Antifungal effects and biocontrol potential of lipopeptide-producing Streptomyces against banana Fusarium wilt fungus Fusarium oxysporum f. sp. cubense.

Fusarium wilt of banana (FWB), caused by Fusarium oxysporum f. sp. cubense (Foc), especially tropical race 4 (TR4), presents the foremost menace to the global banana production. Extensive efforts have been made to search for efficient biological control agents for disease management. Our previous study showed that Streptomyces sp. XY006 exhibited a strong inhibitory activity against several phytopathogenic fungi, including F. oxysporum. Here, the corresponding antifungal metabolites were purified and determined to be two cyclic lipopeptide homologs, lipopeptin A and lipopeptin B. Combined treatment with lipopeptin complex antagonized Foc TR4 by inhibiting mycelial growth and conidial sporulation, suppressing the synthesis of ergosterol and fatty acids and lowering the production of fusaric acid. Electron microscopy observation showed that lipopeptide treatment induced a severe disruption of the plasma membrane, leading to cell leakage. Lipopeptin A displayed a more pronounced antifungal activity against Foc TR4 than lipopeptin B. In pot experiments, strain XY006 successfully colonized banana plantlets and suppressed the incidence of FWB, with a biocontrol efficacy of up to 87.7%. Additionally, XY006 fermentation culture application improved plant growth parameters and induced peroxidase activity in treated plantlets, suggesting a possible role in induced resistance. Our findings highlight the potential of strain XY006 as a biological agent for FWB, and further research is needed to enhance its efficacy and mode of action in planta.

Dynamic alteration in the gut microbiota and metabolome of Huanjiang mini-pigs during pregnancy.

BACKGROUND: Maternal gut microbiota and metabolites are associated with their offspring's health. Our previous study showed that maternal body fat percentage increased from days 45 to 110 of gestation in a Huanjiang mini-pig model. Thus, this study aimed to investigate the changes in gut microbiota composition and microbial metabolite profile of sows from days 45 to 110 of gestation. RESULTS: Twenty-four Huanjiang mini-pigs with average body weight were assigned for sample collection during early- (day 45 of pregnancy), mid- (day 75 of pregnancy), and late-pregnancy (day 110 of pregnancy). The results showed that the relative abundances of Clostridium_sensu_stricto_1, Romboutsia, Turicibacter, and Streptococcus in jejunal contents were higher at day 110 than those at day 45 or 75 of gestation. In the ileum, the relative abundance of Streptococcus was higher (P < 0.05) at day 110 of gestation, as well as the metabolism function of the jejunal and ileal microbiota. The ileal butyrate and acetate concentrations were higher at days 45 and 110 of gestation, respectively. In the colon, the concentrations of cadaverine and spermine were higher (P < 0.05) at days 45 and 110 of gestation, respectively. Metabolomic analyses demonstrated that the metabolic pathways, including D-glutamine and D-glutamate metabolism, phenylalanine/tyrosine/tryptophan biosynthesis, and alanine/aspartate/glutamate metabolism changed during gestation. CONCLUSION: Collectively, our results showed that gut microbiota composition and microbial metabolites changed dramatically from early to late pregnancy in a Huanjiang mini-pig model. These findings will provide new targets in formulating maternal nutritional interventions to alleviate the adverse effects during pregnancy on offspring health outcomes.

Dietary addition of fermented sorghum distiller's dried grains with soluble improves carcass traits and meat quality in growing-finishing pigs.

The fermented sorghum distiller's dried grain with soluble (FS-DDGS) contains numerous nutrients, yet its nutritional effects on growing-finishing pigs remain unclear. The present study evaluated the effects of dietary FS-DDGS addition on growth performance, carcass traits, and meat quality in growing-finishing pigs. A total of 48 healthy male crossbred (Large White × Landrace × Duroc) barrows with initial body weight (BW) of 39.95 ± 2.15 kg were allocated to one of four dietary treatments (12 pigs per treatment). The dietary treatments were as follows: basal diet without (FS-DDGS0 group) or with 50 g/kg (FS-DDGS50 group), 100 g/kg (FS-DDGS100 group), or 150 g/kg (FS-DDGS150 group) FS-DDGS, respectively. Results showed that there were no significant differences in the final BW, average daily gain, average daily feed intake, and feed to gain ratio among these four groups. However, dietary FS-DDGS addition increased (linear, P < 0.05) the pH24h value, contents of ash, crude protein, and proline in Longissimus dorsi muscle, and alanine, arginine, aspartic acid, glutamic acid, isoleucine, leucine, lysine, serine, and tyrosine in Biceps femoris (BF) muscle, when compared with the control group. In addition, dietary FS-DDGS addition decreased (linear, P < 0.05) the drip loss, yellowness (b*) value, and lightness (L*) value, while quadratically improved (P < 0.05) the total bone percentage and glycine and proline contents in BF muscle compared with the control group. Collectively, these findings suggested that dietary FS-DDGS addition could improve the carcass traits and meat quality in growing-finishing pigs although further research is needed to explore the underlying mechanisms.

Comparison of Clinical Efficacy and Safety of Metformin Sustained-Release Tablet (II) (Dulening) and Metformin Tablet (Glucophage) in Treatment of Type 2 Diabetes Mellitus.

Objectives: This study investigated the clinical efficacy and safety of metformin hydrochloride sustained-release (SR) tablet (II) produced by Dulening and the original metformin hydrochloride tablet produced by Glucophage in the treatment of type 2 diabetes mellitus (T2DM). Methods: This randomized, open and parallel controlled clinical trial consecutively recruited a total of 886 patients with T2DM in 40 clinical centers between May 2016 and December 2018. These patients were randomly assigned to the Dulening group (n=446), in which patients were treated with Dulening metformin SR tablets, and the Glucophage group (n=440), in which patients were treated with Glucophage metformin tablets, for 16 weeks. The changes in the levels of glycated hemoglobin (HbAc1) and fasting blood glucose (FBG) as well as weight loss were compared between these two groups. Also, the overall incidence of adverse drug reactions (ADRs) and the incidence of ADR of the gastrointestinal system observed in patients of these two groups were also compared. Results: There were no significant differences in demographic and basal clinical characteristics between these two groups. The Dulening and Glucophage groups showed comparable levels of decrease in HbA1c levels, FBG and weight loss after 12-week treatment (all p>0.05). The Dulening group had a significantly lower overall incidence of ADRs as well as gastrointestinal ADR than the Glucophage group. Conclusions: Metformin SR tablets (II) and the original metformin tablets exhibit similar therapeutic efficacy in the treatment of T2DM, but metformin SR tablets (II) has the significantly lower incidence of ADRs than the original metformin tablets.

New Insights into Stress-Induced ß-Ocimene Biosynthesis in Tea (Camellia sinensis) Leaves during Oolong Tea Processing.

As the major contributors to the floral odors of tea products, terpenoid volatiles play critical roles in the defense response of plants to multiple stresses. Until now, only a few TPS genes in tea plants (Camellia sinensis) have been functionally validated. In this study, by comparative studies conducted at gene, protein, and metabolite levels during oolong tea processing, we isolated an ocimene synthase gene, CsOCS, which displays a low similarity to previously characterized tea ocimene synthases. Further prokaryotic expression and subcellular localization analysis showed that it is plastid-located and could produce (E)-ß-ocimene and (Z)-ß-ocimene using GPP as the substrate. The optimum temperature and pH of the enzyme were 30 °C and 7.5, respectively. Treatment with exogenous methyl jasmonate elevated the transcript level of CsOCS and enhanced the emission of ocimene from tea leaves. Collectively, CsOCS is implicated as a key enzyme for ß-ocimene synthesis during oolong tea processing.

Dietary Supplementation With Xylo-oligosaccharides Modifies the Intestinal Epithelial Morphology, Barrier Function and the Fecal Microbiota Composition and Activity in Weaned Piglets.

The present study determined the effects of dietary xylo-oligosaccharides (XOS) supplementation on the morphology of jejunum and ileum epithelium, fecal microbiota composition, metabolic activity, and expression of genes related to colon barrier function. A total of 150 piglets were randomly assigned to one of five groups: a blank control group (receiving a basal diet), three XOS groups (receiving the basal diet supplemented with 100, 250, and 500 g/t XOS, respectively), as well as a positive control group, used as a matter of comparison, that received the basal diet supplemented with 0.04 kg/t virginiamycin, 0.2 kg/t colistin, and 3,000 mg/kg ZnO. The trial was carried out for 56 days. The results showed that the lowest dose tested (100 g/t XOS) increased (P < 0.05) the ileal villus height, the relative amount of Lactobacillus and Bifidobacterium spp., and the concentration of acetic acid and short-chain fatty acid in feces when compared with the blank control group. In conclusion, dietary 100 g/t XOS supplementation modifies the intestinal ecosystem in weaned piglets in an apparently overall beneficial way.

Dynamic Changes of Metabolite Profiles in Maternal Biofluids During Gestation Period in Huanjiang Mini-Pigs.

The biochemical parameters related to nitrogenous metabolism in maternal biofluids may be linked and even reflect the fetal metabolism and growth. The present study have measured the concentrations of various parameters related to amino acid (AA) and lipid metabolism, as well as different metabolites including the free AAs in maternal plasma and amniotic and allantoic fluid corresponding to fetuses with different body weight (BW) during different gestation periods, in order to identify the possible relationships between biochemical parameters and fetal growth. A total of 24 primiparous Huanjiang mini-pigs were fed with a standard diet. Data showed that, from day 45 to day 110 of gestation, the maternal plasma levels of alanine aminotransferase (ALT), albumin (ALB), Ile, Orn, Car, α-ABA, and ß-AiBA increased (P < 0.05); while the levels of ammonia (AMM), choline esterase (CHE), high density lipoprotein-cholesterol (HDL-C), Leu, Glu, Cys, Asp, and Hypro decreased (P < 0.05). From day 45 to 110 of gestation, the amniotic fluid levels of aspartate transaminase (AST), CHE, total protein (TP), and urea nitrogen (UN) increased (P < 0.05), as well as the level of CHE and TP and concentration of Pro in allantoic fluid; while the amniotic fluid concentrations of Arg, Glu, Orn, Pro, and Tau decreased (P < 0.05), as well as allantoic fluid concentrations of Arg and Glu. At day 45 of gestation, the amniotic fluid concentrations of Arg, Orn, and Tau corresponding to the highest BW (HBW) fetuses were higher (P < 0.05), whereas the allantoic fluid concentrations of His and Pro were lower (P < 0.05) when compared with the lowest BW (LBW) fetuses. At day 110 of gestation, the amniotic fluid concentration of Tau corresponding to the HBW fetuses was higher (P < 0.05) than the LBW fetuses. These findings show that the sows display increased protein utilization and decreased lipid metabolism and deposition from day 75 to 110 of gestation. In addition, our data are indicative of a likely stronger ability of HBW fetuses to metabolize protein; and finally of a possible key role of Arg, Gln, Glu, Pro, Tau, and His for the fetal growth and development.

UPLC-MS-based urine nontargeted metabolic profiling identifies dysregulation of pantothenate and CoA biosynthesis pathway in diabetic kidney disease.

AIMS: Diabetic kidney disease (DKD) is a major prevalent chronic microvascular complication of type 2 diabetes (T2D). However, the present diagnostic indicators have limitations in the early diagnosis of DKD. This study concentrated on the sensitive and specific biomarkers in early diagnosis of DKD by metabolomics. MATERIALS AND METHODS: In this cross-sectional study, we performed a UPLC-MS based nontargeted metabolomics assay to profile the urinary metabolites in patients with DKD. Principal Component Analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA) were used for screening out the metabolomic variables. KEY FINDINGS: A total of 147 urinary metabolites were identified and 5 metabolic pathways were correlated with DKD pathophysiology. Pantothenate and coenzyme A biosynthesis pathway alteration was found the most prominent in DKD subjects. 4 metabolites, including dihydrouracil, ureidopropionic acid, pantothenic acid (PA), and adenosine 3',5'-diphosphate involved in pantothenate and CoA biosynthesis were significantly down-regulated. SIGNIFICANCE: Our finding indicates that PA would be served as a novel predictive biomarker associated with DKD development and progression. Furthermore, our results provide a promising prospect that PA and CoA biosynthesis pathway can be potential therapeutic targets for DKD treatment.

Dietary xylo-oligosaccharide supplementation alters gut microbial composition and activity in pigs according to age and dose.

This study explored the effect of dietary xylo-oligosaccharide (XOS) supplementation on the gut microbial composition and activity in pigs of different ages. Eighty pigs with an average body weight (BW) of 30 kg were randomly divided into eight groups: A control group, a group that received antibiotic treatment, and six groups fed diets supplemented with 100, 250, and 500 g/t XOS, of which three groups were in the growing period (GP, 30-65 kg BW) and three groups in the growing and fattening period (GFP, 30-100 kg BW). At the end of the experiment, the intestinal contents were sampled for analyses of gut microbiota and bacterial metabolites including short-chain fatty acids (SCFAs) and bioamines. The results showed that 100 g/t XOS supplementation during the GFP significantly reduced the relative abundances of presumably pathogenic bacteria (Proteobacteria and Citrobacter), but enhanced the relative abundances of likely beneficial bacteria (Firmicutes and Lactobacillus). However, XOS supplementation during the GP showed little effect on the gut microbiota when pigs were killed at 100 kg BW. Meanwhile, 100 g/t XOS supplementation during the GFP decreased the level of 1,7-heptane diamine and increased the acetic acid, straight-chain fatty acids, and total SCFAs concentrations in the intestinal contents. Statistical analysis showed that both the dose and exposure time to XOS supplementation affected the microbial communities. In summary, 100 g/t XOS supplementation during the GFP modified the gut microbiota composition and metabolic activity. Possible consequences of such changes for the host are discussed.

Dietary supplementation with fermented Mao-tai lees beneficially affects gut microbiota structure and function in pigs.

Gut microbiota positively contribute to livestock nutrition and metabolism. The manipulation of these microbes may improve animal health. Some feed additives improve livestock health and metabolism by regulating gut microbiota composition and activity. We fed hybrid pigs diets supplemented with 0% (control), 5% (treat 1), 10% (treat 2), or 15% (treat 3) fermented Mao-tai lees (FML) for 90 days. Short-chain fatty acids (SCFAs), bioamines, and microbial communities found in colonic contents were analyzed to investigate microbiota composition and metabolic profiles. Concentrations of straight-chain fatty acids (e.g., acetate, propionate, and butyrate) and tyramine increased with FML supplementation content. Contrary to the minor effects of 5% and 10% FML on gut microbiota, 15% FML influenced beta diversity (Jaccard or Bray-Curtis dissimilarity) but not alpha diversity (number of operational taxonomic units and Shannon diversity) of pig gut microbial communities compared to the control group. Notably, 15% FML animals were characterized by a higher abundance of potentially beneficial bacteria (Lactobacillus and Akkermansia) but lower abundances of potential pathogens (Escherichia). Numerous genes associated with metabolism (e.g., starch, sucrose, and sulfur-compounds metabolism) showed a higher relative abundance in the 15% FML than in the control group. Additionally, most Phascolarctobacterium, Treponema, Prevotella, and Faecalibacterium bacterial markers in the 15% FML group were positively correlated with straight-chain fatty acid concentrations, suggesting that these bacteria are likely associated with SCFA production. Taken together, our findings demonstrate the beneficial effects of 15% FML on fermentation of undigested compounds and gut microbiota composition in the colon. Thus, 15% FML supplementation in pig feed may possibly represent a way to optimize pig colon health for livestock farming.

Fetal Huanjiang mini-pigs exhibit differences in nutrient composition according to body weight and gestational period.

Low birth weight may negatively affect energy storage and nutrient metabolism, and impair fetal growth and development. We analyzed effects of body weight (BW) and gestational period on nutrient composition in fetal Huanjiang mini-pigs. Fetuses with the lowest BW (LBW), middle BW (MBW), and highest BW (HBW) were collected at days 45, 75, and 110 of gestation. Crude protein (CP), crude fat, amino acid (AA), and fatty acid (FA) concentrations were determined. The BW gain, carcass weight, fat percentage, and uterus weight of sows increased as gestation progressed, as did litter weight, average individual fetal weight, fetal body weight, and dry matter (DM). The concentrations of Ala, Arg, crude fat, Gly, Pro, Tyr, C14:0, C16:0, C16:1, C18:1n9c, C18:2n6c, C18:3n3, C18:3n6, C20:0, C20:3n6, saturated FA (SFA), and monounsaturated FA (MUFA) increased significantly as gestation progressed. The percentage of skeleton, and the ratio of the liver, lung, and stomach to BW decreased as gestation progressed. There were also significant reductions in the concentrations of CP, Asp, Glu, His, Ile, Leu, Lys, Phe, Ser, Thr, essential AA (EAA), acidic AA, C17:0, C20:4n6, C22:6n3, unsaturated FA (UFA), polyunsaturated FA (PUFA), n-3PUFA, n-6PUFA as gestation progressed, and reductions in EAA/total AA (TAA), PUFA/SFA, and n-3/n-6 PUFA. The LBW fetuses exhibited the lowest BW and crude fat, C14:0, C16:1, C17:0, C18:2n6c, and MUFA concentrations at days 75 and 110 of gestation. They also exhibited lower Tyr concentration at day 45 of gestation and lower Glu concentration at day 75 of gestation than HBW fetuses. These findings suggest that LBW fetuses exhibit lower amounts of crude fat and several FAs during mid-gestation and late-gestation, which may in turn affect adaptability, growth, and development.

Tang-Luo-Ning Improves Mitochondrial Antioxidase Activity in Dorsal Root Ganglia of Diabetic Rats: A Proteomics Study.

Tang-luo-ning (TLN) is a traditional Chinese herbal recipe for treating diabetic peripheral neuropathy (DPN). In this study, we investigated mitochondrial protein profiles in a diabetic rat model and explored the potential protective effect of TLN. Diabetic rats were established by injection of streptozocin (STZ) and divided into model, alpha lipoic acid (ALA), and TLN groups. Mitochondrial proteins were isolated from dorsal root ganglia and proteomic analysis was used to quantify the differentially expressed proteins. Tang-luo-ning mitigated STZ-induced diabetic symptoms and blood glucose level, including response time to cold or hot stimulation and nerve conductive velocity. As compared to the normal, there were 388 differentially expressed proteins in the TLN group, 445 in ALA group, and 451 in model group. As compared to the model group, there were 275 differential proteins in TLN group and 251 in ALA group. As compared to model group, mitochondrial complex III was significantly decreased, while glutathione peroxidase and peroxidase were increased in TLN group. When compared with ALA group, the mitochondrial complex III was increased, and mitochondrial complex IV was decreased in TLN group. Together, TLN should have a strong antioxidative activity, which appears to be modulated through regulation of respiratory complexes and antioxidases.

Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa/Izm rats by improving insulin resistance in skeletal muscle.

BACKGROUND: Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) have been associated with insulin-resistance; however, the effective therapies in improving insulin sensitivity are limited. This study is aimed at investigating the effect of Guava Leaf (GL) extracts on glucose tolerance and insulin resistance in SHRSP.Z-Leprfa/Izm rats (SHRSP/ZF), a model of spontaneously metabolic syndrome. METHODS: Male rats at 7 weeks of age were administered with vehicle water or treated by gavage with 2 g/kg GL extracts daily for six weeks, and their body weights, water and food consumption, glucose tolerance, and insulin resistance were measured. RESULTS: Compared with the controls, treatment with GL extracts did not modulate the amounts of water and food consumption, but significantly reduced the body weights at six weeks post treatment. Treatment with GL extracts did not alter the levels of fasting plasma glucose and insulin, but significantly reduced the levels of plasma glucose at 60 and 120 min post glucose challenge, also reduced the values of AUC and quantitative insulin sensitivity check index (QUICKI) at 42 days post treatment. Furthermore, treatment with GL extracts promoted IRS-1, AKT, PI3Kp85 expression, then IRS-1, AMKP, and AKT308, but not AKT473, phosphorylation, accompanied by increasing the ratios of membrane to total Glut 4 expression and adiponectin receptor 1 transcription in the skeletal muscles. CONCLUSIONS: These data indicated that GL extracts improved glucose metabolism and insulin sensitivity in the skeletal muscles of rats by modulating the insulin-related signaling.