Intestinal Structural Integrity Research Articles

Fucoidan from Apostichopus japonicus enhances intestinal barrier function and promotes intestinal immunity via regulating the gut microbiota and tryptophan metabolism.

Apostichopus japonicus is one of the most popular types of sea cucumber among consumers in Southeast Asia. Fucoidan from Apostichopus japonicus (Aj-FUC) has attracted considerable attention because of its immunomodulatory activities. Aj-FUC is indigestible in the human upper gastrointestinal tract but can be utilized by the gut microbiota. Thus, we suspect that Aj-FUC interacts with the gut to enhance immune y76kjfunction. This study showed that after a three-week intervention with Aj-FUC (100 mg/kg/d), the gut microbiota in mice developed a new homeostasis. Subsequently, in the condition of intestinal flora homeostasis, the effects of Aj-FUC on intestinal health in normal mice and the prevention of intestinal mucosal damage in cyclophosphamide-induced mice were investigated. Aj-FUC preserved intestinal structural integrity, increased the number of goblet cells, upregulated the expression of ZO-1 and Occludin, stimulated the secretion of sIgA and IgA, and maintained the Th1/Th2 balance. Importantly, beneficial bacteria were enriched, and tryptophan metabolism-related metabolites such as 5-hydroxyindole-3-acetic acid, and indole-3-lactic acid were upregulated following Aj-FUC administration. In summary, a three-week Aj-FUC intervention could result in the formation of a new homeostasis in intestinal flora, while the effect of Aj-FUC on intestinal immunity was related to the regulation of tryptophan metabolism by gut microbiota.

Role of the Probiotic Supplementation on Intestinal Inflammation and Structural Integrity in Wistar Rats Subjected to a Cafeteria Diet during Development

Role of the Probiotic Supplementation on Intestinal Inflammation and Structural Integrity in Wistar Rats Subjected to a Cafeteria Diet during Development

Mechanism of fumonisin B1 on growth performance and intestinal structural integrity of juvenile grass carp (Ctenopharyngodon idella)

Mechanism of fumonisin B1 on growth performance and intestinal structural integrity of juvenile grass carp (Ctenopharyngodon idella)

Itaconic Acid Alleviates Perfluorooctanoic Acid-Induced Oxidative Stress and Intestinal Damage by Regulating the Keap1/Nrf2/Ho-1 Pathway and Reshaping the Gut Microbiota.

Itaconic acid (IA) is recognized for its potential application in treating intestinal diseases owing to the anti-inflammatory and antioxidant properties. Perfluorooctanoic acid (PFOA) can accumulate in animals and result in oxidative and inflammatory damages to multi-tissue and organ, particularly in the intestinal tract. This study aimed to explore whether IA could mitigate intestinal damage induced by PFOA exposure in laying hens and elucidate its potential underlying mechanisms. The results showed that IA improved the antioxidant capacity of laying hens and alleviated the oxidative damage induced by PFOA, as evidenced by the elevated activities of T-SOD, GSH-Px, and CAT, and the decreased MDA content in both the jejunum and serum. Furthermore, IA improved the intestinal morphological and structural integrity, notably attenuating PFOA-induced villus shedding, length reduction, and microvillus thinning. IA also upregulated the mRNA expression of ZO-1, Occludin, Claudin-1, and Mucin-2 in the jejunum, thereby restoring intestinal barrier function. Compared with the PF group, IA supplementation downregulated the gene expression of Keap1 and upregulated the HO-1, NQO1, SOD1, and GPX1 expression in the jejunum. Meanwhile, the PF + IA group exhibited lower expressions of inflammation-related genes (NF-κB, IL-1β, IFN-γ, TNF-α, and IL-6) compared to the PF group. Moreover, IA reversed the PFOA-induced imbalance in gut microbiota by reducing the harmful bacteria such as Escherichia-Shigella, Clostridium innocuum, and Ruminococcus torques, while increasing the abundance of beneficial bacteria like Lactobacillus. Correlation analysis further revealed a significant association between gut microbes, inflammatory factors, and the Keap1/Nrf2/HO-1 pathway expression. In conclusion, dietary IA supplementation could alleviate the oxidative and inflammatory damage caused by PFOA exposure in the intestinal tract by reshaping the intestinal microbiota, modulating the Keap1/Nrf2/HO-1 pathway and reducing oxidative stress and inflammatory response, thereby promoting intestinal homeostasis.

Physiological and immune responses of largemouth bass (Micropterus salmoides) under the regulation of exercise intensity: An integrated perspective of blood, liver and intestinal analysis

This study examined the effects of different water flow durations on serum biochemical indices, liver antioxidant capacity, and intestinal health of largemouth bass (Micropterus salmoides) in a recirculating aquaculture system (RAS). During a 90-day experiment, 270 largemouth bass (initial weight 96.05 ± 18.87 g) were randomly assigned to three groups: a control group (CG) with a constant flow velocity of 0.3 cm/s, an interval exercise group (IE) with a water flow velocity of 2 bl/s for 8 h/day, and a sustained exercise group (SE) with a continuous flow velocity of 2 bl/s for 24 h/day. The results showed that the IE group had higher total protein (TP) levels than the CG and SE groups (P < 0.05). In contrast, the SE group had lower triglyceride (TG) and cholesterol (CHO) levels (P < 0.05), indicating that exercise intensity significantly affects serum biochemical parameters. The study also evaluated the effects of sustained swimming on liver antioxidant capacity, digestive enzyme activity, intestinal health, and microbial community composition. Antioxidant assays revealed significantly increased activities of superoxide dismutase (T-SOD) and catalase (CAT) in the SE group, along with the lowest malondialdehyde (MDA) levels (P < 0.05), indicating enhanced antioxidant defenses. Enzyme assays showed a significant increase in trypsin and lipase activities due to swimming exercise (P < 0.05). Intestinal morphology analysis showed increased villus height and wall thickness in the SE group, without visible tissue damage, suggesting improved intestinal structural integrity. Gene expression analysis showed a significant upregulation of pro-inflammatory genes in the IE group and an increase in anti-inflammatory gene expression in the SE group. Microbial community analysis showed no significant differences in alpha diversity, species richness, or total diversity among the groups. However, variations in microbial species distribution at the phylum and genus level were observed, which were likely influenced by exercise intensity. In conclusion, sustained swimming exercise significantly improved antioxidant capacity, intestinal health, and modulated the immune response in largemouth bass. This highlights its potential to improve fish health and sustainability in RAS.

Effects of Dietary Ursolic Acid on Growth Performance and Intestinal Health of Largemouth Bass (Micropterus salmoides).

This study aimed to investigate the effects of ursolic acid (UA) on the growth performance and intestinal health of largemouth bass (Micropterus salmoides). Four diets were formulated with UA supplementation at 0, 250, 500, and 1000 mg/kg, defined as the control (CON), UA250, UA500, and UA1000, respectively. After an 8-week feeding experiment, the results showed that, in the UA500 group, the final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR) increased, and the feed conversion ratio (FCR) and hepatosomatic index decreased. Total superoxide dismutase (T-SOD) activity exhibited a significant increase, and malondialdehyde (MDA) content decreased. An intestinal histological analysis revealed an improvement in the intestinal structural integrity of the UA500 group. The mRNA relative expression levels of physical barrier-related genes [occludin, claudin-1, and zonula occluden-1 (zo-1)] were upregulated. The mRNA relative expression of interlenkin 10 (il-10) increased, and the mRNA relative expression of interlenkin 1β (il-1β) and tumor necrosis factor-α (tnf-α) significantly decreased. The abundance of Firmicutes and Proteobacteria decreased, and the abundance of Tenericutes increased. The abundance of Mycoplasma, Cyanobium, and Staphylococcus decreased, while the abundance of Clostridium increased. In conclusion, dietary supplementation of UA significantly enhanced the growth performance and antioxidant capacity of largemouth bass while improving intestinal barrier function through its influence on the abundance of intestinal flora, such as Tenericutes, Firmicutes, and Mycoplasma. Optimal dietary UA levels for largemouth bass were determined to be between 498 and 520 mg/kg based on quadratic regression analyses of WGR, SGR, and FCR or T-SOD and MDA content.

Fecal Microbiota Transplantation Regulates Blood Pressure by Altering Gut Microbiota Composition and Intestinal Mucosal Barrier Function in Spontaneously Hypertensive Rats.

Hypertension is accompanied by gut microbiota imbalance, but the role of bacteria in the pathogenesis of hypertension requires further study. In this study, we used fecal microbiota transplantation to determine the impact of microbiota composition on blood pressure in spontaneous hypertensive rats (SHRs), using normotensive Wistar Kyoto (WKY) rats as controls. SHRs were randomly divided into two groups (n = 10/group), SHR and SHR-T (SHR plus fecal transplantation) and WKY into WKY and WKY-T (WKY plus fecal transplantation). SHR-T received fecal transplantation from WKY, while WKY-T received fecal transplantation from SHR. Blood pressure was measured from the tail artery in conscious rats. 16S rDNA gene amplicon sequencing was used to analyze bacterial composition. Circulating levels of diamine oxidase, D-lactate, FITC-Dextrans, and lipopolysaccharide were determined. Hematoxylin and eosin (H&E) staining was used to observe structural changes in the intestinal mucosa. Immunofluorescence, Western blot, and RT-PCR were utilized to determine changes in the expression of tight junction proteins. Following cross fecal transplantation, blood pressure decreased in SHR and increased in WKY. Significant differences in gut microbial composition were found between hypertensive and normotensive rats, specifically regarding the relative abundance of lactic and butyric acid-producing bacteria. Changes in gut microbiota composition also impacted the intestinal mucosal barrier integrity. Moreover, fecal transplantation affected the expression of tight junction proteins that may impact intestinal mucosal permeability and structural integrity. Blood pressure may be associated with butyric acid-producing intestinal microbiota and its function in regulating the integrity of intestinal mucosal barrier.

Rumen Microbiota Transplantation Alleviates Gossypol Diet-Induced Reproductive, Liver, and Intestinal Damage in Male Mice.

Ruminants exhibit stronger tolerance to gossypol, an anti-nutritional factor, compared to monogastric animals. We transplanted Hu sheep rumen microbiota into male mice to investigate the role of rumen microbiota in animal gossypol tolerance. Thirty specific-pathogen-free (SPF) male C57BL/6 mice were randomly divided into three groups: normal diet (CK group), gossypol diet (FG group), and rumen microbiota transplantation (FMT group, gossypol diet). The pathological changes in the liver and small intestine of the mice, the organ coefficient, and sperm parameters were analyzed. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the blood and lactate dihydrogen-X (LDH-X) levels in the testicular tissue were also measured. The results showed that body weight, feed intake, sperm concentration, sperm motility, and LDH-X levels in the FMT group increased (p < 0.05) compared with the FG group, while the enzyme activities of ALT, AST, and AST/ALT decreased (p < 0.05). In the FMT group, the injury to liver cells was alleviated, the structure of the small intestine was intact, and the villus height and the ratio of villus height to crypt depth (V/C) were higher than those in the FG group (p < 0.05). And there were no differences in various organ coefficients and sperm deformity rates among the three groups (p > 0.05), but compared with the FG group, mice in the FMT group showed tendencies closer to those in the CK group. Rumen microbiota transplantation relieved the reproductive toxicity and liver damage induced by gossypol in male mice and improved the tolerance of recipient animals to gossypol. Additionally, rumen microbes improved the intestinal structural integrity of recipients.

Lactobacillus reuteri alleviates LPS-induced intestinal mucosal damage by stimulating the expansion of intestinal stem cells via activation of the Wnt/β-catenin signaling pathway in broilers

The continuous expansion of intestinal stem cells (ISCs) is crucial for maintaining the renewal of the intestinal epithelium, particularly in inflammatory conditions. It remains largely unknown how the internal microbiota repair damage to the internal mucosal barrier. Hence, investigating potential anti-inflammatory probiotics from the intestinal symbolic microbes of broilers and analyzing their mechanism of action to support the intestinal mucosal barrier function can offer novel regulatory tools to alleviate broiler enteritis. In this research, we utilized in vivo broilers plus ex vivo organoids model to thoroughly examine the effectiveness of Lactobacillus reuteri (LR) in protecting the integrity of the intestinal mucosa during lipopolysaccharide-induced (LPS-induced) enteritis in broilers. The findings indicated that LR feeding maintained intestinal morphological and structural integrity, enhanced proliferation of intestinal epithelial cells, and inhibited cell apoptosis and inflammatory response against the deleterious effects triggered by LPS. Simultaneously, LR enhanced ISCs activity and stimulated intestinal epithelial regeneration to protect the intestinal barrier during LPS-induced injury conditions. The coculture system of LR and ileum organoids revealed that LR increased the growth of organoids and attenuated LPS-stimulated damage to organoids. Furthermore, the LPS-induced decrease in ISC activity was rescued by reactivation of Wnt/β-catenin signaling by LR ex vivo and in vivo. This research revealed that LR promoted the expansion of ISCs and intestinal epithelial cell renewal by regulating the Wnt/β-catenin signaling pathway, thereby maintaining the integrity of the intestinal mucosal barrier. This finding provided theoretical support for lactobacillus as a probiotic additive in livestock feed to improve intestinal inflammation and treat intestinal diseases.

Long-term disinfectant exposure on intestinal immunity and microbiome variation of grass carp

The gut microbiome is crucial in maintaining fish health homeostasis. Disinfectants can kill important pathogens and disinfect fish eggs, yet their effect on the immune pathways and intestinal microbiome in healthy fish remains unknown. In this study, we investigated the effects of two disinfectants on the transcriptome profiles, immunological response, and gut microbiota dynamics of grass carp over a four-week trial. In particular, aquatic water was disinfected with 80 μg/L glutaraldehyde or 50 μg/L povidone-iodine. We found that glutaraldehyde and povidone-iodine induced gut antioxidant system and depressed the function of grass carp digestive enzymes. The results of the 16S rDNA high-throughput sequencing identified a reduction in the diversity of grass carp gut microbiota following the disinfectant treatment. Moreover, transcriptome profiling revealed that disinfectant exposure altered the immune-related pathways of grass carp and inhibited the expression of inflammation and tight junction related genes. Finally, the histopathological observation and apoptosis detection results suggested that the long-term diet of disinfectant destroyed intestinal structural integrity and promoted apoptosis. In conclusion, long-term exposure to disinfectants was observed to reduce oxidation resistance, suppress the immune response, dysbiosis of the intestinal flora, and resulted in increasing the apoptosis in intestinal of grass carp.

Pleurotus eryngii root waste and soybean meal co-fermented protein improved the growth, immunity, liver and intestinal health of largemouth bass (Micropterus salmoides)

The present study aimed to evaluate the effect of king oyster mushroom (Pleurotus eryngii) root waste and soybean meal co-fermented protein (CFP) on growth performance, feed utilization, immune status, hepatic and intestinal health of largemouth bass (Micropterus salmoides). Largemouth bass (12.33 ± 0.18 g) were divided into five groups, fed with diets containing 0 %, 5 %, 10 %, 15 % and 20 % CFP respectively for 7 weeks. The growth performance and dietary utilization were slightly improved by the supplementation of CFP. In addition, improved immunoglobulin M (IgM) content and lysozyme activity in treatments confirm the enhancement of immunity in fish by the addition of CFP, especially in fish fed 20 % CFP (P < 0.05). Furthermore, CFP significantly improved liver GSH (glutathione) content in groups D10 and D15 (P < 0.05), and slightly improved total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity while slightly reduced malondialdehyde (MDA) content. Simultaneously, the upregulation of lipolysis-related genes (PPARα, CPT1 and ACO) expression and downregulation of lipid synthesis-related genes (ACC and DGAT1) expression was recorded in the group D20 compared with the control (P < 0.05), which were consistent with the decreased liver lipid contents, suggests that lipid metabolism was improved by CFP. In terms of intestinal structural integrity, ameliorated intestinal morphology in treatments were consistent with the upregulated Occludin, Claudin-1 and ZO-1 genes expression. The intestinal pro-inflammatory cytokines (TNF-α and IL-8) expression were suppressed while the anti-inflammatory cytokines (IL-10 and TGF-β) were activated in treatments. The expression of antimicrobial peptides (Hepcidin-1, Piscidin-2 and Piscidin-3) and intestinal immune effectors (IgM and LYZ) were slightly up-regulated in treatments. Additionally, the relative abundance of intestinal beneficial bacteria (Firmicutes) increased while the relative abundance of potential pathogenic bacteria (Fusobacterium and Proteobacteria) decreased, which indicated that the intestinal microbial community was well-reorganized by CFP. In conclusion, dietary CFP improves growth, immunity, hepatic and intestinal health of largemouth bass, these data provided a theoretical basis for the application of this novel functional protein ingredient in fish.

Dietary copper improves intestinal structural integrity in juvenile grass carp (Ctenopharyngodon idella) probably related to its increased intestinal antioxidant capacity and apical junction complex

This research evaluated the effects of copper (Cu) on intestinal antioxidant capacity and apical junctional complex (AJC) in juvenile grass carp. A total of 1080 healthy juvenile grass carp (11.16 ± 0.01 g) were fed six diets including different dosages of Cu, namely 0, 2, 4, 6, 8 mg/kg (Cu citrate [CuCit] as Cu source) and 3 mg/kg (CuSO4·5H2O as Cu source). The trial lasted for 9 weeks. The findings revealed that dietary optimal Cu supplementation (2.2 to 4.1 mg/kg) promoted intestinal growth, including intestinal length, intestinal length index, intestinal weight, and intestinal somatic index (P < 0.05). Furthermore, optimal Cu boosted the intestinal mucosal barrier in juvenile grass carp. On the one hand, optimal Cu reduced diamine oxidase and D-lactate levels in serum (P < 0.05), reduced levels of the oxidative damage indicators malondialdehyde, reactive oxygen species (ROS), protein carbonyl, superoxide dismutase (P < 0.05), and catalase mRNA levels were elevated (P < 0.05), thus boosting intestinal antioxidant capacity, the binding protein Keap1a/1b/Nrf2 signaling pathway might be involved. Optimal Cu had no impact on glutathione peroxidase 1b (GPx1b) gene expression (P > 0.05). On the other hand, optimal Cu increased intestinal tight junction (TJ) proteins (except for claudin 15b) and adherens junction (AJ) proteins (E-cadherin, α-catenin, β-catenin, nectin and afadin) mRNA levels (P < 0.05), which could be connected to the signaling pathway formed by the Ras homolog gene family, member A (RhoA), Rho-associated kinase (ROCK), and myosin light chain kinase (MLCK). Finally, based on serum indicator D-lactate and intestinal oxidative damage index (ROS), Cu requirement (CuCit as Cu source) for juvenile grass carp from initial weight to final weight (from 11 to 173 g) was determined to be 4.14 and 4.12 mg/kg diet, respectively. This work may provide a theoretical foundation for identifying putative Cu regulation pathways on fish intestinal health.

Aerial parts of Angelica sinensis supplementation for improved broiler growth and intestinal health

This research examined the impact of incorporating Angelica sinensis's aerial components (APA), commonly referred to as "female ginseng", into broilers' diet. Two hundred eighty-eight 1-day-old Cobb 500 broilers were randomly assigned to the 4 experimental groups with 6 replications and 12 birds/replicate. The 4 groups were fed the diets included 4 concentrations of APA (0 %, 1 %, 2 %, and 3%, respectively). The study spanned 42 days, categorized as the starter phase (1-21 days) and the finisher phase (22-42 days). Notably, broilers fed with 3% APA demonstrated a pronounced surge in feed consumption and weight gain during the 22-42 days and over the full 42-day period (P<0.05). Furthermore, when examining the broilers' intestinal structure, there was a notable increase in the villus height and villi ratio across the duodenum, jejunum, and ileum, with a decrease in crypt depth upon 3% APA inclusion (P<0.05). On a molecular note, certain genes connected to the intestinal mechanical barrier, such as Zona Occludens 1 and Claudin-2, saw significant elevation in the jejunum (P<0.05). The jejunum also displayed heightened levels of antimicrobial peptides like lysozyme, mucin 2, sIgA, IgG, and IgM, showcasing an enhanced chemical and immune barrier(P<0.05). Delving into the 16SrDNA sequencing of intestinal content, a higher microbial diversity was evident with a surge in beneficial bacteria, particularly Firmicutes, advocating a resilient and balanced microecosystem. The findings imply that a 3% APA dietary addition bolsters growth metrics and fortifies the intestinal barrier's structural and functional integrity in broilers.

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.

Structural characterization and immunomodulatory effect of a starch-like Grifola frondosa polysaccharides on cyclophosphamide-induced immunosuppression in mice

In this study, a pure Grifola frondosa polysaccharide (GFP-1) was extracted and purified from Grifola frondosa. By HPLC, GC-MS, FT-IR, and NMR analysis, GFP-1 was determined to be a starch-like polysaccharide with an average molecular weight of 3370 kDa. It included three monosaccharides, i.e., glucose, galactose, and mannose. The backbone of GFP-1 consisted of →4)-α-Glcp-(1→ and →4,6)-α-Glcp-(1 → . The side branches were composed of →6)-α-Galp-(1→, α-Glcp-(1→, and a small amount of α-Manp-(1 → . By using a cyclophosphamide (CTX)-induced immunosuppressed mice model, we evaluated the immunomodulatory activity of GFP-1. The results showed that GFP-1 increased the thymic and spleen indices, promoted the level of IgG and IgA in serum, and activated the mitogen-activated protein kinase (MAPK) pathway in CTX-induced mice. Also, GFP-1 significantly promoted the mRNA expression of intestinal barrier factors and protected intestinal structural integrity in immunosuppressed mice. In conclusion, the data presented here suggested that GFP-1 might be a potential immune-enhancing supplement.

Effects of dietary enzymatically treated Artemisia annua L. in low fish meal diet on growth, antioxidation, metabolism and intestinal health of Micropterus salmoides

The excessive substitution of fish meal (FM) by Clostridium autoethanogenum protein (CAP) could reduce the growth performance and disrupt the intestinal structural integrity of Micropterus salmoides. In order to solve this problem, an eight-week feeding trial was conducted to investigate the effects of dietary enzymatically treated Artemisia annua L. (EA) in low FM diet containing high-CAP on growth, antioxidation capacity, lipid and carbohydrate metabolism and intestinal microbiota of M. salmoides. Six isonitrogenous and isolipid experimental diets were produced containing 0 g/kg, 0.25 g/kg, 0.5 g/kg, 1.0 g/kg, 2.0 g/kg and 4.0 g/kg of dietary EA, which were named EA0, EA0.25, EA0.5, EA1.0, EA2.0 and EA4.0, respectively. After the feeding trial, the weight gain rate (WGR) and specific growth rate (SGR) were significantly increased in EA0.25, EA0.5 and EA 1.0 groups compared to EA0 group. The digestive enzyme activities in stomach and intestine, and the villus width and muscular layer thickness of the intestine were increased by dietary EA. Dietary EA improved the antioxidation capacity and serum lipid level of M. salmoides. The expression levels of sterol regulatory element-binding protein 1-c (srebp1-c), acetyl-coa carboxylase alpha (accα), fatty acid synthase (fan), 3-hydroxy-3-methylglutaryl-coa reductase (hmgcr) and accβ were significantly upregulated by 4.0 g/kg of dietary EA. The mRNA level of peroxisome proliferator-activated receptor alpha (pparα) and carnitine palmitoyltransferase 1 (cpt-1) were upregulated by 4.0 g/kg and 0.5 g/kg of dietary EA, respectively. Besides, the glucose content in serum was decreased by EA. The expressions of forkhead box o1 (foxo1), phosphoenolpyruvate carboxykinase (pepck), fructose bisphosphatase (fbp), glucokinase (gk) and pyruvate kinase (pk) were significantly improved by 4.0 g/kg of dietary EA, and the level of phosphofructokinase (pfk) was upregulated by 0.5 g/kg of dietary EA. The addition of 0.5 g/kg of dietary EA could optimize beneficial Cetobacterium and reduce harmful Mycoplasmataceae abundances in intestine of M. salmoides. In summary, the appropriate amount of dietary EA could be added to the high-CAP diet to improve the growth performance, antioxidation, lipid and carbohydrate metabolism, liver and intestinal health of M. salmoides. This study will provide scientific guidance for replacing FM with non-food proteins.

Effect of dietary supplementation of the quenching enzyme AiiO-AIO6 on growth performance, digestion and absorption capacity, and intestinal barrier function of grass carp (Ctenopharyngodon idella)

Quenching enzymes have attracted wide attention as one of the alternatives to antibiotics because their positive effects on inhibiting pathogenic microorganism. Therefore, the objective of this study was to investigate the impact of dietary quenching enzyme AiiO-AIO6 on the growth performance, digestion and absorption capacity, intestinal structural integrity, and gut microbiota composition in juvenile grass carp. Healthy grass carp (4.73 ± 0.01 g) were assigned to 36 fish tanks (1.2 × 0.6 × 0.9 m), randomly divided into 6 groups, and fed on six diets with different levels of AiiO-AIO6 (0, 2.5, 5.0, 7.5, 10.0 and 12.5 U/g feed) for a duration of 10 weeks. The present findings demonstrated that dietary AiiO-AIO6 supplementation positively influenced the final body weight (FBW), specific growth rate (SGR), percent weight gain (PWG), and feed intake (FI) of juvenile grass carp. Moreover, our results indicated that the appropriate dietary AiiO-AIO6 supplementation promoted the number of goblet cells and improved the activities of chymotrypsin, trypsin, lipase, amylase, Na+-K+-ATPase, γ-GT and CK, which ultimately contributed to the enhancement of digestion and absorption capacity of juvenile grass carp. Additionally, the present study further found that dietary AiiO-AIO6 supplementation up-regulated the relative mRNA levels of tight junctions (TJs) and adhesive junctions (AJs) proteins, including ZO-1, occludin, claudin-b, −c, −f, −7a, −7b, −11, −12, α-catenin, nectin, afadin, and E-cadherin, thereby enhancing the physical barrier function, potentially attributed to the reduction in abundance of intestinal pathogenic bacteria, such as Pseudomonas. Ultimately, the optimal level of AiiO-AIO6 for juvenile grass carp, as determined by the percent weight gain (PWG), was found to be 4.5 U/g.

INT-767-A Dual Farnesoid-X Receptor (FXR) and Takeda G Protein-Coupled Receptor-5 (TGR5) Agonist Improves Survival in Rats and Attenuates Intestinal Ischemia Reperfusion Injury.

Intestinal ischemia is a potentially catastrophic emergency, with a high rate of morbidity and mortality. Currently, no specific pharmacological treatments are available. Previous work demonstrated that pre-treatment with obeticholic acid (OCA) protected against ischemia reperfusion injury (IRI). Recently, a more potent and water-soluble version has been synthesized: Intercept 767 (INT-767). The aim of this study was to investigate if intravenous treatment with INT-767 can improve outcomes after IRI. In a validated rat model of IRI (60 min ischemia + 60 min reperfusion), three groups were investigated (n = 6/group): (i) sham: surgery without ischemia; (ii) IRI + vehicle; and (iii) IRI + INT-767. The vehicle (0.9% NaCl) or INT-767 (10 mg/kg) were administered intravenously 15 min after start of ischemia. Endpoints were 7-day survival, serum injury markers (L-lactate and I-FABP), histology (Park-Chiu and villus length), permeability (transepithelial electrical resistance and endotoxin translocation), and cytokine expression. Untreated, IRI was uniformly lethal by provoking severe inflammation and structural damage, leading to translocation and sepsis. INT-767 treatment significantly improved survival by reducing inflammation and preserving intestinal structural integrity. This study demonstrates that treatment with INT-767 15 min after onset of intestinal ischemia significantly decreases IRI and improves survival. The ability to administer INT-767 intravenously greatly enhances its clinical potential.

An emerging role of arecoline on growth performance, intestinal digestion and absorption capacities and intestinal structural integrity of adult grass carp (Ctenopharyngodon idella)

Arecoline is an alkaloid with important pharmacological effects in the plant areca nut, which has been demonstrated to be an agonist of muscarinic receptors (M receptor). This study explored the influences of dietary arecoline on growth performance, intestinal digestion and absorption abilities, antioxidant capacity, and the apical junction complex (AJC) of adult grass carp (Ctenopharyngodon idella). Adult grass carp (608 to 1512 g) were fed at 6 graded levels of dietary arecoline (0, 0.5, 1.0, 1.5, 2.0, and 2.5 mg/kg diet) for 9 weeks. The results suggested that appropriate dietary supplementation of arecoline (1.0 mg/kg) increased growth parameters and intestinal growth in adult grass carp (P < 0.05), enhanced digestion and absorption capacities (P < 0.05), up-regulated muscarinic receptor 3 (M3) mRNA level (P < 0.05), increased the content of neuropeptide fish substance P (P < 0.05), improved antioxidant capacity by activating the Keap1a/Nrf2 signaling pathway (P < 0.05), reduced intestinal mucosal permeability (P < 0.05), and increased mRNA levels of tight junction (TJ) and adherent junction AJ-related proteins in fish by inhibiting the RhoA/ROCK signaling pathway (RhoA/ROCK/MLCK/NMII) (P < 0.05). In addition, the appropriate arecoline supplementation for adult grass carp was determined to be 1.20, 1.21, 1.07, and 1.19 mg/kg based on percentage weight gain, lipase activity, serum diamine oxidase, and protein carbonyl, respectively. Overall, to the best of our knowledge, we investigated for the first time the effects and possible mechanisms of dietary arecoline on intestinal digestive and absorptive capacities and structural integrity in fish and evaluated the appropriate level of supplementation.

Dietary high β-conglycinin reduces the growth through enhancing hepatic lipid peroxidation and impairing intestinal barrier function of orange-spotted grouper (Epinephelus coioides)

β-conglycinin is one of the major soy antigen proteins in soybean meal (SBM) and exhibits growth inhibition and intestinal health damage in grouper, but the underlying mechanisms are still poorly understood. In this study, orange-spotted grouper (Epinephelus coioides) was used to investigate whether the poor growth performance induced by dietary β-conglycinin levels is associated with intestinal structural integrity disruption, the intestinal apoptosis and intestinal microbiota. The basal diet (FM diet) was formulated to contained 48% protein and 12% fat without SBM supplementation. Fish meal protein in the FM diet was replaced by SBM to prepare a high SBM diet (SBM diet). β-conglycinin at 3% and 7% were added into FM diets to prepare two diets (B-3 and B-7). Triplicate groups of fish (20 fish/tank) were fed one of the experimental diets twice daily in a feeding period of 8 weeks. Compared with FM diet, fish fed diets SBM and B-7 had decreased the growth rate, hepatosomatic index, whole-body lipid and ash contents, and increased whole-body moisture content. However, the maximum growth was observed for diet B-3 and was not different from that of FM diet. The liver total antioxidant capacity and glutathione peroxidase activity, the muscle layer thickness of middle and distal intestine, and the mucosal fold length of distal intestine were lower, while liver malondialdehyde content, intestinal diamine oxidase activity, d-lactic acid and endotoxin contents, and the number of intestinal apoptosis were higher in SBM and B-7 groups than that in FM and/or B-3 groups. SBM and B-7 diets down-regulated the intestinal expression of tight junction genes (occludin, claudin-3 and ZO-1), apoptosis genes (bcl-2 and bcl-xL) and anti-inflammatory factor genes (IκBα, TGF-β1 and IL-10), but up-regulated the intestinal expression of apoptosis genes (caspase-3, caspase-8 and caspase-9) and pro-inflammatory factor genes (NF-κB1, RelA, TAK1, IKK, MyD88, TNF-α, IL-1β, and IL-8) vs FM and/or B-3 diets. The richness and diversity indexes of OTUs, Chao1, ACE, Shannon and Simpson were not affected by dietary treatments. The relative abundances of intestinal bacteria (phylum Proteobacteria and genus Vibrio) were generally higher, and relative abundance of phylum Tenericutes was lower in SBM and/or B-7 groups than that in B-3 group. The above results indicate that high dietary β-conglycinin level, rather than intermediate level could decrease liver antioxidant capacity, reshape the intestinal microbiota, and impair the intestinal normal morphology through disrupting the intestinal tight junction structure, increasing intestinal mucosal permeability, and promoting intestinal apoptosis, which in turn triggers intestinal inflammatory responses and the occurrence of enteritis, and ultimately leads to poor growth performance in fish.