Lowered dietary phosphorus affects intestinal and renal gene expression to maintain mineral homeostasis with immunomodulatory implications in weaned piglets.
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ABSTRACT: In monogastric animals, phosphorus (P) homeostasis is maintained by regulating intestinal absorption, bone mobilization, and renal excretion. Since P is a non-renewable resource, a shortage is imminent due to widespread over-usage in the farming and animal husbandry industries. As a consequence, P efficiency should be improved in pig production. We sought to characterize the transcriptional response in re-/absorbing and excreting tissues in pigs to diets varying in calcium: phosphorus ratios. Weaned piglets were assigned to one of three groups fed diets varying in digestible P content for a period of five weeks. Gene expression profiles were analyzed in jejunum, colon, and kidney.Transcriptome analysis revealed that reduced dietary P intake affects gene expression in jejunum and kidney, but not in colon. The regulation of mineral homeostasis was reflected via altered mRNA abundances of CYP24A1, CYP27A1, TRPM6, SPP1, and VDR in jejunum and kidney. Moreover, lowered abundances of transcripts associated with the classical complement system pathway were observed in the jejunum. In kidney, shifted transcripts were involved in phospholipase C, calcium signaling, and NFAT signaling, which may have immunomodulatory implications.Our results revealed local transcriptional consequences of variable P intake in intestinal and renal tissues. The adaptive responses are the result of organismal efforts to maintain systemic mineral homeostasis while modulating immune features at local tissue sites. Therefore, the deviation from the currently recommended dietary P supply must be carefully considered, as the endogenous mechanisms that respond to low P diets may impact important adaptive immune responses.
Lowered dietary phosphorus affects intestinal and renal gene expression to maintain mineral homeostasis with immunomodulatory implications in weaned piglets.
<h4>Background</h4>In monogastric animals, phosphorus (P) homeostasis is maintained by regulating intestinal absorption, bone mobilization, and renal excretion. Since P is a non-renewable resource, a shortage is imminent due to widespread over-usage in the farming and animal husbandry industries. As a consequence, P efficiency should be improved in pig production. We sought to characterize the transcriptional response in re-/absorbing and excreting tissues in pigs to diets varying in calcium: ph ...[more]
Project description:Homeostasis during the perinatal period is critical for the correct development of mammals and unbalances in the redox potential are common in this stage. Thus, enrichment of maternal diets with antioxidants may be useful to improve piglet early development. We have tested the effects of sows’ diet enrichment with different antioxidants on the piglets’ adipose tissue functioning, in comparison to a control diet with a basal antioxidant level, by studying gene expression and cellularity. The maternal diet strongly influenced adipose tissue transcriptome of the offspring post-weaning. Piglets born to sows supplemented with either vitamin E or hydroxytyrosol show improved metabolic and antioxidant status of adipose tissue, while animals from control group show impaired homeostasis and activation of oxidative stress, immune signalling, and inflammation pathways. Moreover, vitamin E, when supplemented alone at a high dose, activated lipid metabolism and increased adipocyte size. When both vitamin E and hydroxytyrosol were combined, the gene expression profile was scarcely affected in comparison to the control, showing a prooxidant/proinflamatory adipose tissue, which is an unexpected result with different potential explanations. Findings deepen in the processes taking place in adipose tissue of genetically fat individuals and highlight the crucial role of antioxidants in fat cells metabolism
Project description:Vitamin A (VA) is an important nutrient for weaning piglets. It plays a significant role in the normal formation, development, and maintenance of epithelial cells. Previous studies have shown that VA supplements could improve the host's intestinal barrier function. Therefore, we hypothesized that VA supplements can affect intestinal function in weaned piglets by regulating intestinal stem cells. Thirty-two 21-d-old weaned [(Yorkshire × Landrace) × Duroc] piglets with an average weight of 8.34 ± 0.13 kg were randomly divided into 4 treatment groups, with 1) 2 mg/kg (control), 2) 4 mg/kg, 3) 8 mg/kg, and 4) 16 mg/kg doses of VA, respectively. The experiment lasted for 14 d. Weaned piglets were given ad libitum access to food and water during the test. The ADG (linear, P = 0.020) and G:F (linear, P = 0.005) of the piglets were found to increase significantly from days 8 to 14. The Lgr5+ gene expression (P = 0.012) in the jejunum mucosa of the 16 mg/kg VA group was increased. The jejunum villus height (P = 0.027) and villi surface area (P = 0.035) were significantly increased in the 4 mg/kg VA treatment group. The crypt depth increased significantly in the 4 and 8 mg/kg VA treatment groups (quadratic, P = 0.043), and the ratios of villus height to crypt depth significantly increased in the 16 mg/kg VA group (quadratic, P = 0.015). The maltase (P = 0.032), sucrose (P = 0.041), and alkaline phosphatase activity (linear, P = 0.024) were significantly increased when further supplemented with 4 mg/kg VA. Slc2a2 mRNA abundance was significantly increased in the 2 mg/kg VA group (linear, P = 0.024). Moreover, the budding rates, buddings number per organoid, and Chromogranin A and Muc2 expression of piglet intestinal organoids were significantly reduced (P < 0.05) by VA and its metabolites (retinoic acid). Compared with the control group, the expression of Spp1 and Trop2 increased. These results indicated that VA may increase the stemness of intestinal stem cell in vitro. This study suggested that VA could affect growth performance and intestinal function by regulating intestinal stem cells in the jejunum of weaned piglets.
Project description:Transcriptional profiling of 25d old piglets comparing control untreated suckling jejunum with weaned piglets' jejunum. The goal was to gain new insight into the interaction between weaning and intestinal function.A keen interest is paid in deciphering expression changes of apoptosis or cell cycle control genes. The statistical analysis of gene ontology revealed that most of these altered genes are metabolic-related enzymes and regulators which may involved in the biological regulation, developmental process, and cellular process. Weaning also causes alterations in various immune response pathways. Results likely indicate that weaning induced cell cycle arrest, enhanced apoptosis, and inhibited cell proliferation.
Project description:Transcriptional profiling of 25d old piglets comparing control untreated suckling jejunum with weaned piglets' jejunum. The goal was to gain new insight into the interaction between weaning and intestinal function.A keen interest is paid in deciphering expression changes of apoptosis or cell cycle control genes. The statistical analysis of gene ontology revealed that most of these altered genes are metabolic-related enzymes and regulators which may involved in the biological regulation, developmental process, and cellular process. Weaning also causes alterations in various immune response pathways. Results likely indicate that weaning induced cell cycle arrest, enhanced apoptosis, and inhibited cell proliferation. Two-condition experiment, suckling control piglets' jejunum vs. weaned piglets' jejunum. Biological replicates: 4 control replicates, 4 weaned replicates.
Project description:Phosphorus (P) is an important element of various metabolic and signalling processes, including bone metabolism and immune function. To elucidate the routes of P homeostasis and utilization, a five-week feeding study was conducted with weaned piglets receiving a diet with recommended amounts of P and Ca (M), or a diet with lower (L) or higher (H) P values and a constant Ca:P ratio. Routes of P utilization were deduced via bone characteristics (MicroCT), genome-wide transcriptomic profiles of peripheral blood mononuclear cells (PBMCs), and serum mineral levels. MicroCT revealed significantly lower bone mineral density, trabecular number, and mechanical fracture load in (L). Gene expression analyses showed transcripts of 276 and 115 annotated genes with higher or lower abundance in (H) than (L) that were related to basic cellular and metabolic processes as well as response to stimuli, developmental processes and immune system processes. This study shows the many molecular routes involved in P homeostasis that should be considered to improve endogenous mechanisms of P utilization.
Project description:Ferulic acid (FA) is a phenolic compound that has antioxidant, hepatoprotective, anticarcinogenic, anti-inflammatory, antiallergic, antimicrobial, antiviral, and vasodilatory effects. This study was conducted to explore the effects of dietary FA supplementation on antioxidant capacity and lipid metabolism in weaned piglets. Eighteen 21-day-old castrated male DLY (Duroc × Landrace × Yorkshire) weaned piglets were randomly divided into control, 0.05%, and 0.45% FA groups. The results showed that, in serum, CAT and T-SOD activities and content of HDL-C were increased, but the content of MDA and the activities of T-CHO and LDL-C were decreased, by FA supplementation. In liver, dietary FA supplementation increased CAT, T-SOD, and GSH-PX activities and upregulated the mRNA levels of SOD1, SOD2, CAT, GST, GPX1, GR, Nrf2, HSL, CPT1b, and PPARα but decreased the contents of MDA and TG. Furthermore, dietary FA supplementation increased the protein level of Nrf2, HO-1, and NQO-1. In longissimus dorsi muscle, dietary FA supplementation increased the activity of T-SOD and the mRNA abundance of SOD1, SOD2, CAT, GST, GPX1, GR, and Nrf2 but decreased the contents of MDA and T-CHO. Additionally, dietary FA supplementation increased the protein expressions of Nrf2, HO-1, and NQO1. Together, our data suggest that FA could improve antioxidant capacity and lipid metabolism in weaned piglets.
Project description:The impact of dietary phosphorus on chronic renal disease in cats, humans and other species is receiving increasing attention. As Ca and P metabolism are linked, the ratio of Ca:P is an important factor for consideration when formulating diets for cats and other animals. Here, we describe a fully randomised crossover study including twenty-four healthy, neutered adult cats, investigating postprandial responses in plasma P, ionised Ca and parathyroid hormone (PTH) following one meal (50 % of individual metabolic energy requirement) of each of six experimental diets. Diets were formulated to provide P at either 0·75 or 1·5 g/1000 kcal (4184 kJ) from the soluble phosphorus salt sodium tripolyphosphate (STPP, Na5P3O10), variable levels of organic Ca and P sources, and an intended total Ca:P of about 1·0, 1·5 or 2·0. For each experimental diet, baseline fasted blood samples were collected prior to the meal, and serial blood samples collected hourly for 6 h thereafter. For all diets, a significant increase from baseline was observed at 120 min in plasma PTH (P < 0·001). The diet containing the highest STPP inclusion level and lowest Ca:P induced the highest peaks in postprandial plasma P and PTH levels (1·8 mmol/l and 27·2 pg/ml, respectively), and the longest duration of concentrations raised above baseline were observed at 3 h for P and 6 h for PTH. Data indicate that Ca:P modulates postprandial plasma P and PTH. Therefore, when formulating diets containing soluble P salts for cats, increasing the Ca:P ratio should be considered.
Project description:Development of immune competence in pigs is important for resilience, disease resistance, and performance later in life. Dietary interventions in early life can contribute to immune system development. Use of model dietary interventions, such as diets with a high concentration of zinc, can contribute to the understanding of the interactions between the diet, the intestinal microbiota and intestinal tissues. The aim of the present study was to evaluate the effects of provision of a diet with a high concentration of zinc (Zn, 2690 mg/kg), as model intervention, as compared to provision of a control diet with a regular Zn concentration (100 mg/kg) during a period of nine days during the post weaning period (d 14-23 post weaning (pw)), on the composition of the intestinal microbiota and gene expression in the intestinal mucosa on d 23 and 35 pw (12 d after the termination of the Zn intervention). Whole genome gene expression analysis of the jejunal and ileal mucosa revealed a small overall time-treatment interaction effect at d 23 pw in both intestinal tissues. In both jejunal and ileal mucosa various genes/probes were differentially up or down regulated between treatments. In intestinal tissue samples obtained on d 35 no differences in gene expression were observed. Probes of d 23 pw that were differently expressed and had an annotation were subsequently used as input for further functional analysis using DAVID and Gene Decks databases. The analysis did not result in the identification of gene sets that were differentially expressed between dietary treatments. However, it was shown that a number of upregulated genes in the jejunal mucosa on d 23 pw by the high zinc intervention are involved in pathways related to mineral absorption, immune signalling and cell energy metabolism (glycolysis and gluconeogenesis). A few down regulated genes by the Zn intervention are also involved in immune signalling pathways. It was concluded from the present study that provision of a diet with a high concentration of zinc as zinc oxide during a short period of time (9 days) to piglets in the post weaning period (d 14-23 pw) induces differences on the intestinal expression of genes in part related to the functioning of the local innate immune system. The high dietary zinc intervention can therefore be considered as a suitable model for studying relationships between dietary interventions and development of immune competence in post weaning piglets.
Project description:Dietary zinc oxide (ZnO) at pharmacological level has been widely used to prevent and treat diarrhea in weaning piglets. Despite its importance for promoting animal health and performance, the influence of microbiome profiles in intestinal tracts by ZnO needs to be comprehensively investigated. In this study, we conducted a comparative microbial community analysis in the ileum and colon of piglets fed by either control diet, high ZnO (3,000 mg/kg) supplement or antibiotics (300 mg/kg chlortetracycline and 60 mg/kg colistin sulfate) supplement. Our results showed that both high dietary ZnO and in-feed antibiotics supplementations significantly increased 5 phyla of Spirochaetes, Tenericutes, Euryarchaeota, Verrucomicrobia, TM7, and reduced 1 phyla of Chlamydiae in ileal digesta. The relative abundance of opportunistic pathogens Campylobacterales were decreased while Enterobacteriales were increased in ZnO or antibiotics-supplemented group when compared to the control. In the colon, the phyla Euryarchaeota, the genus Methanobrevibacter, and the species Methanobrevibacter smithii were drastically increased by high dietary ZnO supplementation when compared with other groups. The microbial functional prediction analysis showed that high dietary ZnO and in-feed antibiotics had a higher abundance of transporter pathway enrichment in the ileum when compared with the control. While in the colon high dietary ZnO had a higher abundant enrichment of methane metabolism involving energy supply when compared with other groups. Both high dietary ZnO and antibiotics increased the microbiota diversity of ileal digesta while they decreased the microbiota diversity of the colonic digesta. Collectively, these results suggested that dietary ZnO and in-feed antibiotics supplementations presented similar effect on ileal microbiota, and mainly affected the non-predominant microbiota.
Project description:The present study aimed to investigate the effects of dietary zinc sources on the growth performance and gut health of weaned piglets. In total, 96 Duroc × Landrace × Yorkshire (DLY) weaned piglets with an initial average body weight of 8.81±0.42kg were divided into four groups, with six replicates per treatment and four pigs per replicate. The dietary treatment groups were as follows: (1) control group, basal diet; (2) zinc sulphate (ZnSO4) group, basal diet +100mg/kg ZnSO4; (3) glycine zinc (Gly-Zn) group, basal diet +100mg/kg Gly-Zn and (4) zinc lactate group, and basal diet +100mg/kg zinc lactate. The whole trial lasted for 28days. Decreased F/G was noted in the Gly-Zn and zinc lactate groups (p<0.05). The zinc lactate group had a lower diarrhea rate than the control group (p<0.05). Moreover, the ZnSO4, Gly-Zn, and zinc lactate groups had significantly higher apparent total tract digestibility of dry matter (DM), crude protein (CP), ether extract (EE), crude ash, and zinc than the control group (p<0.05). The Gly-Zn and zinc lactate groups had higher jejunal villus height and a higher villus height:crypt depth ratio than the control group (p<0.05). In addition, the ZnSO4, Gly-Zn and zinc lactate groups had a significantly lower mRNA expression level of jejunal ZRT/IRT-like protein 4 (ZIP4) and higher mRNA expression level of jejunal interleukin-1β (IL-1β) than the control group (p<0.05). The mRNA expression level of jejunal zinc transporter 2 (ZNT2) was higher and that of jejunal Bcl-2-associated X protein (Bax) was lower in the Gly-Zn and zinc lactate groups than in the control group (p<0.05). Moreover, the zinc lactate group had a higher count of Lactobacillus spp. in the cecal digesta and higher mRNA expression levels of jejunal occludin and mucin 2 (MUC2) than the control group (p<0.05). In conclusion, dietary supplementation with 100mg/kg ZnSO4, Gly-Zn, or zinc lactate could improve the growth performance and gut barrier function of weaned piglets. Dietary supplementation with organic zinc, particularly zinc lactate, had the best effect.