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Introduction: Global warming augments the risk of adverse pregnancy outcomes in vulnerable expectant mothers. Pioneering investigations into heat stress (HS) have predominantly centered on its direct impact on reproductive functions, while the potential roles of gut microbiota, despite its significant influence on distant tissues, remain largely unexplored. Our understanding of deleterious mechanisms of HS and the development of effective intervention strategies to mitigate the detrimental impacts are still limited. Objectives: In this study, we aimed to explore the mechanisms by which melatonin targets gut microbes to alleviate HS-induced reproductive impairment. Methods: We firstly evaluated the alleviating effects of melatonin supplementation on HS-induced reproductive disorder in pregnant mice. Microbial elimination and fecal microbiota transplantation (FMT) experiments were then conducted to confirm the efficacy of melatonin through regulating gut microbiota. Finally, a lipopolysaccharide (LPS)-challenged experiment was performed to verify the mechanism by which melatonin alleviates HS-induced reproductive impairment. Results: Melatonin supplementation reinstated gut microbiota in heat stressed pregnant mice, reducing LPS-producing bacteria (Aliivibrio) and increasing beneficial butyrate-producing microflora (Butyricimonas). This restoration corresponded to decreased LPS along the maternal gut-placenta-fetus axis, accompanied by enhanced intestinal and placental barrier integrity, safeguarding fetuses from oxidative stress and inflammation, and ultimately improving fetal weight. Further pseudo-sterile and fecal microbiota transplantation trials confirmed that the protective effect of melatonin on fetal intrauterine growth under HS was partially dependent on gut microbiota. In LPS-challenged pregnant mice, melatonin administration mitigated placental barrier injury and abnormal angiogenesis via the inactivation of the TLR4/MAPK/VEGF signaling pathway, ultimately leading to enhanced nutrient transportation in the placenta and thereby improving the fetal weight. Conclusion: Melatonin alleviates HS-induced low fetal weight during pregnancy via the gut-placenta-fetus axis, the first time highlighting the gut microbiota as a novel intervention target to mitigate the detrimental impact of global temperature rise on vulnerable populations.

Abstract Background The benefits of combining benzoic acid and essential oils (BAO) to mitigate intestinal impairment during the weaning process have been well established, while the detailed underlying mechanism has not been fully elucidated. Previous research has primarily focused on the reparative effects of BAO on intestinal injury, while neglecting its potential in enhancing intestinal stress resistance. Methods In this study, we investigated the pre-protective effect of BAO against LPS-induced stress using a modified experimental procedure. Piglets were pre-supplemented with BAO for 14 d, followed by a challenge with LPS or saline to collect blood and intestinal samples. Results Our findings demonstrated that BAO supplementation led to significant improvements in piglets' final weight, average daily gain, and feed intake/body gain ratio. Additionally, BAO supplementation positively influenced the composition of intestinal microbiota, increasing beneficial Actinobacteriota and Alloprevotella while reducing harmful Desulfobacterota, Prevotella and Oscillospira. Furthermore, BAO supplementation effectively mitigated oxidative disturbances and inflammatory responses induced by acute LPS challenge. This was evidenced by elevated levels of T-AOC, SOD, and GSH, as well as decreased levels of MDA, TNF-α, and IL-6 in the plasma. Moreover, piglets subjected to LPS challenge and pre-supplemented with BAO exhibited significant improvements in intestinal morphological structure and enhanced integrity, as indicated by restored expression levels of Occludin and Claudin-1 compared to the non-supplemented counterparts. Further analysis revealed that BAO supplementation enhanced the jejunal antioxidative capacity by increasing GSH-Px levels and decreasing MDA levels under the LPS challenge and stimulated the activation of the Nrf2 signaling pathway. Additionally, the reduction of TLR4/NF-κB/MAPK signaling pathways activation and proinflammatory factor were also observed in the jejunal of those piglets fed with BAO. Conclusions In summary, our study demonstrates that pre-supplementation of BAO enhances the anti-stress capacity of weaned piglets by improving intestinal microbiota composition, reinforcing the intestinal barrier, and enhancing antioxidative and anti-inflammatory capabilities. These effects are closely associated with the activation of Nrf2 and TLR4/NF-κB/MAPK signaling pathways.

Abstract Background Intrauterine growth restriction (IUGR) is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth (CUG) before weanling could significantly restore this negative influence. But there was limited knowledge about the underlying mechanism of CUG occurrence. Methods Eighty litters of newborn piglets were divided into normal birth weight (NBW) and IUGR groups according to birth weight. At 26 d, those piglets with IUGR but over average body weight of eighty litters of weaned piglets were considered as CUG, and the piglets with IUGR still below average body weight were considered as NCUG. This study was conducted to systemically compare the intestinal difference among NBW, CUG and NCUG weaned piglets considering the crucial role of the intestine for piglet growth. Results The results indicated that the mRNA expression of nutrients (amino acids, glucose, and fatty acids) transporters, and mitochondrial electron transport chain (ETC) I were upregulated in CUG piglets’ gut with improved morphology compared with those NCUG, as well as the ratio of P-AMPK/AMPK protein expression which is the indicator of energy metabolism. Meanwhile, CUG piglet’s gut showed higher antioxidative capacity with increased SOD and GSH-Px activity, decreased MDA levels, as well as higher mRNA expressions of Nrf2, Keap1, SOD, and GSH-Px. Furthermore, inflammatory parameters including TNF-α, IL-1β, IL-6, and IL-12 factors, and the activation of MAPK and NF-κB signaling pathways were significantly elevated in the NCUG intestine, while the protein expression of ZO-1, Occludin and Claudin-1 was reduced. The alpha diversity of fecal microbiota was higher in CUG piglets in contrast with NCUG piglets, and the increased beneficial bacteria and decreased pathogenic bacteria was also observed in CUG piglets. Conclusions CUG piglet’s intestine showed comprehensive restoration including higher nutrients transport, energy metabolism, antioxidant capacity, and intestinal physical barrier, while lower oxidative stress, inflammatory response, and pathogenic microbiota.

Comprehensive studies have been conducted to compare the effect of organic and inorganic selenium previously, but there is still limited knowledge about the difference between organic selenium (Se) from varied sources despite the widely use of organic Se in both animal and human being nutrient additives. In the present study, we systemically compared the effect of two different types of organic Se including selenium yeast (SeY) and selenium methionine (Sel-Met) on cell viability, selenoprotein transcriptome, and antioxidant status in porcine mammary epithelial cells (PMECs) and the results indicated that appropriate addition of SeY and Sel-Met both significantly promoted cell viability and up-regulated the mRNA expression of most selenopreoteins including DIOs, GPXs, and TrxRs family et al. (P < 0.05). Besides, two different sources of Se supplementation both greatly improved redox status with higher levels of T-AOC, SOD, and CAT (P < 0.05), while less content of MDA (P < 0.05), and reduced protein expression of cleaved-caspase-3 (P < 0.05) to mitigate cell apoptosis. Furthermore, the key proteins related to p38/JNK pathway including p38, p-p38, JNK, and p-JNK were apparently reduced in the groups with both of SeY and Sel-Met (P < 0.05). Interestingly we found that the changes induced by SeY supplementation in cell viability, selenoprotein transcriptome, antioxidative capacity, and anti-apoptosis were comprehensively greater compared with same levels addition of Sel-Met in PEMCs (P < 0.05). In conclusion, both SeY and Sel-Met promoted cell viability and attenuated cell apoptosis by regulating the selenoprotein expression and antioxidative capacity via p38/JNK signaling pathway in PMEC, but SeY has more efficient benefits than that of Sel-Met.

Frequent occurrence of intrauterine growth restriction (IUGR) causes huge economic losses in the pig industry. Accelerated catch-up growth (CUG) in the early stage of life could restore multiple adverse outcomes of IUGR offspring; however, there is little knowledge about this beneficial phenomenon. We previously found that nutrient absorption related to intestinal function was globally promoted in CUG-IUGR piglets before weaning, which might be the dominant reason for CUG, but what this alteration could lead to in subsequent liver metabolism is still unknown. Firstly, a Normal, CUG, and non-catch-up growth (NCUG) piglet model before weaning was established by dividing eighty litters of newborn piglets into normal birth weight (NBW) and IUGR groups according to birth weight, and those piglets with IUGR but above-average weanling body weight were considered CUG, and the piglets with IUGR still below average body weight were considered NCUG at weaning day (d 26). Liver samples were collected and then systematically compared in glycolipid metabolism, mitochondrial function, antioxidant status, and inflammatory status among these three different growth models. Enhanced hepatic uptake of fatty acids, diminished de novo synthesis of fatty acids, and increased oxidation of fatty acids were observed in CUG livers compared to Normal and NCUG. In contrast, the NCUG liver showed enhanced glucose uptake and gluconeogenesis compared to Normal and CUG. We also observed deteriorating hepatic vacuolation in NCUG piglets, while increasing hepatic lipid deposition in CUG piglets. Besides, the expression of genes related to mitochondrial energy metabolism and biogenesis was reduced in CUG piglets and the phosphorylation level of AMPK was significantly higher compared to Normal (p < 0.05). Moreover, NCUG liver showed decreased T-AOC (p < 0.01) and GSH-PX (p < 0.05), increased MDA concentrations (p < 0.01), upregulated phosphorylation levels of ERK and NF-κB (p < 0.05), and elevated pro-inflammatory factors IL-1β, IL-6 and TNF-α (p < 0.05) compared to Normal. Furthermore, correlation analysis revealed a significant positive correlation between glucose metabolism and inflammatory factors, while a negative correlation between mitochondrial function-related genes and fatty acid transport. NGUG piglets showed simultaneous enhancement of glucose uptake and gluconeogenesis, as well as reduced antioxidant capacity and increased inflammatory status, whereas CUG comes at the expense of impaired hepatic mitochondrial function and pathological fat accumulation.

This study was conducted to investigate the effect of dietary Yucca schidigera extract (YSE) supplementation to sow performance, nutrients digestibility and ammonia emission of manure. Total 80 sows were randomly divided into 4 groups and fed with either control, control + 0.06% YSE, control + 0.12% YSE or control + 0.24% YSE diet from day 80 of gestation to day 21 of lactation. The results showed that dietary YSE supplementation resulted in trends toward a reduced number of stillbirth piglets (P = 0.08), weak piglets (P = 0.06), pre-weanling mortality (P = 0.04) and diarrhea (P = 0.03), and improved apparent digestibility of dry matter (P = 0.04). Besides, YSE supplementation significantly increased catalase activity (P = 0.02) while decreasing malonaldehyde levels (P = 0.04) in sow blood. Furthermore, the loss of total nitrogen, urea nitrogen and ammonia nitrogen in sow manure were significantly reduced with supplementation of YSE. In summary, supplementation of YSE in sow diet during late gestation and lactation could improve sow and litter performance, nutrient digestibility, and reduce nitrogen loss in sow manure during storage.