Dietary protein restriction regulates skeletal muscle fiber metabolic characteristics associated with the FGF21-ERK1/2 pathway.

Under conditions of dietary amino acid balance, decreasing the dietary crude protein (CP) level in pigs has a beneficial effect on meat quality. To further elucidate the mechanism, we explored the alteration of muscle fiber characteristics and key regulators related to myogenesis in the skeletal muscle of pigs fed a protein restricted diet. Compared to pigs fed a normal protein diet, dietary protein restriction significantly increased the slow-twitch muscle fiber proportion in skeletal muscle, succinic dehydrogenase (SDH) activity, the concentrations of ascorbate, biotin, palmitoleic acid, and the ratio of s-adenosylhomocysteine (SAM) to s-adenosylhomocysteine (SAH), but the fast-twitch muscle fiber proportion, lactate dehydrogenase (LDH) activity, the concentrations of ATP, glucose-6-phosphate, SAM, and SAH in skeletal muscle, and the ratio of serum triiodothyronine (T3) to tetraiodothyronine (T4) were decreased. In conclusion, we demonstrated that dietary protein restriction induced skeletal muscle fiber remodeling association the regulation of FGF21-ERK1/2-mTORC1 signaling in weaned piglets.

Selenomethionine Supplementation Mitigates Liver Dysfunction, Oxidative Injury and Apoptosis through Enhancing Antioxidant Capacity and Inhibiting JNK MAPK Pathway in Piglets Fed Deoxynivalenol-Contaminated Diets.

This research evaluated the impacts of selenomethionine (Se-Met) on hepatic functions, oxidative stress, mitochondrial function, and apoptosis of piglets fed deoxynivalenol (DON)-contaminated diets. Twenty-four piglets were allocated four dietary treatments (n = 6) in a 28-day feeding trial. The four treatments included the control group, which received 0.3 mg/kg of Se (as Se-Met) without DON treatment, and the DON treatment groups received 0, 0.3, or 0.5 mg/kg Se as Se-Met. A dietary addition of 0.5 mg/kg Se improved liver pathology and reduced serum aspartate aminotransferase and lactate dehydrogenase levels in piglets fed DON-contaminated diets. Furthermore, 0.5 mg/kg Se mitigated the oxidative stress and apoptosis of piglets fed DON-contaminated diets, as indicated by the decreased reactive oxygen species level, and the down-regulated mRNA levels of NRF-1, Bax, and CASP9 in the liver. Importantly, 0.5 mg/kg Se enhanced the hepatic antioxidant capacity, as evidenced by increased hepatic total antioxidant capacity, catalase, glutathione peroxidase, and total superoxide dismutase activities, as well as the up-regulated mRNA levels of Nrf2, Gclm, NQO1, SOD1, and GPX1 in the liver. Moreover, 0.5 mg/kg Se down-regulated the p-JNK protein level in the liver of piglets fed DON-contaminated diets. Collectively, Se-Met supplementation mitigated liver dysfunction, oxidative injury, and apoptosis through enhancing antioxidant capacity and inhibiting the JNK MAPK pathway in piglets fed DON-contaminated diets.

Selenomethionine Alleviates Deoxynivalenol-Induced Oxidative Injury in Porcine Intestinal Epithelial Cells Independent of MAPK Pathway Regulation.

Deoxynivalenol (DON) is a prevalent contaminant in feed and food, posing a serious threat to the health of both humans and animals. The pig stands as an ideal subject for the study of DON due to its recognition as the most susceptible animal to DON. In this study, the IPEC-J2 cells were utilized as an in vitro model to explore the potential of SeMet in alleviating the intestinal toxicity and oxidative injury in intestinal epithelial cells when exposed to DON. Cells were treated either with or without 4.0 µM SeMet, in combination with or without a simultaneous treatment with 0.5 µg/mL DON, for a duration of 24 h. Then, cells or related samples were analyzed for cell proliferation, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) level, gene expressions, and protein expressions. The results showed that SeMet mitigated the cellular toxicity caused by DON, evidenced by elevated cell proliferation and the reduced LDH release of IPEC-J2 cells in the SeMet + DON group vs. the DON group. Moreover, the SeMet treatment markedly promoted antioxidant functions and decreased the oxidative injury in IPEC-J2 cell, which is indicated by the decreased ROS level and up-regulated mRNA levels of GPX1, TXNRD1, Nrf2, and GCLC in IPEC-J2 cells in the SeMet + DON group vs. the DON group. However, in both the absence and presence of exposure to DON, the SeMet treatment did not affect the protein expression of MAPK (JNK, Erk1/2, and P38) and phosphorylated MAPK (p-JNK, p-Erk1/2, and p-P38) in IPEC-J2 cells. Collectively, SeMet alleviated the DON-induced oxidative injury in porcine intestinal epithelial cells independent of the MAPK pathway regulation.

Fibroblast growth factor 21: An emerging pleiotropic regulator of lipid metabolism and the metabolic network.

Fibroblast growth factor 21 (FGF21) was originally identified as an important metabolic regulator which plays a crucial physiological role in regulating a variety of metabolic parameters through the metabolic network. As a novel multifunctional endocrine growth factor, the role of FGF21 in the metabolic network warrants extensive exploration. This insight was obtained from the observation that the FGF21-dependent mechanism that regulates lipid metabolism, glycogen transformation, and biological effectiveness occurs through the coordinated participation of the liver, adipose tissue, central nervous system, and sympathetic nerves. This review focuses on the role of FGF21-uncoupling protein 1 (UCP1) signaling in lipid metabolism and how FGF21 alleviates non-alcoholic fatty liver disease (NAFLD). Additionally, this review reveals the mechanism by which FGF21 governs glucolipid metabolism. Recent research on the role of FGF21 in the metabolic network has mostly focused on the crucial pathway of glucolipid metabolism. FGF21 has been shown to have multiple regulatory roles in the metabolic network. Since an adequate understanding of the concrete regulatory pathways of FGF21 in the metabolic network has not been attained, this review sheds new light on the metabolic mechanisms of FGF21, explores how FGF21 engages different tissues and organs, and lays a theoretical foundation for future in-depth research on FGF21-targeted treatment of metabolic diseases.

Neonatal resveratrol administration promotes skeletal muscle growth and insulin sensitivity in intrauterine growth-retarded suckling piglets associated with activation of FGF21-AMPKα pathway.

BACKGROUND: Skeletal muscle is a major insulin-sensitive tissue with a pivotal role in modulating glucose homeostasis. This study aimed to investigate the effect of resveratrol (RES) intervention during the suckling period on skeletal muscle growth and insulin sensitivity of neonates with intrauterine growth retardation (IUGR) in a pig model. RESULTS: Twelve pairs of normal birth weight (NBW) and IUGR neonatal male piglets were selected. The NBW and IUGR piglets were fed basal formula milk diet or identical diet supplemented with 0.1% RES from 7 to 21 days of age. Myofiber growth and differentiation, inflammation and insulin sensitivity in skeletal muscle were assessed. Early RES intervention promoted myofiber growth and maturity in IUGR piglets by ameliorating the myogenesis process and increasing thyroid hormone level. Administering RES also reduced triglyceride concentration in skeletal muscle of IUGR piglets, along with decreased inflammatory response, increased plasma fibroblast growth factor 21 (FGF21) concentration and improved insulin signaling. Meanwhile, the improvement of insulin sensitivity by RES may be partly regulated by activation of the FGF21/AMP-activated protein kinase α/sirtuin 1/peroxisome proliferator activated receptor-γ coactivator-1α pathway. CONCLUSION: Our results suggest that RES has beneficial effects in promoting myofiber growth and maturity and increasing skeletal muscle insulin sensitivity in IUGR piglets, which open a novel field of application of RES in IUGR infants for improving postnatal metabolic adaptation. © 2023 Society of Chemical Industry.

Fibroblast Growth Factor 21: A Fascinating Perspective on the Regulation of Muscle Metabolism.

Fibroblast growth factor 21 (FGF21) plays a vital role in normal eukaryotic organism development and homeostatic metabolism under the influence of internal and external factors such as endogenous hormone changes and exogenous stimuli. Over the last few decades, comprehensive studies have revealed the key role of FGF21 in regulating many fundamental metabolic pathways, including the muscle stress response, insulin signaling transmission, and muscle development. By coordinating these metabolic pathways, FGF21 is thought to contribute to acclimating to a stressful environment and the subsequent recovery of cell and tissue homeostasis. With the emphasis on FGF21, we extensively reviewed the research findings on the production and regulation of FGF21 and its role in muscle metabolism. We also emphasize how the FGF21 metabolic networks mediate mitochondrial dysfunction, glycogen consumption, and myogenic development and investigate prospective directions for the functional exploitation of FGF21 and its downstream effectors, such as the mammalian target of rapamycin (mTOR).

Dietary puerarin supplementation improves immune function in the small intestines of oxidized oil-challenged broilers.

Puerarin has possessed a wide range of pharmacological activities. However, little is known about the protective effects of puerarin on the oxidized oil-induced injury. Here, we describe the anti-inflammatory effects of puerarin in chickens. A total of 360 broilers were arranged in four treatments. Diets included two types of soybean oil (fresh or oxidized) and two levels of puerarin (0 or 750 mg/kg). Results showed that puerarin alleviated oxidized soybean oil-induced intestinal immune injury by decreasing the expressions of HSP and pro-inflammatory factor (P < 0.05) and enhancing the mRNA levels of anti-inflammatory factor and CATH-1 (P < 0.05) in broilers. Moreover, puerarin supplementation decreased the mRNA abundances of TLR4 and MyD88 (P < 0.05) and upregulated the expressions of A20 and SOCS-1 (P < 0.05) in the small intestine of oxidized soybean oil-challenged broilers. Collectively, this study demonstrates puerarin may be a potential nutrient supplement in the treatment of oxidized oil-induced damage in poultry.

A Critical Review of Kaempferol in Intestinal Health and Diseases.

Kaempferol, a secondary metabolite found in plants, is a naturally occurring flavonoid displaying significant potential in various biological activities. The chemical structure of kaempferol is distinguished by the presence of phenyl rings and four hydroxyl substituents, which make it an exceptional radical scavenger. Most recently, an increasing number of studies have demonstrated the significance of kaempferol in the regulation of intestinal function and the mitigation of intestinal inflammation. The focus of the review will primarily be on its impact in terms of antioxidant properties, inflammation, maintenance of intestinal barrier function, and its potential in the treatment of colorectal cancer and obesity. Future research endeavors should additionally give priority to investigating the specific dosage and duration of kaempferol administration for different pathological conditions, while simultaneously conducting deeper investigations into the comprehensible mechanisms of action related to the regulation of aryl hydrocarbon receptor (AhR). This review intends to present novel evidence supporting the utilization of kaempferol in the regulation of gut health and the management of associated diseases.

Effects of Equol Supplementation on Growth Performance, Redox Status, Intestinal Health and Skeletal Muscle Development of Weanling Piglets with Intrauterine Growth Retardation.

Animals with intrauterine growth retardation (IUGR) usually undergo injured postnatal growth and development during the early period after birth. Equol (Eq), an isoflavan produced by gut bacteria in response to daidzein intake, has various health benefits. Therefore, the objective of this study was to evaluate whether Eq supplementation can influence the growth performance, redox status, intestinal health and skeletal muscle development of weanling piglets with IUGR. A total of 10 normal-birth-weight (NBW) newborn female piglets and 20 newborn female piglets with IUGR were selected. After weaning at the age of 21 d, 10 NBW piglets and 10 IUGR piglets were allocated to the NBW group and IUGR group, respectively, and offered a basal diet. The other 10 IUGR piglets were allocated to the IUGR + Eq group and offered a basal diet with 50 mg of Eq per kg of diet. The whole trial lasted for 21 d. At the end of the feeding trial, all piglets were sacrificed for the collection of serum, intestinal tissues and skeletal muscles. Supplementation with Eq increased the average daily gain (ADG), average daily feed intake (ADFI), duodenal villus height to crypt depth ratio (V/C), jejunal villus height and V/C, but reduced the duodenal crypt depth in neonatal piglets with IUGR. Meanwhile, Eq supplementation elevated the activities of superoxide dismutase (SOD) and catalase (CAT) in the serum and duodenum and the activity of SOD in the jejunum, but lowered malondialdehyde (MDA) content in the serum, jejunum and ileum of piglets with IUGR. In addition, supplementation with Eq reduced diamine oxidase (DAO) activity and the levels of D-lactate and endotoxin in serum, and the tumor necrosis factor-α (TNF-α) level in jejunum and ileum, whereas the concentration of serum immunoglobulin G (IgG) and the mRNA levels of intestinal barrier-related markers in jejunum and ileum of IUGR piglets were increased. Furthermore, supplementation with Eq elevated the percentage of fast-fibers and was accompanied with higher mRNA expression of myosin heavy chain IIb (MyHC IIb) and lower mRNA levels in MyHC I in the longissimus thoracis (LT) muscle of IUGR piglets. In summary, Eq supplementation can promote antioxidant capacity, maintain intestinal health and facilitate skeletal muscle development, thus resulting in the higher growth performance of IUGR piglets.

Research Progress on Lycopene in Swine and Poultry Nutrition: An Update.

Oxidative stress and in-feed antibiotics restrictions have accelerated the development of natural, green, safe feed additives for swine and poultry diets. Lycopene has the greatest antioxidant potential among the carotenoids, due to its specific chemical structure. In the past decade, increasing attention has been paid to lycopene as a functional additive for swine and poultry feed. In this review, we systematically summarized the latest research progress on lycopene in swine and poultry nutrition during the past ten years (2013-2022). We primarily focused on the effects of lycopene on productivity, meat and egg quality, antioxidant function, immune function, lipid metabolism, and intestinal physiological functions. The output of this review highlights the crucial foundation of lycopene as a functional feed supplement for animal nutrition.

Plant-derived polyphenols in sow nutrition: An update.

Oxidative stress is a potentially critical factor that affects productive performance in gestating and lactating sows. Polyphenols are a large class of plant secondary metabolites that possess robust antioxidant capacity. All polyphenols are structurally characterized by aromatic rings with multiple hydrogen hydroxyl groups; those make polyphenols perfect hydrogen atoms and electron donors to neutralize free radicals and other reactive oxygen species. In the past decade, increasing attention has been paid to polyphenols as functional feed additives for sows. Polyphenols have been found to alleviate inflammation and oxidative stress in sows, boost their reproductivity, and promote offspring growth and development. In this review, we provided a systematical summary of the latest research advances in plant-derived polyphenols in sow nutrition, and mainly focused on the effects of polyphenols on the (1) antioxidant and immune functions of sows, (2) placental functions and the growth and development of fetal piglets, (3) mammary gland functions and the growth and development of suckling piglets, and (4) the long-term growth and development of progeny pigs. The output of this review provides an important foundation, from more than 8,000 identified plant phenols, to screen potential polyphenols (or polyphenol-enriched plants) as functional feed additives suitable for gestating and lactating sows.

Polysaccharide-rich fractions from Enteromorpha prolifera improve hepatic steatosis and gut barrier integrity in high-fat diet-induced obese mice linking to modulation of gut microbiota.

Polysaccharides from Enteromorpha prolifera (EP) possess important benefits in the management of obesity and associated metabolic diseases, but to date, the underlying mechanism linking this alleviative effect of EP to gut microbiota remains obscure. This study aimed to investigate the effects of EP in improving lipid metabolism disorders and intestinal barrier disruption in mice with high-fat diet (HFD), and its association with modulation of gut microbiota. C57BL/6 mice were fed a control diet or a HFD with or without 5% EP for 12 weeks. Factors related to lipid metabolism, insulin signaling and intestinal barrier integrity, as well as the involvement of gut microbiota and metabolites, were measured. EP supplementation reduced HFD-induced adiposity and mitigated insulin resistance, hepatic steatosis and elevation of serum lipopolysaccharides (LPS). HFD impaired intestinal barrier integrity while improved due to EP. Moreover, EP administration ameliorated HFD-induced gut dysbiosis, as revealed by the increased short-chain fatty acid (SCFA)-producing bacteria (e.g., Bacteroides, Parabacteroides, Alloprevotella, and Ruminococcus) and gut barrier-protective Akkermansia muciniphila and decreased endotoxin-producing bacteria (e.g., Desulfovibrionaceae and Bilophila), accompanied by enrichment in intestinal SCFA content and reduction in circulating LPS level. The change of dominant bacterial genera is significantly correlated with improved metabolic profiles and intestinal permeability induced by EP. In conclusion, our results indicate that EP can attenuate HFD-induced metabolic disorders along with restoration of gut barrier integrity and lowering of circulating endotoxin, and these improvements are associated with modulation of gut microbiota composition and related metabolites. These data deepen mechanistic understanding of the anti-obesity and metabolic improving effects of EP.

A blend of formic acid, benzoic acid, and tributyrin alleviates ETEC K88-induced intestinal barrier dysfunction by regulating intestinal inflammation and gut microbiota in a murine model.

This study aimed to investigate the effects of an organic acid (OA) blend on intestinal barrier function, intestinal inflammation, and gut microbiota in mice challenged with enterotoxigenic Escherichia coli K88 (ETEC K88). Ninety female Kunming mice (7 weeks old) were randomly allotted to five treatments with six replicates per treatment and three mice per replicate. The five treatments were composed of the non-ETEC K88 challenge group and ETEC K88 challenge + OA blend groups (0, 0.6 %, 1.2 %, and 2.4 % OA blend). The OA blend consisted of 47.5 % formic acid, 47.5 % benzoic acid, and 5 % tributyrin. The feeding trial lasted for 15 days, and mice were intraperitoneally injected with PBS or ETEC K88 solution on day 15. At 24 h post-challenge, one mouse per replicate was selected for sample collection. The results showed that a dosage of 0.6 % OA blend alleviated the ETEC K88-induced intestinal barrier dysfunction, as indicated by the elevated villus height and the ratio of villus height to crypt depth of jejunum, and the reduced serum diamine oxidase (DAO) and D-lactate levels, as well as the up-regulated mRNA levels of ZO-1, Claudin-1, and Occludin in jejunum mucosa of mice. Furthermore, dietary addition with 0.6 % OA blend decreased ETEC K88-induced inflammation response, as suggested by the decreased TNF-α and IL-6 levels, and the increased IgA level in the serum, as well as the down-regulated mRNA level of TNF-α, IL-6, IL-1ß, TLR-4, MyD88, and MCP-1 in jejunum mucosa of mice. Regarding gut microbiota, the beta-diversity analysis revealed a remarkable clustering between the 0.6 % OA blend group and the ETEC K88 challenge group. Supplementation of 0.6 % OA blend decreased the relative abundance of Firmicutes, and increased the relative abundance of Bacteroidota, Desulfobacterota, and Verrucomicrobiota of colonic digesta in mice. Also, the butyric acid content in the colonic digesta of mice was increased by dietary 0.6 % OA blend supplementation. Collectively, a dosage of 0.6 % OA blend could alleviate the ETEC K88-induced intestinal barrier dysfunction by regulating intestinal inflammation and gut microbiota of mice.

Plant-Derived Polyphenols as Nrf2 Activators to Counteract Oxidative Stress and Intestinal Toxicity Induced by Deoxynivalenol in Swine: An Emerging Research Direction.

The contamination of deoxynivalenol (DON) in feed is a global problem, which seriously threatens the productivity efficiency and welfare of farm animals and the food security of humans. Pig is the most sensitive species to DON, and is readily exposed to DON through its grain-enriched diet. The intestine serves as the first biological barrier to ingested mycotoxin, and is, therefore, the first target of DON. In the past decade, a growing amount of attention has been paid to plant-derived polyphenols as functional compounds against DON-induced oxidative stress and intestinal toxicity in pigs. In this review, we systematically updated the latest research progress in plant polyphenols detoxifying DON-induced intestinal toxicity in swine. We also discussed the potential underlying mechanism of action of polyphenols as Nrf2 activators in protecting against DON-induced enterotoxicity of swine. The output of this update points out an emerging research direction, as polyphenols have great potential to be developed as feed additives for swine to counteract DON-induced oxidative stress and intestinal toxicity.

Methyl-Donor Micronutrient for Gestating Sows: Effects on Gut Microbiota and Metabolome in Offspring Piglets.

This study aimed to investigate the effects of maternal methyl-donor micronutrient supplementation during gestation on gut microbiota and the fecal metabolic profile in offspring piglets. Forty-three Duroc × Erhualian gilts were assigned to two dietary groups during gestation: control diet (CON) and CON diet supplemented with MET (folic acid, methionine, choline, vitamin B6, and vitamin B12). The body weights of offspring piglets were recorded at birth and weaning. Besides this, fresh fecal samples of offspring piglets were collected at 7, 14, and 21 days. The gut microbiota composition, metabolic profile, and short-chain fatty acid (SCFA) profiles in the fecal samples were determined using 16S rDNA sequencing, liquid chromatography-mass spectrometry metabolomics, and gas chromatography methods, respectively. The results showed that maternal methyl-donor micronutrient supplementation increased the microbiota diversity and uniformity in feces of offspring piglets as indicated by increased Shannon and Simpson indices at 7 days, and greater Simpson, ACE, Chao1 and observed species indices at 21 days. Specifically, at the phylum level, the relative abundance of Firmicutes and the Firmicutes to Bacteroidetes ratio were elevated by maternal treatment. At the genus level, the relative abundance of SCFA-producing Dialister, Megasphaera, and Turicibacter, and lactate-producing Sharpea as well as Akkermansia, Weissella, and Pediococcus were increased in the MET group. The metabolic analyses show that maternal methyl-donor micronutrient addition increased the concentrations of individual and total SCFAs of 21-day piglets and increased metabolism mainly involving amino acids, pyrimidine, and purine biosynthesis. Collectively, maternal methyl-donor micronutrient addition altered gut microbiota and the fecal metabolic profile, resulting in an improved weaning weight of offspring piglets.

Curcumin improves insulin sensitivity and increases energy expenditure in high-fat-diet-induced obese mice associated with activation of FNDC5/irisin.

OBJECTIVE: Curcumin (Cur) has a beneficial role in preventing metabolic dysfunctions; however, the underlying mechanism are not yet fully understood. The aim of this study was to evaluate whether the beneficial metabolic effects of curcumin are associated with the regulation of energy metabolism and activation of fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin. METHODS: We used cellular and molecular techniques to investigate the effects of Cur on C57 BL/6 mice that were fed either a control diet or a high-fat diet (HFD) with or without 0.2% Cur for 10 wk. Factors involved in energy metabolism, inflammatory responses, and insulin signaling, as well as the involvement of FNDC5/irisin pathway, were assessed. RESULTS: Cur alleviated adiposity and suppressed inflammatory response in white adipose tissue (WAT) of HFD mice. Meanwhile, Cur administration increased plasma irisin concentration and improved insulin sensitivity of HFD mice. Cur increased the oxygen consumption and heat production and reduced respiratory exchange ratio (RES) in HFD mice, which were accompanied by the enhancement of metabolic activity in brown fat and inguinal WAT. Additionally, the improvement of basal metabolic rate by Cur may be partly regulated by the FNDC5/ p38 mitogen-activated protein kinase (p38 MAPK)/extracellular signal-related kinase (ERK) 1/2 pathway. CONCLUSIONS: These findings demonstrated that dietary Cur alleviated diet-induced adiposity by improving insulin sensitivity and whole body energy metabolism via the FNDC5/p38 MAPK/ERK pathways.

Curcumin alleviates high-fat diet-induced hepatic steatosis and obesity in association with modulation of gut microbiota in mice.

Curcumin (Cur) is a natural polyphenol with beneficial effect against obesity and related metabolic disorders, but its precise mechanisms of action remain to be defined due to its limited systemic bioavailability. We hypothesized that gut microbiota may be a prospective therapeutic target for Cur-induced metabolic benefits. This study aimed to investigate whether the metabolic adaptations resulting from Cur supplementation were mediated by the gut microbiota in high-fat diet (HFD)-fed obese mice. C57BL/6 mice were fed a control diet or a HFD diet with or without 0.2% Cur for 10 weeks. Lipid profiles, insulin sensitivity, hepatic metabolism, gut microbiota composition and short-chain fatty acid (SCFA) production were determined. Dietary Cur reduced fat mass, hepatic steatosis and circulating lipopolysaccharide levels and improved the insulin sensitivity in HFD-fed mice. More importantly, Cur supplementation modulated the gut microbiota composition and ameliorated intestinal dysbiosis by decreasing the ratio of Firmicutes/Bacteroidetes and endotoxin-producing Desulfovibrio bacteria and increasing the abundance of Akkermansia population and SCFA-producing bacteria, such as Bacteroides, Parabacteroides, Alistipes and Alloprevotella, along with increases in caecal and colonic SCFA concentrations. These dominant bacterial genera altered by Cur showed strong correlations with the obesity-related metabolic parameters in HFD-fed mice. In conclusion, our data suggest that Cur alleviated metabolic features of hepatic steatosis and insulin resistance in HFD-fed obese mice, which might be associated with the modulation of gut microbiota composition and metabolites.

Seaweed polysaccharide mitigates intestinal barrier dysfunction induced by enterotoxigenic Escherichia coli through NF-κB pathway suppression in porcine intestinal epithelial cells.

This study aimed to investigate the protective effects and underlying mechanism of seaweed polysaccharide (SWP) on intestinal epithelial barrier dysfunction induced by E. coli in an IPEC-J2 model. A preliminary study was done to screen optimum SWP concentrations by cell viability, cytotoxicity, apoptosis and proliferation evaluation. The regular study was conducted to evaluate the protective effects of SWP against E. coli challenge via the analysis of transepithelial electrical resistance (TEER), tight junction proteins, NF-κB signalling pathway, proinflammatory cytokines and the E. coli adhesion and invasion. Our results show that 4 h E. coli challenge down-regulated tight junction proteins expression, decreased TEER, activated NF-κB signalling pathway and increased proinflammatory response, which indicates that the E. coli infection model was well-established. Pre-treatment with 240 µg/ml SWP for 24 h alleviated the 4 h E. coli -induced intestinal epithelial barrier dysfunction, as evidenced by the up-regulated expression of Occludin, Claudin-1 and ZO-1 at both mRNA and protein level and the increased TEER of IPEC-J2 cells. Pre-incubation with 240 µg/ml SWP for 24 h inhibited the activation of the NF-κB signalling pathway by 4 h E. coli challenge, including the decreased mRNA expression of TLR-4, MyD88, IκBα, p-65, as well as the reduced ratio of protein expression of p-p65/p65. Also, pre-treatment with 240 µg/ml SWP for 24 h decreased proinflammatory response (IL-6 and TNF-α) induced by 4 h E. coli challenge and decreased the E. coli adhesion and invasion. In conclusion, SWP mitigated intestinal barrier dysfunction caused by E. coli through NF-κB pathway in IPEC-J2 cells and 240 µg/ml SWP exhibited better effect. Our results also provide a fundamental basis for SWP in reducing post-weaning diarrhoea of weaned piglets, especially under E. coli -infected or in-feed antibiotic-free conditions.

Dietary seaweed-derived polysaccharides improve growth performance of weaned pigs through maintaining intestinal barrier function and modulating gut microbial populations.

BACKGROUND: Seaweed-derived polysaccharides (SDP) represent an attractive source of prebiotic nutraceuticals for the food and animal husbandry industry. However, the mechanism by which SDP from Enteromorpha mediates pig growth are not fully understood. This study aimed to investigate how SDP supplementation influences the growth performance and intestinal health in weaned pigs. RESULTS: In Exp. 1, 240 weaned pigs were randomly assigned to four dietary treatments and fed with a basal diet or a basal diet containing 200, 400 or 800 mg/kg SDP, respectively, in a 21-day trial. Pigs on the 400 or 800 mg/kg SDP-supplemented group had greater ADG and lower F/G ratio than those on the control group (P<0.05). In Exp. 2, 20 male weaned pigs were randomly assigned to two treatments and fed with a basal diet (CON group) or a basal diet supplemented with 400 mg/kg SDP (the optimum does from Exp. 1), in a 21-day trial. Pigs fed the SDP diet had greater ADG, the concentrations of serum IL-6 and TNF-α and the activities of glutathione peroxidase, superoxide dismutase and catalase (P<0.05), and lower F/G, diarrhea rate, as well as serum D-lactate concentrations and diamine oxidase activity (P<0.05). Moreover, dietary SDP supplementation enhanced secretory immunoglobulin A content, villus height and villous height: crypt depth ratio in small intestine, as well as the lactase and maltase activities in jejunum mucosa (P<0.05). SDP supplementation elevated the mRNA levels of inflammatory response-related genes (IL-6, TNF-α, TLR4, TLR6 and MyD88), and the mRNA and protein levels of ZO-1, claudin-1 and occludin in jejunum mucosa (P<0.05). Importantly, SDP not only increased the Lactobacillus population but also reduced the Escherichia coli population in cecum (P<0.05). Furthermore, SDP increased acetic acid and butyric acid concentrations in cecum (P<0.05). CONCLUSIONS: These results not only suggest a beneficial effect of SDP on growth performance and intestinal barrier functions, but also offer potential mechanisms behind SDP-facilitated intestinal health in weaned pigs.

Bacteriophage as an Alternative to Antibiotics Promotes Growth Performance by Regulating Intestinal Inflammation, Intestinal Barrier Function and Gut Microbiota in Weaned Piglets.

This study aimed to investigate the effects of dietary bacteriophage supplementation on growth performance, intestinal morphology, barrier function, and intestinal microbiota of weaned piglets fed antibiotic-free diet. A total of 120 weaned piglets were allotted to four dietary treatments with five pens/treatment and six piglets/pen in a 21-d feeding trial. The control diet was supplemented with 25 mg/kg quinocetone and 11.25 mg/kg aureomycin in the basal diet, while the three treatment diets were supplemented with 200, 400, or 600 mg/kg bacteriophage in the basal diet, respectively. There was no difference for growth performance and all measured indices of serum and intestinal tissues between 200 mg/kg bacteriophage group and the control group with antibiotics (P > 0.05). More importantly, compared with the control diet, dietary 400 mg/kg bacteriophage inclusion increased average daily gain and average daily feed intake, and decreased feed/gain ratio and diarrhea incidence of weaned piglets (P < 0.05). Also, piglets fed 400 mg/kg bacteriophage had elevated villi height (VH) in jejunum and ileum, reduced crypt depth (CD) in jejunum and ileum, and elevated VH/CD ratio in duodenum, jejunum and ileum (P < 0.05). Compared to the control group, piglets fed 400 mg/kg bacteriophage had lower interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and higher interleukin-10 (IL-10) concentration in serum, and higher secretory immunoglobulin A (sIgA), intestinal trefoil factor (ITF), and tumor growth factor-alpha (TGF-α) content in the ileal mucosa (P < 0.05). Besides, dietary addition with 400 mg/kg bacteriophage decreased the D-lactate concentration and diamine oxidase (DAO) activity in serum, and increased the relative mRNA expression of ZO-1, Claudin-1, Occludin, TLR2, TLR4, and TLR9, as well as the relative protein expression of Occludin in the jejunum (P < 0.05). However, the growth performance and all analyzed parameters in serum and intestinal tissues were not further improved when piglets fed 600 vs. 400 mg/kg bacteriophage (P > 0.05). MiSeq sequencing analysis showed that bacteriophage regulated the microbial composition in caecum digesta, as indicated by higher observed_species, Chao1, and ACE richness indices, as well as changes in the relative abundance of Firmicutes, Bacteroidetes, and Tenericutes (P < 0.05). Collectively, 400 mg/kg bacteriophage can be used as an antibiotics alternative for promoting the growth of weaned piglets. The underlying mechanism is associated with a positive effect of bacteriophage on intestinal inflammation, intestinal barrier function and gut microbiota in weaned piglets.