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Blidingia sp. extracts improve intestinal health and reduce diarrhoea in weanling piglets
Abstract
Blidingia sp. is a prominent fouling green macroalga and we previously found that extracts from Blidingia sp. alleviated intestinal inflammation in mice challenged with lipopolysaccharides. However, whether these extracts are effective in weanling piglets remains unknown. In the present study, Blidingia sp. extracts were supplemented in the diet and their effects on growth performance, incidence of diarrhoea and intestinal function in weanling piglets were explored. The results showed that diets supplemented with 0.1% or 0.5% Blidingia sp. extract significantly increased average daily body weight gain and feed intake in weanling piglets. Meanwhile, piglets supplemented with 0.5% Blidingia sp. extract showed decreased incidence of diarrhoea as well as reduced fecal water and Na+ content. Furthermore, the diet supplemented with 0.5% Blidingia sp. extracts improved intestinal morphology, as indicated by the results of hematoxylin and eosin staining. Diet supplemented with 0.5% Blidingia sp. extracts also improved tight junction function, as indicated by increased expression of Occludin, Claudin-1 and Zonula occludens-1, and alleviated the inflammatory response, as indicated by decreased tumor necrosis factor-α and interleukin-6 (IL6) contents and increased IL10 levels. Taken together, our results showed that Blidingia sp. extracts had beneficial effects in weanling piglets and we suggest that Blidingia sp. extracts could be potentially used as an additive for piglets.
... In our study, the higher level of expression of these tight junction proteins in rabbits fed Ulva lactuca may indicate a potential mechanism of action of this macroalgae, even though the improvement in the intestinal barrier was insufficient to maintain gut health during infection, as the worst results regarding coccidia counts and morphometric measures of jejunal mucosa were obtained in the rabbits in these groups. To our knowledge, this potential mechanism of action of Ulva lactuca has not previously been assessed in rabbits, but similar results have been observed in weanling piglets fed with 0.1-0.5% of an extract derived from another green macroalgae-Blidingia spp.-which increased the expression of CLDN-1, OCLN and ZO-1 [56]. ...
Rabbit meat production faces challenges due to the prevalence of gastrointestinal diseases in rabbits, exacerbated by restrictions on antibiotic use in European animal production. Marine macroalgae, rich in bioactive compounds such as soluble polysaccharides, represent promising solutions to this problem. However, research on the effects of macroalgae and the underlying mechanisms in rabbits is limited, especially in commercial settings. This study aimed to evaluate the impact of Saccharina latissima (dehydrated) and Ulva lactuca (dehydrated and hydrolyzed extract) on rabbit on growth performance and gut health in a commercial farm context. A total of 96 litters (8 rabbits/litter) of crossbred rabbits weaned at 33 days of age were randomly assigned to 4 experimental groups (control, Saccharina latissima dehydrated, Ulva lactuca dehydrated and Ulva lactuca hydrolyzed extract; 24 replicates/treatment) and monitored from weaning to slaughter at 61 days of age. The key indicators of gut health were assessed 14 days post-weaning by counting coccidia, isolating specific microflora and examining histological samples. Additionally, the relevant intestinal markers (microbiome composition, mucin content and gene expression related to immune response and tight junction proteins) were determined in order to elucidate the potential mechanisms involved. The inclusion of macroalgae in the diet did not influence growth performance of the animals. S. latissima had a positive effect in reducing coccidia counts (p = 0.10) and improving mucosal morphology (p < 0.001), which can possibly be attributed to modulation of the microbiota and improved mucosal functionality. Ulva lactuca had a favorable effect on gut tight junction proteins (p < 0.001), enhancing intestinal barrier function. These findings suggest the potential of macroalgae to modify the intestinal microbiome by reducing the presence of inflammatory bacteria. Further research is warranted to elucidate the mechanisms involved and optimize macroalgae supplementation in rabbit nutrition for enhanced gut health.
Diarrheal disease is a common health problem with complex causality. Although diarrhea is accompanied by disturbances in microbial diversity, how gut microbes are involved in the occurrence of diarrhea remains largely unknown. Here, using a pig model of post-weaning stress-induced diarrhea, we aim to elucidate and enrich the mechanistic basis of diarrhea. We found significant alterations in fecal microbiome, their metabolites, and microRNAs levels in piglets with diarrhea. Specifically, loss of ssc-miRNA-425-5p and ssc-miRNA-423-3p, which inhibit the gene expression of fumarate reductase (frd) in Prevotella genus, caused succinate accumulation in piglets, which resulted in diarrhea. Single-cell RNA sequencing indicated impaired epithelial function and increased immune response in the colon of piglet with diarrhea. Notably, the accumulated succinate increased colonic fluid secretion by regulating transepithelial Cl-secretion in the epithelial cells. Meanwhile, succinate promoted colonic inflammatory responses by activating MyD88-dependent TLR4 signaling in the macrophages. Overall, our findings expand the mechanistic basis of diarrhea and suggest that colonic accumulation of microbiota-produced succinate caused by loss of miRNAs leads to diarrhea in weanling piglets.
Scope
To investigate the anti‐ageing and anti‐diabetic effects of Enteromorpha prolifera oligosaccharide (EPO) in age‐matched streptozocin‐induced diabetic mice.
Methods and Results
LC‐MS metabolomics and 16S rRNA sequencing is used to identify the brain metabolites and gut microbiota, respectively. EPO could significantly improve glucose metabolism and activity of total superoxide dismutase in serum. It also could regulate the tricarboxylic acid cycle, arginine, and inosine‐related metabolic pathways in the brain of aged diabetic mice. Inosine is found to enhance the relative expressions of daf‐2, daf‐16, and skn‐1 in insulin‐resistant Caenorhabditis elegans. Additionally, EPO could alter the composition and diversity of gut microbiota in mice. It could upregulate the Signal Transducer and Activator of Transcription 3/Forkhead Box O1 (FOXO1)/B cell lymphoma 6 (Bcl‐6) pathways in the brain and the c‐Jun N‐terminal Kinase (JNK)/FOXO1/Bcl‐6 signaling axis in the intestine to regulate glucose metabolite status and ageing in mice. EPO could also improve the levels of glucagon‐like peptide type 1 (GLP1) expression in the gut, thereby inducing high expression of GLP1 receptor in the brain to control glucose metabolites through the brain–gut axis. Enterococcus is negatively correlated with AMP in the brain and could be a potential hallmark species in age‐related diabetes.
Conclusions
These results suggest that EPO could be a potential novel natural drug for the treatment of diabetes in the elderly.
Post weaning diarrhea (PWD) caused by enterotoxigenic strains of E. coli (ETEC) remains a major problem in the industry, causing decreases in performance and survival of weaned pigs. Traditionally, antimicrobials have been used for its mitigation/control. This study tested the hypothesis that a combination of two organic acid (OA)-based commercial feed additives, Presan FX [an OA, medium-chain fatty acid (MCFA) and phenolic compound-based product] and Fysal MP (free and buffered OA based on formic acid), would reduce PWD and improve post-weaning performance in pigs challenged with an F4-ETEC. This combination was assessed against a Negative control diet without any feed additives and a diet containing amoxicillin. Combined with a reduction in temperature during the infection period, inoculation with F4-ETEC resulted in 81% of pigs developing diarrhea, but with no differences between treatments (P > 0.05). However, between d 14-20 of the study and due to colonization by Salmonella serovars, pigs fed the combination of Presan FX and Fysal MP showed less (P = 0.014) diarrhea commensurate with a lower (P = 0.018) proportion of Salmonella numbers relative to total bacterial numbers. This caused less (P = 0.049) therapeutic antibiotic administrations relative to the diet with amoxicillin during this time. The diversity of bacteria within amoxicillin-treated pigs was lower (P = 0.004) than the diversity in control or Presan + Fysal MP-treated pigs (P = 0.01). Pair-wise comparisons showed that amoxicillin-treated pigs had altered (P < 0.001) fecal microbial communities relative to both Presan FX + Fysal MP-treated pigs and control pigs. Amoxicillin-treated pigs were characterized by an increased abundance of bacterial families generally linked to inflammation and dysbiosis in the gastrointestinal tract (GIT), whereas Presan FX + Fysal MP-treated pigs had an increased abundance of bacterial families considered beneficial commensals for the GIT. Control pigs were characterised by an increased abundance of Spirochaetaceae associated with healthy piglets, as well as bacterial families associated with reduced feed intake and appetite. The combination of two OA-based feed additives did not reduce the incidence of F4 ETEC-associated diarrhea nor enhance performance. However, the combination markedly reduced diarrhea caused by Salmonella that occurred following the ETEC infection, commensurate with less therapeutic administrations relative to the diet with amoxicillin.
Feces are enriched with miRNAs that shape the gut microbiota. These miRNAs are differentially expressed in the feces of healthy and diseased subjects. However, whether fecal miRNAs in subjects with inflammatory bowel diseases are involved in regulating microbiota composition and whether they have any beneficial effects, remains unknown. Here, we studied the fecal microbiome composition and miRNA abundance in mice with dextran sulfate sodium (DSS)-induced colitis and mice at the recovery phase, to explore different miRNAs expressed, and their relations with microbial abundance, and their effects on colitis. We found that miR-142a-3p expression was significantly increased in the feces of mice recovered from colitis and that it could alleviate disease symptoms in mice treated with DSS in a microbiome-dependent manner. Specifically, miR-142a-3p promoted the growth of Lactobacillus reuteri, which had a high abundance in the feces of mice recovered from colitis, by regulating transcripts of polA and locus tag LREU_RS03575. Moreover, L. reuteri, as well as its metabolite reuterin, could alleviate DSS-induced disease symptoms. These results highlight the role of fecal miR-142a-3p in the prevention of colitis. We propose that the feces of subjects who have recovered from diseases might be enriched with miRNAs with preventive effects against those diseases.
In pigs and broiler chickens, the gastrointestinal tract or gut is subjected to many challenges which alter performance, animal health, welfare and livability. Preventive strategies are needed to mitigate the impacts of these challenges on gut health while reducing the need to use antimicrobials. In the first part of the review, we propose a common definition of gut health for pig and chickens relying on four pillars, which correspond to the main functions of the digestive tract: (i) epithelial barrier and digestion, (ii) immune fitness, (iii) microbiota balance and (iv) oxidative stress homeostasis. For each pillar, we describe the most commonly associated indicators. In the second part of the review, we present the potential of functional amino acid supplementation to preserve and improve gut health in piglets and chickens. We highlight that amino acid supplementation strategies, based on their roles as precursors of energy and functional molecules, as signaling molecules and as microbiota modulators can positively contribute to gut health by supporting or restoring its four intertwined pillars. Additional work is still needed in order to determine the effective dose of supplementation and mode of administration that ensure the full benefits of amino acids. For this purpose, synergy between amino acids, effects of amino acid-derived metabolites and differences in the metabolic fate between free and protein-bound amino acids are research topics that need to be furtherly investigated.
Serine and glycine are 2 of the first-affected nonessential amino acids in low crude protein (CP) diets for pigs. Therefore, we explored the effects of different dietary serine-to-glycine ratios on growth performance and lipid metabolism in growing-finishing pigs. A total of 160 crossbred healthy barrows, with a similar body weight of around 59.50 kg, were randomly allotted into 1 of 5 treatments (8 pens per treatment and 4 pigs per pen). The serine-to-glycine ratios of the 5 dietary treatments were as follows: diet A (NORMAL group), 1.18:1 (16% CP); diet B (LOW group), 1.2:1 (12% CP); diet C (S2G1 group), 2:1 (12% CP); diet D (S1G2 group), 1:2 (12% CP); and diet E (S1G1 group), 1:1 (12% CP).We found that the pigs fed a low CP diet (12% CP), when maintaining serine-to-glycine ratio at 1:2 and a total amount of 1.44%, had the same average daily gain as the pigs fed a normal CP diet (16% CP) (P > 0.05), but they had increased intramuscular fat (P < 0.05). Furthermore, they exhibited higher expression of genes involved in lipid oxidation (P < 0.05), which was regulated by modulating methylation levels in the promoters of acyl-CoA oxidase 1 (ACOX1) and acyl-CoA dehydrogenase medium chain (ACADM). When compared with the pigs fed a normal CP diet, these pigs had more oxidative myofibers (P < 0.05), which were regulated by AMPK-PGC-1α and Calcineurin-MEF2/NFAT pathways in a coordinated manner. Our findings suggested that a dietary serine-to-glycine ratio of 1:2 is beneficial for improving meat quality in pigs fed a low CP diet.
Simple Summary
Zinc oxide (ZnO) supplementation at pharmacological doses in post-weaning piglets is a consolidated practice that allows efficient control of post-weaning diarrhea (PWD), a condition exacerbated by Escherichia coli F4 (K88) infections. Far from being completely elucidated, the multifactorial ZnO mechanism of action is in all likelihood exerted at the gastrointestinal level. However, increasing environmental concerns are arising from prolonged ZnO use. This article reviews the utilization of ZnO in piglets, the biological rationale behind its powerful activity, and the emerging threats that are leading towards a significant reduction in its use. Finally, a wide analysis of the strengths and weaknesses of innovative alternative strategies to manage PWD at the nutritional level is given.
Abstract
Zinc oxide (ZnO) at pharmacological doses is extensively employed in the pig industry as an effective tool to manage post-weaning diarrhea (PWD), a condition that causes huge economic losses because of its impact on the most pivotal phase of a piglet’s production cycle. In a multifactorial way, ZnO exerts a variety of positive effects along the entire gastrointestinal tract by targeting intestinal architecture, digestive secretions, antioxidant systems, and immune cells. ZnO also has a moderate antibacterial effect against Escherichia coli F4 (K88), the main causative agent of PWD. However, the environmental impact of ZnO and new emerging threats are posing serious questions to the sustainability of its extensive utilization. To work towards a future free from pharmacological ZnO, novel nutritional approaches are necessary, and many strategies have been investigated. This review article provides a comprehensive framework for ZnO utilization and its broad mode of action. Moreover, all the risks related to pharmacological ZnO levels are presented; we focus on European institutions’ decisions subsequently. The identification of a novel, complete solution against PWD should be accompanied by the adoption of holistic strategies, thereby combining good management practices to feeding approaches capable of mitigating Escherichia coli F4 (K88) infections and/or lowering ZnO utilization. Promising results can be obtained by adjusting diet composition or employing organic acids, natural identical compounds, polyphenol-rich extracts, prebiotics, and probiotics.
This research evaluated a feed additive (benzoic acid, eugenol, thymol and piperine), associated or not with colistin, in weaned piglets feeding. The parameters evaluated were growth performance, apparent total tract digestibility (ATTD) of nutrients, diarrhea incidence, intestinal morphology, relative weights of digestive organs, microbial diversity and the percentages of operational taxonomic units of microorganisms in the caecum content of pigs. One hundred and eight crossbred piglets (5.3 ± 0.5 kg) were used in a three-phase feeding program (21-35, 36-50, 51-65 days of age), and fed a control diet with no inclusion of growth promoter feed additive, a diet with 40 ppm of colistin, a diet with 0.3% of alternative additive and a diet with 0.3% of alternative additive and 40 ppm of colistin. The diets were based on corn, soybean meal, dairy products, and spray-dried blood plasma, formulated to provide 3.40, 3.38, and 3.20 Mcal of ME/kg; and 14.5, 13.3, and 10.9 g/kg of digestible lysine, in phases 1, 2, and 3, respectively. The piglets were housed three per pen, with 9 replicates per diet, in a complete randomized block design based on initial BW. The data was submitted to ANOVA and means were separated by Tukey test (5%), using SAS. Pigs fed diets with the alternative feed additive had greater (P < 0.05) ADG (114.3 g vs. 91.8 g) and ADFI (190.1 g vs. 163.3) in phase 1 than pigs fed diets without the product. The alternative additive improved (P < 0.05) ATTD of CP in phase 1 (71.0% vs. 68.6%), GE in phases 1 (77.4% vs. 75.2%) and 3 (79.0% vs. 77.1%), and DM in phase 3 (79.1% vs. 77.1%). The antibiotic inclusion in the diets increased (P < 0.05) ATTD of CP in phase 1 (71.5% vs. 68.2%). The alternative feed additive tended (P = 0.06) to increase (46%) normal feces frequency, decreased (P < 0.05) goblet cells count (104.3 vs. 118.1) in the jejunum, and decreased (P < 0.05) small intestine (4.60% vs. 4.93%) and colon (1.41% vs. 1.65%) relative weights, compared to pigs not fed with the alternative additive. There was a tendency (P = 0.09) for a lower concentration of Escherichia-Shigella (1.46 vs. 3.5%) and lower (P < 0.05) percentage of Campylobacter (0.52 vs. 10.21%) in the cecum content of piglets fed diets containing essential oils and benzoic acid compared to pigs fed diets without the alternative feed additive. The alternative feed additive was effective in improving growth performance, diets digestibility and gut health in piglets soon after weaning.
Blidingia sp. is a green alga that has spread rapidly in Subei Shoal, China. To explore the potential beneficial effects of Blidingia sp., we investigated the anti-inflammatory activity of its water-methanol extract of Blidingia sp. in a mouse model of lipopolysaccharide (LPS)-induced intestinal inflammation. The results revealed that the administration of Blidingia extract significantly alleviated the LPS-induced increase of the inflammatory cytokine content in the serum, as well as latter's gene expression in the ileum. Moreover, the extract inhibited the phosphorylation of NF-κB and IκBα in LPS-challenged mice. Apart from these changes, the extract also averted intestinal morphology damage(s) and cell apoptosis in mice. Interestingly, the extract also had beneficial effects on the diversity and composition of caecal microbiota in LPS-challenged mice. In conclusion, the results suggested that Blidingia extract had beneficial effects on the recovery of intestinal function by reducing the inflammatory response, improving the maintenance of intestinal morphology, and decreasing cell apoptosis in LPS-induced intestinal inflammation. In addition, the beneficial effects of the extract on caecal microbiota composition may play a role in its anti-inflammatory activity. These results suggested that Blidingia extract could be potentially used in preventing intestinal inflammation.
Intensive farming may involve the use of diets, environments or management practices that impose physiological and psychological stressors on the animals. In particular, early weaning is nowadays a common practice to increase the productive yield of pig farms. Still, it is considered one of the most critical periods in swine production, where piglet performance can be seriously affected and where they are predisposed to the overgrowth of opportunistic pathogens. Pig producers nowadays face the challenge to overcome this situation in a context of increasing restrictions on the use of antibiotics in animal production. Great efforts are being made to find strategies to help piglets overcome the challenges of early weaning. Among them, a nutritional strategy that has received increasing attention in the last few years is the use of probiotics. It has been extensively documented that probiotics can reduce digestive disorders and improve productive parameters. Still, research in probiotics so far has also been characterized as being inconsistent and with low reproducibility from farm to farm. Scientific literature related to probiotic effects against gastrointestinal pathogens will be critically examined in this review. Moreover, the actual practical approach when using probiotics in these animals, and potential strategies to increase consistency in probiotic effects, will be discussed. Thus, considering the boost in probiotic research observed in recent years, this paper aims to provide a much-needed, in-depth review of the scientific data published to-date. Furthermore, it aims to be useful to swine nutritionists, researchers and the additive industry to critically consider their approach when developing or using probiotic strategies in weaning piglets.
Two experiments (E) were carried out to evaluate the effects of fumaric acid and an acidifier blend [composed by calcium formate, calcium lactate and medium-chain fatty acids (capric and caprylic)] in piglet diets containing colistin (40 ppm) or halquinol (120 ppm) on performance, diarrhea incidence (E1), organs relative weight, pH values, intestinal morphometry and microbiota (E2). In E1, 192 and E2, 24 piglets weaned at 21-day-old were randomly assigned to blocks with 2x2 factorial arrangement of treatments [absence or presence of fumaric acid x absence or presence of acidifier blend], six replicates of eight (E1) and one piglet per pen (E2). For E1, the treatments were control (CD): no acidifier product + 40 ppm of colistin, FA: fumaric acid in absence of acidifier blend, AB: acidifier blend in absence of fumaric acid and, AF+AB: presence of fumaric acid and acidifier blend. For E2, the pre-starter I diet were used and the same treatments as E1 evaluated. No treatment effects (P>0.05) were observed on performance, diarrhea incidence (E1), gut pH values and duodenum morphometry of piglets (E2). However, the addition of AB increased (P<0.05) large intestine relative weight and, FA addition decreased (P<0.05) pancreas relative weight, jejunum villi height and, total coliform and E. coli counts in cecum. The inclusion of FA and AB in diets containing colistin or halquinol did not improve performance, although FA exerted an inhibitory effect on cecum microbiota.
Ulva prolifera
is the major causative species in the green tide, a serious marine ecological disaster, which bloomed in the Yellow Sea and the Bohai Sea of China. However, it is also a popular edible seaweed and its extracts exerts anti-inflammatory and antioxidant effects. The present study investigated the effects of ethanol extract ofU. prolifera(EUP) on insulin sensitivity, inflammatory response, and oxidative stress in high-fat-diet- (HFD-) treated mice. HFD-treated mice obtained drinking water containing 2% or 5% EUP. The results showed that EUP supplementation significantly prevented HFD-induced weight gain of liver and fat. EUP supplementation also improved glucose tolerance and insulin resistance in HFD-treated mice. Moreover, EUP supplementation prevented the increased expression of genes involved in triglyceride synthesis and proinflammatory genes and the decreased expression of genes involved in fatty acid oxidation in liver of HFD-treated mice. Furthermore, EUP supplementation decreased reactive oxygen species content, while increasing glutathione content and glutathione peroxidase activity in HFD-treated mice. In conclusion, our results showed that EUP improved insulin resistance and had antilipid accumulation and anti-inflammatory and antioxidative effects on HFD-treated mice. We suggested thatU. proliferaextracts may be regarded as potential candidate for the prevention of nonalcoholic fatty liver disease.
A study was conducted to evaluate the effects of resveratrol and essential oils from medicinal plants on the growth performance, immunity, digestibility, and fecal microbial shedding of weaned piglets. A total of 48 weaned piglets (8 kg initial weight, 28-d-old) were randomly allotted to four dietary treatments with 3 replications of 4 piglets each. The dietary treatments were NC (negative control; basal diet), PC (positive control; basal diet+0.002% apramycin), T1 (basal diet+0.2% resveratrol), and T2 (basal diet+0.0125% essential oil blend). All piglets were orally challenged with 5 ml culture fluid containing 2.3×10(8) cfu/ml of Escherichia coli KCTC 2571 and 5.9×10(8) cfu/ml Salmonella enterica serover Typhimurium. The PC group (p<0.05) showed the highest average daily gain (ADG) and average daily feed intake (ADFI) throughout the experimental period, although feed conversion ratio (FCR) was improved in the T1 group (p>0.05). Serum IgG level was increased in the T1 group, whereas TNF-α levels was reduced in the supplemented groups compared to control (p<0.05). The PC diet improved the dry matter (DM) digestibility, whereas PC and T2 diets improved nitrogen (N) digestibility compared to NC and T1 diets (p<0.05). Fecal Salmonella and E. coli counts were reduced in all treatment groups compared to control (p<0.05). Fecal Lactobacillus spp. count was increased in the T2 group compared to others (p<0.05). Dietary treatments had no significant effect on fecal Bacillus spp. count throughout the entire experimental period. Based on these results, resveratrol showed strong potential as antibiotic alternatives for reversing the adverse effects of weaning stress on growth performance, immunity and microbial environment in E. coli and Salmonella-challenged piglets.
The objective of this study was to evaluate effects of dietary L-lysine on the intestinal mucosa and expression of cationic amino acid transporters (CAT) in weaned piglets. Twenty-eight piglets weaned at 21 days of age (Duroc × Landrace × Yorkshire; 6.51 ± 0.65 kg body weight) were assigned randomly into one of the four groups: Zein + LYS (zein-based diet + 1.35 % supplemental lysine), Zein - LYS (zein-based diet), NF (nitrogen-free diet), and CON (basal diet). The experiment lasted for 3 weeks, during which food intake and body weight were recorded. At the end of the trial, blood was collected from the jugular vein of all pigs, followed by their euthanasia. Dietary supplementation with lysine enhanced villus height and crypt depth in the jejunum (P < 0.05). Jejunal mRNA levels for the b(0,+)-AT, y(+)LAT1 and CAT1 genes were greater (P < 0.05) in the Zein + LYS group than in the control, and the opposite was observed for CAT1. Dietary content of lysine differentially affected intestinal CAT expression to modulate absorption of lysine and other basic amino acids. Thus, transport of these nutrients is a key regulatory step in utilization of dietary protein by growing pigs and lysine in the diet influences the expression of amino acid transporters in the small intestine.
Background
Obesity-related metabolic diseases have recently evoked worldwide attention. Studies have demonstrated that Enteromorpha polysaccharide (EP) exerts lipid-lowering effects, but the underlying mechanism remains unclear.
Objective
To investigate whether EP regulates lipid metabolism disorders in mice with high-fat diet (HFD)-induced obesity via an AMP-activated protein kinase (AMPK)-dependent pathway.
Methods
Six-week-old male C57BL/6J mice (18 ± 2 g) were fed a normal diet (ND; 10% energy from fats) or a HFD (60% energy from fats) for 6 weeks to induce obesity and treated intragastrically with EP (200 mg/kg body weight) or distilled water (10 mL/kg body weight) for 8 weeks. Biochemical indicators, AMPK-dependent pathways and lipid metabolism-related genes were evaluated to assess the effects of EP on HFD-induced lipid metabolism disorders. The essential role of AMPK in the EP-mediated regulation of lipid metabolism was confirmed using HFD-fed male Ampka2-knockout mice (aged 6 weeks, 17 ± 2 g) treated or not treated with the above-mentioned dose of EP. The data were analyzed by t tests and two-factor and one-way ANOVAs.
Results
Compared to the ND, the HFD resulted in the greater body weight (24.3%), perirenal fat index (2.2-fold), and serum TC (24.66%) and LDL cholesterol (1.25-fold) concentrations (P < 0.05) and dysregulated the AMPK-dependent pathway and the expression of most lipid metabolism-related genes (P < 0.05). Compared to the HFD, EP treatment resulted in the lower perirenal fat index (31.22%) and the LDL-C concentration (23.98%) and partly reversed the dysregulation of the AMPK-dependent pathway and the altered expression of lipid metabolism-related genes (P < 0.05). Ampka2 knockout abolished the above-mentioned effects of EP in obese mice and the EP-mediated effects on the expression of lipid metabolism-related genes (P > 0.05).
Conclusions
These findings suggest that EP can ameliorate lipid metabolism disorders in mice with HFD-induced obesity via an AMPK-dependent pathway.
Organic acids and phytogenic compounds have been used in pig feeding as alternatives to antibiotic growth promoters. However, few studies have evaluated the systemic effect of the combination of these additives. The aim of this study was to assess the impact of a feed additive (OAFA), containing a blend of organic acids and cinnamaldehyde, on the tissue integrity of bacterially challenged piglets. Thirty weaned piglets 21 days old were used in a 19-d trial. Pigs received a standard diet during the first seven days and afterwards were allotted to five treatments. Dietary treatments were: Control (basal diet), Escherichia coli (basal diet and challenge with E. coli), colistin (basal diet+ 200mg colistin/kg feed+ challenge with E. coli), organic acid based feed additive (OAFA) 1 (basal diet + 1kg OAFA/ton feed+ challenge with E. coli), and OAFA 2 (basal diet + 2kg OAFA/ton feed+ challenge with E. coli). Seven days after the beginning of the treatment, the animals were challenged with an enterotoxic strain of E. coli (K88) for pigs. Five days after the challenge, all animals were euthanized for tissue sampling for histological and oxidative stress (intestine and liver) analysis. The reduced glutathione (GSH), ferric-reducing ability potential (FRAP) and free-radical scavenging ability (ABTS) assays were used to evaluate the intestinal antioxidant defence. Lipid peroxidation and superoxide anion production were evaluated through the levels of thiobarbituric acid-reactive substances (TBARS) and nitroblue tetrazolium (NBT) reduction assay, respectively. Animals fed the OAFA (1-2) diets had a decrease (P<0.05) on histological changes in the intestine, liver, mesenteric lymph nodes and spleen. Greater villus height and higher ratio of villus height to crypt depth were observed in animals of the OAFA2 group compared with the control and E. coli groups. The colistin and OAFA groups decreased (P<0.05) the number of inflammatory cells in intestinal lamina propria. OAFA2 group increased (P<0.05) intestinal cell proliferation. Colistin and OAFA2 supplementation induced a decrease (P<0.05) in the levels of TBARS in both the intestine and liver compared to E. coli group. In addition, an increase (P<0.05) in GSH and FRAP ileal levels was observed in OAFA2 group compared to E. coli group. These results show that the supplementation with OAFA in the diet of weaned piglets, especially at a dose of 2kg/ton (OAFA2) protected tissues against ETEC damage.
Blidingia minima is a green alga that is ubiquitous on many coastlines. To explore the potentially beneficial effects of polysaccharides extracted from Blidingia minima (BMP), in vitro and in vivo studies were performed using dextran sulfate sodium (DSS)-treated intestinal epithelial cells (IPEC-J2 cells) and mice with DSS-induced colitis, respectively. BMP showed an anti-inflammatory effect on DSS-treated cells. Furthermore, BMP alleviated colitis symptoms in DSS-treated mice. BMP repaired colonic dysfunction, and colonic morphology, infiltration, and the expression of tight junction proteins were all improved. Moreover, the mRNA expression and level of pro-inflammatory cytokines, as well as the phosphorylated protein levels of AKT, IκB-α, and NF-κB in colonic tissue, were all decreased by BMP supplementation. We suggest that the anti-inflammatory effects of BMP may be associated with the modulation of NF-κB pathways. These results promote the potential application of BMP as a novel, next-generation therapeutic for treatment of inflammatory bowel disease.
Apple polyphenols (APPs) are biologically active flavonoids that have antioxidant, anti‐inflammatory, improving insulin sensitivity, hypocholesterolaemic effect and antiviral properties. This study was conducted to explore effects of dietary APPs supplementation on antioxidant activities and lipid metabolism in weaned piglets. Fifty‐four weaned piglets (half male and female) were randomly divided into three groups with six replicates in each group and three piglets in each repetition. Piglets were fed control diet (basal diet) or a control diet supplemented with 400 mg/kg or 800 mg/kg APPs for 6 weeks. Blood and liver samples were collected to determine biochemical, antioxidant and lipid metabolism parameters. Here we showed that dietary APPs supplementation increased HDL‐C and decreased T‐CHO, TG and LDL‐C concentrations. Dietary APPs supplementation increased antioxidative capacity in serum and CAT activity in liver, and significantly increased the mRNA expressions of CAT, GST and SOD1 in liver. ACC mRNA level and LPL activity were tended to decrease by APPs. HMG‐CoAR, CTP7A1, CD36 and FATP1 mRNA levels were decreased by APPs, while LDL‐R, PGC‐1α, Sirt1 and CPT1b mRNA levels were increased by 400 mg/kg APPs. No alterations in growth performance were found in all treatments. This study firstly provided the evidence that dietary APPs supplementation could enhance systemic antioxidant capacity and improve lipid metabolism in weaned piglets. The mechanism by which APPs improve lipid metabolism might be through regulating hepatic cholesterol metabolism and increasing fatty acid oxidation, and decreasing fatty acid uptake and de novo synthesis.
Scope:
serine lies at the central node linking biosynthetic flux from glycolysis to glutathione synthesis and one-carbon metabolic cycle which are closely related to antioxidant capacity. The present study was conducted to determine the effects of serine supplementation on oxidative stress and its relative mechanisms.
Methods and results:
diquat treatment was performed to induce oxidative stress in mice and primary hepatocytes. The results showed that hepatic glutathione anti-oxidant systems were impaired and reactive oxygen species and homocysteine were increased in diquat-induced mice and hepatocytes, while such disadvantageous changes were diminished by serine supplementation both in vivo and in vitro. However, when cystathionine β-synthase expression was inhibited by interference RNA in hepatocytes, the effects of serine supplementation on the improvement of glutathione synthesis and the alleviation of oxidative stress were diminished. Moreover, when hepatocytes were treated with cycloleucine, an inhibitor of methionine adenosyltransferase, the effects of serine supplementation on the improvement of methionine cycle and the alleviation of DNA hypomethylation and oxidative stress were also diminished.
Conclusion:
our results indicated that serine supplementation alleviated oxidative stress via supporting glutathione synthesis and methionine cycle, mostly by condensing with homocysteine to synthesize cysteine and providing one-carbon units for homocysteine remethylation. This article is protected by copyright. All rights reserved.
Diarrhea is a host response to enteric pathogens, but its impact on pathogenesis remains poorly defined. By infecting mice with the attaching and effacing bacteria Citrobacter rodentium, we defined the mechanisms and contributions of diarrhea and intestinal barrier loss to host defense. Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. Permeability increases were limited to small molecules, as expected for the paracellular water and Na⁺ channel formed by claudin-2. Relative to wild-type, claudin-2-deficient mice experienced severe disease, including increased mucosal colonization by C. rodentium, prolonged pathogen shedding, exaggerated cytokine responses, and greater tissue injury. Conversely, transgenic claudin-2 overexpression reduced disease severity. Chemically induced osmotic diarrhea reduced colitis severity and C. rodentium burden in claudin-2-deficient, but not transgenic, mice, demonstrating that claudin-2-mediated protection is the result of enhanced water efflux. Thus, IL-22-induced claudin-2 upregulation drives diarrhea and pathogen clearance.
Probiotics have gained considerable attention with respect to their beneficial effects on livestock performance and health. The most significant effects of probiotics on the gut microbiota and the host animals take place when they are included in diets during particularly stressful periods such as weaning and/or at the beginning of the lactation period. The probiotics Bacillus mesentericus strain TO-A at 1 × 10(8) colony forming units (CFU)/g, Clostridium butyricum strain TO-A at 1 × 10(8) CFU/g and Enterococcus faecalis strain T-100 at 1 × 10(9) CFU/g were used. Litter weight at delivery and ratio of return to estrous improved significantly (17% and 24% improvement, respectively) by probiotic administration to sows (0.2% (w/w)). Furthermore, the feed intake of the probiotics-administered sows was greater than that of the control sows during the late lactation period. Post-weaning diarrheal incidence and growth performance was improved by probiotics administration to neonates (0.02% (w/w)), while the combined use of probiotics in sows and their neonates induced the enlargement of villous height and prevented muscle layer thinning in the small intestine of weaning piglets. The administration of probiotics of three species of live bacteria improved the porcine reproductive performance around stressful periods of sows (farrowing) and piglets (weaning).
Diarrhoeal disease remains a major health burden worldwide. Secretory diarrhoeas are caused by certain bacterial and viral infections, inflammatory processes, drugs and genetic disorders. Fluid secretion across the intestinal epithelium in secretory diarrhoeas involves multiple ion and solute transporters, as well as activation of cyclic nucleotide and Ca(2+) signalling pathways. In many secretory diarrhoeas, activation of Cl(-) channels in the apical membrane of enterocytes, including the cystic fibrosis transmembrane conductance regulator and Ca(2+)-activated Cl(-) channels, increases fluid secretion, while inhibition of Na(+) transport reduces fluid absorption. Current treatment of diarrhoea includes replacement of fluid and electrolyte losses using oral rehydration solutions, and drugs targeting intestinal motility or fluid secretion. Therapeutics in the development pipeline target intestinal ion channels and transporters, regulatory proteins and cell surface receptors. This Review describes pathogenic mechanisms of secretory diarrhoea, current and emerging therapeutics, and the challenges in developing antidiarrhoeal therapeutics.
Background & Aims: Unlike the intestine of normal subjects, small-intestinal epithelia of cystic fibrosis patients and cystic fibrosis transmembrane conductance regulator protein-null (CFTR−) mice do not respond to stimulation of intracellular cyclic adenosine monophosphate with inhibition of electroneutral NaCl absorption. Because CFTR-mediated anion secretion has been associated with changes in crypt cell volume, we hypothesized that CFTR-mediated cell volume reduction in villus epithelium is required for intracellular cyclic adenosine monophosphate inhibition of Na+/H+ exchanger (primarily Na+/H+ exchanger 3) activity in the proximal small intestine. Methods: Transepithelial 22Na flux across the jejuna of CFTR+, CFTR−, the basolateral membrane Na+/K+/2Cl− co-transporter protein NKCC1+, and NKCC1− mice were correlated with changes in epithelial cell volume of the midvillus region. Results: Stimulation of intracellular cyclic adenosine monophosphate resulted in cessation of Na+/H+ exchanger-mediated Na+ absorption (JmsNHE) in CFTR+ jejunum but had no effect on JmsNHE across CFTR− jejunum. Cell volume indices indicated an approximately 30% volume reduction of villus epithelial cells in CFTR+ jejunum but no changes in CFTR− epithelium after intracellular cyclic adenosine monophosphate stimulation. In contrast, cell shrinkage induced by hypertonic medium inhibited JmsNHE in both CFTR+ and CFTR− mice. Bumetanide treatment to inhibit Cl− secretion by blockade of the Na+/K+/2Cl− co-transporter, NKCC1, of stimulated CFTR+ jejunum prevented maximal volume reduction of villus epithelium and recovered approximately 40% of JmsNHE. Likewise, JmsNHE and cell volume were unaffected by intracellular cyclic adenosine monophosphate stimulation in NKCC1− jejuna. Conclusions: These findings show a previously unrecognized role of functional CFTR expressed in villus epithelium: regulation of Na+/H+ exchanger 3-mediated Na+ absorption by alteration of epithelial cell volume.
Previous studies indicate that certain probiotic bacterial strains or their soluble products can alleviate proinflammatory cytokine secretion by intestinal epithelial cells (IEC), but their impact on epithelial chloride (Cl(-)) secretion remains elusive. To further decipher the mechanisms of the cross-talk between bacteria/soluble factors and epithelial cells, we analyzed the capacity of the probiotic strain Bifidobacterium breve C50 (Bb C50), its conditioned medium, and other commensal Gram (+) bacteria to modulate epithelial Cl(-) secretion. The effect of Bb C50 on carbachol- (CCh) or forskolin (Fsk)-induced Cl(-) secretion was measured in an IEC line in Ussing chambers. The mechanisms involved in the regulation of Cl(-) secretion were assessed by measuring intracellular Ca(2+) concentration, phosphatase activity, protein kinase (PK) C and PKA activation, and cystic fibrosis transmembrane conductance regulator (CFTR) expression. CCh- or Fsk-induced Cl(-) secretion [short-circuit current (Isc): 151 +/- 28 and 98 +/- 14 microA/cm(2), respectively] was inhibited dose-dependently by Bb C50 (Isc 33 +/- 12 and 49 +/- 7 microA/cm(2) at multiplicity of infection 100; P < 0.02). Fsk-induced Cl(-) secretion was also inhibited by Lactobacillus rhamnosus 10893. No other inhibitory effect was recorded with the other Gram (+) bacteria tested. The inhibitory effect of Bb C50 on CCh-induced Cl(-) secretion targeted a step downstream of epithelial Ca(2+) mobilization and was associated with decreased PKC activity. Thus, Bb C50 and secreted soluble factors, by inhibiting phosphorylation processes, may promote intestinal homeostasis by controlling Cl(-) secretion.
Chloride secretion is the major determinant of mucosal hydration throughout the gastrointestinal tract, and chloride transport is also pivotal in the regulation of fluid secretion by organs that drain into the intestine. Moreover, there are pathological consequences if chloride secretion is either reduced or increased such as in cystic fibrosis and secretory diarrhea, respectively. With the molecular cloning of many of the proteins and regulatory factors that make up the chloride secretory mechanism, there have been significant advances in our understanding of this process at the cellular level. Similarly, emerging data have clarified the intercellular relationships that govern the extent of chloride secretion. The goal of our article is to review this area of investigation, with an emphasis on recent developments and their implications for the physiology and pathophysiology of chloride transport.