Intestinal Mucosal Integrity Research Articles

Intestinal Mucosal Wound Healing and Barrier Integrity in IBD-Crosstalk and Trafficking of Cellular Players.

The intestinal epithelial barrier is carrying out two major functions: restricting the entry of potentially harmful substances while on the other hand allowing the selective passage of nutrients. Thus, an intact epithelial barrier is vital to preserve the integrity of the host and to prevent development of disease. Vice versa, an impaired intestinal epithelial barrier function is a hallmark in the development and perpetuation of inflammatory bowel disease (IBD). Besides a multitude of genetic, molecular and cellular alterations predisposing for or driving barrier dysintegrity in IBD, the appearance of intestinal mucosal wounds is a characteristic event of intestinal inflammation apparently inducing breakdown of the intestinal epithelial barrier. Upon injury, the intestinal mucosa undergoes a wound healing process counteracting this breakdown, which is controlled by complex mechanisms such as epithelial restitution, proliferation and differentiation, but also immune cells like macrophages, granulocytes and lymphocytes. Consequently, the repair of mucosal wounds is dependent on a series of events including coordinated trafficking of immune cells to dedicated sites and complex interactions among the cellular players and other mediators involved. Therefore, a better understanding of the crosstalk between epithelial and immune cells as well as cell trafficking during intestinal wound repair is necessary for the development of improved future therapies. In this review, we summarize current concepts on intestinal mucosal wound healing introducing the main cellular mediators and their interplay as well as their trafficking characteristics, before finally discussing the clinical relevance and translational approaches to therapeutically target this process in a clinical setting.

Xylooligosaccharide attenuates lipopolysaccharide-induced intestinal injury in piglets via suppressing inflammation and modulating cecal microbial communities.

Xylooligosaccharide (XOS) has been considered to be an effective prebiotic, but its exact mechanisms remain unknown. This research was conducted to evaluate the effects of XOS on pig intestinal bacterial community and mucosal barrier using a lipopolysaccharide (LPS)-caused gut damage model. Twenty-four weaned pigs were assigned to 4 treatments in a 2 × 2 factorial design involving diet (with or without XOS) and immunological challenge (saline or LPS). After 21 d of feeding 0% or 0.02% commercial XOS product, piglets were treated with saline or LPS. After that, blood, small intestinal mucosa and cecal digesta were obtained. Dietary XOS enhanced intestinal mucosal integrity demonstrated by higher villus height, villus height-to-crypt depth ratio, disaccharidase activities and claudin-1 protein expression and lower crypt depth. XOS also caused down-regulation of the gene expression of toll-like receptor 4 and nucleotide-binding oligomerization domain protein signaling, accompanied with decreased pro-inflammatory cytokines and cyclooxygenase 2 contents or mRNA expression and increased heat shock protein 70 mRNA and protein expression. Additionally, increased Bacteroidetes and decreased Firmicutes relative abundance were observed in the piglets fed with XOS. At the genus level, XOS enriched the relative abundance of beneficial bacteria, e.g., Faecalibacterium, Lactobacillus, and Prevotella. Moreover, XOS enhanced short chain fatty acids contents and inhibited histone deacetylases. The correlation analysis of the combined datasets implied some potential connections between the intestinal microbiota and pro-inflammatory cytokines or cecal metabolites. These results suggest that XOS inhibits inflammatory response and beneficially modifies microbes and metabolites of the hindgut to protect the intestine from inflammation-related injury.

Gastrointestinal manifestations in COVID-19.

Coronavirus disease 2019 (COVID-19), a respiratory viral infection, has affected more than 78 million individuals worldwide as of the end of December 2020. Previous studies reported that severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome–related coronavirus infections may affect the gastrointestinal (GI) system. In this review we outline the important GI manifestations of COVID-19 and discuss the possible underlying pathophysiological mechanisms and their diagnosis and management. GI manifestations are reported in 11.4–61.1% of individuals with COVID-19, with variable onset and severity. The majority of COVID-19-associated GI symptoms are mild and self-limiting and include anorexia, diarrhoea, nausea, vomiting and abdominal pain/discomfort. A minority of patients present with an acute abdomen with aetiologies such as acute pancreatitis, acute appendicitis, intestinal obstruction, bowel ischaemia, haemoperitoneum or abdominal compartment syndrome. Severe acute respiratory syndrome coronavirus 2 RNA has been found in biopsies from all parts of the alimentary canal. Involvement of the GI tract may be due to direct viral injury and/or an inflammatory immune response and may lead to malabsorption, an imbalance in intestinal secretions and gut mucosal integrity and activation of the enteric nervous system. Supportive and symptomatic care is the mainstay of therapy. However, a minority may require surgical or endoscopic treatment for acute abdomen and GI bleeding.

Dietary Tryptophan Levels Impact Growth Performance and Intestinal Microbial Ecology in Weaned Piglets via Tryptophan Metabolites and Intestinal Antimicrobial Peptides.

Simple SummaryTryptophan (Trp) plays an important role in piglet growth. However, the effect of dietary Trp on microbial flora is still poorly understood. A total of 40 28-d weaned piglets were fed a corn and soybean meal-based diet with 0.14%, 0.21%, 0.28%, or 0.35% Trp for four weeks. The average daily body weight gain, average daily feed intake, feed conversion ratio, spleen index, pancreas index, longissimus dorsi muscle index, plasma insulin, 5-hydroxytryptamine, kynurenine, and Trp concentrations of weaned piglets increased in a Trp dose-dependent manner. Compared with the 0.14% Trp diet, the adequate-Trp diets (0.21%, 0.28%, or 0.35%) down-regulated the relative abundances of 12 genera including Turicibacter, Prevotella, Mitsuokella, Anaerovibrio, Megasphaera, Succinivibrio, Sutterella, Desulfovibrio, and Methanobrevibacter; up-regulated the abundances of Ruminococcaceae, Lactobacillus, and Muribaculaceae in the colon; and augmented the mRNA level and concentration of porcine β-defensin 2 in the small intestinal mucosa. Moreover, Trp-adequate diets increased the abundances of Trp hydroxylase, indoleamine 2,3-dioxygenase, porcine β-defensin 2, phosphorylated mammalian target of rapamycin, and phosphorylated protein kinase B in the small intestinal mucosa. In summary, a corn and soybean meal-based diet with 0.35% Trp may be a nutritional strategy to improve growth performance, intestinal mucosal barrier integrity, and intestinal microbial ecology in weaned piglets.Tryptophan (Trp) plays an important role in piglet growth. However, the effect of dietary Trp on microbial flora is still poorly understood. A total of 40 28-d weaned piglets were allocated to four groups with 10 barrows per group and one pig per replicate. Piglets were fed a corn and soybean meal-based diet with 0.14%, 0.21%, 0.28%, or 0.35% Trp for four weeks. Five piglets from each diet group were euthanized, and blood and tissue samples were collected. The average daily body weight gain, average daily feed intake, feed conversion ratio, spleen index, pancreas index, longissimus dorsi muscle index, plasma insulin, 5-hydroxytryptamine, kynurenine, and Trp concentrations of weaned piglets increased in a dose-dependent manner (p < 0.05). Compared with the 0.14% Trp diet, the adequate-Trp diets (0.21%, 0.28%, or 0.35%) down-regulated the relative abundances of 12 genera including Turicibacter, Prevotella, Mitsuokella, Anaerovibrio, Megasphaera, Succinivibrio, Sutterella, Desulfovibrio, and Methanobrevibacter (p < 0.05); up-regulated the abundances of Ruminococcaceae, Lactobacillus, and Muribaculaceae in the colon (p < 0.05); and augmented the mRNA level and concentration of porcine β-defensin 2 in the small intestinal mucosa (p < 0.05). Moreover, Trp-adequate diets increased the abundances of Trp hydroxylase, indoleamine 2,3-dioxygenase, porcine β-defensin 2, phosphorylated mammalian target of rapamycin, and phosphorylated protein kinase B in the small intestinal mucosa (p < 0.05). We noted that a corn and soybean meal-based diet with 0.35% Trp may be a nutritional strategy to improve growth performance, intestinal mucosal barrier integrity, and intestinal microbial ecology in weaned piglets.

Necrotizing enterocolitis intestinal barrier function protection by antenatal dexamethasone and surfactant-D in a rat model

BackgroundNecrotizing enterocolitis (NEC) is the most common gastrointestinal disorder in premature neonates. Possible therapeutic approaches are centered on promoting maturation of the gastrointestinal mucosal barrier. Studies have demonstrated that antenatal administration of corticosteroids can decrease NEC incidence and mortality.MethodsPregnant rat dams were administered dexamethasone 48 h prior to delivery. The pups were subjected to an experimental NEC-like injury protocol. Ileal tissues and sera were collected and evaluated for inflammatory cytokines, gut permeability and expressions and localizations of tight junction proteins, and surfactant protein-D by immunohistochemistry/immunofluorescent staining. Intestinal epithelial cells (IEC-6) were pretreated with SP-D to examine the effect of SP-D on tight junction protein expressions when challenged with platelet-activating factor and lipopolysaccharide to model proinflammatory insults.ResultsAntenatal dexamethasone reduced systemic inflammation, preserved intestinal barrier integrity, and stimulated SP-D expression on the intestinal mucosal surface in pups exposed to NEC-like injury. Pretreatment of SP-D blocked platelet-activating factor/lipopolysaccharide-induced tight junction disruption in IEC-6 cells in vitro.ConclusionsAntenatal dexamethasone preserves the development of intestinal mucosal barrier integrity and reduces incidence and morbidity from an experimental NEC-like injury model. Dexamethasone upregulation of intestinal SP-D-protective effects on tight junction proteins.ImpactAntenatal administration of dexamethasone can function in concert with intestinal surfactant protein-D to decrease systemic inflammatory responses, and protect intestinal barrier integrity in a neonatal rat model of NEC.A novel role of intestinal SP-D in preserving tight junction protein structures under inflammatory conditions.We describe the intestinal SP-D—an overlooked role of antenatal dexamethasone in neonatal NEC?

Effects of Qing Hua Chang Yin on lipopolysaccharide‑induced intestinal epithelial tight junction injury in Caco‑2 cells

Disruption of the intestinal mucosal barrier integrity is a pathogenic process in inflammatory bowel disease (IBD) development, and is therefore considered a drug discovery target for IBD. The well-known traditional Chinese formulation Qing Hua Chang Yin (QHCY) has been suggested as a potential therapeutic agent for the treatment of ulcerative colitis. However, the possible underlying molecular mechanisms regarding its therapeutic effect remain unclear. Consequently, the present study investigated the effects of QHCY on lipopolysaccharide (LPS)-induced loss of intestinal epithelial barrier integrity in vitro using the Caco-2 cell model of intestinal epithelium. QHCY reversed the LPS-induced decrease in transepithelial electrical resistance and significantly alleviated the increased fluorescently-labeled dextran 4 flux caused by LPS. Moreover, QHCY upregulated the mRNA and protein expression levels of occludin, zona occludens-1 and claudin-1 in LPS-exposed Caco-2 cells. In conclusion, QHCY was able to protect intestinal epithelial barrier integrity following an inflammatory insult; the protective effects of QHCY may be mediated by modulation of the expression of tight junction proteins.

Avian intestinal ultrastructure changes provide insight into the pathogenesis of enteric diseases and probiotic mode of action

Epithelial damage and loss of barrier integrity occur following intestinal infections in humans and animals. Gut health was evaluated by electron microscopy in an avian model that exposed birds to subclinical necrotic enteritis (NE) and fed them a diet supplemented with the probiotic Bacillus amyloliquefaciens strain H57 (H57). Scanning electron microscopy of ileal mucosa revealed significant villus damage, including focal erosions of epithelial cells and villous atrophy, while transmission electron microscopy demonstrated severe enterocyte damage and loss of cellular integrity in NE-exposed birds. In particular, mitochondria were morphologically altered, appearing irregular in shape or swollen, and containing electron-lucent regions of matrix and damaged cristae. Apical junctional complexes between adjacent enterocytes were significantly shorter, and the adherens junction was saccular, suggesting loss of epithelial integrity in NE birds. Segmented filamentous bacteria attached to villi, which play an important role in intestinal immunity, were more numerous in birds exposed to NE. The results suggest that mitochondrial damage may be an important initiator of NE pathogenesis, while H57 maintains epithelium and improves the integrity of intestinal mucosa. Potential actions of H57 are discussed that further define the mechanisms responsible for probiotic bacteria’s role in maintaining gut health.

Dietary betaine supplementation improves growth performance, digestive function, intestinal integrity, immunity, and antioxidant capacity of yellow-feathered broilers

To investigate the effects of dietary betaine supplementation on the growth performance, digestive function, intestinal integrity, immunity, and antioxidant capacity of yellow-feathered broilers, a total of 400 one-day-old female yellow-feathered broilers were randomly allocated into 5 dietary treatments with 8 replicates of 10 chicks each, and fed a basal diet supplemented with 0 (control group), 125, 250, 500 and 1000 mg/kg betaine for 74 days, respectively. During the 1–37 days and 1–74 days, betaine linearly increased (p < .05) average daily gain, and decreased (p < .05) daily feed intake and feed conversion ratio. At 37 days, betaine linearly increased (p < .05) the apparent utilisation of crude protein, dry matter, and ether extract, jejunal digesta amylase and trypsin activities, villus height of jejunum and ileum, and ileal secretory immunoglobulin A content, glutathione peroxidase activity, and claudin-1 mRNA abundance, and linearly decreased (p < .05) serum D-lactate content and diamine oxidase activity, jejunal malondialdehyde content and nuclear factor kappaB mRNA abundance, ileal toll-like receptor 4 and myeloid differentiation factor 88 mRNA abundance. At 74 days, betaine linearly increased (p < .05) pancreatic lipase activity, jejunal glutathione peroxidase activity, and ileal glutathione content, and linearly decreased (p < .05) serum diamine oxidase activity and ileal malondialdehyde content. In conclusion, dietary supplementation with betaine improved growth performance, digestive function, intestinal mucosal barrier integrity, immune function, and antioxidant capacity of yellow-feathered broilers, and its optimal dosage in this study is 1000 mg/kg. HIGHLIGHTS Betaine improved growth performance. Betaine increased digestive function. Betaine enhanced intestinal antioxidant capacity. Betaine improved intestinal integrity and barrier function. Betaine improved intestinal immunity.

Extra Virgin Olive Oil Nanoemulsion Attenuated Inflammatory Response in Lipopolysaccharide-Induced Sepsis

The provision of nutritional components in critical illness such as sepsis remains a big issue in clinical application, particularly through oral route due to intestinal integrity damaged-associated absorption problem. The aim of this research was to develop Extra Virgin Olive Oil (EVOO) nanoemulsion as a nutrient carrier to improve its permeability while maintaining the intestinal mucosa integrity in mouse model of lipopolysaccharide-induced sepsis. EVOO nanoemulsion was prepared by using ultrasonication-mild agitation method. EVOO nanoemulsion (1.5 mL) was administered to the mice through orogastric tube. The effect of EVOO nanoemulsion was evaluated by assessing the histopathological alterations in lung, measuring the activation of NFκB-p65 by immunohistochemistry of lung tissue, the levels of circulating Surfactant Protein-D (SP-D), tumor necrosis factor-alpha, interleukin (IL)-8, and IL-10. The main result, EVOO nanoemulsion decreased circulating SP-D level after 24 h. In conclusion, EVOO nanoemulsion is a promising carrier to improve nutrition absorption and decrease circulating SP-D as organ injury biomarker.

Protection of the intestinal epithelium of poultry against deleterious effects of dietary lectins by a multi-strain bacterial supplement

The intake of antinutritional factors produce impairment on the intestinal digestive function, impeding the efficient use of nutrients. Probiotics could be useful in poultry breeding to prevent negative effects of antinutritional factors, like the dietary lectins soybean agglutinin (SBA) and wheat germ agglutinin (WGA). Therefore, this investigation aimed to verify that SBA and wheat, which contains WGA, exert harmful effects on the intestinal mucosa and the digestive system of young poultry, and determine if the administration of probiotics able to capture lectins could counteract their effects. The trials performed demonstrated that a mixture of Bifidobacterium infantis CRL 1395, Enterococcus faecium LET 301, Lactobacillus salivarius LET 201, L. reuteri LET 210, and Propionibacterium acidipropionici LET 103, strains with ex vivo ability to interfere with the interaction of lectins and epithelial cells, has no negative effect on young chickens health. Middle levels of SBA, as well as wheat as a source of WGA, resulted in lower activities of intestinal and brush border enzymes and alterations in the integrity and morphological parameters of the chicks jejunal mucosa. The bacteria blend increased the activity of several digestive enzymes and the intestinal maturation marker alkaline phosphatase in birds fed with a conventional diet. Besides, it partially countered the deleterious effects of increased content of SBA, as well as the negative effect of a dietary source of WGA, on digestive enzymes activity and intestinal mucosa integrity. The results highlight the capability of multifunctional bacterial mixtures to protect the digestive system of avian against residual dietary lectins.

Canna x generalis L.H. Bailey rhizome extract ameliorates dextran sulfate sodium-induced colitis via modulating intestinal mucosal dysfunction, oxidative stress, inflammation, and TLR4/ NF-ҡB and NLRP3 inflammasome pathways

Ethnopharmacological relevanceGenus Canna is used in folk medicine as demulcent, diaphoretic, antipyretic, mild laxative and in gastrointestinal upsets therapy. Canna x generalis (CG) L.H. Bailey is traditionally used as anti-inflammatory, analgesic and antipyretic. Besides, CG is used in Ayurvedic medicines’ preparations and in the treatment of boils, wounds, and abscess. Nevertheless, its anti-inflammatory effects against ulcerative colitis (UC) are not yet investigated. AimThis study aimed to investigate the phytoconstituents of CG rhizome ethanol extract (CGE). Additionally, we aimed to comparatively evaluate its therapeutic effects and underlying mechanisms against the reference drug “sulphasalazine (SAS)” in dextran sodium sulfate (DSS)-induced UC in mice. Material and methodsMetabolic profiling of CG rhizomes was performed via UHPLC/qTOF-HRMS; the total phenolic, flavonoid and steroid contents were determined, and the main phytoconstituents were isolated and identified. Next, DSS-induced (4%) acute UC was established in C57BL/6 mice. DSS-induced mice were administered either CGE (100 and 200 mg/kg) or SAS (200 mg/kg) for 7 days. Body weight, colon length, disease activity index (DAI) and histopathological alterations in colon tissues were examined. Colon levels of oxidative stress (GSH, MDA, SOD and catalase) and pro-inflammatory [Myeloperoxidase (MPO), nitric oxide (NO), IL-1β, IL-12, TNF-α, and INF-γ] markers were colourimetrically determined. Serum levels of lipopolysaccharide (LPS) and relative mRNA expressions of occludin, TLR4 and ASC (Apoptosis-Associated Speck-Like Protein Containing CARD) using RT-PCR were measured. Protein levels of NLRP3 inflammasome and cleaved caspase-1 were determined by Western blot. Furthermore, immunohistochemical examinations of caspase-3, NF-ҡB and claudin-1 were performed. ResultsMajor identified constituents of CGE were flavonoids, phenolic acids, phytosterols, beside five isolated phytoconstituents (β-sitosterol, triacontanol fatty alcohol, β-sitosterol-3-O-β-glucoside, rosmarinic acid, 6-O-p-coumaroyl-β-D-fructofuranosyl α-D-glucopyranoside). The percentage of the phenolic, flavonoid and steroid contents in CGE were 20.55, 6.74 and 98.09 μg of gallic acid, quercetin and β-sitosterol equivalents/mg extract, respectively. In DSS-induced mice, CGE treatment ameliorated DAI, body weight loss and colon shortening. CGE attenuated the DSS-induced colonic histopathological alternations, inflammatory cell infiltration and histological scores. CGE elevated GSH, SOD and catalase levels, and suppressed MDA, pro-inflammatory mediators (MPO and NO) as well as cytokines levels in colonic tissues. Moreover, CGE downregulated LPS/TLR4 signaling, caspase-3 and NF-ҡB expressions. CGE treatment inhibited NLRP3 signaling pathway as indicated by the suppression of the protein expression of NLRP3 and cleaved caspase-1, and the ASC mRNA expression in colonic tissues. Additionally, CGE restored tight junction proteins’ (occludin and claudin-1) expressions. ConclusionOur findings provided evidence for the therapeutic potential of CGE against UC. CGE restored intestinal mucosal barrier's integrity, mitigated oxidative stress, inflammatory cascade, as well as NF-ҡB/TLR4 and NLRP3 pathways activation in colonic tissues. Notably, CGE in a dose of 200 mg/kg was more effective in ameliorating DSS-induced UC as compared to SAS at the same dose.

Puerarin improves the bone micro-environment to inhibit OVX-induced osteoporosis via modulating SCFAs released by the gut microbiota and repairing intestinal mucosal integrity

ScopeHalf of women over the age of 50 will experience a fracture related osteoporosis in their lifetime. The common treatment is estrogen replacement therapy, which can cause many side effects. Puerarin as a phytoestrogen has been proven to improve postmenopausal osteoporosis. However, the mechanisms of anti-osteoporosis remain unclear due to its low bioavailability. The aim of this study is to investigate whether the anti-osteoporosis effects of puerarin are related to modulations in the gut microbiota and focus on the mechanism of gut / bone axis. MethodsWe established ovariectomized (OVX) rats as osteoporosis model. The femur was analyzed by microcomputed tomography (μ-CT) and we measured serum biochemical indices and inflammatory factors. 16S rRNA sequencing was employed to evaluate the gut microbiota composition in the fecal samples. Short-chain fatty acids (SCFAs) was analyzed by GC. The expression of intestinal inflammatory factors and adhesion proteins was confirmed by western blotting and qPCR. ResultsPuerarin increased the BMD and improved the intestinal mucosal integrity to reduce the systemic inflammation. The disorder of gut microbiota was improved and its metabolites SCFAs were elevated. Metabolic pathways such as amino acid metabolism, LPS biosynthesis and butyrate metabolism were enriched. ConclusionPuerarin treatment modulated the gut microbiota disorder to elicit the anti-osteoporosis effects in OVX rats, by improving the bone micro-environment via regulating the SCFAs levels and repairing the intestinal mucosal integrity.

Contributions of HO-1-Dependent MAPK to Regulating Intestinal Barrier Disruption.

The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.

Gut-lymph-lung pathway mediates sepsis-induced acute lung injury.

This review attempts to unveil the possible mechanisms underlying how gut lymph affects lung and further gives rise to acute respiratory distress syndrome, as well as potential interventional targets under the condition of ischemia-reperfusion injury. We searched electronic databases including PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Web of Science, and Embase to identify relevant literatures published up to December 2019. We enrolled the literatures including the Mesh Terms of “gut lymph or intestinal lymph and acute lung injury or acute respiratory distress syndrome.” Gut is considered to be the origin of systemic inflammation and the engine of multiple organ distress syndrome in the field of critical care medicine, whereas gut lymph plays a pivotal role in initiation of ischemia-reperfusion injury-induced acute respiratory distress syndrome. In fact, in the having been established pathologic model of sepsis leading to multiple organ dysfunction named by Gut Lymph theory, a variety of literatures showed the position and role of changes in gut lymph components in the initiation of systemic inflammatory response, which allows us to screen out potential intervention targets to pave the way for future clinic and basic research.

Stachyose Prevents Intestinal Mucosal Injury in the Immunosuppressed Mice

AbstractStachyose (STA) is extracted from sugar beet and is used as a functional food. In this study, the effects of STA on immunosuppressed mice with intestinal mucosal damage induced by cyclophosphamide (CTX) are investigated. STA treatment can improve the amount of the leukocyte in the blood, the bone marrow cell density, and natural killer (NK) cell activity in the immunosuppressed mice. Furthermore, in immunosuppressed mice, the balance of intestinal bacteria is broken and intestinal mucosal integrity is disrupted. After treatment with STA, the amount of Enterococcus (6.504 ± 0.70) decreases and Bifidobacterium (7.207 ± 0.14) in cecum increases significantly (p &lt; 0.05). Compared with CTX group, the ratio of villous height and crypt depth (V/C) in ileum increases from 2.525 ± 0.10 to 4.891 ± 0.16 (p &lt; 0.001), and in jejunum increases from 2.719 ± 0.03 to 5.827 ± 0.19 (p &lt; 0.001). The expression level of IL‐2 and IL‐1β gene in the spleen, and IL‐1β and tumor necrosis factor alpha gene in the ileum in STA group significantly increases (p &lt; 0.001) compared with the CTX group. In conclusion, STA is a potential prebiotic which exerts indirect and direct effects on the immune system and can counteract the side effects of CTX in the immunosuppressed mice.

Probiotic Bacillus amyloliquefaciens H57 ameliorates subclinical necrotic enteritis in broiler chicks by maintaining intestinal mucosal integrity and improving feed efficiency

Subclinical necrotic enteritis (NE) was induced in broiler chicks using a high dose of Eimeria spp. vaccine in the drinking water on day 9, and Clostridium perfringens (Cp) culture mixed in the feed on days 14 and 15. The aim was to evaluate the effects of probiotic Bacillus amyloliquefaciens strain H57 (H57) in preventing NE in chicks. Day-old Ross 308, male broilers were weighed and randomly assigned to 6 treatment groups (6 replicate cages/treatment and 8 birds/cage). Birds in group 1 (control) were fed the basal wheat-soybean diet without H57 or NE infection; in group 2 (Eimeria) were treated with Eimeria alone; in group 3 (Cp) were treated with Cp alone; in group 4 (NE) received both Eimeria and Cp; in group 5 (NE-H57) received NE infection and H57; and group 6 (H57) received H57. The basal diet of chicks in groups 5 and 6 was supplemented with H57 at a density of 2 × 108 spores/g feed from 1 D of age. On day 21, there were no significant treatment effects on BW and feed intake between control and H57 birds. However, on day 21, the feed conversion ratio of NE-H57 birds was significantly improved when compared with NE birds (1.28 vs. 1.36; P < 0.001). Birds challenged with NE had a higher occurrence of pasty vent than birds infected with either Eimeria, Cp, or NE-H57 (41 vs. 27 vs. 29 vs. 19%, respectively; P < 0.001). Intestinal lesion scores of NE birds were also higher than those of Eimeria, Cp, and NE-H57 birds (5.67 vs. 2.56 vs. 2.78 vs. 2.10, respectively; P < 0.001) and correlated with pasty vent (Pearson's r = 0.56; P < 0.001). Microscopic evaluation showed mucosal damage and necrosis in NE birds. In contrast, villi from NE-H57 birds were normal, with no damage or infiltration with Eimeria or Cp. H57 appears to be effective in challenged birds, as it maintained epithelial barrier integrity and improved feed efficiency.

MicroRNA-674-5p induced by HIF-1\u03b1 targets XBP-1 in intestinal epithelial cell injury during endotoxemia

Intestinal mucosal integrity dysfunction during endotoxemia can contribute to translocation of intestinal bacteria and a persistent systemic inflammatory response, which both fuel the pathophysiological development of sepsis or endotoxemia. The pathogenesis of intestinal damage induced by endotoxemia remains poorly understood. Here, we identified the microRNA (miR)-674-5p/X-box binding protein 1 (XBP-1) axis as a critical regulator and therapeutic target in preventing intestinal crypt cell proliferation during endotoxemia. MiR-674-5p was markedly increased in intestinal epithelial cells (IECs) during endotoxemia and its induction depended on hypoxia-inducible factor-1α (HIF-1α). Intriguingly, gene expression microanalysis revealed that expression of XBP-1 was down-regulated in IECs with over-expression of miR-674-5p. miR-674-5p was found to directly target XBP-1 protein expression. Upon in vitro, anti-miR-674-5p enhanced sXBP-1 expression and facilitated intestinal crypt cell proliferation. Blockade of miR-674-5p promoted XBP-1 activity, attenuated intestinal inflammation, and expedited intestinal regeneration, resulting in protection against endotoxemia-induced intestinal injury in mice. More importantly, the survival in endotoxemia mice was significantly improved by inhibiting intestinal miR-674-5p. Collectively, these data indicate that control of a novel miR-674-5p/XBP-1 signaling axis may mitigate endotoxemia -induced intestinal injury.

A novel histidine-tryptophan-ketoglutarate formulation ameliorates intestinal injury in a cold storage and ex vivo warm oxygenated reperfusion model in rats.

The present study aims to evaluate protective effects of a novel histidine-tryptophan-ketoglutarate solution (HTK-N) and to investigate positive impacts of an additional luminal preservation route in cold storage-induced injury on rat small bowels. Male Lewis rats were utilized as donors of small bowel grafts. Vascular or vascular plus luminal preservation were conducted with HTK or HTK-N and grafts were stored at 4°C for 8 h followed by ex vivo warm oxygenated reperfusion with Krebs-Henseleit buffer for 30 min. Afterwards, intestinal tissue and portal vein effluent samples were collected for evaluation of morphological alterations, mucosal permeability and graft vitality. The novel HTK-N decreased ultrastructural alterations but otherwise presented limited effect on protecting small bowel from ischemia-reperfusion injury in vascular route. However, the additional luminal preservation led to positive impacts on the integrity of intestinal mucosa and vitality of goblet cells. In addition, vascular plus luminal preservation route with HTK significantly protected the intestinal tissue from edema. HTK-N protected the intestinal mucosal structure and graft vitality as a luminal preservation solution. Additional luminal preservation route in cold storage was shown to be promising.

Duan-Nai-An, A Yeast Probiotic, Improves Intestinal Mucosa Integrity and Immune Function in Weaned Piglets

Post-weaning diarrhea commonly occurs in piglets and results in significant economic loss to swine producers. Non-antibiotic measures for managing post-weaning diarrhea are critically needed. Duan-Nai-An, a probiotic produced from the yeast fermentation of egg whites, was previously shown to optimize intestinal flora and reduce the incidence of clinical diarrhea in weaning piglets. To study the effects of Duan-Nai-An on mucosal integrity and immunity in pig intestine, we examined the microstructure and ultrastructure of the intestines of weaned pigs with or without Duan-Nai-An as a feed supplement. The piglets of the Duan-Nai-An-fed group developed intestines with intact columnar epithelia covered by tightly packed microvilli on the apical surface. However, piglets of the control group (no supplement) showed villous atrophy and thinning, microvillus slough, and in the severe cases, damage of intestinal epithelia and exposure of the underlying lamina propria. Moreover, piglets of the Duan-Nai-An-fed group showed apparent plasmocyte hyperplasia, increased lymphoid nodule numbers, well-developed Peyer’s Patchs, and apparent germinal centers. The lymphoid tissues of the control group were far less developed, showing lymph node atrophy, lymphocyte reduction, degeneration, and necrosis. These results indicate that Duan-Nai-An improves the development of the intestinal structures and lymphoid tissues and promotes intestinal health in weaned piglets.

Irritable bowel syndrome in Indonesian adolescents

ObjectiveIrritable bowel syndrome is a frequent functional gastrointestinal disorder. The aims of this study were to investigate its epidemiology, focusing on the role of intestinal mucosal integrity and to evaluate the impact on the quality of life. MethodsA community-based survey applying a comparative cross sectional approach was conducted in six high schools in Palembang. Subjects were recruited using multistage random sampling divided in two groups. Rome III criteria were used to establish a diagnosis of IBS in combination with a questionnaire to determine risk factors. Determination of fecal alpha-1-antitrypsin and calprotectin levels was performed to determine impaired intestinal mucosal integrity. A questionnaire was used to evaluate how quality of life was affected by irritable bowel syndrome. ResultsThe survey was performed in 454 14−18years old adolescents, of whom 30.2% fulfilled the Rome III criteria for IBS, with the following subtypes: 36.5% diarrhea, 18.9% constipation, 21.9% mixed, and 22.6% unclassified. Major risk factors were female gender, bullying, age 14–16 years, history of constipation and diarrhea, eating nuts, and drinking coffee, tea, and soft drinks. There was a significant association with intestinal inflammation (p=0.013). A significantly impaired quality of life was found (p=0.001). ConclusionsThe prevalence of irritable bowel syndrome in adolescents was high, with bullying, female gender, age 14–16 years, constipation and diarrhea, and dietary consumption of soft drinks, coffee, and tea as risk factors. A significant association with intestinal inflammation was found.