Search

Abstract Background The antibacterial and immunomodulatory activities of bacteriocins make them attractive targets for development as anti-infective drugs. Although the importance of the enteric nervous system (ENS) in the struggle against infections of the intestine has been demonstrated, whether it is involved in bacteriocins anti-infective mechanisms is poorly defined. Results Here, we demonstrated that the bacteriocin Microcin J25 (J25) significantly alleviated diarrhea and intestinal inflammation in piglets caused by enterotoxigenic Escherichia coli (ETEC) infection. Mechanistically, macrophage levels were significantly downregulated after J25 treatment, and this was replicated in a mouse model. Omics analysis and validation screening revealed that J25 treatment induced significant changes in the dopaminergic neuron pathway, but little change in microbial structure. The alleviation of inflammation may occur by down-regulating dopamine receptor (DR) D1 and the downstream DAG-PKC pathway, thus inhibiting arachidonic acid decomposition, and the inhibition of macrophages may occur through the up-regulation of DRD5 and the downstream cAMP-PKA pathway, thus inhibiting NF-κB. Conclusions Our studies’ findings provide insight into the changes and possible roles of the ENS in J25 treatment of ETEC infection, providing a more sophisticated foundational understanding for developing the application potential of J25.

Background: To investigate the retinal microcirculation in mild preeclampsia (PE) without obvious retinopathy in high-altitude native Tibetans by optical coherence tomography angiography (OCTA). Methods: This study enrolled 64 mild preeclamptic pregnant women without retinopathy (group PPW), 63 healthy pregnant women (group HPW), and 61 healthy non-pregnant women (group HNPW). All participants were high-altitude native Tibetans who underwent OCTA, retinal thickness (RT), vascular density (VD), perfusion density (PD) and foveal avascular zone (FAZ) parameters were measured in the macula. Differences in these parameters among the groups were compared, and the correlations of these parameters with blood pressure were evaluated. Results: In the entire macula, VD and PD were significantly lower in group PPW than in group HPW and HNPW (p < 0.05). In the subregions, VD was significantly different in fovea, parafovea and perifovea, PD was significantly different in parafovea and perifovea among the three groups (p < 0.05), the further pairwise comparisons showed VD and PD in parafovea and perifovea were lower in group PPW than in group HPW, and VD and PD in perifovea were lower in group PPW than in group HNPW (p < 0.05). RT and FAZ parameters did not differ among the groups (P > 0.05). VD and PD exhibited negative correlations with SBP and DBP (p < 0.05). Conclusion: OCTA can objectively evaluate diminished microcirculation in mild PE without obvious retinopathy among high-altitude native Tibetans, and provide a crucial time window for early screening of PE-induced retinopathy.

Abstract Background 5-Aminolevulinic acid (ALA) recently received much attention due to its potential application in many fields such as medicine, nutrition and agriculture. Metabolic engineering is an efficient strategy to improve microbial production of 5-ALA. Results In this study, an ALA production strain of Escherichia coli was constructed by rational metabolic engineering and stepwise improvement. A metabolic strategy to produce ALA directly from glucose in this recombinant E. coli via both C4 and C5 pathways was applied herein. The expression of a modified hemA RS gene and rational metabolic engineering by gene knockouts significantly improved ALA production from 765.9 to 2056.1 mg/L. Next, we tried to improve ALA production by RGMS-directed evolution of eamA gene. After RGMS, the ALA yield of strain A2-ASK reached 2471.3 mg/L in flask. Then, we aimed to improve the oxidation resistance of cells by overexpressing sodB and katE genes and ALA yield reached 2703.8 mg/L. A final attempt is to replace original promoter of hemB gene in genome with a weaker one to decrease its expression. After 24 h cultivation, a high ALA yield of 19.02 g/L was achieved by 108-ASK in a 5 L fermenter. Conclusions These results suggested that an industrially competitive strain can be efficiently developed by metabolic engineering based on combined rational modification and optimization of gene expression.

Abstract Background The proliferation of porcine ovarian granulosa cells (GCs) is essential to follicular development and the ubiquitin–proteasome system is necessary for maintaining cell cycle homeostasis. Previous studies found that the deubiquitinase ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) regulates female reproduction, especially in ovarian development. However, the mechanism by which UCHL1 regulates porcine GC proliferation remains unclear. Results UCHL1 overexpression promoted GC proliferation, and knockdown had the opposite effect. UCHL1 is directly bound to cyclin B1 (CCNB1), prolonging the half-life of CCNB1 and inhibiting its degradation, thereby promoting GC proliferation. What’s more, a flavonoid compound-isovitexin improved the enzyme activity of UCHL1 and promoted the proliferation of porcine GCs. Conclusions UCHL1 promoted the proliferation of porcine GCs by stabilizing CCNB1, and isovitexin enhanced the enzyme activity of UCHL1. These findings reveal the role of UCHL1 and the potential of isovitexin in regulating proliferation and provide insights into identifying molecular markers and nutrients that affect follicle development.

The reduced nutrient digestibility of low-protein (LP) diets has been shown to be caused by the weakened fermentative capacity of the post-gut flora. The dynamic regulation of dietary protein contents on post-gut microbial population and fermentative metabolism is unclear. Twelve growing barrows (19.9 ± 0.8 kg) fitted with a T-cannula at the blind end of the cecum were randomly administered a high-protein (HP, 21.5% crude protein [CP]) diet or an LP (15.5% CP) diet for 28 d. The cecal content and feces were collected at d 1, 14, and 28 of the experiment for microflora structures and metabolite concentrations analysis. The nutrient digestibility coefficient and plasma biochemical parameters were also determined. Compared with the HP treatment, the LP treatment showed decreased plasma urea nitrogen concentration and apparent total tract digestibility of dry matter, gross energy, and CP (P

Introduction: Ovarian steroidogenesis not only affects the embryonic development and pregnancy outcome, but also associates with many diseases in mammals and women. Exploring the nutrients and mechanisms influencing ovarian steroidogenesis is critical to maintaining the optimal reproductive performance, as well as guaranteeing body health. Objectives: This research aimed to explore the effect of retinol metabolism on ovarian steroidogenesis and the underlying mechanisms. Methods: Comparative transcriptomic analysis of ovaries from normal and low reproductive performance sows were performed to identify the main causes leading to low fertility. The metabolites regulating steroid hormones synthesis were investigated in ovarian granulosa cells. Gene interference, overexpression, dual-luciferase reporter assays, chromatin immunoprecipitation and transcriptome analysis were further conducted to explore the underlying mechanisms of Aldh1a1 mediating ovarian steroidogenesis. Results: Transcriptome analysis of ovaries from normal and low reproductive performance sows showed the significant differences in both retinol metabolism and steroid hormones synthesis, indicating retinol metabolism probably influenced steroid hormones synthesis. The related metabolite retinoic acid was furtherly proven a highly active and potent substance strengthening estrogen and progesterone synthesis in ovarian granulosa cells. For the first time, we revealed that retinoic acid synthesis in porcine and human ovarian granulosa cells was dominated by Aldh1a1, and required the assistance of Aldh1a2. Importantly, we demonstrated that Aldh1a1 enhanced the proliferation of ovarian granulosa cells by activating PI3K-Akt-hedgehog signaling pathways. In addition, Aldh1a1 regulated the expression of transcription factor MESP2, which targeted the transcription of Star and Cyp11a1 through binding to corresponding promoter regions. Conclusion: Our data identified Aldh1a1 modulates ovarian steroidogenesis through enhancing granulosa cell proliferation and MESP2/STAR/CYP11A1 pathway. These findings provide valuable clues for improving ovarian health in mammals.

Abstract In the nearshore area, ocean current display intricate complexities due to interactions among tide, river, and coastline, which makes accurate current modeling challenging. Continuous in situ observation with high spatial and temporal resolution helps to better understand the dynamics of these currents. In this study, we used a 10‐km long submarine fiber‐optic cable with distributed acoustic sensing technology to record seismic signals associated with ocean waves. The current velocity and water depth were obtained from the velocity dispersion using frequency‐wave number analysis matched against theoretical ocean wave propagation equations. The results show remarkable agreement with observation of a nearby current meter, confirming the dominance of tidal currents as well as a small‐scale residual current. The temporal variation of water depth is consistent with observation by a nearby tidal gauge. This study demonstrates the potential of using submarine fiber‐optic cable for long‐term, high‐resolution, near real‐time nearshore current monitoring.

Earthquake occurrence depth in the crust is related to stress, temperature, and brittle–ductile transition, which is also near the transition depth of the upper to lower crust. The composition variation between the upper and lower crust causes remarkable changes of rheological properties and variation in stress distribution. Clarifying the detailed stress distribution in the upper and lower crust is crucial for understanding the brittle–ductile transition and the stress environment of the seismogenic zone. The Southeastern Tibetan Plateau (SETP), with wide spread of active strike−slip faults and clustered earthquakes, provides a natural field for investigating the relationships between crustal stresses, deformation behaviors, and earthquake mechanics. By considering the rheological properties of granite and anorthite, this paper established stress models with different boundary depths (15, 20 and 25 km) between the upper and lower crust along the Anninghe, Xianshuihe, and Longmenshan Faults in the SETP with a horizontal strain of 6 × 10−4 extracted from in situ stress data. The stress model with different geothermal gradients and a boundary depth of 20 km between the upper and lower crust suggests two distinct types of the brittle–ductile transition below these three faults. Simultaneously, the stress model can account for the continuity of earthquake depth distribution below the Longmenshan Fault and the seismic gap below the Anninghe and Xianshuihe Faults. The continuity of earthquake depth distribution or seismic gap below these three faults can be explained by their different geothermal gradients. These findings provide new insights for understanding the stress environment of the seismogenic zone in the SETP. Our model reveals the relationships between differential stress, seismicity, brittle–ductile transition, and boundary depth of the upper and lower crust in the continental crust, and connects the multiple observations from geophysics and geology. Furthermore, our model provides insights for studying multiple processes in the continental crust, such as crustal deformation, fault slip, and earthquake occurring.

Abstract Background The host–microbiota interaction plays a crucial role in maintaining homeostasis and disease susceptibility, and microbial tryptophan metabolites are potent modulators of host physiology. However, whether and how these metabolites mediate host–microbiota interactions, particularly in terms of inter-microbial communication, remains unclear. Results Here, we have demonstrated that indole-3-lactic acid (ILA) is a key molecule produced by Lactobacillus in protecting against intestinal inflammation and correcting microbial dysbiosis. Specifically, Lactobacillus metabolizes tryptophan into ILA, thereby augmenting the expression of key bacterial enzymes implicated in tryptophan metabolism, leading to the synthesis of other indole derivatives including indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). Notably, ILA, IPA, and IAA possess the ability to mitigate intestinal inflammation and modulate the gut microbiota in both DSS-induced and IL-10−/− spontaneous colitis models. ILA increases the abundance of tryptophan-metabolizing bacteria (e.g., Clostridium), as well as the mRNA expression of acyl-CoA dehydrogenase and indolelactate dehydrogenase in vivo and in vitro, resulting in an augmented production of IPA and IAA. Furthermore, a mutant strain of Lactobacillus fails to protect against inflammation and producing other derivatives. ILA-mediated microbial cross-feeding was microbiota-dependent and specifically enhanced indole derivatives production under conditions of dysbiosis induced by Citrobacter rodentium or DSS, but not of microbiota disruption with antibiotics. Conclusion Taken together, we highlight mechanisms by which microbiome-host crosstalk cooperatively control intestinal homoeostasis through microbiota-derived indoles mediating the inter-microbial communication. These findings may contribute to the development of microbiota-derived metabolites or targeted “postbiotic” as potential interventions for the treatment or prevention of dysbiosis-driven diseases. Video Abstract

Indole-3-acetic acid (IAA), a metabolite derived from microbial tryptophan metabolism, plays a crucial role in regulating intestinal homeostasis. However, the influence and potential applications of IAA in the context of animal pathogen infections remain underexplored. This study investigates the prophylactic effects of IAA pretreatment against Salmonella typhimurium (ST) SL1344 infection, focusing on its ability to attenuate inflammatory responses, enhance intestinal barrier integrity, inhibit bacterial colonization, and restore colonic microbiota dysbiosis. The results demonstrated that IAA ameliorated the clinical symptoms in mice, as evidenced by reduced weight loss and histopathological damage. Furthermore, IAA inhibited the inflammatory response by downregulating the gene expression of pro-inflammatory cytokines IL-17A, TNF-α, IL-1β, and IL-6 in colon, ileum, and liver. IAA also preserved the integrity of the intestinal mucosal barrier and promoted the expression of tight junction proteins. Additionally, 16S rRNA gene sequencing revealed significant alterations in intestinal microbiota structure induced by ST infection following IAA treatment. Notable changes in β diversity and species richness were characterized by the enrichment of beneficial bacteria including Bacteroideaceae, Spirillaceae, and Bacillus. The proliferation of Salmonella enterica subspecies enterica serovar Typhi was significantly inhibited, thereby enhancing the intestinal health of the host. In summary, the oral administration of IAA contributes to the alleviation of inflammation, restoration of the intestinal barrier, and correction of colonic microbiota disturbance in mice challenged with ST.

Background: Rotavirus (RV) is a major cause of diarrhea in young children and animals, especially piglets, leading to substantial economic losses in the global pig industry. Isoleucine (Ile), a branched-chain amino acid, plays an important role in regulating nutrient metabolism and has been shown to improve diarrhea. This study aimed to evaluate the effects of Ile supplementation on the mucosal immune barrier of the small intestine in RV-infected weaned piglets. Methods: Forty-eight 21-day-old weaned piglets were randomly divided into three dietary treatments (each treatment was subdivided into two groups, eight replicates per group), with 0%, 0.5%, or 1% Ile added for 15 days, and then, one group from each treatment was challenged with RV. Results: The results showed that 1% Ile added to the diet promoted the healthy development of the intestinal mucosa. Ile could restore the reduced villus height in the ileum and the goblet cell number in the duodenum and ileum to normal levels, improving the intestinal epithelial tight junctions in RV-infected piglets. Additionally, Ile increased the activity of lipase, amylase, and sucrase, as well as superoxide dismutase (SOD) and glutathione (GSH), along with the expression of SIgA, DEFβ1, and DEFβ2 in parts of the small intestine. Conclusions: The addition of Ile to the diet mitigated the effects of RV infection on intestinal morphology and mucosal barrier function, as well as the physiological functions of weaned piglets, and improved the antioxidant and immune functions of the piglets to some extent. These findings offer valuable insights, contributing to a deeper understanding of the role of Ile in supporting intestinal health.

Despite mounting evidence for dietary protease benefits, the mechanisms beyond enhanced protein degradation are poorly understood. This study aims to thoroughly investigate the impact of protease addition on the growth performance, intestinal function, and microbial composition of weaned piglets. Ninety 28-day-old weaned pigs were randomly assigned to the following three experimental diets based on their initial body weight for a 28-day experiment: (1) control (CC), a basic diet with composite enzymes without protease; (2) negative control (NC), a diet with no enzymes; and (3) dietary protease (PR), a control diet with protease. The results show that dietary proteases significantly enhanced growth performance and boosted antioxidant capacity, increasing the total antioxidant capacity (T-AOC) levels (p < 0.05) while reducing malonaldehyde levels (p < 0.05). Additionally, protease addition reduced serum levels of inflammatory markers TNF-α, IL-1β, and IL-6 (p < 0.05), suppressed mRNA expression of pro-inflammatory factors in the jejunum (p < 0.01), and inhibited MAPK and NF-κB signaling pathways. Moreover, protease-supplemented diets improved intestinal morphology and barrier integrity, including zonula occludens protein 1(ZO-1), Occludin, and Claudin-1 (p < 0.05). Microbiota compositions were also significantly altered by protease addition with increased abundance of beneficial bacteria (Lachnospiraceae_AC2044_group and Prevotellaceae_UCG-001) (p < 0.05) and reduced harmful Terrisporobacter (p < 0.05). Further correlation analysis revealed a positive link between beneficial bacteria and growth performance and a negative association with inflammatory factors and intestinal permeability. In summary, dietary protease addition enhanced growth performance in weaned piglets, beneficial effects which were associated with improved intestinal barrier integrity, immunological response, and microbiota composition.

Milk yield and composition are critical determining factors for the early growth and development of neonates. The objective of this experiment was to comprehensively evaluate the effects of dietary sodium acetate (SA) supplementation on the milk yield and composition of sows and the growth performance of their offspring. A total of 80 sows (Landrace × Yorkshire, 3 to 6 parity) were randomly assigned to 2 groups (with or without 0.1% SA) from d 85 of gestation to d 21 of lactation. The result shows that maternal 0.1% SA supplementation significantly increased sows milk yield, milk fat, immunoglobulin A (IgA) and IgG content in milk (P

We investigated the effects of finely ground wheat bran on the nutrient digestibility, digesta passage rate, and gut microbiota structure in sows. A 3 × 3 Latin square design with 3 test periods and 3 experimental diets was used. Six non-pregnant sows (parity: 5 to 7) were randomly assigned to 3 experimental diets with 2 replicates per treatment in each period. Each period lasted 19 d (12 d for adaptation and 7 d for experiment). The experimental diets included (a) a basal corn and soybean meal diet (CON), (b) a basal diet with 20% coarse wheat bran (CWB; particle size: 605 μm), and (c) a basal diet with 20% fine wheat bran (FWB; particle size: 438 μm). The results demonstrated that the apparent total tract digestibility of neutral detergent fiber, acid detergent fiber and energy were reduced (P

Abstract Fatty acids are not only widely known as energy sources, but also play important roles in many metabolic pathways. The significance of fatty acids in modulating the reproductive potential of livestock has received greater recognition in recent years. Functional fatty acids and their metabolites improve follicular development, oocyte maturation and embryo development, as well as endometrial receptivity and placental vascular development, through enhancing energy supply and precursors for the synthesis of their productive hormones, such as steroid hormones and prostaglandins. However, many studies are focused on the impacts of individual functional fatty acids in the reproductive cycle, lacking studies involved in deeper mechanisms and optimal fatty acid requirements for specific physiological stages. Therefore, an overall consideration of the combination and synergy of functional fatty acids and the establishment of optimal fatty acid requirement for specific stages is needed to improve reproductive potential in livestock.

Abstract Background The immature neonatal fecal microbiota substantially impacts the development of gut health and greatly increases the risk of disease. Developing effective strategies to modulate the development of neonatal fecal microbiota has great significance. Herein, we investigated whether the maternal dietary supplementation and oral administration of Lactobacillus reuteri could effectively promote the development and maturation of the fecal microbiome in piglets from birth to weaning. Results Metagenomic analysis of colostrum showed that maternal dietary L. reuteri supplementation influenced the overall microbiota composition, decreased the abundance of the phylum Proteobacteria and increased that of the species Bifidobacterium choerinum. KEGG pathway analysis revealed that maternal L. reuteri supplementation enriched the lysine biosynthesis and glycolysis/gluconeogenesis pathways and downregulated the bacterial invasion of epithelial cells in the colostrum. In addition, L. reuteri supplementation significantly altered the metabolite features and modules in umbilical cord blood serum based on metabolomics. Further, a significant covariation was observed between these differential metabolites and the species in colostrum. Maternal dietary L. reuteri supplementation also significantly influenced the microbiota composition and increased the meconium abundance of beneficial bacteria (such as Romboutsia, Lactobacillus, Blautia, Butyricicoccus, and Ruminococcus), some of which were markedly associated with several differential metabolites in umbilical cord blood serum between two groups. Notably, both the maternal dietary supplementation and oral intake of L. reuteri had strong impacts on the overall microbial composition and maturation of fecal microbiota in piglets during early life, and these effects were dependent on the growth stage. Oral administration of L. reuteri promoted diarrhea resistance in neonates, while maternal supplementation of L. reuteri enhanced the abilities of antioxidants and decreased inflammation. Moreover, the administration of L. reuteri via both methods in combination improved the growth performances of piglets. Conclusion Overall, our data demonstrated that L. reuteri had the ability to modulate the composition of fecal microbiota in newborn piglets by influencing the microbial community and functional composition in the colostrum and by altering several key metabolites in the umbilical cord blood serum. Also, both the maternal dietary supplementation and oral administration of L. reuteri effectively promoted the development and maturation of the fecal microbiome in piglets during early life. Both the maternal dietary supplementation and oral administration of L. reuteri in combination optimized the growth performances of piglets. Video Abstract

Abstract Background 5-Aminolevulinic acid (ALA) recently received much attention due to its potential application in many fields. In this study, an ALA production strain of Escherichia coli was constructed by rational metabolic engineering and stepwise improvement based on known regulatory and metabolic information and CRISPR/Cas9 mediated gene knockout. Results A metabolic strategy to produce ALA directly from glucose in this recombinant E. coli via the C5 pathway was applied herein. The rational metabolic engineering by gene knockouts significantly improved ALA production from 662.3 to 1601.7 mg/L. In addition, we managed to synergistically produce ALA via the C4 pathway in recombinant strain. The expression of a modified hemA gene, encoding an ALA synthase from Rhodobacter sphaeroides, improved ALA production from 1601.7 to 2099.7 mg/L. After 24 h cultivation, a yield of 0.210 g ALA per g glucose was achieved by constructed E. coli D5:FYABD-RSA. Conclusion Our study revealed that an industrially competitive strain can be efficiently developed by metabolic engineering based on combined rational modification and optimization of gene expression.

This study aimed to evaluate the effects of a complex comprising formic acid, benzoic acid, and essential oils (AO3) on the growth performance of weaned piglets and explore the underlying mechanism. Dietary AO3 supplementation significantly enhanced the average daily gain (ADG) and average daily feed intake (ADFI), while decreasing the feed conversion rate (FCR) and diarrhea rate (p < 0.05). Additionally, AO3 addition altered the fecal microflora composition with increased abundance of f_Prevotellaceae. LPS challenges were further conducted to investigate the detailed mechanism underlying the benefits of AO3 supplementation. The piglets fed with AO3 exhibited a significant increase in villus height and decrease in crypt depth within the jejunum, along with upregulation of ZO-1, occludin, and claudin-1 (p < 0.05) compared with those piglets subjected to LPS. Furthermore, AO3 supplementation significantly ameliorated redox disturbances (T-AOC, SOD, and GSH) and inflammation (TNF-α, IL-1β, IL-6, and IL-12) in both the serum and jejunum of piglets induced by LPS, accompanied by suppressed activation of the MAPK signaling pathway (ERK, JNK, P38) and NF-κB. The LPS challenge downregulated the activation of the AMPK signaling pathway, mRNA levels of electron transport chain complexes, and key enzymes involved in ATP synthesis, which were significantly restored by the AO3 supplementation. Additionally, AO3 supplementation restored the reduced transport of amino acids, glucose, and fatty acids induced by LPS back to the levels observed in the control group. In conclusion, dietary AO3 supplementation positively affected growth performance and gut microbiota composition, also enhancing intestinal barrier integrity, nutrient uptake, and energy metabolism, as well as alleviating oxidative stress and inflammation under LPS stimulation.

This study aims to investigate the impact of dietary supplementation with selenium yeast (SeY) and glycerol monolaurate (GML) on the transfer of antioxidative capacity between the mother and fetus during pregnancy and its underlying mechanisms. A total of 160 sows with similar body weight and parity of 3–6 parity sows were randomly and uniformly allocated to four groups (n = 40) as follows: CON group, SeY group, GML group, and SG (SeY + GML) group. Animal feeding started from the 85th day of gestation and continued to the day of delivery. The supplementation of SeY and GML resulted in increased placental weight and reduced lipopolysaccharide (LPS) levels in sow plasma, placental tissues, and piglet plasma. Furthermore, the redox balance and inflammatory markers exhibited significant improvements in the plasma of sows fed with either SeY or GML, as well as in their offspring. Moreover, the addition of SeY and GML activated the Nrf2 signaling pathway, while downregulating the expression of pro-inflammatory genes and proteins associated with inflammatory pathways (MAPK and NF-κB). Vascular angiogenesis and nutrient transportation (amino acids, fatty acids, and glucose) were upregulated, whereas apoptosis signaling pathways within the placenta were downregulated with the supplementation of SeY and GML. The integrity of the intestinal and placental barriers significantly improved, as indicated by the increased expression of ZO-1, occludin, and claudin-1, along with reduced levels of DLA and DAO with dietary treatment. Moreover, supplementation of SeY and GML increased the abundance of Christensenellaceae_R-7_group, Clostridium_sensus_stricto_1, and Bacteroidota, while decreasing levels of gut microbiota metabolites LPS and trimethylamine N-oxide. Correlation analysis demonstrated a significant negative relationship between plasma LPS levels and placental weight, oxidative stress, and inflammation. In summary, dietary supplementation of SeY and GML enhanced the transfer of antioxidative capacity between maternal-fetal during pregnancy via gut–placenta axis through modulating sow microbiota composition.

Objective The study was aimed to investigate the rules of postprandial changes in intestine digesta dry matter (DM) flow and amino acid digestibility of growing pigs fed low-protein (LP) diets made of different starch. Methods Eight barrows (28.8±2.1 kg) with a T-cannula at the distal ileum were randomly allotted to an 8×3 Youden square design. Treatments included: waxy corn starch LP (WLP); corn starch LP (CLP) and pea starch LP (PLP). Diets were given at 08:00 and 20:00. Digesta samples were collected in six 2-h stages from 08:00 to 20:00. Results The Cr concentrations of ileal digesta increased and then decreased in WLP and CLP, while increased continuously in PLP as time passed after postprandial (p

Abstract Background Protein releases amino acids faster than starch releases glucose in digestive tract of pigs fed low-protein (LP) diets. Poor synchronization of dietary glucose and amino acids supply leads to compromised nitrogen efficiency. Dietary starch patterns modulation may improve this situation. Methods Growing barrows (29.7 ± 2.0 kg) were randomly allotted into 5 dietary treatments with LP diets consisting of different purified starches. Treatments included: waxy corn starch (W LP), corn starch + waxy corn starch (C + W LP), corn starch (C LP), pea starch + waxy corn starch (P + W LP) and pea starch (P LP). In the experiment, growth performance, protein deposition, nutrient metabolism, and fecal microbial community of pigs were investigated. In vitro starch digestion was used for predicting the in vivo glucose response. Results Dietary starch in vitro glucose release profile was determined by starch source and the ratio of amylopectin and amylose. C + W LP treatment showed decreased total nitrogen excretion and plasma citrulline concentration and improved plasma leptin concentration among treatments (P

BackgroundFat is a critical component in milk, which provided energy for the early growth and development of mammals. Milk fat is positively related to the concentration of acetate in the blood, while the underlying mechanism is still unclear.ObjectiveThis study is to investigate the effects of sodium acetate (NaAc) on milk fat synthesis in the mammary gland, and explored the underlying mechanism.MethodsIn vitro experiments were carried out in mouse mammary epithelial cell line (HC11) cells cultured with NaAc to explore the potential pathway of NaAc on milk fat synthesis. Furthermore, 24 pregnant mice (from d 18.5 of gestation to d 7 of lactation, exposed to 200 mM NaAc drinking water) were used as an in vivo model to verify the results.ResultsIn this study, we found that NaAc promoted milk fat synthesis and the expression of related genes and proteins in HC11 mammary epithelial cells with the activation of GPCR and mTORC1 signaling pathways (p

With sustainable development of biotechnology, increasing attention has been placed on utilization of solid-state fermented feed (SFF). Solid-state fermented feed has been a candidate strategy to alleviate the contradiction between supply and demand of feed resources, ensure food hygiene safety, promoting energy conservation, and emission reduction. In production of SFF, a variety of organic acids, enzymes, vitamins, peptides, and other unknown growth factors are produced, which could affect performance of animals. Solid-state fermented feed produced by different fermentation techniques has great instability on different physiological stages of different animals, which hinders the application and standardized production of SFF. Herein, we summarize the current advances in the role of the characteristics of SFF prepared by different manufacturing technique and its research progress in animal experiments on growth performance, gastrointestinal ecology, and immune system, so as to provide references for further acquiring a relatively perfect set of SFF production and evaluation systems.

Microcin C7 (McC) as a viable form of antimicrobial has gained substantial attention due to its distinctive antimicrobial activity, by targeting aspartyl tRNA synthetase. McC can be a potential solution against pathogenic microbial infections in the postantibiotic era. However, considering that degradation by digestive enzymes can disrupt the function of this peptide in the gastrointestinal tract, in this study, we attempt to design McC variants to overcome several barriers that may affect its stability and biological activity. The mccA gene encoding the McC peptide precursor was mutated and 12 new McC variants with trypsin resistance were found. The Yej+rimL− strain was used as an indicator to determine the minimum inhibitory concentrations (MICs). The results showed that three variants, including R2A, R2T and R2Q, among 12 variants formed by the replacement of the second arginine of the McC peptide with different amino acids, were resistant to trypsin and had an outstanding antimicrobial ability, with MIC values of 12.5, 25, and 25 μg/mL, respectively. Taken together, our findings show that the engineering of the site-directed mutagenesis of McC significantly enhances McC trypsin resistance and maintains a great antimicrobial activity.

The involvement of alterations in gut microbiota composition due to the use of antibiotics has been widely observed. However, a clear picture of the influences of gentamicin, which is employed for the treatment of bacterial diarrhea in animal production, are largely unknown. Here, we addressed this problem using piglet models susceptible to enterotoxigenic Escherichia coli (ETEC) F4, which were treated with gentamicin. Gentamicin significantly alleviated diarrhea and intestinal injury. Through 16s RNS sequencing, it was found that gentamicin increased species richness but decreased community evenness. Additionally, clear clustering was observed between the gentamicin-treated group and the other groups. More importantly, with the establishment of a completely different microbial structure, a novel metabolite composition profile was formed. KEGG database annotation revealed that arachidonic acid metabolism and vancomycin resistance were the most significantly downregulated and upregulated pathways after gentamicin treatment, respectively. Meanwhile, we identified seven possible targets of gentamicin closely related to these two functional pathways through a comprehensive analysis. Taken together, these findings demonstrate that gentamicin therapy for diarrhea is associated with the downregulation of arachidonic acid metabolism. During this process, intestinal microbiota dysbiosis is induced, leading to increased levels of the vancomycin resistance pathway. An improved understanding of the roles of these processes will advance the conception and realization of new therapeutic and preventive strategies.

Abstract T7 Expression System is a common method of ensuring tight control and high-level induced expression. However, this system can only work in some bacterial strains in which the T7 RNA Polymerase gene resides in the chromosome. In this study, we successfully introduced a chromosomal copy of the T7 RNA Polymerase gene under control of the lacUV5 promoter into Escherichia coli BW25113. The T7 Expression System worked efficiently in this mutant strain named BW25113-T7. We demonstrated that this mutant strain could satisfactorily produce 5-Aminolevulinic Acid via C5 pathway. A final study was designed to enhance the controllability of T7 Expression System in this mutant strain by constructing a T7 Promoter Variants Library. These efforts advanced E. coli BW25113-T7 to be a practical host for future metabolic engineering efforts.

Distributed acoustic sensing (DAS) is a novel seismological observation technology based on the fiber-optic sensing method, and can transform existing urban fiber-optic cables into ultra-dense array for urban seismological researches, thus opening abundant opportunities for resolving fine details of near surface structures. While high frequency ambient noise recorded on DAS has been applied in surface wave tomography, it is often difficult to extract a clear dispersion curve for the data recorded by urban internet cable because of the effect of precursor signals on noise correlation functions due to uneven distribution of noise sources, and weak coupling between the cable and the solid earth. In this study, we investigate the performance of the three-station interferometry method for improving the noise cross-correlation functions of the linear array. We applied this method to a DAS dataset acquired in an urban area, suppressed the precursor signal, improved the measurement of the dispersion curve, and constructed a 2D S-wave profile that reveals the hidden fault beneath the city. We also observed that the convergence of noise cross-correlation functions with weak coupling was significantly accelerated using this method. We employed this method to improve the signal quality of surface waves at far offset for the long segment, thus obtaining a more accurate dispersion curve. In conclusion, the three-station interferometry is an effective method to enhance the surface wave signal and suppress the precursor signal retrieved from the data recorded by urban internet cable, which could help in providing high resolution images of shallow structures in built-up areas.

Pipeline transportation is the most common means used in the petroleum industry, and its safety monitoring has attracted wide attention from the domestic and foreign researchers. The detection and alarm of intrusion events is one of the most important objects of pipeline research. Based on the optical fiber sensing technology, the pipeline can be monitored with the optical cables in the same trench to acquire various signals including intrusion events. However, no phase information is provided in the signals recorded by the traditional distributed fiber-optic vibration sensor, and thus the event cannot be located. Herein, the intrusion event signals at two different places along the 10 km buried pipeline were recorded with the distributed fiber-optic vibration sensor, and the signals were identified with the STA/LTA method. Based on the arrival time differences, the events were located through grid search, and the hazards of the event were evaluated according to the locating result. Additionally, the feasibility of the detection and alarm of intrusion event with the distributed optical fiber acoustic sensing technology was explored preliminarily by tests.

As a key regulator of gene transcription and post-transcriptional modification, miRNAs play a wide range of roles in skeletal muscle development. Skeletal muscle satellite cells contribute to postnatal growing muscle fibers. Thus, the goal of this study was to explore the effects of novel miRNA Y-56 on porcine skeletal muscle satellite cells (PSCs). We found that Y-56 was highly expressed in porcine muscle tissues, and its expression was higher in Bama Xiang pigs than in Landrace pigs. The EdU assay, cell counting kit-8, and flow cytometry results showed that Y-56 overexpression suppressed cell proliferation and cell cycle, whereas Y-56 inhibition resulted in the opposite consequences. The results of qRT-PCR and Western blot showed that Y-56 remarkably inhibited the expression levels of cyclin-dependent kinase 4 (CDK4), proliferating cell nuclear antigen (PCNA), and cyclin D1. We identified that IGF-1R was a direct target of Y-56 by dual-luciferase reporter assay. Moreover, IGF-1R overexpression promoted the proliferation and cell cycle process of PSCs and upregulated the expression of CDK4, PCNA, and cyclin D1. Conversely, IGF-1R knockdown had the opposite effect. Furthermore, IGF-1R overexpression partially reversed the inhibition of the cell proliferation and cell cycle process of PSCs and the downregulation of the expression of CDK4, PCNA, and Cyclin D1 caused by Y-56 overexpression. Finally, Y-56 inhibited the protein expression levels of p-AKT and p-ERK. Collectively, our findings suggested that Y-56 represses the proliferation and cell cycle process of PSCs by targeting IGF-1R-mediated AKT and ERK pathways.

Multidrug resistant (MDR) bacterial infection has emerged, raising concerns about untreatable infections, and posing the highest health risks. Antimicrobial peptides (AMPs) are thought to be the best remedy for this problem. Here, we showed biosynthetic microcin J25 (MccJ25) exhibited excellent bactericidal activity against standard and clinically relevant veterinary MDR strains with high stability, no cytotoxicity, and no increase in drug resistance. Analysis of antimicrobial mechanism possessed by sensitive enterotoxigenic Escherichia coli (ETEC) based on electron microscopy and Sytox Green methods was carried out. Results showed excellent activity against ETEC was due to permeabilizing bacterial membranes and strong affinity. MccJ25 exhibited high endotoxin-neutralizing activity in both in vivo and in vitro environments, and mice exposed to lipopolysaccharide (LPS) showed decreased plasma LPS levels and improved survival after administration of MccJ25. In an LPS-treated mouse septicemia model, MccJ25 treatment significantly alleviated inflammatory responses by inhibiting proinflammatory factor secretion and expression. In a mouse E. coli infection model, administration of MccJ25 effectively improved host defense against clinically source cocktail of multidrug-resistant E. coli strains induced intestinal inflammation and bacteria dissemination. Results of studies on anti-inflammatory mechanisms showed that MccJ25 downregulated nuclear factor kappa B kinase and mitogen-activated protein kinase, thereby reducing the production of toll-like receptor 4, myeloid differentiation factor 88 and decreasing the key proinflammatory cytokines. These findings clarify MccJ25 may be an ideal antibacterial/antiendotoxic drug candidate that has the potential to further guide the development of anti-inflammatory and/or antimicrobial agents in the war against MDR bacterial infection.

Microcin C7 is an antimicrobial peptide produced by Escherichia coli, composed of a heptapeptide with a modified adenosine monophosphate. This study was performed to evaluate the effects of Microcin C7 as a potential substrate to traditional antibiotics on growth performance, immune functions, intestinal barrier, and cecal microbiota of broilers. In the current study, 300 healthy Arbor Acres broiler chicks were randomly assigned to one of five treatments including a corn–soybean basal diet and basal diet supplemented with antibiotic or 2, 4, and 6 mg/kg Microcin C7. Results showed that Microcin C7 significantly decreased the F/G ratio of broilers; significantly increased the levels of serum cytokine IL-10, immunoglobulins IgG and IgM, and ileal sIgA secretion; significantly decreased the level of serum cytokine TNF-α. Microcin C7 significantly increased villus height and V/C ratio and significantly decreased crypt depth in small intestine of broilers. Microcin C7 significantly increased gene expression of tight junction protein Occludin and ZO-1 and significantly decreased gene expression of pro-inflammatory and chemokine TNF-α, IL-8, IFN-γ, Toll-like receptors TLR2 and TLR4, and downstream molecular MyD88 in the jejunum of broilers. Microcin C7 significantly increased the number of Lactobacillus and decreased the number of total bacteria and Escherichia coli in the cecum of broilers. Microcin C7 also significantly increased short-chain fatty acid (SCFA) and lactic acid levels in the ileum and cecum of broilers. In conclusion, diet supplemented with Microcin C7 significantly improved growth performance, strengthened immune functions, enhanced intestinal barrier, and regulated cecal microbiota of broilers. Therefore, the antimicrobial peptide Microcin C7 may have the potential to be an ideal alternative to antibiotic.

The effects and safety of dietary supplementation with Microcin C7 (C7) were evaluated in 216 weaned piglets. The pigs were given a control corn–soybean meal basal diet or C7 diet (control diet supplemented with 250, 500, 750, 1000, or 5000 mg C7/kg diets). Compared with the control group, the 500 mg/kg C7 supplementation group had better intestinal morphological indicators (p < 0.05), which may help maintain intestinal epithelial function and increase the growth performance (p < 0.05) and apparent total tract digestibility (p < 0.05). The diarrhea indexes of the 250, 500, and 750 mg/kg groups were significantly lower than that of the control group at 0–28 d (p < 0.05), and the 500 mg/kg group had the lowest diarrhea indexes (linear and quadratic, p < 0.05). A comprehensive analysis showed that microbial structure was significantly correlated with the degree of diarrhea, and the diarrhea-alleviating effect of C7 may be related to its selective regulation of specific microbial taxa. The 250 and 500 mg/kg C7 supplementation also significantly improved several immune indices of piglets (p < 0.05). Compared with the control diet, 5000 mg/kg C7 supplementation had no significant adverse effect on all parameters. Overall, the 250–500 mg/kg dose had the best effect, and the highest dose (5000 mg/kg) posed no toxicity risk. Therefore, C7 appears safe for use as an alternative to antibiotic growth promoters in weaned piglets.

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.

Abstract Background The early-life microbiota exerts a profound and lifelong impact on host health. Longitudinal studies in humans have been informative but are mostly based on the analysis of fecal samples and cannot shed direct light on the early development of mucosa-associated intestinal microbiota and its impact on GI function. Using piglets as a model for human infants, we assess here the succession of mucosa-associated microbiota across the intestinal tract in the first 35 days after birth. Results Although sharing a similar composition and predicted functional profile at birth, the mucosa-associated microbiome in the small intestine (jejunum and ileum) remained relatively stable, while that of the large intestine (cecum and colon) quickly expanded and diversified by day 35. Among detected microbial sources (milk, vagina, areolar skin, and feces of sows, farrowing crate, and incubator), maternal milk microbes were primarily responsible for the colonization of the small intestine, contributing approximately 90% bacteria throughout the first 35 days of the neonatal life. Although maternal milk microbes contributed greater than 90% bacteria to the large intestinal microbiota of neonates upon birth, their presence gradually diminished, and they were replaced by maternal fecal microbes by day 35. We found strong correlations between the relative abundance of specific mucosa-associated microbes, particularly those vertically transmitted from the mother, and the expression levels of multiple intestinal immune and barrier function genes in different segments of the intestinal tract. Conclusion We revealed spatially specific trajectories of microbial colonization of the intestinal mucosa in the small and large intestines, which can be primarily attributed to the colonization by vertically transmitted maternal milk and intestinal microbes. Additionally, these maternal microbes may be involved in the establishment of intestinal immune and barrier functions in neonates. Our findings strengthen the notion that studying fecal samples alone is insufficient to fully understand the co-development of the intestinal microbiota and immune system and suggest the possibility of improving neonatal health through the manipulation of maternal microbiota.

Abstract Since the 2008 great M w 7.9 Wenchuan earthquake, two destructive earthquakes, the 2013 M w 6.6 Lushan earthquake and the 2017 M w 6.5 Jiuzhaigou earthquake, struck the eastern margin of the Tibetan Plateau, causing many casualties and significant property damage. The rupture processes and Coulomb stress change of the Lushan and Jiuzhaigou earthquakes are investigated in this study. The general patterns of the slip models of the two events are similar, where the slip is concentrated around the hypocenter and the primary ruptured zone extends about 20 km along strike. The rupture zone of the 2017 Jiuzhaigou earthquake spans a depth range of 4–16 km with a peak slip of ~ 115 cm, whereas the rupture zone of the 2013 Lushan earthquake is concentrated at 8 to 20 km depth with a peak slip of 125 cm. The coseismic static Coulomb stress changes induced by the two events are computed with the obtained slip models. The Tazang fault and the northern extremities of the Minjiang and Huya faults were strongly loaded by the Jiuzhaigou earthquake, whereas the Lushan earthquake mainly affected its surrounding faults. Therefore, we infer that the seismic hazard potential in these regions has probably been increased further, and the Lushan earthquake did not contribute significantly the occurrence of the Jiuzhaigou earthquake. Additionally, we also compute the stress changes imparted by the 2008 Wenchuan earthquake. The computed stress changes in both events’ hypocenters exceed the trigger threshold (0.1 bar), which suggests that the Wenchuan earthquake played a pivotal role in the occurrence of these two earthquakes.

Abstract Background Lysine is used widely in livestock production due to the shortage of feed protein resources. L-lysine·H2SO4 contains L-lysine sulphate as well as fermentation co-products which contain other amino acids and phosphorus. However, there are few articles about L-lysine·H2SO4 product regarding intestinal morphology and liver pathology of broiler chickens. In this article, we focus on the absorption and metabolism of L-lysine·H2SO4 revealed in the variation of intestinal morphology and liver pathology to determine the tolerance of chicks for L-lysine·H2SO4. Methods To evaluate the tolerance of broilers for L-lysine·H2SO4, 240 one day old broilers were allocated randomly to one of five dietary treatments which included corn-soybean diets containing 0, 1%, 4%, 7% or 10% L-lysine·H2SO4 (L-lysine content = 55%). Results Supplementation of 1% L-lysine·H2SO4 in the diet had no negative effects. However, 4%, 7% or 10% L-lysine·H2SO4 supplementation produced negative responses on broiler performance, carcass characteristics, blood biochemistry, and particularly on intestinal morphology and liver pathology compared with broilers fed the control diet. Conclusion Our results show that supplementation with 1% L-lysine·H2SO4 had no negative effects on performance, carcass characteristics, blood biochemistry, intestinal morphology and liver pathology in broilers, but supplementation with 4%, 7% or 10% L-lysine·H2SO4 produced a negative response, particularly with respect to intestinal morphology and liver pathology.

The fecal bacteria transplantation (FMT) technique is indispensable when exploring the pathogenesis and potential treatments for microbiota-related diseases. For FMT clinical treatments, there are already systematic guidelines for donor selection, fecal bacterial separation, FMT frequency, and infusion methods. However, only a few studies have demonstrated the use of standardized FMT procedures for animal models used in theoretical research, creating difficulties for many new researchers in this field. In the present paper, we provide a brief overview of FMT and discuss its contribution to the current understanding of disease mechanisms that relate to microbiota. This protocol can be used to generate a commonly used FMT mouse model and provides a literature reference of customizable steps.

Abstract Recent years have witnessed the great advantages of reducing dietary crude protein (CP) with free amino acids (AA) supplementation for sustainable swine industry, including saving protein ingredients, reducing nitrogen excretion, feed costs and the risk of gut disorders without impairing growth performance compared to traditional diets. However, a tendency toward increased fatness is a matter of concern when pigs are fed low-protein (LP) diets. In response, the use of the net energy system and balanced AA for formulation of LP diets has been proposed as a solution. Moreover, the extent to which dietary CP can be reduced is complicated. Meanwhile, the requirements for the first five limiting AA (lysine, threonine, sulfur-containing AA, tryptophan, and valine) that growing-finishing pigs fed LP diets were higher than pigs fed traditional diets, because the need for nitrogen for endogenous synthesis of non-essential AA to support protein synthesis may be increased when dietary CP is lowered. Overall, to address these concerns and give a better understanding of this nutritional strategy, this paper reviews recent advances in the study of LP diets for swine and provides some insights into future research directions.

In order to study the potential for efficient fiber degradation by intestinal microorganisms in Diqing Tibetan pigs, we first investigated the dietary structure of Diqing Tibetan pigs in their original habitat, then 60 healthy adult Diqing Tibetan pigs were randomly divided into 2 groups with 6 replicates each and 5 pigs in each replicate. The content of neutral detergent fiber in treatment 1 and 2 were adjusted to 20% and 40%, respectively. The total tract digestibility of nutrients and the degradation efficiency of fecal microorganisms to different types of fiber were determined. Results showed that the composition and nutritional level of Diqing Tibetan pig original diet differed greatly in different seasons. The content of crude fiber in the original diet was as high as 12.3% and the neutral detergent fiber was 32.5% in April, while the content of crude fiber was 4.9% and the neutral detergent fiber was 13.3% in October. With the increase of dietary fiber level, the total tract apparent digestibility of dry matter, crude fiber, crude protein, acid detergent fiber, neutral detergent fiber, ether extract, and organic matter decreased significantly (p < 0.05), and the contents of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid in the feces were also significantly (p < 0.05) reduced. The ability of Diqing Tibetan pig fecal microorganisms to degrade neutral detergent fiber was significantly higher (p < 0.05) than “Duroc × Landrace × Yorkshire” pig. In addition, there was no significant difference (p > 0.05) in the degradation efficiency of the same type of fiber between NDF-20 and NDF-40 groups. Our results strongly suggested that Diqing Tibetan pigs have the potential to efficiently utilize fiber, and their unique intestinal microbial composition is the main reason for their efficient utilization of dietary fiber.

Low protein intake causes a decrease in protein deposition in most animal tissues. The purpose of this study was to investigate whether leucine supplementation would increase the synthesis rate of protein and muscle weight in adult rats, which chronically consume only 58.8% of their protein requirements. Thirty-six male Sprague-Dawley rats were assigned to one of three dietary treatments including a 20% casein diet (CON), a 10% casein + 0.44% alanine diet (R), and a 10% casein + 0.87% leucine diet (RL). After a 10 d dietary treatment, plasma amino acid levels were measured after feeding, the gastrocnemius muscles and soleus muscles were harvested and weighed, and the fractional synthesis rate (FSR) and mammalian target of rapamycin (mTOR) signaling proteins in skeletal muscle were measured. Regarding the plasma amino acid level, the RL group had the highest concentration of leucine (P < 0.05) and the lowest concentration of isoleucine (P < 0.05) among the three groups, and the CON group had a lower concentration of valine (P < 0.05) than the R and RL groups. Compared with the R and RL groups, the CON group diet significantly increased (P < 0.05) feed intake, protein synthesis rate, and the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and decreased the weight of abdominal adipose. Compared with the R group, the RL group significantly increased in gastrocnemius muscle weight, protein synthesis rate, and phosphorylation of both ribosomal protein S6 kinase 1 (S6K1) and 4E-BP1. In conclusion, when protein is chronically restricted in adult rat diets, leucine supplementation moderately improves body weight gain and increases muscle protein synthesis through mTOR activation.

Natural microcin J25 (MccJ25) represent promising alternatives to traditional antibiotics for the treatment of drug-resistant infections. However, little is known about the antibacterial activity of recombinant MccJ25 against foodborne pathogens. Here, the activity of recombinant MccJ25 was examined using a matrix of conditions in order to assess the efficacy of recombinant MccJ25 as a mitigation against foodborne pathogens, such as Salmonella species and Escherichia coli (E. coli) O157:H7. Results showed that recombinant MccJ25 displayed excellent antimicrobial activity against these foodborne pathogens, including clinical isolates of Salmonella and E. coli, as well as clinical antibiotic-resistant Salmonella and E. coli isolates with different minimal inhibitory concentrations. In addition, antimicrobial activity curves and Live/Dead assay evidenced that recombinant MccJ25 harbors strong bactericidal activity against Salmonella and E. coli O157:H7. Notably, recombinant MccJ25 also had great potency and induced fast mortality against different growth phase of Salmonella and E. coli. The stability analysis results showed that the activity of recombinant MccJ25 was not influenced by temperatures as high as 121°C. Varying the pH from 2.0 to 9.0 did not appear to affect the activity of recombinant MccJ25. Under the challenge of several proteases, simulated gastrointestinal fluids and serum, recombinant MccJ25 still maintained exceptionally strong antimicrobial activity. Significant reductions in Salmonella Pullorum levels were also achieved in food biological environments, such as milk, egg and meat. Moreover, we demonstrated that recombinant MccJ25 appeared to act by inducing membrane breaks, thinning, and disintegration in the Salmonella Pullorum cytoplasmic membrane. Taken together, these results indicated that recombinant MccJ25 could be an effective alternative for mitigating and prevention of Salmonella and E. coli infection in food, animal and agriculture applications.

Intestinal macrophages constitute the largest pool of macrophages in the body and have emerged as crucial sentinels for pathogen recognition and elimination. The source and development of intestinal macrophages, as well as their distinct properties have been well documented. Intestinal macrophages exert their functions in the maintenance of intestinal homeostasis by shaping host-microbiota symbiosis, managing gut inflammation, crosstalking with T cells, and facilitating wound repair. Recently, nutritional regulation of intestinal macrophages has attracted substantial attention and is becoming a promising approach to disease prevention and control. Understanding the mechanisms employed by intestinal macrophages in mediating intestinal immune homeostasis and inflammation, as well as the mode of action of dietary nutrients in the modulating functions of intestinal macrophages, represents an opportunity to prevent and control inflammatory bowel diseases.

Methicillin-resistant Staphylococcus aureus (MRSA) is the major pathogen responsible for community and hospital bacterial infections. Sublancin, a glucosylated antimicrobial peptide isolated from Bacillus subtilis 168, possesses antibacterial infective effects. In this study, we investigated the role and anti-infection mechanism of sublancin in a mouse model of MRSA-induced sublethal infection. Sublancin could modulate innate immunity by inducing the production of IL-1β, IL-6, TNF-α, and nitric oxide, enhancing phagocytosis and MRSA-killing activity in both RAW264.7 cells and mouse peritoneal macrophages. The enhanced macrophage function by the peptide in vitro correlated with stronger protective activity in vivo in the MRSA-invasive sublethal infection model. Macrophage activation by sublancin was found to be partly dependent on TLR4 and the NF-κB and MAPK signaling pathways. Moreover, oral administration of sublancin increased the frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes. The protective activity of sublancin was associated with in vivo augmenting phagocytic activity of peritoneal macrophages and partly improving T cell-mediated immunity. Macrophages thus represent a potentially pivotal and novel target for future development of innate defense regulator therapeutics against S. aureus infection.

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic and relapsing inflammation within the gastrointestinal tract. Antibiotics have been used to treat IBD, primarily utilizing metronidazole. Although there does seem to be a treatment effect, the broad-spectrum antibiotics that have been used to date are crude tools and have many adverse effects. Available evidence suggests that the host microbiome is implicated in the pathogenesis of IBD, though the key bacteria remain unknown. If the bacterial population can be modified appropriately, the use of antibiotics will have a better therapeutic effect. In this study, mice were fed dextran sodium sulfate (DSS) solution for 5 days, followed by 5 days of normal drinking water, to investigate the gut microbiota response to colitis and the initial alteration of microbiota in recovery phase. Day 0 was considered the normal control, while day 5 and day 10 were considered the colitis mouse model progressive phase and recovery phase, respectively. Results showed that inflammation could induce proportional changes in the gut microbiota. Furthermore, transplanting the microbiota in progressive phase to antibiotic-induced microbiota-depleted mice could induce inflammation similar to colitis, which proves the importance of initial alteration of the microbiota for IBD recovery and the potential of the microbiota as a target for the treatment of IBD. Meanwhile, we have also identified three possible target microorganisms in the development of colitis, namely genera Muribaculaceae (negative correlation), Turicibacter (positive correlation) and Lachnospiraceae (negative correlation) in inflammation status through comprehensive analysis.