Regulation of oxidative stress in the intestine of piglets after enterotoxigenic Escherichia coli (ETEC) infection.

Enterotoxigenic Escherichia coli (ETEC) is recognized globally as a major gastrointestinal pathogen that impairs intestinal function. ETEC infection can lead to oxidative stress and disruption of intestinal integrity. The present study investigated the mechanism of increased oxidative stress and whether restoration of antioxidant defense could improve intestinal integrity in a piglet model with ETEC infection. Weaned piglets were divided into three groups: control, ETEC-infection and ETEC-infection with antibiotic supplementation. The infection caused a significant elevation of serum diamine oxidase activity and D-lactate levels coupled with a reduced intestinal (mid-jejunum) tight-junction protein expression, suggesting increased intestinal permeability and impaired gut function. The infection also inhibited nuclear factor erythroid 2-related factor 2 (Nrf2) activation, decreased the expression of glutathione synthesizing enzymes, superoxide dismutase-1 (SOD1), and heme oxygenase-1 (HO-1) in the intestine. This led to a decreased antioxidant glutathione level and an increased lipid peroxidation in the intestine and serum, indicating oxidative stress. The infection stimulated the expression of pro-inflammatory cytokines (IL-6, TNF-α). Antibiotic supplementation attenuated oxidative stress, in part, through restoration of glutathione levels and antioxidant enzyme expression in the intestine. Such a treatment enhanced tight-junction protein expression and improved intestinal function. Furthermore, induction of oxidative stress in Caco2 cells by hydrogen peroxide inhibited tight-junction protein expression and stimulated inflammatory cytokine expression. Glutathione supplementation effectively attenuated oxidative stress and restored tight-junction protein expression. These results suggest that downregulation of Nrf2 activation may weaken antioxidant defense and increase oxidative stress in the intestine. Mitigation of oxidative stress can improve intestinal function after infection.

d-Aspartate in Low-Protein Diets Improves the Pork Quality by Regulating Energy and Lipid Metabolism via the Gut Microbes.

d-Aspartate is critical in maintaining hormone secretion and reproductive development in mammals. This study investigated the mechanism of different d-aspartate levels (0, 0.005, 0.05, and 0.5% d-aspartate) in low-protein diets on growth performance and meat quality by mediating the gut microbiota alteration in pigs. We found that adding 0.005% d-aspartate to a low-protein diet could dramatically improve the growth performance during the weaned and growing periods. Dietary d-aspartate with different levels markedly increased the back fat, and 0.5% d-aspartate significantly increased the redness in 24 h and reduced the shear force of the longissimus dorsi (LD) muscle. Moreover, d-aspartate treatments decreased the mRNA expression of MyHC II a and MyHC IIx in the LD muscle. The protein expression of MyH1, MyH7, TFAM, FOXO1, CAR, UCP2, and p-AMPK was upregulated by 0.005% d-aspartate. Additionally, the abundance of Alistipes, Akkermansia, and the [Eubacterium]_coprostanoligenes_group in the intestinal chyme of pigs was significantly decreased by d-aspartate treatments at the genus level, which was also accompanied by a significant decrease in acetate content. These differential microorganisms were significantly correlated with meat quality characteristics. These results indicated that d-aspartate in low-protein diets could improve the growth performance and meat quality in pigs by regulating energy and lipid metabolism via the alteration of gut microbiota.

Crosstalk between trace elements and T-cell immunity during early-life health in pigs.

With gradual ban on the use of antibiotics, the deficiency and excessive use of trace elements in intestinal health is gaining attention. In mammals, trace elements are essential for the development of the immune system, specifically T-cell proliferation, and differentiation. However, there remain significant gaps in our understanding of the effects of certain trace elements on T-cell immune phenotypes and functions in pigs. In this review, we summarize the specificity, development, subpopulations, and responses to pathogens of porcine T cells and the effects of functional trace elements (e.g., iron, copper, zinc, and selenium) on intestinal T-cell immunity during early-life health in pigs. Furthermore, we discuss the current trends of research on the crosstalk mechanisms between trace elements and T-cell immunity. The present review expands our knowledge of the association between trace elements and T-cell immunity and provides an opportunity to utilize the metabolism of trace elements as a target to treat various diseases.

Effects of high- and low-fiber diets on intestinal oxidative stress in growing-finishing pigs.

Feed is the most expensive facet of commercial pork production. In order to reduce feed costs, using high-fiber ingredients has become a common practice. Moderate levels of fiber can maintain intestinal physiological function and promote intestinal health. Oxidative stress is linked to impaired nutrient absorption and growth performance. This study investigated the effects of high-fiber (5.26% crude fiber) and low-fiber (2.46% crude fiber) diets on growth performance and intestinal oxidative stress parameters in growing-finishing pigs. Forty growing pigs with initial body weight (27.07 ± 1.26 kg) were randomly assigned to 2 treatment groups with 10 replicates of 2 pigs per pen. Pigs were weighed on day 35, 42, and 70. The feed intake was recorded daily to calculate growth performance parameters. On day 70, eight pigs in each treatment group were randomly selected and euthanized to obtain jejunum to measure oxidative stress status. Pigs fed a high-fiber diet were heavier than those fed a low-fiber diet on days 35, 42, and 70 (P < 0.05). During the whole feeding period, pigs fed a high-fiber diet had a higher average daily gain than those fed a low-fiber diet (P < 0.05). The low-fiber diet resulted in increased levels of malondialdehyde (P < 0.05) in the jejunum, suggesting that the low-fiber diet contributed to oxidative stress in the jejunum. The low-fiber diet also led to a significant increase in glutathione and oxidized glutathione levels (P < 0.05) in the jejunum, indicating that pigs fed a low-fiber diet needed to produce more antioxidant substances to cope with oxidative stress in the intestine. This was accompanied by a significant increase in the expression of glutathione synthesizing enzymes in the jejunum of the low-fiber group (P < 0.05). These results suggest that the high-fiber diet can improve growth performance and maintain intestinal health in growing-finishing pigs by reducing intestinal oxidative stress.

The gastrointestinal tract provides the location for the digestion and absorption of nutrients. It has physical and chemical barriers to protect body from pathogens and toxins. Oxidative stress tends to weaken the physical and chemical barriers of the intestine, which in turn can lead to intestinal dysfunction. Fiber has been suggested to have beneficial effects on the intestine health of pigs. Revealing how fiber can maintain intestinal health is important for pig production. In the present research, we investigated the effect of fiber on the oxidative stress status and antioxidant content in the pig intestine. Our data revealed that a low-fiber diet contributed to oxidative stress in the pig intestine (jejunum). Pigs fed a high-fiber diet had less intestinal oxidative stress and grew heavier. Pigs fed a low-fiber diet may produce more antioxidants to cope with the increased oxidative stress in the intestine.

Glutamate and aspartate alleviate testicular/epididymal oxidative stress by supporting antioxidant enzymes and immune defense systems in boars.

Several potential oxidative agents have damaging effects on mammalian reproductive systems. This study was conducted to investigate the effects of glutamate (Glu) and aspartate (Asp) supplementation on antioxidant enzymes and immune defense systems in the outer scrotum of boars injected with H2O2. A total of 24 healthy boars were randomly divided into 4 treatment groups: control (basal diet, saline-treated), H2O2 (basal diet, H2O2-challenged outer scrotum (1 mL kg-1 BW)), Glu (basal diet +2% Glu, H2O2-challenged), and Asp (basal diet+2% Asp, H2O2-challenged). Our results showed that both Glu and Asp supplementation improved testicular morphology and decreased the genital index in the H2O2-treated boars. Glu and Asp administration increased the antioxidant enzyme activities and affected the testicular inflammatory cytokine secretion but had no effect on sex hormone levels. Furthermore, the mRNA expression of CAT, CuZnSOD, and GPx4 was altered in the testes and epididymis of boars treated with Asp and Glu. Glu and Asp supplementation also modulated the expression of TGF-ß1, IL-10, TNF-α, IL-6 and IL-1ß in the testis and epididymis. These results indicate that dietary Glu and Asp supplementation might enhance antioxidant capacity and regulate the secretion and expression of inflammatory cytokines to protect the testes and epididymis of boars against oxidative stress.

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.