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Maternal nucleotide supplementation improves the intestinal morphology and immune function in lipopolysaccharide-challenged newborn piglets

ABSTRACT: This study aimed to evaluate the effects of maternal nucleotide (NT) supplementation on intestinal morphology and immune function in lipopolysaccharide-challenged newborn piglets. At 85 d gestation, 12 sows were selected and assigned to two groups: the CON group (basal diet, n = 6) and the NT group (basal diet with 1 g/kg NT mixture, n = 6). After parturition, newborn piglets were collected without suckling. Piglets from the CON group were intraperitoneally injected with sterile saline or lipopolysaccharide (LPS, 10 mg/kg body weight), and divided into the C-CON (n = 6) and C-LPS groups (n = 6). Piglets from the NT group received the same treatment and were divided into the N-CON (n = 6) and N-LPS groups (n = 6). The blood and small intestinal samples of piglets were collected 1 h after injection. The results showed that: (1) maternal NT supplementation increased the concentrations of serum complement C3 and C4 (P < 0.05), and suppressed the increase in serum hypersensitive C-reactive protein in LPS-challenged newborn piglets (P < 0.05); (2) maternal NT supplementation increased the villus height and the ratio of villus height to crypt depth in the duodenum of newborn piglets (P < 0.05) and inhibited the LPS-induced decrease in the villus height in the jejunum and ileum (P < 0.05). (3) The LPS-induced increased levels of interleukin-6 in the jejunum and tumor necrosis factor-α in the ileum of newborn piglets were suppressed by maternal NT supplementation (P < 0.05). (4) In the jejunum of newborn piglets, maternal NT supplementation inhibited the LPS-induced increase in toll-like receptor 4 (TLR4) mRNA and protein expression (P < 0.05) and the decrease of nuclear factor-κB inhibitor α (IκBα) protein expression (P < 0.05). In the ileum, piglets had a lower nuclear factor-κB (NFκB) mRNA expression in the NT groups than the CON groups (P < 0.05), and maternal NT supplementation suppressed the decrease of IκBα mRNA in LPS-treated piglets (P < 0.05). In conclusion, maternal NT supplementation could promote the intestinal development and immune function of newborn piglets, and may improve LPS-induced intestinal inflammatory responses via the TLR4/IκBα/NFκB pathway.

SUBMITTER: Li Q

PROVIDER: S-EPMC9643262 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Project description:Tryptophan (Trp) can modify the gut microbiota. However, there is no information about the effect of Trp on intestinal microbiota after lipopolysaccharide (LPS) challenge. This study aimed to investigate the effect of Trp on intestinal barrier function, inflammation, antioxidant status, and microbiota in LPS-challenged piglets. A total of 18 weaned castrated piglets were randomly divided into three treatments with 6 replicate per treatment, namely, (i) non-challenged control (CON); (ii) LPS-challenged control (LPS-CON); and (iii) LPS + 0.2% Trp (LPS-Trp). After feeding with control or 0.2% tryptophan-supplemented diets for 35 days, pigs were intraperitoneally injected with LPS (100 μg/kg body weight) or saline. At 4 h post-challenge, all pigs were slaughtered, and colonic samples were collected. The samples were analyzed for gut microbiota, fatty acids, antioxidant parameters, and the expression of mRNA and protein. The community bar chart showed that Trp supplementation to LPS-challenged pigs increased the relative abundance of Anaerostipes (P < 0.05) and tended to increase the relative abundance of V9D2013_group (P = 0.09), while decreased the relative abundance of Corynebacterium (P < 0.05) and unclassified_c__Bacteroidia (P < 0.01). Gas chromatography showed that Trp increased the concentrations of acetate, propionate, butyrate, and isovalerate in the colonic digesta (P < 0.05). Trp reduced the mRNA level of pro-inflammatory cytokines (P < 0.01), and increased mRNA level of aryl hydrocarbon receptor, cytochrome P450 (CYP) 1A1 and CYP1B1 (P < 0.05). Correlation analysis results showed that acetate, propionate, and butyrate concentrations were positively correlated with mRNA level of occludin and CYP1B1 (P < 0.05), and were negatively correlated with pro-inflammatory cytokines gene expression (P < 0.05). Isovalerate concentration was positively correlated with catalase activity (P < 0.05), and was negatively correlated with pro-inflammatory cytokines gene expression (P < 0.05). Furthermore, Trp enhanced the antioxidant activities (P < 0.01), and increased mRNA and protein expressions of claudin-1, occludin, and zonula occludens-1 (P < 0.01) after LPS challenge. These results suggest that Trp enhanced intestinal health by a modulated intestinal microbiota composition, improved the short chain fatty acids synthesis, reduced inflammation, increased antioxidant capacity, and improved intestinal barrier function.

Project description:?-Conglycinin (?-CG), an anti-nutritional factor, is a major allergen in soybeans to induce intestinal dysfunction and diarrhea in neonatal animals, including piglets and human infants. This study with a piglet model determined the effects of N-acetylcysteine (NAC) on intestinal function and autophagy in response to ?-CG challenge. Twenty-four 12-day-old piglets (3.44?±?0.28 kg), which had been weaned at 7 days of age and adapted for 5 days after weaning, were randomly allocated to the control, ?-CG, and ?-CG?+?NAC groups. Piglets in the control group were fed a liquid diet containing 10% casein, whereas those in the ?-CG and ?-CG?+?NAC groups were fed the basal liquid diets containing 9.5% casein and 0.5% ?-CG for 2 days. Thereafter, pigs in the ?-CG?+?NAC group were orally administrated with 50 mg (kg BW)-1 NAC for 3 days, while pigs in the other two groups were orally administrated with the same volume of sterile saline. NAC numerically reduced diarrhea incidence (-?46.2%) and the concentrations of hydrogen peroxide and malondialdehyde, but increased claudin-1 and intestinal fatty-acid binding protein (iFABP) protein abundances and activities of catalase and glutathione peroxidase in the jejunum of ?-CG-challenged piglets. Although ?-CG challenge decreased the villus height, villus height/crypt depth ratio, and mRNA levels of claudin-1 and occludin, no significant differences were observed in these indices between the control and ?-CG?+?NAC groups, suggesting the positive effects of NAC supplementation on intestinal mucosal barrier function. Moreover, NAC increased the concentrations of citrulline and D-xylose in the plasma, as well as the expression of genes for aquaporin (AQP) 3, AQP4, peptide transporter 1 (PepT1), sodium/glucose co-transporter-1 (SGLT-1), potassium inwardly-rectifying channel, subfamily J, member 13 (KCNJ13), and solute carrier family 1 member 1 (SLC1A1) in the jejunum, demonstrating that NAC augmented intestinal metabolic activity and absorptive function. Remarkably, NAC decreased Atg5 protein abundance and the LC3II/LC3I ratio (an indicator of autophagy) in the jejunum of ?-CG-challenged piglets. Taken together, NAC supplementation improved intestinal function and attenuated intestinal autophagy in ?-CG-challenged piglets.

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Project description:This study was conducted to investigate the effects of pyrroloquinoline quinone disodium (PQQ·Na2) on inflammatory responses, oxidative stress, and intestinal morphology of broiler chickens challenged with lipopolysaccharide (LPS). A 2 × 2 factorial arrangement in a complete randomized design experiment was used to study the effect of dietary PQQ·Na2 (0 or 1 mg/kg) on broiler chickens with or without a challenge with LPS. A total of two hundred eighty-eight 1-day-old Arbor Acre broiler chickens were randomly assigned to 4 treatments with 6 replicate cages of 12 birds per cage. All experimental broilers were injected intraperitoneally with 0.5 mg/kg body weight of either Escherichia coli LPS or sterile saline at 16, 18, and 20 d of age. Results showed that injecting LPS significantly increased the concentrations of interleukin-1beta (IL-1β) in serum of birds on day 20 and day 21. Meanwhile, LPS injection increased (P < 0.05) the relative mRNA expression of interleukin-6 (IL-6) in the duodenal mucosa of broilers on day 21. However, dietary supplementation with PQQ·Na2 decreased (P < 0.05) the concentration of IL-6 in serum of birds on day 20 and the levels of IL-1β, IL-6, and interleukin-10 (IL-10) in serum of broiler chickens on day 21. Besides, supplementation of PQQ·Na2 within diet decreased (P < 0.05) the mRNA expressions of IL-1β and IL-10 in the duodenal mucosa of birds on day 20. Relative to saline injection, the activity of glutathione peroxidase (GSH-Px) in serum and the activities of total superoxide dismutase (T-SOD) and catalase (CAT) in liver were found to be lower (P < 0.05) in broilers after LPS challenge on day 21. However, birds fed with PQQ·Na2 showed higher (P < 0.05) GSH-Px activity in serum and higher (P < 0.05) T-SOD activities in liver on day 21 and day 42. Pyrroloquinoline quinone disodium also significantly attenuated the LPS-induced decreases in villus height to crypt depth ratio in the duodenum of broilers. In conclusion, dietary PQQ·Na2 supplementation significantly exerted protective effects on inflammation damage and oxidant stress of broilers under LPS challenge by regulating the expression of inflammatory cytokines (IL-1β, IL-6, and IL-10) and activities of antioxidant enzymes (GSH-Px, T-SOD, and CAT). Moreover, dietary PQQ·Na2 supplementation significantly ameliorated the LPS-impaired intestinal morphology in broilers. Therefore, it has been considered that PQQ·Na2 can be used as a potential feed additive in broiler production.

Project description:The present study explored the potential effect of pterostilbene as a prophylactic treatment on the lipopolysaccharide (LPS)-induced intestinal injury of broiler chickens by monitoring changes in mucosal injury indicators, redox status, and inflammatory responses. In total, 192 one-day-old male Ross 308 broiler chicks were randomly divided into four groups. This trial consisted of a 2 × 2 factorial design with a diet factor (supplemented with 0 or 400 mg/kg pterostilbene from 1 to 22 d of age) and a stress factor (intraperitoneally injected with saline or LPS at 5.0 mg/kg BW at 21 da of age). The results showed that LPS challenge induced a decrease in BW gain (P < 0.001) of broilers during a 24-h period postinjection; however, this decrease was prevented by pterostilbene supplementation (P = 0.031). Administration of LPS impaired the intestinal integrity of broilers, as indicated by increased plasma diamine oxidase (DAO) activity (P = 0.014) and d-lactate content (P < 0.001), reduced jejunal villus height (VH; P < 0.001) and the ratio of VH to crypt depth (VH:CD; P < 0.001), as well as a decreased mRNA level of jejunal tight junction protein 1 (ZO-1; P = 0.002). In contrast, pterostilbene treatment increased VH:CD (P = 0.018) and upregulated the mRNA levels of ZO-1 (P = 0.031) and occludin (P = 0.024) in the jejunum. Consistently, pterostilbene counteracted the LPS-induced increased DAO activity (P = 0.011) in the plasma. In addition, the LPS-challenged broilers exhibited increases in nuclear accumulation of nuclear factor kappa B (NF-κB) p65 (P < 0.001), the protein content of tumor necrosis factor α (P = 0.033), and the mRNA abundance of IL-1β (P = 0.042) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3; P = 0.019). In contrast, pterostilbene inhibited the nuclear translocation of NF-κB p65 (P = 0.039) and suppressed the mRNA expression of IL-1β (P = 0.003) and NLRP3 (P = 0.049) in the jejunum. Moreover, pterostilbene administration induced a greater amount of reduced glutathione (P = 0.017) but a lower content of malondialdehyde (P = 0.023) in the jejunum of broilers compared with those received a basal diet. Overall, the current study indicates that dietary supplementation with pterostilbene may play a beneficial role in alleviating the intestinal damage of broiler chicks under the conditions of immunological stress.

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Maternal nucleotide supplementation improves the intestinal morphology and immune function in lipopolysaccharide-challenged newborn piglets

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