. However, few studies have observed C. difficile’s pathogenicity in real UC patients’ gastrointestinal microenvironments, and the actual role of C. difficile in UC development remains unknown. We found zinc concentrations among UC patients’ feces were significantly higher than those among Crohn’s disease patients and healthy subjects. Additionally, we previously reported that excessive zinc would promote the growth and virulence of C. difficile. Therefore, we hypothesized that the increased UC patients’ luminal zinc may up-regulate C. difficile virulence and promote intestinal inflammatory responses, leading to an exacerbated UC progression. Methods UC patients’ stool samples (n=40) were collected and analyzed by qPCR and ICP-MS to determine the presence of C. difficile and the fecal zinc concentrations. C. difficile was cultured in BHIs with or without zinc (ZnSO4) in an anaerobic chamber. Expression of virulence genes was analyzed using RT-qPCR, transcriptome sequencing, and western blot. Human colonic organoids and Caco-2 cells were co-cultured with C. difficile or zinc-treated C. difficile, and cytotoxicity, permeability, and inflammatory cytokine release were assessed. TLR5 knock-out Caco-2 cells were constructed using sgRNA-guided Cas9 nuclease and co-cultured with C. difficile or zinc-treated C. difficile to verify whether zinc-induced C. difficile’s pathogenicity was mainly through flagellar formation. Results C. difficile was detected in ~35% of UC patients’ fecal samples. Luminal zinc concentrations (~915μM, p&amp;lt;0.01) were significantly higher among UC patients than CD patients or healthy subjects. The UC patients’ luminal concentration of zinc promoted C. difficile growth, suppressed its exotoxins release, and induced higher expression of its flagella-related genes, resulting in higher cytotoxicity and inflammatory responses in human colonic organoids and Caco-2 cells. However, zinc-treated C. difficile did not induce higher inflammation and pathogenicity in TLR5 knock-out Caco-2 cells. Conclusion The association between C. difficile and UC aggravation may partially stem from UC patients’ excess luminal zinc promoting C. difficile flagellin expression, inducing inflammatory responses, and worsening UC progression.

Effects of Salmonella Outer Membrane Vesicles on Intestinal Microbiota and Intestinal Barrier Function.

Salmonella enterica is one of the most important zoonotic pathogens causing foodborne gastroenteritis worldwide. Outer membrane vesicles (OMVs) are lipid-bilayer vesicles produced by Gram-negative bacteria, which contain biologically active components. We hypothesized that OMVs are an important weapon of S. enterica to initiate enteric diseases pathologies. In this study, the effects of S. enterica OMVs (SeOMVs) on intestinal microbiota and intestinal barrier function were investigated. In vitro fecal culture experiments showed that alpha diversity indexes and microbiota composition were altered by SeOMV supplementation. SeOMV supplementation showed an increase of pH, a decrease of OD630 and total short chain fatty acid (SCFA) concentrations. In vitro IPEC-J2 cells culture experiments showed that SeOMV supplementation did not affect the IPEC-J2 cell viability and the indicated genes expression. In vivo experiments in mice showed that SeOMVs had adverse effects on average daily gain (p < 0.05) and feed:gain ratio (p < 0.05), and had a tendency to decrease the final body weight (p = 0.073) in mice. SeOMV administration decreased serum interleukin-10 level (p < 0.05), decreased the relative abundance of bacteria belonging to the genera BacC-u-018 and Akkermansia (p < 0.05). Furthermore, SeOMV administration damaged the ileum mucosa (p < 0.05). These findings suggest that SeOMVs play an important role in the activation of intestinal inflammatory response induced by S. enterica, and downregulation of SCFA-producing bacteria is a possible mechanism.

Rhodiola rosea L. improved intestinal digestive enzyme activities, inflammatory response, barrier and microbiota dysbiosis in Lateolabrax maculatus juveniles fed with high-carbohydrate diets

A 56-d feeding trial was conducted to evaluate the influences of Rhodiola rosea L. on digestive enzyme activities, intestinal barrier, inflammatory response, and microbiota dysbiosis in Lateolabrax maculatus juveniles (9.37 ± 0.03 g) fed with high-carbohydrate diets. Six diets were designed: a control diet (20% corn starch, Control), high-carbohydrate diet (30% corn starch, HC1), and four high-carbohydrate diets supplemented with Rhodiola rosea L. at 30, 60, 90 and 120 mg/kg (HC2, HC3, HC4 and HC5, respectively). Compared with the control group, the HC1 diet remarkably increased α-amylase, lipase, and chymotrypsin activities in the intestine (p < 0.05), as well as the mRNA levels of Claudin-15, NF-κB, TNF-α, IL-1β, and IL-8 (p < 0.05) and the relative abundance of Proteobacteria and Photobacterium in the intestine, which belong to the phylum and genus level, respectively. But the opposite trend was found in muscular thickness and villus lengths (p < 0.05), the mRNA levels of Occludin, ZO-1, and TGF-β (p < 0.05), at the level of phylum and genus level in the HC1 group, and the relative abundance of Firmicutes, Bacteroidetes, and Bacillus in the intestine compared with the control group. Intestinal chymotrypsin activity was significantly higher in the HC3 group and intestinal muscular thickness and villus lengths were also significantly higher in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). In addition, Occludin mRNA expression in the intestine was significantly increased in the HC2, HC4, and HC5 groups compared to the HC1 group. ZO-1 and TGF-β mRNA expression in the intestine were significantly increased in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). At the phylum level, the relative abundance of Firmicutes and Bacteroidetes was higher in the intestine in the HC2, HC3, HC4, and HC5 groups than that in the HC1 group. On the contrary, intestinal lipase and chymotrypsin activities were significantly decreased in the HC2 group compared to the HC1 group, respectively (p < 0.05). The Claudin-15, NF-κB, TNF-α, IL-1β, and IL-8 mRNA expression in the intestine were significantly decreased in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). Besides, at the genus level, compared to the HC1 group, the relative abundance of Photobacterium in the intestine and the diversity of the intestinal microbiota in the HC2, HC3, HC4, and HC5 groups were all decreased. In conclusion, these results demonstrated that the addition of Rhodiola rosea L. in high-carbohydrate diets can improve intestinal digestive enzyme activities, inflammatory response and intestinal barrier-related gene expression, and microbiota dysbiosis in L. maculatus. The suitable supplemental level of Rhodiola rosea L. in high-carbohydrate diets of L. maculatus is 60 mg/kg.

Porcine Intestinal Mucosal Peptides Target Macrophage-Modulated Inflammation and Alleviate Intestinal Homeostasis in Dextrose Sodium Sulfate-Induced Colitis in Mice.

Porcine intestinal mucosal proteins are novel animal proteins that contain large amounts of free amino acids and peptides. Although porcine intestinal mucosal proteins are widely used in animal nutrition, the peptide bioactivities of their enzymatic products are not yet fully understood. In the present study, we investigated the effect of porcine intestinal mucosal peptides (PIMP) on the RAW264.7 cell model of LPS-induced inflammation. The mRNA expression of inflammatory factors (interleukin 6, tumor necrosis factor-α, and interleukin-1β) and nitrous oxide levels were all measured by quantitative real-time PCR and cyclooxygenase-2 protein expression measured by Western blot. To investigate the modulating effect of PIMP and to establish a model of dextran sodium sulfate (DSS)-induced colitis in mice, we examined the effects of hematoxylin-eosin staining, myeloperoxidase levels, pro-inflammatory factor mRNA content, tight junction protein expression, and changes in intestinal flora. Nuclear factor κB pathway protein levels were also assessed by Western blot. PIMP has been shown in vitro to control inflammatory responses and prevent the activation of key associated signaling pathways. PIMP at doses of 100 and 400 mg/kg/day also alleviated intestinal inflammatory responses, reduced tissue damage caused by DSS, and improved intestinal barrier function. In addition, PIMP at 400 mg/kg/day successfully repaired the dysregulated gut microbiota and increased short-chain fatty acid levels. These findings suggest that PIMP may positively influence inflammatory responses and alleviate colitis. This study is the first to demonstrate the potential of PIMP as a functional food for the prevention and treatment of colitis.

Mechanism of action of vinegared Cornu Cervi Degelatinatum in suppressing spleen kidney yang deficient ulcerative colitis through NCK2-JNK pathway

BackgroundAs a traditional Chinese herbal medicine, Cornu Cervi Degelatinatum (CCD) has the effect of warming the kidney to support yang, astringing, and stopping bleeding, and is used for spleen kidney yang deficient (SKYD). This experiment was to investigate the therapeutic effects of different processes of CCD on SKYD type ulcerative colitis (UC) rats and to explore its impact on the intestinal flora of rats. Methods: ELISA was used to study the anti-inflammatory activity of Cornu Cervi Degelatinatum processed with water (WCCD) and Cornu Cervi Degelatinatum processed with vinegar (VCCD). 16SrRNA and transcriptome sequencing were used to detect the composition of rat intestinal flora and gene expression; RT-PCR and Western blot were used to verify the role of WCCD and VCCD in treating UC. Results: WCCD and VCCD have therapeutic effects on UC, could reduce tissue damage. VCCD performed better in improving Bacteroidetes/Firmicutes ratios and species evenness and abundance; performed better in increasing the quantity of lactobacillus. VCCD simultaneously inhibit the intestinal inflammatory response through NCK2, PAK4, and JNK signaling pathways. Conclusions: WCCD and VCCD play a therapeutic role in UC by regulating the proportion of different flora in the intestinal flora. VCCD regulates the intestinal flora and inflammatory response by interfering with the NCK2, PAK4 and JNK signaling pathways.

Cucurbitacin E Alleviates Colonic Barrier Function Impairment and Inflammation Response and Improves Microbial Composition on Experimental Colitis Models.

Cucurbitacins, which are found in a variety of medicinal plants, vegetables and fruits, were known for their diverse pharmacological and biological activities, including anticancer, anti-oxidative and anti-inflammatory effects. Cucurbitacin E, one of the major cucurbitacins, was recently proved to inhibit inflammatory response. To explore the therapeutic effects of cucurbitacin E on colitis and the underlying mechanisms, male mice drunk water containing 2.5% dextran sulfate sodium (DSS) to establish colitis model and administrated with cucurbitacin E during and after DSS treatment. The disease activity index was scored and colonic histological damage was observed. Intestinal tight junction and inflammatory response were determined. 16S rRNA and transcriptome sequencing were performed to analyze gut microbiota composition and gene expression, respectively. We found that cucurbitacin E alleviated DSS-induced body weight loss and impaired colonic morphology. Cucurbitacin E decreased the expression of inflammatory cytokines and cell apoptosis, and maintained barrier function. Additionally, cucurbitacin E retrieved DSS-induced alterations in the bacterial community composition. Furthermore, a variety of differentially expressed genes (DEGs) caused by cucurbitacin E were enriched in several pathways including the NFκB and TNF signaling pathways as well as in Th17 cell differentiation. There was a close relationship between DEGs and bacteria such as Escherichia-Shigella and Muribaculaceae. Our results revealed that cucurbitacin E may exert protective effects on colitis via modulating inflammatory response, microbiota composition and host gene expression. Our study supports the therapeutic potential of cucurbitacin E in colitis and indicates that gut microbes are potentially therapeutic targets.

Isoquercitrin alleviates lipopolysaccharide-induced intestinal mucosal barrier damage in mice by regulating TLR4/MyD88/NF-κB signaling pathway and intestinal flora.

Intestinal mucosal barrier damage is closely associated with the development of several intestinal inflammatory diseases. Isoquercitrin (IQ) is a natural flavonoid compound derived from plants, which exhibits high antioxidant and anti-inflammatory activity with minimal side effects in humans. Therefore, it shows great potential for preventing and treating intestinal mucosal barrier damage. This study aims to investigate the ameliorative effect and mechanism of IQ on lipopolysaccharide (LPS)-induced intestinal mucosal barrier damage in mice. The mice were treated with IQ for 7 days and then injected with LPS to induce intestinal mucosal barrier damage. The results revealed that IQ treatment alleviated LPS-induced intestinal mucosal barrier damage in mice, which can be evidenced by the improvements in intestinal morphology and the promotion of expression in intestinal tight junctions (ZO-1, Claudin-1, and Occludin), as well as MUC2 mucin. IQ also attenuated intestinal inflammatory responses by inhibiting the TLR4/MyD88/NF-κB signaling pathway and reducing the expression and plasma levels of IL-6, IL-1β, and TNF-α. Furthermore, IQ significantly increased the relative abundance of beneficial bacteria, including Dubosiella, Akkermansia muciniphila and Faecalibaculum rodentium, while suppressing the growth of harmful bacteria such as Mucispirillum schaedleri in the intestinal flora of mice. Consequently, IQ can alleviate the LPS-induced intestinal mucosal barrier damage in mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway and modulating the intestinal flora.

The Interaction of Microbiome and Pancreas in Acute Pancreatitis.

Acute pancreatitis (AP) is a common acute abdomen disease characterized by the pathological activation of digestive enzymes and the self-digestion of pancreatic acinar cells. Secondary infection and sepsis are independent prognosticators for AP progression and increased mortality. Accumulating anatomical and epidemiological evidence suggests that the dysbiosis of gut microbiota affects the etiology and severity of AP through intestinal barrier disruption, local or systemic inflammatory response, bacterial translocation, and the regulatory role of microbial metabolites in AP patients and animal models. Recent studies discussing the interactions between gut microbiota and the pancreas have opened new scopes for AP, and new therapeutic interventions that target the bacteria community have received substantial attention. This review concentrates on the alterations of gut microbiota and its roles in modulating gut-pancreas axis in AP. The potential therapies of targeting microbes as well as the major challenges of applying those interventions are explored. We expect to understand the roles of microbes in AP diagnosis and treatment.

Effects of Dietary Bile Acids on Growth Performance, Lipid Deposition, and Intestinal Health of Rice Field Eel (Monopterus albus) Fed with High-Lipid Diets.

The purpose of this trial was to study the positive effects of bile acids (BAs) on growth performance and intestinal health of rice field eel fed with high-lipid diets (HLDs). Rice field eels (initial weight 17.00 ± 0.10 g) were divided into four groups, each group containing four repetitions and feeding with different isonitrogenous diet: control diet containing 7% lipid content, HLDs containing the lipid content increased to 13%, HLDs supplementing with 0.025% BAs and 0.05% BAs, respectively. After 8 weeks, compared control group, the fish fed HLDs had no significant effect on weight gain rate and specific growth rate (P > 0.05), but increased the lipid deposition in tissues and intestinal lipase activity, and damaged to intestinal oxidative stress, inflammatory response, physical barrier, and structural integrity (P < 0.05). Dietary BAs significantly increased weight gain rate and specific growth rate in fish fed with HL diets (P < 0.05) and reduced feed conversation rate (P < 0.05). Further, the eels fed with BAs reduced the total lipid content in liver, muscle, and whole body (P < 0.05). Dietary BAs decreased the activity of intestinal lipase (P < 0.05). Meanwhile, BAs supplemented in HLDs improved intestinal antioxidant capacity through increasing the activities of T-SOD (total superoxide dismutase), GSH-PX (glutathione peroxidase), CAT (catalase), T-AOC (total antioxidant capacity), whereas reducing MDA (malondialdehyde) content (P < 0.05). Moreover, dietary BAs regulated the mRNA expression related to inflammatory response, oxidative stress, and physical barrier in intestine, such as tnf-α, il-8, tlr-8, il-10, nrf2, keap1, claudin12, and claudin15 (P < 0.05). Dietary BAs supplementation also enhanced the intestinal structural integrity characterized by increased fold height and lamina propria width (P < 0.05). This study showed that dietary BAs supplemented in HLDs (13% lipid) could increase the growth performance of rice field eel, reduce lipid deposition in tissues and whole body, and enhance intestinal health.

Influence of artificial digestion on characteristics and intestinal cellular effects of micro-, submicro- and nanoplastics

The production of plastics is rising since they have been invented. Micro, submicro- and nanoplastics are produced intentionally or generated by environmental processes, and constitute ubiquitous contaminants which are ingested orally by consumers. Reported health concerns include intestinal translocation, inflammatory response, oxidative stress and cytotoxicity. Every digestive milieu in the gastrointestinal tract does have an influence on the properties of particles and can cause changes in their effect on biological systems. In this study, we subjected plastic particles of different materials (polylactic acid, polymethylmethacrylate, melamine formaldehyde) and sizes (micro- to nano-range) to a complex artificial digestion model consisting of three intestinal fluid simulants (saliva, gastric and intestinal juice). We monitored the impact of the digestion process on the particles by performing Dynamic Light Scattering, Scanning Electron Microscopy and Asymmetric Flow Field-Flow Fractionation. An in vitro model of the intestinal epithelial barrier was used to monitor cellular effects and translocation behavior of (un)digested particles. In conclusion, artificial digestion decreased cellular interaction and slightly increased transport of all particles across the intestinal barrier. The interaction with organic matter resulted in clear differences in the agglomeration behavior. Moreover, we provide evidence for polymer-, size- and surface-dependent cellular effects of the test particles.

Role of Intestinal Inflammation and Permeability in Patients with Acute Heart Failure.

Background and Objectives: Heart failure (HF) represents a major health burden. Although several treatment regimens are available, their effectiveness is often unsatisfactory. Growing evidence suggests a pivotal role of the gut in HF. Our study evaluated the prognostic role of intestinal inflammation and permeability in older patients with acute HF (AHF), and their correlation with the common parameters traditionally used in the diagnostic-therapeutic management of HF. Materials and Methods: In a single-center observational, prospective, longitudinal study, we enrolled 59 patients admitted to the Emergency Department (ED) and then hospitalized with a diagnosis of AHF, from April 2022 to April 2023. Serum routine laboratory parameters and transthoracic echocardiogram were assayed within the first 48 h of ED admission. Fecal calprotectin (FC) and both serum and fecal levels of zonulin were measured, respectively, as markers of intestinal inflammation and intestinal permeability. The combined clinical outcome included rehospitalizations for AHF and/or death within 90 days. Results: Patients with increased FC values (>50 µg/g) showed significantly worse clinical outcomes (p < 0.001) and higher median levels of NT-proBNP (p < 0.05). No significant correlation was found between the values of fecal and serum zonulin and the clinical outcome. Median values of TAPSE were lower in those patients with higher values of fecal calprotectin (p < 0.05). After multivariate analysis, NT-proBNP and FC values > 50 µg/g resulted as independent predictors of a worse clinical outcome. Conclusions: Our preliminary finding supports the hypothesis of a close relationship between the gut and heart, recognizing in a specific marker of intestinal inflammation such as FC, an independent predictive prognostic role in patients admitted for AHF. Further studies are needed to confirm these results, as well as investigate the reliability of new strategies targeted at modulation of the intestinal inflammatory response, and which are able to significantly impact the course of diseases, mainly in older and frail patients.