Maternal supplementation with rumen-protected arginine reshapes the ileal microbiome and enhances neonatal lamb growth

Yeast-based nucleotide supplementation in mother sows modifies the intestinal barrier function and immune response of neonatal pigs.

Effects of rumen-protected glucose on ileal microbiota and genes involved in ileal epithelial metabolism and immune homeostasis in transition dairy cows

Metabolic blood profiles were studied in a total of 30 female mink (Mustela vison) at different planes of nutrition prior to the breeding season in a control (CON; n = 10), a flushed (FLUSH; n = 10) and a negative energy balance group (NEG; n = 10). The animals were kept in metabolism cages or under normal farm conditions, respectively. The experiment, which was divided into six 1-week periods, started on 6 February and continued until 20 March. Flushing was performed by restricted feeding in periods 2 and 3 and refeeding in periods 4 and 5. The animals were weighted weekly and blood sampled at the end of periods 1, 2 and 4, 1 week after changes in the food supply of the FLUSH group. Plasma was analysed for insulin, insulin-like growth factor-1, total triiodothyronine, total thyroxine, free thyroxine, glucose and fructosamine. Generally, within the FLUSH group, animal live weights and blood metabolites were strongly influenced by energy supply, these variables remained almost constant in the CON group. In the NEG group the live weight, total triiodothyronine, total thyroxine, insulin and glucose concentrations decreased significantly. Differences in blood metabolites between the FLUSH and CON groups were non-significant, reflecting only small differences when considered over the total experimental period, thus reflecting an acute response to a varied energy supply, while the differences between the NEG group and the CON and FLUSH groups were significant, indicating a considerable chronic response in all metabolites to a constantly low energy supply.

Background/Objectives: Wound infections cause significant morbidity, yet current diagnostics rely on time-consuming microbial culture. Volatile organic compounds (VOCs) from bacterial metabolism offer potential for early diagnosis. This study aimed to validate the volatile metabolites profiled by gas chromatography-ion mobility spectrometry (GC-IMS) combined with machine learning for rapid identification of wound infections and certain bacterial infections. Methods: Headspace of clinical wound samples were analyzed using GC-IMS. Volatile metabolite profiles were compared between infected and non-infected groups and between Escherichia coli (E. coli)-positive and negative samples. Partial least squares discriminant analysis (PLS-DA) and Mann-Whitney U test were used for preliminary screening with variable importance in projection (VIP) > 1 and p-value < 0.05. Three machine learning algorithms, namely support vector machine (SVM), logistic regression (LR), and random forest (RF), were trained on the selected features for classification, using 5-fold cross-validation with 10 repeated runs. Model performance was assessed using key evaluation metrics, including accuracy, sensitivity, specificity, the area under the curve (AUC) and feature importance ranking to identify the most relevant biomarkers. Results: A total of 19 volatile metabolites associated with clinical wound samples were identified. The RF model achieved 90.15% sensitivity and 0.91 AUC for bacterial infection detection. For E. coli identification, LR reached 85.35% sensitivity and 0.89 AUC. Potential volatile metabolic biomarkers including elevated 3-methyl-1-butanol, 2-methyl-1-butanol, and ethyl hexanoate for identifying bacterial infection were selected through the cross-validation results of the three algorithms. Conclusions: Untargeted metabolomics by GC-IMS effectively captures infection-specific volatile metabolic signatures in complex wound samples. Integration with machine learning enables rapid, high-accuracy diagnosis of bacterial infections and E. coli identification at point of care. This approach addresses clinical metabolomics translational challenges by providing a portable and cost-effective method, potentially reducing antibiotic misuse through more timely and targeted therapy.

Patients with chronic liver disease have low insulin-like growth factor 1 (IGF-1) levels, but it is not known whether this is secondary to primary hepatic dysfunction and/or to malnutrition. In order to distinguish between these possibilities, serum and liver IGF-1 concentrations and liver IGF-1 mRNA content were compared in three groups of Sprague-Dawley rats; fifteen rats underwent bile duct obstruction (OP); 10 rats were sham-operated and pair-fed with OP rats (PF) to control for nutritional status; and 12 rats were sham-operated controls fed ad libitum (CON). Serum and liver were extracted and assayed by RIA using an antibody that recognizes rat IGF-1 (gift of L.Underwood). Liver ICF-1 mRNA content was measured by dot blot hybridization using a cDNA probe, quantitated by videodensitometry and expressed as a percent of internal control RNA values (adult rat pool). In addition, IGF-1 peptide and mRNA were compared with food intake, nitrogen balance, total weight gain, tail length increase and leg muscle weight. All the parameters were found significantly lower (p<0.001) in OP and PF animals than in CON animals. In the 10 paired OP and PF animals serum and hepatic IGF-1 and liver IGF-1 mRNA Values were not significantly different, despite lower nitrogen balance, tail length gain, and leg muscle weight in the OP animals. For all animals, there was a significant correlation (p<0.001) between serum IGF-1 levels and food intake (r=0.84), liver IGF-1 levels (r=0.64), and liver IGF-1 mRNA (r=0.89). These studies suggest that in chronic bile duct obstruction, the low serum and hepatic IGF-1 levels are primarily due to decreased food intake and appear unrelated to cholestatic liver disease itself. Decreased IGF-1 synthesis is the most probable cause of these low levels. However, factors other than suboptimal nutrition and decreased IGF-1 levels must also contribute to cholestasis-induced growth failure in this animal model.

Effect of dietary arginine supplementation on protein synthesis, meat quality and flavor in growing lambs

It is the purpose of this viewpoint article to delineate the regulatory network of growth hormone (GH), insulin, and insulin-like growth factor-1 (IGF-1) signalling during puberty, associated hormonal changes in adrenal and gonadal androgen metabolism, and the impact of dietary factors and smoking involved in the pathogenesis of acne. The key regulator IGF-1 rises during puberty by the action of increased GH secretion and correlates well with the clinical course of acne. In acne patients, associations between serum levels of IGF-1, dehydroepiandrosterone sulphate, dihydrotestosterone, acne lesion counts and facial sebum secretion rate have been reported. IGF-1 stimulates 5alpha-reductase, adrenal and gonadal androgen synthesis, androgen receptor signal transduction, sebocyte proliferation and lipogenesis. Milk consumption results in a significant increase in insulin and IGF-1 serum levels comparable with high glycaemic food. Insulin induces hepatic IGF-1 secretion, and both hormones amplify the stimulatory effect of GH on sebocytes and augment mitogenic downstream signalling pathways of insulin receptors, IGF-1 receptor and fibroblast growth factor receptor-2b. Acne is proposed to be an IGF-1-mediated disease, modified by diets and smoking increasing insulin/IGF1-signalling. Metformin treatment, and diets low in milk protein content and glycaemic index reduce increased IGF-1 signalling. Persistent acne in adulthood with high IGF-1 levels may be considered as an indicator for increased risk of cancer, which may require appropriate dietary intervention as well as treatment with insulin-sensitizing agents.

High-protein foods and physical activity are crucial for bone growth in early life. This study first examined whether a protein-rich multi-nutrient intervention combined with rope-skipping training could prevent bone loss during winter in prepubertal children. A 10 week randomized controlled trial involving 120 children aged 9-12 years in rural northwestern China was conducted. Participants were assigned to a treatment group (protein-rich multi-nutritional drink plus rope-skipping training) or a control group (rope-skipping training only). Forearm bone mineral density (BMD) was measured at the baseline and week 10 of the trial, along with serum calcium, parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), and bone turnover biomarkers. Second, we estimated the effects of three protein sources enriched in the drink, milk protein concentrates (MPC), collagen peptides (CP), and whey protein hydrolysates (WPH), on zebrafish backbone development. In children, BMD decreased in both groups, but the treatment group showed a smaller reduction and a positive intervention effect (relative change: 0.023 g cm-2, P = 0.037). The treatment group also had a smaller increase in PTH (relative change: -8.53 ng L-1, P = 0.012) and a smaller decrease in IGF-1 (relative change: 20.75 ng mL-1, P = 0.076). No significant differences were found in bone turnover biomarkers. In zebrafish, MPC, CP, and WPH individually and synergistically promoted bone growth without adverse effects, as shown by dose-dependent increases in the backbone fluorescence intensity. These findings suggest that protein-rich multi-nutrient supplementation combined with rope-skipping training could prevent bone loss in prepubertal children during winter, potentially through changes in serum PTH and IGF-1, and highlight the synergistic effects of these proteins on bone development.

Feeding Allium mongolicum Regel (AMR) could improve lamb growth, immunity, and antioxidant capacity. These effects were supposed to be mediated by the rumen microbiota, as reported in our previous studies, but further verification is required. The purpose of this study was to verify whether changes in serum immunity, antioxidant, and biochemical indicators of meat sheep mediated by AMR are achieved via rumen microbiota regulation. The experiment included two phases. In phase I, twelve 90-day-old male lambs (25 ± 1 kg) were used as rumen fluid donors and consumed a basal diet with 15 g/day AMR for 135 days to induce changes in their rumen microbiota. In phase II, thirty 90-day-old male lambs (23 ± 2 kg) were split into three groups (n = 10 each): the control group (CON) fed the basal diet; the AMR-supplemented group (AMG) fed the basal diet supplemented with 15 g/day of AMR; and the rumen fluid recipient group (RTG) fed the basal diet and received rumen fluid transplantation. The CON and AMG groups received four oral infusions of 250 mL saline, while the RTG group received four oral infusions of 250 mL donor rumen fluid. Phase II lasted for 75 days, and the blood samples were collected on the last day. Rumen fluid transplantation was performed every 15 days, with a total of four infusions of 250 mL each. The results showed that the final body weight and average daily gain (ADG) of the AMG and RTG groups were higher than those of the CON group (p < 0.05), while there were no significant differences between the AMG and RTG groups (p > 0.05). On day 30, the levels of interleukin-10 (IL-10), immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) in the AMG and RTG groups were increased (p < 0.05), and malondialdehyde (MDA) was significantly decreased (p < 0.05), with no significant differences between the AMG and RTG groups. On day 60, total antioxidant capacity (T-AOC), IgM, IgG, and catalase (CAT) were increased in the AMG and RTG groups, while tumor necrosis factor alpha (TNF-α), low-density lipoprotein cholesterol (LDL-C), and blood urea nitrogen (BUN) were decreased (p < 0.05), and there were no significant differences between the AMG and RTG groups (p > 0.05). High-density lipoprotein cholesterol (HDL-C) in the RTG group was significantly lower than in the CON and AMG groups, while the AMG group had significantly higher HDL-C than the CON group (p < 0.05). Microbial analysis indicated that Mitsuokella, VUNI01, and Caecibacter were positively correlated with IgM; Mitsuokella, CAG 791, Desulfovibrio R, Porcincola, VUNI01, and UBA 7741 were negatively correlated with TNF-α; CAG 791 was positively correlated with T-AOC; VUNI01 was positively correlated with CAT; MDA was negatively correlated with Mitsuokella; Allisonella and UBA 7741 were negatively correlated with HDL-C; and Porcincola, VUNI01, Allisonella, and UBA 7741 were negatively correlated with LDL-C. Therefore, the study indicates that both supplementation with AMR and transplantation of rumen fluid from sheep fed with AMR can enhance the immunity and antioxidant capacity of lambs by increasing the abundance of the aforementioned bacteria. It also verified that the improvement in immunity and antioxidant capacity mediated by Allium mongolicum Regel is driven by the rumen microbiota.

Heat stress (HS) during pregnancy adversely affects uterine vascular perfusion and foetal development. L-arginine (L-Arg), a nitric oxide (NO) precursor, has been proven to enhance an organ's vascular perfusion. Therefore, this study aimed to examine the effect of L-Arg administration on the pregnant buffaloes' uterine haemodynamics and uteroplacental thickness under environmental HS conditions. For this purpose, pluriparous (n=12) HS-pregnant buffaloes (mid-gestation, 180-190 days; temperature humidity index >85) were haphazardly assigned into two groups, either administered a single intravenous (IV) bolus of 5mg/kg BW of L-Arg Hcl (n=6; ARG) or received normal saline (0.9%; IV; 25 ml) that served as a control group (n=6; CON). Combined uteroplacental thickness (CUPT, mm), middle uterine arteries' (MUA) diameter (mm) and uterine Doppler haemodynamics (ipsilateral and contralateral to the pregnant horn) were examined utilizing B-mode and colour Doppler ultrasonography, respectively. The serum levels of progesterone (P4), estradiol 17β (E2), nitric oxide (NO) and total antioxidant capacity (TAC) were assayed using commercial kits. The experimental time points were - 1, 0, 2, 4, 24, 48, 72, 96 and 120 h post-L-Arg administration. The ARG group showed higher (p < .05) CUPT and MUA diameter values starting at 24 h post-treatment and onward than the control buffalo cows. In addition, there were improvements (p < .05) in the blood flow parameters in the ipsilateral MUA after L-Arg treatment evidenced by lower values of pulsatility and resistive indices starting at 48 and 4h, respectively and onward, and higher values of peak systolic velocity, coloured areas towards the pregnant uterine horn (both 24-72 h). Increases in the NO levels were found during the period between 4 and 120 h in the ARG group compared to the CON group. Moreover, significant increases in the E2 and P4 means were noted in the ARG group, especially at 24 h onward, respectively compared to the CON group. Concerning the TAC status, neither the administration nor the hours affected serum TAC levels in the HS pregnant buffaloes (CON and ARG). In conclusion, L-Arg administration improved uteroplacental thickness and enhanced uterine haemodynamics, NO levels, and steroids production in mid-pregnant buffalo cows under environmental heat stress conditions which could improve foetal growth and development.

SummaryExposure of sheep to a long-day photoperiod during late pregnancy results in greatly increased plasma prolactin concentrations in both the ewe and her fetuses compared to values in animals experiencing short days. To investigate whether the endocrine changes resulting from provision of additional lighting might also influence the pre- and postnatal growth of lambs or udder development in winter-housed ewes, two experiments were carried out. In the first, a group of housed Mule ewes, lambing in early January 1989, were given additional lighting to provide a long-day photoperiod [16 h light: 8 h dark] from 6 weeks before delivery until 6 weeks after lambing. In the second experiment, 50 housed Mule ewes were given additional light for 7 weeks before delivery at the end of March 1990. In both experiments, comparable groups of housed Mule ewes experiencing only the natural shortday winter photoperiod served as controls.In both experiments, provision of the long-day photoperiod resulted, within 3 weeks, in highly significant increases in plasma prolactin concentrations in the ewes. Plasma prolactin concentrations in the lambs from ewes experiencing the long-day photoperiod were also increased at birth (8-fold) and throughout the suckling period (3–5-fold) compared to values in short-day control lambs.Despite these large differences in plasma prolactin concentrations, there was no significant effect of photoperiod on the birth weight of the lambs in either experiment. There was also no effect of photoperiod on the postnatal growth of lambs in Experiment 1.Provision of a long-day photoperiod resulted in some increase in the rate of growth of linear measurements of udder size in ewes during both experiments, but only resulted in a significant increase in estimated udder size at delivery in ewes with twins or larger numbers of fetuses in the first experiment. In both experiments the effect of a long-day photoperiod on udder size was similar to or less than the effect of one additional fetus.The results do not suggest that prenatal photoperiodic experience results in any major alteration in somatic development in lambs at birth or during early postnatal life. They do, however, give some support to other observations that ambient photoperiod may influence pre-partum udder development in the ewe.

Schizophrenia is a severe psychiatric disorder that affects approximately 1% of the population. Despite the availability of antipsychotic therapies, about 30% of patients develop treatment-resistant schizophrenia (TRS), defined by a lack of response to at least two different antipsychotic trials. Although several genetic and environmental factors have been proposed to explain treatment resistance, metabolomic studies investigating circulating metabolites in TRS remain limited. In this pilot cross-sectional study, we conducted untargeted 1H NMR-based metabolomics to profile serum metabolites in TRS versus non-TRS patients. Notably, multivariate analysis revealed distinct serum metabolome profiles between the two groups. Additionally, Variable Importance in Projection (VIP) analysis and robust volcano plots showed significant differences between TRS versus non-TRS patients in metabolites involved in lipid and amino acid metabolism. Specifically, serine and glycine emerged as key discriminating molecules, prompting a complementary targeted HPLC analysis in the same serum samples. Although no significant group differences were observed in L-serine, D-serine, the D-serine/total serine ratio, or glycine levels, we found a positive correlation between D-serine levels and cognitive performance, particularly in the area of executive function, across the entire patient cohort. Additionally, a significant correlation between glycine and disorganization symptoms was found selectively in TRS patients. In conclusion, our study offers new insights into potential biomarkers for TRS, highlighting serine-glycine pathway as a possible crossroad between systemic dysmetabolism, NMDA receptor dysfunction, and cognitive impairment in TRS.

E-waste contains hazardous chemicals that may be a direct health risk for workers involved in recycling. We conducted an untargeted metabolomics analysis of urine samples collected from male e-waste processing workers to explore metabolic changes associated with chemical exposures in e-waste recycling in Belgium, Finland, Latvia, Luxembourg, the Netherlands, Poland, and Portugal. Questionnaire data and urine samples were obtained from workers involved in the processing of e-waste (sorting, dismantling, shredding, pre-processing, metal, and non-metal processing), as well as from controls with no known occupational exposure. Pre- and post-shift urine samples were collected and analysed using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS). A total of 32 endogenous urinary metabolites were annotated with a Variable Importance in Projection (VIP) above 2, indicating that e-waste recycling is mainly associated with changes in steroid hormone and neurotransmitter metabolism, energy metabolism, bile acid biosynthesis, and inflammation. The highest VIP was observed for dopamine-o-quinone, which is linked to Parkinson's disease. These and other changes in metabolism in workers employed in the processing of e-waste need further verification in targeted studies.

Untargeted metabolomics in the aqueous humor reveals the involvement of TAAR pathway in glaucoma

The objective of this study was to evaluate the effect of supplying ruminally-protected lysine (RPL), methionine (RPM), or the two in combination (RPML) to transition dairy cows on the immunity and performance of their offspring. Eighty heifer calves (n = 20 calves per group) were assigned to four treatments based on their dam diet; basal diet (CON), a basal diet with lysine [RPL, 0.33% of dry matter (DM)], a basal diet with methionine (RPM, 0.16% DM), or with the combination (RPML). Calves were fed colostrum from their dams within 2 h of birth. Calves were then fed milk only (d 2–22), a combination of milk and milk replacer (d 23–25), and milk replacer (d 25–60). Starter feed was fed to the calves twice daily after liquid feeding. Calves blood samples were collected after calving on 0, 12, 24, and 48 h and 5 and 7 d after birth. Data were analyzed by SAS software v9.4. Providing ruminally-protected amino acids (RPAA) to transition cows improved colostrum quality compared to the CON (Brix; P < 0.01). Serum total protein concentrations were higher in calves from supplemented cows than in calves from unsupplemented cows (P < 0.01). Calves born to dams in the RPM, RPL, and RPML groups had higher plasma immunoglobulin G (IgG) concentrations 0, 12, 24, and 48 h and 7 d after birth than those born to dams in the CON group (P < 0.05). The percentage of calves with adequate passive immunity transfer was increased with RPM and RPL or the two in combination (P < 0.01). However, there was no difference in the percentage of calves with adequate passive immunity transfer between the RPM and RPL groups (P = 0.21). Calves from cows that receive supplemental RPAA have a greater average daily gain (ADG) than those born to cows in the CON group (P < 0.01). These results indicate that maternal supplementation with RPM or RPL or the two in combination during the periparturient period could be an alternative strategy to improve the performance of calves, especially in accelerated growth programs in calves.