Mucosal Lipid Research Articles

Lactobacillus rhamnosus GG powder supplementation alleviates intestinal injury in piglets challenged by porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) has become a challenging problem in pig industry worldwide, causing significant profit losses. Lactobacillus rhamnosus GG (LGG) has been regarded as a safe probiotic strain and has been shown to exert protective effects on the intestinal dysfunction caused by PEDV. This study evaluated the effect of LGG on the gut health of lactating piglets challenged with PEDV. Fifteen piglets at 7 days of age were equally assigned into 3 groups (5 piglets per group): 1) control group (basal diet); 2) PEDV group: (basal diet + PEDV challenged); 3) LGG + PEDV group (basal diet + 3×109 CFU/pig/day LGG + PEDV). The trial lasted 11 days including 3 days of adaptation. The treatment with LGG was from D4 to D10. PEDV challenge was carried out on D8. PEDV infection disrupted the cell structure, undermined the integrity of the intestinal tract, and induced oxidative stress, and intestinal damage of piglets. Supplementation of LGG improved intestinal morphology, enhanced intestinal antioxidant capacity, and alleviated jejunal mucosal inflammation and lipid metabolism disorders in PEDV-infected piglets, which may be regulated by LGG by altering the expression of TNF signaling pathway, PPAR signaling pathway, and fat digestion and absorption pathway.

Zinc methionine improves the lipid metabolism that is associated with the alteration of intestine mucosal proteomes and microbiota of newborn Holstein dairy calves

AbstractSupplementation of diets with a modest amount of zinc methionine (ZM) has been documented to improve the growth performance and antioxidant function of dairy calves, but the underlying mechanisms remain elusive. In the present study, 16 dairy calves were allocated to a control (CON) group (calves consumed a basal diet) and a ZM group (calves ingested the basal diet and had an additional 455 mg ZM/day, corresponding to 80 mg zinc/day). The calves were fed these diets for 2 weeks, after which their serum antioxidant parameters, lipids, and jejunal mucosal proteome and microbiota were analyzed. The ZM group had lower levels of total cholesterol, triglycerides, and malondialdehyde but higher high‐density lipoprotein cholesterol and glutathione peroxidase activity in the serum. A total of 142 differentially expressed proteins in the intestinal mucosa between the CON and ZM groups had been identified (ZM upregulated 117 proteins and downregulated 25 proteins). In addition, the protein expression of acyl‐coenzyme A oxidase 1, fatty acid binding protein 2, and peroxisome proliferator‐activated receptor gamma was higher in the ZM group. 16S rRNA gene sequencing indicated beneficial microbes, such as Veillonellaceae, Akkermansia_muciniphila, and Bifidobacterium adolescentis, which were more abundant, whereas Acinetobacter lwoffii was less abundant in calf jejunal mucosa in the ZM group. Finally, the propionate, butyrate, and iso‐valerate concentrations in the jejunal digesta were greater in the ZM group than those in the CON group. Collectively, the present study shows that ZM supplementation improves the serum and intestine mucosal lipid metabolism associated with the alterations in mucosal fatty acids β‐oxidation and microbiota.

Dietary Prebiotic Oligosaccharides and Arachidonate Alter the Fecal Microbiota and Mucosal Lipid Composition of Suckling Pigs

BackgroundEarly intestinal development is important to infant vitality, and optimal formula composition can promote gut health. ObjectivesThe objectives were to evaluate the effects of arachidonate (ARA) and/or prebiotic oligosaccharide (PRE) supplementation in formula on the development of the microbial ecosystem and colonic health parameters. MethodsNewborn piglets were fed 4 formulas containing ARA [0.5 compared with 2.5% of dietary fatty acids (FAs)] and PRE (0 compared with 8 g/L, containing a 1:1 mixture of galactooligosaccharides and polydextrose) in a 2 x 2 factorial design for 22 d. Fecal samples were collected weekly and analyzed for relative microbial abundance. Intestinal samples were collected on day 22 and analyzed for mucosal FAs, pH, and short-chain FAs (SCFAs). ResultsPRE supplementation significantly increased genera within Bacteroidetes and Firmicutes, including Anaerostipes, Mitsuokella, Prevotella, Clostridium IV, and Bulleidia, and resulted in progressive separation from controls as determined by Principal Coordinates Analysis. Concentrations of SCFA increased from 70.98 to 87.37 mM, with an accompanying reduction in colonic pH. ARA supplementation increased the ARA content of the colonic mucosa from 2.35–5.34% of total FAs. PRE supplementation also altered mucosal FA composition, resulting in increased linoleic acid (11.52–16.33% of total FAs) and ARA (2.35–5.16% of total FAs). ConclusionsPrebiotic supplementation during the first 22 d of life altered the gut microbiota of piglets and increased the abundance of specific bacterial genera. These changes correlated with increased SCFA, which may benefit intestinal development. Although dietary ARA did not alter the microbiota, it increased the ARA content of the colonic mucosa, which may support intestinal development and epithelial repair. Prebiotic supplementation also increased unsaturation of FAs in the colonic mucosa. Although the mechanism requires further investigation, it may be related to altered microbial ecology or biohydrogenation of FA.

Long-term consumption of different doses of Grifola frondosa affects immunity and metabolism: correlation with intestinal mucosal microbiota and blood lipids.

Grifola frondosa (GF) is an edible mushroom with hypoglycemic and hypolipidemic effects. In this study, the specific pathogen-free male mice were randomized into the normal (NM), low-dose GF (LGF), medium-dose GF (MGF), and high-dose GF (HGF) groups. The LGF, MGF, and HGF groups were fed with 1.425g/(kgd), 2.85g/(kgd), and 5.735g/(kgd) of GF solution for 8weeks. After feeding with GF solution, compared with the NM group, the thymus index was significantly increased in the LGF group, and TC, TG, and LDL of mice were significantly increased in the HGF group, while HDL was significantly decreased. Compared with the NM group, the uncultured Bacteroidales bacterium, Ligilactobacillus increased in the LGF group, and Candidatus Arthromitus increased in the MGF group. The characteristic bacteria of the HGF group included Christensenellaceae R7, unclassified Clostridia UCG 014, unclassified Eubacteria coprostanoligenes, and Prevotellaceae Ga6A1. Among them, Ligilactobacillus showed a negative correlation with HDL. Unclassified Eubacterium coprostanoligenes group and Ligilactobacillus showed a positive correlation with TG. In summary, our experiments evidenced that GF improves lipid metabolism disorders by regulating the intestinal microbiota, providing a new pathway for hypolipidemic using GF dietary.

Association between Mucosal Healing and Lipid Profiles in Patients with Ulcerative Colitis: A Cross-Sectional Study

Introduction: Recent meta-analysis showed that ulcerative colitis (UC) is a risk factor for cardiovascular disease (CVD). Dyslipidemia is a well-established risk factor for CVD. However, evidence regarding inflammatory bowel disease (IBD), including UC and lipid profiles, is limited. Additionally, no study has assessed the association between endoscopic activity and lipid profiles in patients with IBD. Therefore, we aimed to clarify the association between mucosal healing (MH) and lipid profiles in patients with UC. Methods: A total of 221 Japanese patients with UC were enrolled in this analysis. Total cholesterol (T-chol), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were divided into tertiles (high, moderate, and low) based on the distributions, respectively. Self-administered questionnaire was used to obtain information regarding medication for dyslipidemia. Complete MH and MH are based on Mayo endoscopic subscore 0 and 0–1, respectively. Results: The percentage of complete MH was 30.8%. In patients without medication for dyslipidemia, high HDL-C (>66 mg/dL) was significantly positively associated with complete MH (adjusted odds ratio [OR] 2.58, 95% CI: 1.04–6.64, p for trend = 0.037). In patients with nonproctitis, a positive association between HDL-C and complete MH was found (adjusted OR 3.54, 95% CI: 1.22–11.01, p for trend = 0.020). T-chol and TG were not associated with MH, regardless of medication for dyslipidemia. Conclusions: Complete MH was significantly positively associated with HDL-C in UC patients without medication for lipid. The disease extent might affect the association between complete MH and HDL-C.

Saudi honey alleviates indomethacin-induced gastric ulcer via improving antioxidant and anti-inflammatory responses in male albino rats

Recent years have reported a rise in the occurrence of gastric ulceration especially among young children and adults. This study investigated the mechanism by which two types of Saudi honey: AlnahalAljawal honey (Wadi) or Bin Ghaithan honey (Talh) exerted their antiulcer potential in indomethacin-induced gastric ulceration. Four cohorts of rats were used: Group 1; Healthy controls, Group 2; Ulcerative animals, Group 3; Ulcerative + Wadi honey treatment, Group 4; Ulcerative + Talh honey treatment. We profiled the levels of different indicators of oxidative stress including the activities of gastric mucosal glutathione superoxide dismutase (SOD), catalase (CAT), peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation (measured as malondialdehyde; MDA). CRP content, IL-10, and plasma tumor necrosis factor-α were also evaluated. The stomach was visually examined for macroscopic lesions and using light microscope for histopathological changes in the glandular mucosa.Wadi or Talh honey significantly reduced the ulcer indices, and essentially protected the glandular mucosa from lesions. Wadi or Talh honey also significantly reduced the gastric mucosal concentrations of GPx, SOD and GSH. In addition, the administration of Wadi or Talh honey decreased gastric mucosal plasma TNF-α and MDA, CRP content, and IL-10 levels. In conclusion, Wadi or Talh honey possibly exerted their antiulcer potential via restoring the homeostasis and stabilizing the enzymatic (SOD and GPx) and non-enzymatic (GSH) antioxidants as well as reducing the levels of inflammatory cytokines (TNF-α, CRP content, IL-10 and, NF-κB activity), and inhibiting the lipid peroxidation in the gastric mucosa. Consequently, Wadi or Talh honey may be of beneficial therapy for patients diagnosed with gastric ulceration. Clinical studies need to be conducted to further support these findings.

Mucosal Genomics Implicate Lymphocyte Activation and Lipid Metabolism in Refractory Environmental Enteric Dysfunction

Background & AimsEnvironmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED.MethodsThe Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome were determined in 52 undernourished SEEM participants and 42 North American controls and patients with celiac disease.ResultsAfter accounting for growth at study entry, circulating insulin-like growth factor-1 (IGF-1) and ferritin predicted linear growth, whereas leptin correlated with future weight gain. The EED transcriptome exhibited suppression of antioxidant, detoxification, and lipid metabolism genes, and induction of anti-microbial response, interferon, and lymphocyte activation genes. Relative to celiac disease, suppression of antioxidant and detoxification genes and induction of antimicrobial response genes were EED-specific. At the epigenetic level, EED showed hyper-methylation of epithelial metabolism and barrier function genes, and hypo-methylation of immune response and cell proliferation genes. Duodenal coexpression modules showed association between lymphocyte proliferation and epithelial metabolic genes and histologic severity, fecal energy loss, and wasting (weight-for-length/height Z < -2.0). Leptin was associated with expression of epithelial carbohydrate metabolism and stem cell renewal genes. Immune response genes were attenuated by giardia colonization.ConclusionsChildren with reduced circulating IGF-1 are more likely to experience stunting. Leptin and a gene signature for lymphocyte activation and dysregulated lipid metabolism are implicated in wasting, suggesting new approaches for EED refractory to nutritional intervention.ClinicalTrials.gov, Number: NCT03588013. (https://clinicaltrials.gov/ct2/show/NCT03588013)

Sar1b mutant mice recapitulate gastrointestinal abnormalities associated with chylomicron retention disease

Chylomicron retention disease (CRD) is an autosomal recessive disorder associated with biallelic Sar1b mutations leading to defects in intracellular chylomicron (CM) trafficking and secretion. To date, a direct cause-effect relationship between CRD and Sar1b mutation has not been established, but genetically modified animal models provide an opportunity to elucidate unrecognized aspects of these mutations. To examine the physiological role and molecular mechanisms of Sar1b function, we generated mice expressing either a targeted deletion or mutation of human Sar1b using the CRISPR-Cas9 system. We found that deletion or mutation of Sar1b in mice resulted in late-gestation lethality of homozygous embryos. Moreover, compared with WT mice, heterozygotes carrying a single disrupted Sar1b allele displayed lower plasma levels of triglycerides, total cholesterol, and HDL-cholesterol, along with reduced CM secretion following gastric lipid gavage. Similarly, decreased expression of apolipoprotein B and microsomal triglyceride transfer protein was observed in correlation with the accumulation of mucosal lipids. Inefficient fat absorption in heterozygotes was confirmed via an increase in fecal lipid excretion. Furthermore, genetically modified Sar1b affected intestinal lipid homeostasis as demonstrated by enhanced fatty acid β-oxidation and diminished lipogenesis through the modulation of transcription factors. This is the first reported mammalian animal model with human Sar1b genetic defects, which reproduces some of the characteristic CRD features and provides a direct cause-effect demonstration.

Effect of corticosteroid (triamcinolone acetonide) and chlorhexidin on chemotherapy- induced oxidative stress in buccal mucosa of rats.

Oral mucositis (OM) refers to erythematous and ulcerative lesions of the oral mucosa. This pathology can occur by various causes. Cancer therapy is one of the well-known causes of OM such as chemotherapy and/or with radiation therapy. It has been widely mentioned that oxidative stress parameters such as lipid peroxidation (LP) levels increase during cancer process. Glutathione (GSH) is one of the major intracellular enzymes to detoxify oxidant molecules. The aim of this study was to investigate and compare the effects of Triamcinolone Acetonide (TA), a synthetic steroid chlorhexidine (CHX), a chemical antiseptic, on 5- fluorouracil (5-FU), a chemotherapeutic agent and soft abrasion induced OM in buccal mucosa of rats.OM was induced in rats through a combination of 5-FU treatment and mild abrasion of the cheek pouch with a wire brush. Buccal mucosa lipid peroxidation (LP) levels were higher (p< 0.05) in 5-FU group than in control although LP levels were lower (p<0.05) in TA group than in control group. The reduced glutathione levels were lower (p<0.05) in 5-FU group than in the control group although its level was higher (p<0.05) in TA and CHX groups than in the 5-FU group. Glutathione peroxidase activity was also higher (p<0.05) in TA group than the 5- FU group. In histopathological analyses, treatment with TA reduced 5-FU induced inflammatory cell infiltration and ulceration (p<0.001) but not with CHX.In conclusion, we observed that TA and CHX treatment modulated chemotherapy induced oxidative injury in the rat OM. However, only TA histopathologically ameliorated the 5-FU induced OM of rats. These findings suggest that TA is a useful agent for management of experimental oxidative injury and OM caused by the chemotherapy.

Detection of cardiac tissues toxicity caused by Monosodium Glutamate and the protective role of vitamin C by Immunohistochemical method, Heart tissue oxidative stress biomarkers and Cardiac dysfunction biomarkers

Objectives: Monosodium Glutamate (MSG) is one of the world’s most extensively used food additives which are ingested as part of commercially processed foods. MSG is a slow excitotoxin food additive which can cause generation of numerous amounts of free radicals which affects many organs such as heart. Vitamin C is an antioxidant protects the body against oxidative stress. Methodology: the experiment was carried out on 100 albino rats weighing about (150-200) g. The animals randomly were divided into equal 4 groups (n=25/group).The first group was served as control , the second group was administered oral doses of Vit.C (200 mg/Kg), the third group was administered oral doses of Monosodium Glutamate (MSG) dissolved in distilled water equal to 60 mg/kg daily (60 mg/Kg) the fourth group was administered oral doses of Monosodium Glutamate (MSG) dissolved in distilled water equal to 60 mg/kg daily (60 mg/Kg) and Vitamin C (200 mg/Kg) for 90 days respectively. Heart tissue oxidative stress biomarkers (Glutathione GSH and Mucosal Lipid Peroxidation MDA) were estimated spectrophotometrically. Cardiac dysfunction biomarkers as protein kinase C (PKC) and troponin-I (Tn-I) were estimated using ELISA. Immunohistochemically, tissues caspase-3 and tumor necrosis factor- alpha (TNF-α) were estimated. Histopathology: Samples from heart were fixed in Formalin 10% for 48 h. Routine histological procedures followed by routine hematoxylin and eosin stain and Masson’s trichrome stains for collagen identification. Results: In control negative and vitamin C group, a normal histological structure of cardiac muscles could be found. Vitamin C administration corrected the disturbances caused by MSG. Conclusions: MSG may produce oxidative stress via the generation of highly toxic oxygen and nitrogen free-radicals and the inhibition of several antioxidant enzymes, altering several physiological and functional changes in the heart; this resembles human myocardial infarction, which causes sudden death in humans. Vitamin C administration showed their cardiac protective effects.

Effects of curcumin on antioxidant capacity and gastric mucosal injury following strenuous endurance training in rats

Strenuous endurance training (SET) in endurance athletes can cause gastrointestinal problems, such as gastritis. Gastritis is associated with increased oxidative stress and an imbalance between free-radical production and antioxidant defences. The present study investigated the effects of SET and curcumin injection on systemic total antioxidant capacity (TAC), gastric mucosal injury and lipid peroxidation (malondialdehyde – MDA) in male rats. Twenty-six male Wistar rats were randomly divided into four groups including Control, Curcumin, Endurance, and Endurance + curcumin. Incremental endurance training (up to 70 min with 35 m/min), and curcumin injection (30 mg/kg bodyweight, three times per week) was carried out in relevant groups. The pathology of gastritis was measured concerning the restoration factors (the number of neutrophils, the formation of new vessels, and proliferation of fibroblasts), gastric MDA levels and the TAC were measured. SET-induced gastritis symptoms, such as gastric mucosal injury and lipid peroxidation and curcumin decreased systemic TAC. However, curcumin reduced exercise-induced gastric mucosal injury and lipid peroxidation. Also, serum levels of TAC were maintained at normal levels following a combination of SET and curcumin injection. These findings suggest that curcumin injection during SET could be useful for managing gastritis symptoms and improving antioxidant capacity in healthy and eutrophic rats.

Ameliorative effect of Boesenbergin A, a chalcone isolated from Boesenbergia rotunda (Fingerroot) on oxidative stress and inflammation in ethanol-induced gastric ulcer in vivo

Ethnopharmacological relevanceBoesenbergia rotunda (L.) Mansf. Kulturpfl., previously known as Boesenbergia pandurata (Family: Zingiberaceae) is a ginger species, locally known as fingerroot. It is an integral part of Southeast Asian traditional medicine in alleviating many gastrointestinal disorders such as flatulence, carminative, stomach ache, dyspepsia, and peptic ulcer. Aim of the studyEarlier we have investigated the cytoprotective effect of Boesenbergia rotunda extract. In the present study, we investigated the gastroprotection activity of Boesenbergin A (BA), a chalcone isolated from Boesenbergia rotunda extract in ethanol-induced ulcer model in rats. Besides, the contribution of anti-inflammatory and anti-oxidant ability of BA as probable mechanisms involved in the anti-ulcer activity, also been studied. Materials and methodsBA was orally administered in rats before ulcer induction with ethanol. The lesions of the gastric mucosa were evaluated macroscopically and histopathologically. The efficiency of BA in mucus production, NO production, PGE2 synthesis, mucosal nonprotein sulphydryls, glutathione (GSH) level, and lipid peroxidation (MDA) level were studied. The involvement of the anti-inflammatory capacity of BA was analyzed by using the measurement of cytokines such as TNF-α and IL-6. Finally, the expression of biomarkers such as HSP 70 and iNOS was analyzed at the transcriptional and translational levels. ResultsWe confirmed the protective capacity of BA via the reduction of ulcerated and haemorrhagic areas. It has induced the protection through lowering GSH, MDA and increased NP-SH level. The plasma NO levels were significantly less in BA treated rats. Both cytokines TNF-α and IL-6 were decreased together with elevated PGE2. Upregulation of HSP and downregulation of iNOS were determined in immunohistochemical and gene expression studies ConclusionsThe current results suggest that the prophylactic effect found with BA is due to (i) boosting of gastric mucus production and suppression of inflammatory mediators, via pro-inflammatory cytokines and (ii) modulating the oxidative stress response. The usefulness of Boesenbergia rotunda in folk medicine in treating ulcers partially could be due to the presence of this chalcone.

Choline and phosphatidylcholine, but not methionine, cysteine, taurine and taurocholate, eliminate excessive gut mucosal lipid accumulation in Atlantic salmon (Salmo salar L)

Excessive enterocyte lipid accumulation, with the suggested term lipid malabsorption syndrome (LMS), is frequently observed in Atlantic salmon (Salmo salar L), in small fish in fresh water as well as in large fish in seawater. The symptoms indicate insufficient supply of components involved in lipid assimilation. The questions addressed in the present work were whether dietary supply of components involved in phospholipid and sterol metabolism might prevent LMS. Atlantic salmon (35 fish, 330 g per 600 L tank) were fed a low fish meal diet (LF) as such or supplemented with taurocholate at two levels (3.5 and 6.9 g/kg), cholesterol (2.0 g/kg), taurine (0.8 g/kg), phosphatidylcholine (15.1 g/kg), choline (3.7 g/kg), cysteine (0.8 g/kg) or methionine (1.0 g/kg). A high fish meal diet (HF) was also included. The overall growth rate of the fish was high (TGC>4.2) with no significant effects of diet. Fish fed the LF diet showed increased relative weight of the pyloric and mid intestine and excessive lipid accumulation in the enterocytes, characteristics which were nearly absent in fish fed the HF diet and the LF diet supplemented with choline and phosphatidylcholine. The phosphatidylcholine supplemented diet showed significantly higher lipid digestibility than the LF diet. None of the other supplements eliminated the signs of excessive enterocyte lipid accumulation. Phosphatidylcholine down-regulated pcyt1a, involved in the phosphatidylcholine synthesis, and both choline and phosphatidylcholine induced apoaIV, important in lipoprotein assembly, and markedly suppressed the lipid droplet marker plin2. Methionine supplementation did not stimulate endogenous synthesis of choline. Cholesterol supplementation suppressed sterol uptake and de novo cholesterol synthesis, and induced sterol efflux from the intestinal mucosa. Taurocholate and taurine induced their respective metabolic pathways. All feed supplements, in particular cholesterol and cysteine, down-regulated genes related to antiviral, chemokine, antigen presentation, immunoglobulinfunctions, as well as of extracellular proteases. The results of this study confirm the results from our previous study showing that choline or phosphatidylcholine is a necessary ingredient in low fish meal diets.

Isolation of lactic acid bacteria capable of reducing environmental alkyl and fatty acid hydroperoxides, and the effect of their oral administration on oxidative-stressed nematodes and rats.

Reinforcement of the hydroperoxide-eliminating activity in the small and large intestines should prevent associated diseases. We previously isolated a lactic acid bacterium, Pediococcus pentosaceus Be1 that facilitates a 2-electron reduction of hydrogen peroxide to water. In this study, we successfully isolated an alternative lactic acid bacterium, Lactobacillus plantarum P1-2, that can efficiently reduce environmental alkyl hydroperoxides and fatty acid hydroperoxides to their corresponding hydroxyl derivatives through a 2-electron reduction. Each strain exhibited a wide concentration range with regard to the environmental reducing activity for each hydroperoxide. Given this, the two lactic acid bacteria were orally administered to an oxygen-sensitive short-lived nematode mutant, and this resulted in a significant expansion of its lifespan. This observation suggests that P. pentosaceus Be1 and L. plantarum P1-2 inhibit internal oxidative stress. To determine the specific organs involved in this response, we performed a similar experiment in rats, involving induced lipid peroxidation by iron-overloading. We observed that only L. plantarum P1-2 inhibited colonic mucosa lipid peroxidation in rats with induced oxidative stress.

Choline supplementation prevents diet induced gut mucosa lipid accumulation in post-smolt Atlantic salmon (Salmo salar L.)

BackgroundVarious intestinal morphological alterations have been reported in cultured fish fed diets with high contents of plant ingredients. Since 2000, salmon farmers have reported symptoms indicating an intestinal problem, which we suggest calling lipid malabsorption syndrome (LMS), characterized by pale and foamy appearance of the enterocytes of the pyloric caeca, the result of lipid accumulation. The objective of the present study was to investigate if insufficient dietary choline may be a key component in development of the LMS.ResultsThe results showed that Atlantic salmon (Salmo salar), average weight 362 g, fed a plant based diet for 79 days developed signs of LMS. In fish fed a similar diet supplemented with 0.4% choline chloride no signs of LMS were seen. The relative weight of the pyloric caeca was 40% lower, reflecting 65% less triacylglycerol content and histologically normal gut mucosa. Choline supplementation further increased specific fish growth by 18%. The concomitant alterations in intestinal gene expression related to phosphatidylcholine synthesis (chk and pcyt1a), cholesterol transport (abcg5 and npc1l1), lipid metabolism and transport (mgat2a and fabp2) and lipoprotein formation (apoA1 and apoAIV) confirmed the importance of choline in lipid turnover in the intestine and its ability to prevent LMS. Another important observation was the apparent correlation between plin2 expression and degree of enterocyte hyper-vacuolation observed in the current study, which suggests that plin2 may serve as a marker for intestinal lipid accumulation and steatosis in fish. Future research should be conducted to strengthen the knowledge of choline’s critical role in lipid transport, phospholipid synthesis and lipoprotein secretion to improve formulations of plant based diets for larger fish and to prevent LMS.ConclusionsCholine prevents excessive lipid accumulation in the proximal intestine and is essential for Atlantic salmon in seawater.

Ethanol-induced gastric ulcer in rats and intervention of tert-butylhydroquinone: Involvement of Nrf2/HO-1 signalling pathway.

Gastric ulcer (GU) is the most common health concern that occurs due to alcohol consumption, smoking and physiological stress. Ethanol-induced GU in animal model resembles the pathophysiology of human ulcer. The present study was designed to investigate the cytoprotective and anti-inflammatory properties of tert-butylhydroquinone (tBHQ), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, against gastric mucosal damage induced by acute exposure of ethanol (5 ml/kg). The intervention of tBHQ (25 and 50 mg/kg, per os (po)) and omeprazole (20 mg/kg, po) was done for 10 consecutive days. Omeprazole was chosen as a standard drug because it is prescribed for the treatment of GU. Pretreatment of tBHQ decreased gastric mucosal lesion, ulcer index, apoptotic cells and lipid peroxidation level induced by ethanol. Furthermore, the intervention of tBHQ increased gastric mucosa integrity, pH, reduced glutathione, collagen and mucus-producing goblet cells. Intervention of tBHQ increased the expression of antioxidant markers such as Nrf2, haeme oxygenase-1 and catalase and decreased the expressions of inflammatory markers such as nuclear factor kappa-light-chain-enhancer of activated B cells and cyclooxygenase-2. The cytoprotective potential of tBHQ against gastric mucosal damage might be due to its ability to enhance cellular antioxidants and anti-inflammatory responses.

Study on the Influence of Free Radicals and Oxidative Stress on Peptic Ulcers

It can be observed that oxidative stress initiates and aggravates many diseases, including peptic ulcers and gastric carcinoma. An increase in rat mucosal glandular lipid peroxidation (LPO) and superoxide dismutase (SOD) and a decrease in catalase (CAT) levels in gastric ulceration induced by cold retention stress were observed, whereas in patients with ulcerated clinical peptic and gastric carcinoma LPO serum is associated with a decrease in SOD and CAT. It was intended to determine the parameters of oxidative stress in the blood and brain in rats after induction of gastric ulcer, the effect of antioxidant treatment on these parameters and on the appearance of gastric ulcer, determination of correlation between oxidative stress and severity of gastric ulcer in rats and also evaluation of vascular endothelial function by in vitro studies in the organ bath, from rat aortic rings with gastric ulcer vs. normal and others under treatment vs. untreated.

P016 Lipidomics in ulcerative colitis reveal disruption of mucosal lipid composition associated with the disease state

BACKGROUND: Several genetic, bacterial, and environmental factors appear to lead to the onset of ulcerative colitis (UC). Moreover, UC seems to be associated with alterations in lipid metabolism, and a disruption of the balance between pro and anti-inflammatory molecules. Membrane bioactive lipids modulate the immune response by functioning as intra- and intercellular signaling molecules. However, there are only few studies describing the mucosal lipid bio-signatures during IBD. Therefore, our study aims to characterize mucosal lipid profiles in treatment-naive UC patients and deep remission UC patients, compared to healthy subjects. METHODS: Newly diagnosed treatment-naive UC patients (n = 21), UC patients in deep remission (n = 12), and healthy volunteers (n = 14) were recruited. The state of deep remission was defined by histological and immunological remission demonstrated by a normalized TNF-α gene expression. Mucosa biopsies were collected by colonoscopy. Lipid analysis was performed by means of ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). In total, 220 lipids from 11 lipid classes were identified and included for data analysis. RESULTS: Sixteen lipids showed significant concentration differences between the study groups reflecting the inflammatory state. The majority of significantly up- or down- regulated lipids were phosphatidylethanolamines (PE), and ceramides (Cer). Data analysis revealed that changes in Cer18:1/24:1, Cer18:1/24:0, and PE38:3 were most prominent between the groups. The concentration of Cer18:1/24:1 was highly increased in UC patients' inflamed mucosa compared with UC patients' healed mucosa, whereas, PE38:3 is exclusively present in UC patients' colonic mucosa (both treatment naive and remission state patients). Furthermore, Cer18:1/24:0 was elevated in a stepwise manner from control to remission, and active UC. CONCLUSION(S): Lipid analysis in UC revealed alterations in the mucosal lipid composition. In this study, we report several lipids, which might be involved in the inflammatory response and pathogenesis seen in IBD. The PE38:3 is especially interesting in a pathophysiological context since it is found in both active colitis and deep remission but not healthy controls.

Lipidomics in Ulcerative Colitis Reveal Alteration in Mucosal Lipid Composition Associated With the Disease State.

The onset of ulcerative colitis (UC) is associated with alterations in lipid metabolism and a disruption of the balance between pro- and anti-inflammatory molecules. Only a few studies describe the mucosal lipid biosignatures during active UC. Moreover, the dynamics of lipid metabolism in the remission state is poorly defined. Therefore, this study aims to characterize mucosal lipid profiles in treatment-naïve UC patients and deep remission UC patients compared with healthy subjects. Treatment-naïve UC patients (n = 21), UC patients in deep remission (n = 12), and healthy volunteers (n = 14) were recruited. The state of deep remission was defined by histological and immunological remission defined by a normalized TNF-α gene expression. Mucosa biopsies were collected by colonoscopy. Lipid analysis was performed by means of ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). In total, 220 lipids from 11 lipid classes were identified. The relative concentration of 122 and 36 lipids was altered in UC treatment-naïve patients and UC remission patients, respectively, compared with healthy controls. The highest number of significant variations was in the phosphatidylcholine (PC), ceramide (Cer), and sphingomyelin (SM) composition. Multivariate analysis revealed discrimination among the study groups based on the lipid profile. Furthermore, changes in phosphatidylethanolamine(38:3), Cer(d18:1/24:0), and Cer(d18:1/24:2) were most distinctive between the groups. This study revealed a discriminant mucosal lipid composition pattern between treatment-naïve UC patients, deep remission UC patients, and healthy controls. We report several distinctive lipids, which might be involved in the inflammatory response in UC, and could reflect the disease state.

Skin Mucus Fatty Acid Composition of Gilthead Sea Bream (Sparus Aurata): A Descriptive Study in Fish Fed Low and High Fish Meal Diets

Terrestrial protein and lipid sources are commonly used as substitutes for marine fishery-derived raw ingredients in fish diets. However, their use is related with several side-effects on marine fish performance, health, or disease resistance. Physical barriers of the skin, gills, and gut constitute the primary defense mechanism of fish. Skin mucus mucosal mucins, water, proteins, ions, and lipids determine the physical, chemical, and protective characteristics of skin mucus. Very little is known about the influence of diet composition on fish skin mucus fatty acid profile. Gilthead sea bream skin mucus contained 10% of total lipids (TL), which consisted of 50–60% neutral (NL) and 40–50% polar lipids (PL) fractions. Σn−3 long chain polyunsaturated fatty acids (LC-PUFA) deposition was preferential in the NL fraction, whereas Σn−6LC-PUFA accumulation was similar in both lipid classes. Docosahexaenoic acid (DHA; 22:6n−3) was the main LC-PUFA stored in skin mucus (14% TL) in relation to eicosapentaenoic acid (EPA; 20:5n−3) (2–3% TL) and arachidonic acid (ARA; 20:4n−6) (2% TL). This study denotes the importance of DHA as component of skin mucus lipids compared to other essential fatty acids, such as EPA and ARA, as well as importance of maintaining an adequate Σn−3/ Σn−6 ratio, regardless of dietary intake.