Effects of Dietary l-Glutamine Supplementation on the Intestinal Function and Muscle Growth of Piglets.

The aim of this study was to investigate the effects of dietary l-glutamine (Gln) supplementation on the morphology and function of the intestine and the growth of muscle in piglets. In this study, sixteen 21-day-old piglets were randomly divided into two groups: the Control group (fed a basal diet) and the Gln group (fed a basal diet supplemented with 0.81% Gln). Blood, gut, and muscle samples were collected from all piglets on Day 20 of the trial. Compared with the Control group, the supplementation of Gln increased (p < 0.05) the villus height, villus width, villus surface area, and villus height/crypt depth ratio of the small intestine. Furthermore, the supplementation of Gln increased (p < 0.05) total protein, total protein/DNA, and RNA/DNA in both the jejunum and ileum. It also increased (p < 0.05) the concentrations of carnosine and citrulline in the jejunal mucosa, as well as citrulline and cysteine concentrations in the ileum. Conversely, Gln supplementation decreased (p < 0.05) Gln concentrations in both the jejunum and ileum, along with ß-aminoisobutyric acid and 1-Methylhistidine concentrations, specifically in the ileum. Subsequent research revealed that Gln supplementation increased (p < 0.05) the mRNA levels for glutathione-S-transferase omega 2 and interferon-ß in the duodenum. In addition, Gln supplementation led to an increase (p < 0.05) in the number of Lactobacillus genus in the colon, but a decrease (p < 0.05) in the level of HSP70 in the jejunum and the activity of diamine oxidase in plasma. Also, Gln supplementation reduced (p < 0.05) the mRNA levels of glutathione-S-transferase omega 2 and interferon stimulated genes, such as MX1, OAS1, IFIT1, IFIT2, IFIT3, and IFIT5 in both the jejunum and ileum, and the numbers of Clostridium coccoides, Enterococcus genus, and Enterobacterium family in the colon. Moreover, Gln supplementation enhanced (p < 0.05) the concentrations of total protein, RNA/DNA, and total protein/DNA ratio in the longissimus dorsi muscle, the concentrations of citrulline, ornithine, arginine, and hydroxyproline, and the mRNA level of peptide transporter 1, while reducing the contents of hydrogen peroxide and malondialdehyde and the mRNA level of glutathione-S-transferase omega 2 in the longissimus dorsi muscle. In conclusion, dietary Gln supplementation can improve the intestinal function of piglets and promote the growth of the longissimus dorsi muscle.

Meta-analysis and machine learning reveal the antiobesity effects of melatonin on obese rodents.

Melatonin appears to be a promising supplement for obesity treatment. The antiobesity effects of melatonin on obese rodents are influenced by various factors, including the species, sex, the dosage of melatonin, treatment duration, administration via, daily treatment time, and initial body weight (IBW). Therefore, we conducted a meta-analysis and machine learning study to evaluate the antiobesity effect of melatonin on obese mice or rats from 31 publications. The results showed that melatonin significantly reduced body weight, serum glucose (GLU), triglycerides (TGs), low-density lipoprotein (LDL), and cholesterol (TC) levels in obese mice or rats but increased high-density lipoprotein (HDL) levels. Melatonin showed a slight positive effect on clock-related genes, although the number of studies was limited. Meta-regression analysis and machine learning indicated that the dosage of melatonin was the primary factor influencing body weight, with higher melatonin dosages leading to a stronger weight reduction effect. Together, male obese C57BL/6 mice and Sprague-Dawley rats with an IBW of 100-200 g showed better body weight reduction when supplemented with a dose of 10-30 mg/kg melatonin administered at night via injection for 5-8 weeks.

Plant-derived squalene supplementation improves growth performance and alleviates acute oxidative stress-induced growth retardation and intestinal damage in piglets.

Piglets are particularly susceptible to oxidative stress, which causes inferior growth performance and intestinal damage. Squalene (SQ), a natural bioactive substance enriched in shark liver oil, shows excellent antioxidant properties and can currently be obtained at a low cost from deodorizer distillate during the production of plant oil. This study aimed to evaluate the effects of plant-derived SQ supplementation on the growth performance of piglets and explore the beneficial roles of SQ against oxidative stress and intestinal injury in diquat-challenged piglets. Forty piglets were randomly divided into five groups and fed a basal diet supplemented with SQ at 0, 500, 1000, or 2000 mg/kg for 5 weeks. Acute oxidative stress was induced in the piglets with diquat (10 mg/kg BW) at the fourth week of the experiment, followed by a 7-d recovery period. Results showed that before the diquat challenge, SQ supplementation significantly improved growth performance (average daily gain and feed conversion ratio) and serum antioxidant status, and after the diquat challenge, SQ supplementation significantly mitigated diquat-induced growth arrest, intestinal villous atrophy, intestinal epithelial cell apoptosis, intestinal hyperpermeability, and deficiency of intestinal epithelial tight junction proteins (zonula occludens-1, occludin, and claudin-3). Under oxidative stress induced by diquat, SQ supplementation consistently improved the antioxidant status of the small intestine, liver, and muscle. In vitro, SQ was shown to alleviate hydrogen peroxide (H2O2)-induced increase of the levels of intracellular reactive oxygen species and apoptosis of porcine intestinal epithelial cells. Taken together, SQ supplementation improves growth performance and effectively alleviates acute oxidative stress-induced growth retardation and intestinal injury via improving antioxidant capacity in piglets. Our findings may provide an efficient strategy for alleviating oxidative stress-induced inferior growth performance and intestinal damage in piglets.

Effect of Ornithine α-Ketoglutarate on Intestinal Microbiota and Serum Inflammatory Cytokines in Dextran Sulfate Sodium Induced Colitis.

Ornithine α-ketoglutarate (OKG), a nutritional compound, is an amino acid salt with anti-oxidative and anti-inflammatory effects on humans and animals. Ulcerative colitis (UC), as an inflammatory bowel disease (IBD), leads to chronic intestinal inflammatory dysfunction. This study evaluated the optimal dosage of OKG in healthy mice. Then, a mouse model of acute colitis was established using dextran sodium sulfate (DSS), and the preventive effect of OKG on DSS-induced colitis in mice was explored through analysis of serum inflammatory cytokines and fecal microbiota. Initially, the mice were randomly divided into a control group, a group given a low dose of OKG (LOKG: 0.5%), a group given a medium dose of OKG (MOKG: 1%), and a group given a high dose of OKG (HOKG: 1.5%); they remained in these groups for the entire 14-day experimental period. Our results demonstrated that 1% OKG supplementation increased body weight, serum growth hormone (GH), insulin (INS), alkaline phosphatase (ALP), Tyr, and His and decreased urea nitrogen (BUN), NH3L, and Ile. Then, a 2 × 2 factor design was used for a total of 40 mice, with diet (a standard diet or a 1% OKG diet) and challenge (4% DSS or not) as the main factors. During days 14 to 21, the DSS mice were administered 4% DSS to induce colitis. The results revealed that OKG alleviated weight loss and reversed the increases in colonic histological damage induced by DSS. OKG also increased serum IL-10 secretion. Moreover, OKG enhanced the abundance of Firmicutes and decreased that of Bacteriodetes at the phylum level and particularly enhanced the abundance of Alistipes and reduced that of Parabacterioides at the genus level. Our results indicated that OKG promotes growth performance and hormone secretion and regulates serum biochemical indicators and amino acid concentrations. Furthermore, 1% OKG supplementation prevents DSS-induced colitis in mice via altering microbial compositions and reducing the secretion of inflammatory cytokines in serum.

Elevation of Intracellular Alpha-Ketoglutarate Levels Inhibits Osteoclastogenesis by Suppressing the NF-κB Signaling Pathway in a PHD1-Dependent Manner.

Age-related osteoporosis, a high-prevalence disease in the aged population, is generally attributed to the excessive activity of osteoclasts. Most approved drugs treat osteoporosis by inhibition of osteoclasts. Although in vivo studies have shown that alpha-ketoglutarate (AKG), an intermediate in the TCA cycle, can ameliorate age-related osteoporosis, the effects of AKG on osteoclastogenesis and the underlying mechanism of its action have not been studied yet. Here, we showed that the elevation of intracellular AKG levels by supplementing dimethyl AKG (DM-AKG, a cell-permeable derivative of AKG) inhibits the receptor activator of NF-κB ligand (RANKL)-induced osteoclasts differentiation from primary bone marrow-derived macrophages (BMMs) and RAW264.7 cells in vitro. We further found that DM-AKG treatment suppresses NF-κB signaling and oxidative phosphorylation (OXPHOS) during RANKL-induced osteoclastogenesis in RAW264.7 cells. Interestingly, dimethyl oxalylglycine (DMOG), an AKG competitive inhibitor of AKG-dependent prolyl hydroxylases (PHDs), antagonizes the suppression of the RANKL-activated NF-κB signaling pathway caused by DM-AKG treatment. Furthermore, blocked PHD1 expression (also known as EglN2), instead of PHD2 or PHD3, was confirmed to reverse the DM-AKG treatment-induced suppression of the RANKL-activated NF-κB signaling pathway. Accordingly, blocked PHD1 expression antagonized the inhibitory effects of DM-AKG on osteoclastogenesis. Together, our finding suggests that the elevation of intracellular AKG levels inhibits osteoclastogenesis by suppressing RANKL-activated NF-κB signaling in a PHD1-dependent manner, which may provide a novel nutritional strategy for osteoporosis treatment.

Dietary Alpha-Ketoglutarate Supplementation Improves Bone Growth, Phosphorus Digestion, and Growth Performance in Piglets.

Phosphorus (P) pollution from modern swine production is a major environmental problem. Dietary interventions to promote bone growth can improve the utilization of dietary P, and thereby reduce its emission. Recent in vitro studies have shown that alpha-ketoglutarate (AKG) exerts a pro-osteogenic effect on osteoblast cells. This study aimed to evaluate the effects of AKG supplementation on bone growth, P and Ca digestion, and the gut microbial profile in piglets. Thirty-two piglets were randomly assigned into two dietary groups. The piglets were fed a basic diet containing 10 g/kg AKG or 10 g/kg maize starch (control) for 28 days. On days 21-28, titanium dioxide was used as an indicator to determine the apparent digestibility of P. AKG supplementation improved the bone mineral density, length, weight, and geometrical and strength properties of the femur and tibia. Furthermore, AKG supplementation increased apparent ileal and total tract digestibility of P. Colonic microbiota analysis results showed that AKG supplementation increased α-diversity and beneficial bacteria, including Lactobacillus and Clostridium butyricum, and decreased nitrogen fixation and chemoheterotrophy. Together, AKG supplementation improves bone growth, the utilization of dietary P, and the colonic microbial profile, which may provide a nutritional strategy for diminishing P pollution originating from the pig industry.

Dietary supplementation with potassium-magnesium sulfate modulates the antioxidant capacity, immunity, and gut microbiota in weaned piglets.

The purpose of this study was to evaluate the effects of different levels of potassium magnesium sulfateon (PMS) on growth performance, diarrhea rate, intestinal morphology, antioxidant capacity, intestinal immunity, and gut microbiota in weaned piglets. A total of 216 weaned piglets were randomly divided into six dietary groups: the basal diet with 0% (CON), 0.15, 0.3, 0.45, 0.6, and 0.75% PMS. The results showed that the ADFI of 29-42 days and 1-42 days was linearly and quadratically increased by the PMS supplementation (P < 0.05), and significantly reduced the diarrhea rate in weaned piglets (P < 0.05). Moreover, dietary supplementation with PMS significantly reduced the serum adrenaline and noradrenaline levels in weaned piglets (P < 0.05). Furthermore, 0.3% PMS significantly increased the activity of glutathione peroxidase (GSH-Px) in the jejunum (P < 0.05) and tended to increase the activity of superoxide dismutase (SOD) in the jejunal mucosa of piglets (P < 0.1). Additionally, dietary supplementation with PMS significantly reduced the interleukin-1ß (IL-1ß) level in the jejunal mucosa (P < 0.05), and 0.3% PMS increased the serum IgM content in piglets (P < 0.05). Furthermore, the analysis of colonic microbiota by 16S RNA sequencing showed that the addition of PMS increased the Shannon index (P < 0.05) and Observed Species index (P < 0.05). Based on linear discriminant analysis effect size (LEfSe) and T-test analysis, the addition of PMS increased the relative abundance of Ruminococcaceae and Peptostreptococcaceae in the colonic digesta (P < 0.05). Spearman analysis showed that there was a positive correlation between intestinal GSH-Px activity and the relative abundance of Peptostreptococcaceae. These results showed that dietary supplementation with PMS could improve growth performance, alleviate diarrhea incidence, and modulate the antioxidant capacity and intestinal immunity in weaned piglets, which was partially related to the significant changes in colonic microbiota composition.

Ornithine α-Ketoglutarate Alleviates Inflammation via Regulating Ileal Mucosa Microbiota and Metabolites in Enterotoxigenic Escherichia coli-Infected Pigs.

Enterotoxigenic Escherichia coli (ETEC) is one of the main causes of diarrhea in weaned piglets, and ornithine α-ketoglutarate (OKG) as a food supplement has been shown to improve intestinal immune status in animals and humans. However, it remains unknown whether OKG alleviates inflammation through the regulation of gut microbiota and its metabolites on ETEC-infected piglets. This study was conducted to explore the impact of OKG on growth performance, immunity, and ileal mucosa microbiota and its metabolites in piglets infected with ETEC. On a total of 40 pigs, a 2 × 2 factor design was performed; the major factors were diet (basal diet or 1% OKG diet) and challenge (E. coli or LB Broth). The results showed that ETEC-infection inhibited growth performance, and OKG supplementation alleviated growth performance. Interestingly, ETEC-infection increased the serum TNF-α and IL-6, decreased the serum IL-10, downregulated the mRNA expression of IL-1ß, IL-6, MyD88, and improved the mRNA expression of IL-8, IL-18, and TLR4. OKG inhibited serum IL-6, suppressed the phosphorylation of downstream signals of NF-κB/JNK in the ileum, and enhanced serum IL-10 and ileum SIgA in ETEC-challenged piglets. OKG supplementation enhanced the mRNA expression of IL-1ß and IL-10 and reduced NF-κB and MyD88 in the ileum. Importantly, OKG reversed intestinal microbiota dysfunction, including the diversity of ileal microbiota, the relative abundances of Actinobacillus, Turicibacter, and [Acetivibrio]_ethanolgignens_group, which significantly affected arachidonic acid metabolism and primary bile acid biosynthesis. Collectively, our results suggest that OKG improves growth performance, regulates immunity, and ileal mucosa microbiota and its metabolites in ETEC-infected piglets.

Extracellular Vesicle-Derived circITGB1 Regulates Dendritic Cell Maturation and Cardiac Inflammation via miR-342-3p/NFAM1.

Acute myocardial infarction (AMI) is a complication of atherosclerosis-related cardiovascular illness that is caused by prolonged ischemia. Circular RNAs (circRNAs) are concentrated in extracellular vesicles (EVs) and have been linked to cardiovascular disease. However, additional research is needed into the expression and function of circRNAs in AMI. In this study, circITGB1 (has_circRNA_0018146), derived from exon 1 of the ITGB1 gene localized on chromosome 10, was shown to be considerably increased in plasma from patients with AMI compared to healthy controls, as demonstrated by the comparison of EV-circRNA expression patterns. Using a luciferase screening assay and a biotin-labeled circITGB1 probe to identify microRNA(s) complementary to circITGB1 sequences, we discovered that circITGB1 competitively binds to miR-342-3p and inhibits its expression, which in turn increase the expression of NFAT activating molecule 1 (NFAM1). Based on western blotting and immunological studies, circITGB1 controls dendritic cell maturation by targeting miR-342-3p and NFAM1. circITGB1 also exacerbated cardiac damage and regulated miR-342-3p and NFAM1 expression in a mouse AMI model. This implies that EV-circITGB1 is involved in dendritic cell maturation and cardiac damage via miR-342-3p/NFAM1, and that is linked to AMI-associated pathogenic processes.

Effects of dietary alpha-ketoglutarate on bacteria profiles in the faeces of lactating sows and their suckling piglets.

The aim of the study was to investigate the effects of dietary alpha-ketoglutarate (AKG) on the faecal bacteria composition of suckling piglets after supplementation of AKG to the diet of lactating sows. After farrowing, the sows were assigned to either a normal lactation diet (control group, n = 12) or a diet supplemented with 0.25% AKG (AKG group, n = 12) based on body weight (BW) and parity. During the 21-d suckling period, BW and diarrhoea occurrences of piglets were recorded daily, while faeces were sampled weekly from sows and piglets. The levels of pH, ammonia, short-chain fatty acids (SCFA) and lactate in the faeces of piglets were determined. In particular, bacteria profiles in faeces of sows and their suckling piglets were examined by Illumina sequencing. The results showed that the AKG diet altered the faecal bacteria composition in sows during the 21-d lactation period, leading to increases (p < 0.05) in the abundances of genera Prevotella, Lactobacillus, Bacteroides and Methanobrevibacter, but decreases (p < 0.05) in the abundances of genera Oscillospira and Dorea. AKG supplement to the sows during lactation indirectly enhanced (p < 0.05) bacterial richness and SCFA levels (especially, acetate) in the faeces of piglets during the 21-d suckling period. It is suggested that maternal AKG supplementation alters the composition of faecal bacteria in the sows, and increases the faecal bacteria richness and acetate levels in the piglets, which might be associated with an enhanced growth performance of piglets.

Effects of ornithine α-ketoglutarate on growth performance and gut microbiota in a chronic oxidative stress pig model induced by d-galactose.

The aim of this study was to evaluate the protective effects and underlying mechanisms of ornithine α-ketoglutarate (OKG) on d-galactose (d-gal)-induced chronic oxidative stress in a pig model. A total of 40 castrated young pigs were randomly separated into five groups, including a control group, a model group treated with 5 mg per kg body weight (BW) d-gal, and three d-gal + OKG groups in which the pigs received 0.5%, 1%, and 2% OKG (n = 8). The experiment lasted for 28 days. The growth performance, serum oxidative stress index, expression of relative intestinal genes, gut microbiota, and serum amino acid pool were determined. The results demonstrated that administration of d-gal significantly affected growth performance and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels including related mRNA expression suppression, malondialdehyde (MDA) levels enhancement, gut microbiota dysfunction, and serum amino acid alteration in pigs. However, treatment with 0.5% OKG markedly ameliorated the reduction in the growth performance, as evidenced by the reversed final body weight, average feed intake, and average body weight. Also, 0.5% OKG enhanced the SOD and GSH-Px levels including relative mRNA expression in the intestine and inhibited lipid oxidation subsequent to MDA generation. The intestinal abundances of Firmicutes were increased and those of Proteobacteria, Fusobacteria, Bacteriodetes, and Euryarchaeota were decreased in the pigs supplemented with 0.5% OKG. Meanwhile, 0.5% OKG increased the glutamate, proline, aspartate, threonine, valine, isoleucine and leucine levels in the serum. Collectively, these results indicate that d-gal induced chronic oxidative stress and also proved the positive effects of 0.5% OKG on altering the pig gut microbe, restoring serum amino acid and alleviating the growth-suppression induced by d-gal chronic oxidative stress.

The Modulatory Properties of Astragalus membranaceus Treatment on Triple-Negative Breast Cancer: An Integrated Pharmacological Method.

Background: Studies have shown that the natural products of Astragalus membranaceus (AM) can effectively interfere with a variety of cancers, but their mechanism of action on breast cancer remains unclear. Triple-negative breast cancer (TNBC) is associated with a severely poor prognosis due to its invasive phenotype and lack of biomarker-driven-targeted therapies. In this study, the potential mechanism of the target composition acting on TNBC was explored by integrated pharmacological models and in vitro experiments. Materials and Methods: Based on the Gene Expression Omnibus (GEO) database and the relational database of Traditional Chinese Medicines (TCMs), the drug and target components were initially screened to construct a common network module, and multiattribute analysis was then used to characterize the network and obtain key drug-target information. Furthermore, network topology analysis was used to characterize the betweenness and closeness of key hubs in the network. Molecular docking was used to evaluate the affinity between compounds and targets and obtain accurate combination models. Finally, in vitro experiments verified the key component targets. The cell counting kit-8 (CCK-8) assay, invasion assay, and flow cytometric analysis were used to assess cell viability, invasiveness, and apoptosis, respectively, after Astragalus polysaccharides (APS) intervention. We also performed western blot analysis of key proteins to probe the mechanisms of correlated signaling pathways. Results: We constructed "compound-target" (339 nodes and 695 edges) and "compound-disease" (414 nodes and 6458 edges) networks using interaction data. Topology analysis and molecular docking were used as secondary screens to identify key hubs of the network. Finally, the key component APS and biomarkers PIK3CG, AKT, and BCL2 were identified. The in vitro experimental results confirmed that APS can effectively inhibit TNBC cell activity, reduce invasion, promote apoptosis, and then counteract TNBC symptoms in a dose-dependent manner, most likely by inhibiting the PIK3CG/AKT/BCL2 pathway. Conclusion: This study provides a rational approach to discovering compounds with a polypharmacology-based therapeutic value. Our data established that APS intervenes with TNBC cell invasion, proliferation, and apoptosis via the PIK3CG/AKT/BCL2 pathway and could thus offer a promising therapeutic strategy for TNBC.

Effects of maternal alpha-ketoglutarate supplementation during lactation on the performance of lactating sows and suckling piglets.

The aim of the study was to investigate if dietary alpha-ketoglutarate (AKG) supplementation may improve the performance of lactating sows and their suckling piglets. After farrowing, 24 lactating sows (Large White × Landrace) with similar body weight (BW) were assigned to the control and AKG groups based on parity, and their lactation diets were supplemented with 0.00 or 0.25% AKG, respectively. It was found that supplementing the diet of lactating sows with 0.25% AKG enhanced growth performance of the suckling piglets from d 7 to d 21 of the lactation period, improved villus height of ileum and tended (p = 0.085) to increase mean volumetric bone mineral density of femur in the weanling piglets. In the lactating sows, dietary supplementation of AKG decreased plasma urea level on d 14 of lactation, decreased plasma calcium (Ca) concentrations from d 7 to d 21 of lactation and increased lactose and Ca levels in ordinary milk. Thus, it was proposed that AKG supplementation stimulates the capacity for lactose synthesis and Ca uptake in the mammary gland, thereby altering the composition of the ordinary milk which might be associated with the enhanced performance of piglets during the suckling period. These findings could lead to a better application of AKG in lactating nutrition, and therefore, promoting pork production.

The effects of dietary supplementation with porous zinc oxide on growth performance, intestinal microbiota, morphology, and permeability in weaned piglets.

The objective of this experiment was to evaluate the effects of dietary supplementation with porous zinc oxide (HiZox) on growth performance, intestinal microbiota, morphology, and permeability in weaned piglets. A total of 128 weaned piglets [(Landrace × Yorkshire) × Duroc] with an average body weight (BW) of (6.55 ± 0.25 kg; 21 d of age) were randomly assigned to four dietary treatments: (1) a corn-soybean basal diet; (2) basal diet + 3,000 mg/kg conventional ZnO; (3) basal diet + 200 mg/kg HiZox; (4) basal diet + 500 mg/kg HiZox. The experiments lasted for 28 days. Incremental HiZox in the diet increased ADG (linear p = 0.015; quadratic p = 0.043) and ADFI (linear p = 0.027; quadratic p = 0.038), and the diarrhea index decreased linearly and quadratically (p < 0.01) as HiZox supplemented increased. Furthermore, supplementation with HiZox increased the amounts of Lactobacillus spp. (p < 0.05) in the ileum and cecum in comparison with that of control treatment or 3,000 mg/kg ZnO treatment, while decreased the populations of Escherichia coli, Clostridium coccoides, and Clostridium. leptum subgroup (p < 0.05) in the ileum and cecum relative to those in control treatment. The addition of HiZox increased the villus height and villus-to-crypt ratio (VC) of duodenum, jejunum, and ileum (p < 0.05), while decreased the crypt depth of jejunum (p < 0.05) and tended to reduce the crypt depth of duodenum (p < 0.10) compared with the control treatment. Piglets fed with 500 mg/kg HiZox had lower serum D-lactate and diamine oxidase (DAO) than those fed with basal control diet or 3,000 mg/kg ZnO diet (p < 0.01). The results suggested that supplementation with HiZox modulated intestinal microbial composition and improved intestinal morphology, which may exert protective effects on the integrity of the mucosal barrier function of weaned piglets, was as efficacious as pharmaceutical doses of ZnO in enhancing growth performance, indicating that the HiZox may be a promising alternative to pharmaceutical doses of ZnO.

Endoplasmic Reticulum Stress and Unfolded Protein Response Pathways Involved in the Health-Promoting Effects of Allicin on the Jejunum.

Intestinal endoplasmic reticulum stress (ERS) triggered by adverse factors disturbs the normal function of the intestine. Allicin has been reported to promote intestinal health and development. In the present study, we established in vivo (35-day-old weaned piglets, 4-week-old mice) and in vitro (IPEC-J2 cell line) ERS models to explore the possible mechanisms by which allicin may benefit intestinal health. This study revealed the following: (1) allicin supplementation improved intestinal morphological indices and ameliorated mild ERS in the jejunum of the weaned piglets; (2) allicin supplementation decreased cellular reactive oxygen species and upregulated the XBP-1s signaling pathways in IPEC-J2 cells; (3) allicin supplementation reduced the prolonged ERS-mediated apoptosis of IPEC-J2 cells and in the jejunal tissues of the KM mice; (4) allicin supplementation enhanced the intercellular junction protein levels of jejunal cells by alleviating the prolonged ERS. These novel findings suggest that eating garlic could alleviate some intestinal malfunctions associated with ERS.

Effect of Dietary Niacin Supplementation on Growth Performance, Nutrient Digestibility, Hematology, and Lipoprotein Concentrations of Young Turkeys, Meleagris gallopavo.

The growth performance, nutrient digestibility, hematology, serum chemistry, and lipoprotein concentrations of turkey (Meleagris gallopavo) poults fed diets supplemented with high or recommended concentrations of niacin were investigated in this study. A total of 120 four-week-old turkey poults were randomly divided into three treatment groups with five replicates of eight birds in each group. The poult diets were supplemented with 0.0, 60, and 180 mg/kg niacin in the three treatments, termed control, recommended niacin supplementation (RNS), and high niacin supplementation (HNS), respectively. The study lasted for four weeks. The results showed that the HNS treatment reduced the feed intake and increased the body weight gain of poults. The apparent, nitrogen-corrected, and true metabolizable energy contents were the highest in the HNS-group turkey poults (P<0.05). The red and white blood cell counts and hemoglobin concentration of the turkeys improved with increasing niacin supplementation (P<0.01). The serum constituents, including the serum protein and globulin, were significantly increased (P<0.05), while the uric acid and creatinine contents were significantly reduced in the HNS-group turkeys. Similarly, the HNS-group turkeys exhibited significantly reduced alanine aminotransferase (ALT) and alkaline phosphatase (ALP) contents, while the RNS-group turkeys had the least aspartate aminotransferase (AST) content. In addition, the HNS-group turkeys had the least serum low-density lipoprotein (LDL), triglyceride, and total cholesterol concentrations and the highest serum high-density lipoprotein (HDL) (P<0.01) concentrations. In conclusion, the supplementation of 180 mg/kg niacin in the diet reduced the feed intake and serum ALT, ALP, LDL, triglyceride, and cholesterol contents and increased the body weight gain, metabolizable energy, and HDL concentration in turkeys. This study showed that niacin supplementation could reduce the fat content without compromising the body weight gain and increase stress resistance in turkey poults.

Supplementation with α-ketoglutarate to a low-protein diet enhances amino acid synthesis in tissues and improves protein metabolism in the skeletal muscle of growing pigs.

α-Ketoglutarate (AKG) is a crucial intermediate in the tricarboxylic acid (TCA) cycle and can be used for the production of ATP and amino acids in animal tissues. However, the effect of AKG on the expression patterns of genes involved in muscle protein metabolism is largely unknown, and the underlying mechanism remains to be elucidated. Therefore, we used young pigs to investigate the effects of a low crude protein (CP) diet and a low CP diet supplemented with AKG on protein accretion in their skeletal muscle. A total of 27 growing pigs with an initial body weight of 11.96 ± 0.18 kg were assigned randomly to one of the three diets: control (normal recommended 20% CP, NP), low CP (17% CP, LP), or low CP supplemented with 1% AKG (ALP). The pigs were fed their respective diets for 35 days. Free amino acid (AA) profile and hormone levels in the serum, and the expression of genes implicated in protein metabolism in skeletal muscle were examined. Results showed that compared with the control group or LP group, low-protein diets supplemented with AKG enhanced serum and intramuscular free AA concentrations, the mRNA abundances of AA transporters, and serum concentrations of insulin-like growth factor-1 (IGF-1), activated the mammalian target of rapamycin (mTOR) pathway, and decreased serum urea concentration and the mRNA levels for genes related to muscle protein degradation (P < 0.05). In conclusion, these results indicated that addition of AKG to a low-protein diet promotes amino acid synthesis in tissues and improves protein metabolism in skeletal muscle.

Effects of natural dietary supplementation with Macleaya cordata extract containing sanguinarine on growth performance and gut health of early-weaned piglets.

This study was conducted to investigate the effects of dietary supplementation with Sangrovit® (SAG; minimum of 1.5% sanguinarine, a quaternary benzo[c]phenanthridine alkaloid extracted from Macleaya cordata) on growth performance, intestinal morphology, intestinal microflora and its metabolites of early-weaned piglets. A total of 20 healthy weaned piglets (Duroc× [Large White×Landrace]), weaned at 21 days of age with an average body weight (BW) of 6.52 ± 0.23 kg, were randomly assigned to receive either a corn-soybean meal basal diet (CTR) or a basal diet supplemented with 50 mg/kg SAG (SAG). During the 21-days trial, we collected and analysed intestinal tissues and the luminal digesta for their morphology and populations of gut microbiota, as well as for measuring the concentrations of short-chain fatty acids (SCFAs) and ammonia. Compared with the CTR group, supplementation with SAG improved average daily gains (p = 0.011) and average daily feed intake (p = 0.037). Piglets fed the SAG diet had an average lower value for crypt depth of the jejunum (p = 0.011) and greater values for villus height in the ileum (p = 0.015) and ratios of villus height to crypt depth in the jejunum (p < 0.01) and in the ileum (p = 0.027) than did animals receiving the CTR diet. The addition of SAG increased the amounts of Lactobacillus in the ileum (p = 0.033) and caecum (p < 0.01), and tended to increase the amounts of Bifidobacterium (p = 0.058) in the caecum, while decreasing the amounts of Escherichia coli (p = 0.046) and Salmonella spp. (p = 0.035) in the ileum, as well as Salmonella spp. (p = 0.029) in the caecum. Dietary supplementation with SAG enhanced (p < 0.05) the concentrations of acetate, propionate, butyrate and total SCFAs, and also tended to increase the level of valerate (p = 0.055 and p = 0.052) in the ileal and caecal contents when compared with the CTR group. Concentrations of ammonia also declined in the caecal (p = 0.037) and ileal (p = 0.046) digesta in response to SAG. These results indicate that feeding early-weaned piglets a SAG-supplemented diet can potentially improve their growth performance and intestinal morphology, and can modify the intestinal luminal environment in a beneficial manner.

Effect of dietary α-ketoglutarate and allicin supplementation on the composition and diversity of the cecal microbial community in growing pigs.

BACKGROUND: The search for substitutes for antibiotics has recently become urgent. In our previous work, dietary α-ketoglutarate (AKG) combined with allicin improved growth performance and enhanced immunity in growing pigs, whereas the effects on them of intestinal microbiota were unclear. Here, we further investigate the effects of dietary AKG and allicin supplementation on the composition and diversity of intestinal microbiota in growing pigs. RESULTS: Treatment with a combination of AKG and allicin enhanced cecal bacteria richness and diversity, as evidenced by changes in Chao 1, ACE, Shannon, and Simpson values when compared to the control group and antibiotics group. At the phylum level, Bacteroidetes and Firmicutes were the two most abundant phyla. Treatment with a combination of AKG and allicin increased the numbers of Firmicutes and reduced the numbers of Bacteroidetes. Prevotella was the most abundant genus; it was increased by treatment with a combination of AKG and allicin. Furthermore, compared with the antibiotic group, the level of acetate was increased in the AKG group with or without allicin. Treatment with a combination of AKG and allicin increased the levels of cecal butyrate and total volatile fatty acids (VFA) when compared with the control group in growing pigs. CONCLUSION: Dietary 1.0% AKG combined with 0.5% allicin improved cecal microbial composition and diversity, which might further promote VFA metabolism in growing pigs. © 2018 Society of Chemical Industry.

Melatonin alters amino acid metabolism and inflammatory responses in colitis mice.

Inflammatory bowel disease is a chronic inflammatory dysfunction of the gastrointestinal tract. This study explored the hypothesis that melatonin has beneficial functions in the mouse model of colitis induced by dextran sodium sulfate (DSS), with a specific focus on the expression of intestinal inflammatory cytokines and the serum levels of amino acids. The results revealed that mice with melatonin supplementation had a reduction in weight loss and disease index induced by DSS treatment. Melatonin stifled the expression of colonic IL-17 in mice with DSS-induced colitis. Melatonin also lowered the serum levels of Asp, Ser, Met, and Leu (p < 0.05), but increased those of Glu and Cys (p < 0.05). Thus, melatonin treatment is promising and may function as a potential adjuvant therapy to alleviate the clinical symptoms of patients with inflammatory bowel disease.