Serum Concentrations Of Metabolites Research Articles

Altered metabolomic profiling of overweight and obese adolescents after combined training is associated with reduced insulin resistance

Exercise training and a healthy diet are the main non-pharmacological strategies for treating chronic conditions, such as obesity and insulin resistance (IR), in adolescents. However, the isolated metabolic changes caused by exercise training without dietary intervention have not yet been established. We investigated how combined training (CT) without dietary intervention altered the concentrations of serum metabolites, biochemical, anthropometric and functional parameters in overweight and obese adolescents. Thirty-seven adolescents (14.6 ± 1.05 years), of both sexes, were randomly assigned to the control group (CG, n = 19) or the training group (TG, n = 18). The CT was composed by resistance training and aerobic training performed in the same session (~ 60 min), three times a week, for 12 weeks. All assessments were performed pre and post-intervention. Metabolomics analyses were conducted using nuclear magnetic resonance spectroscopy (1H NMR) in a 600 MHz spectrometer. There was a decrease in body weight (BW), body mass index (BMI), waist circumference (WC), % body fat (%BF), fasting glucose, insulin levels, and insulin resistance (IR), by HOMA-IR, in the TG. An increase in fat-free mass (FFM) was also observed in the CG. The metabolic changes were given mainly by changes in the levels of metabolites 2-oxoisocaproate (↓TG), 3-hydroxyisobutyrate (↑CG and ↓TG), glucose (↓TG), glutamine (↓CG and ↑TG) and pyruvate (↓TG). These findings demonstrate the positive effects of CT program without dietary intervention on metabolomic profile, body composition, biochemical markers, and glucose metabolism in overweight and obese adolescents.

Differential effects of vitamin D3 vs vitamin D2 on cellular uptake, tissue distribution and activation of vitamin D in mice and cells

To combat vitamin D deficiency, vitamin D3 and vitamin D2 are commonly used as a supplement or to fortify food sources. Human data show that the response of 25-hydroxyvitamin D (25(OH)D) to supplementation with vitamin D3 is higher than to vitamin D2. To elucidate the metabolic route of both vitamers, we conducted a study with vitamin D-depleted mice, which were allotted into three groups (n = 12) and received equal doses of either deuterated vitamin D3, deuterated vitamin D2 or both for 4 weeks. To further investigate the hepatic uptake and hydroxylation of both D-vitamers to 25(OH)D, we conducted cell culture experiments with murine and human hepatoma cells (Hepa1-6 and HepG2). The vitamin D metabolite concentrations in serum, tissues and cells were analyzed by LC-MS/MS or ELISA.In mice, vitamin D2 resulted in lower serum and tissue concentrations of vitamin D (P < 0.001) than vitamin D3, while the group which received both D-vitamers showed values in between. Interestingly, vitamin D2 fed mice had 1.9-times and 2.9-times higher serum concentrations of total and free 25(OH)D (P < 0.001) than mice fed vitamin D3, while the concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D) was 1.8-times lower (P < 0.001). The gene and protein expression of enzymes, involved in the hydroxylation and renal uptake of vitamin D remained largely unaffected by the D-vitamer. In contrast to the mice data, hepatoma cells preferred vitamin D3 for 25-hydroxylation over vitamin D2 (P < 0.001). In general, the formation of 25(OH)D was much more pronounced in human than in murine hepatoma cells (P < 0.001).To conclude, in contrast to humans, vitamin D2 was more efficient in increasing 25(OH)D than vitamin D3 in mice, although this difference was not caused by a preferential hydroxylation of vitamin D2 in the liver. The metabolic routes of D3 and D2 in mice differ, showing lower circulating 1,25(OH)2D and tissue vitamin D concentrations in D2- than in D3-fed mice.

Inflammatory diseases in dairy cows: Risk factors and associations with pregnancy after embryo transfer

The objectives of the present prospective cohort study were to identify risk factors for inflammatory diseases in Holstein-Gyr crossbred dairy cows and characterize the associations of those diseases with pregnancy per embryo transfer (ET). Diseases were diagnosed in the first 60 d postpartum in 252 primiparous and 481 multiparous cows. Uterine diseases (UTD) included retained placenta, metritis, clinical endometritis, and subclinical endometritis. Nonuterine diseases (NUTD) included mastitis, lameness, pneumonia, and displaced abomasum. Blood was sampled on d 0, 1, and 2 postpartum and analyzed for concentrations of haptoglobin, fatty acids, total Ca (tCa), P, and Mg, and again on d 8 postpartum and analyzed for concentration of β-hydroxybutyrate. The association between concentrations of metabolites in serum and inflammatory diseases was determined. Cows received a timed ET program starting 28 ± 3 d postpartum with first ET at 46 ± 3 d postpartum using fresh in vitro-produced embryos. Pregnancy was diagnosed on d 31 and 59 of presumptive gestation. Overall, 63.3% of the cows were diagnosed with UTD and 20.6% with NUTD. The risk factors for UTD included season of calving, parity group, calving problems, days with subclinical hypocalcemia, and serum concentrations of haptoglobin and Mg, whereas the risk factors for NUTD were parity group and serum Mg concentration. Cows that developed UTD had increased concentrations of haptoglobin on d 2 and fatty acids on d 1 and 2, and reduced concentrations of tCa on d 1 and 2 and of P and Mg on d 2 postpartum compared with cows without UTD. Cows that developed NUTD had increased concentrations of fatty acids on d 0 to 2 postpartum, and decreased concentrations of tCa and P on d 0 and 1, and of Mg on d 1 and 2 postpartum compared with cows without NUTD. Cows that developed NUTD had a 340-kg reduction in milk yield in the first 60 d postpartum. Inflammatory diseases were associated with lesser body condition score and increased loss of body condition in the first 70 d postpartum. Maintenance of pregnancy after ET was reduced in UTD cows following the first (41.7 vs. 25.4%) or all ET (46.4 vs. 36.2%), whereas maintenance of pregnancy was reduced in NUTD cows only at the second ET (39.0 vs 25.9%). The reduced pregnancy maintenance in UTD cows combined with a reduced 21-d service rate (61.9 vs. 54.8%) decreased the 21-d cycle pregnancy rate (28.6 vs. 19.9%) and the hazard of pregnancy to 300 d postpartum by 35%, resulting in an extra 32 d open. In conclusion, inflammatory diseases depressed fertility in dairy cows receiving ET, with the greatest impact observed in UTD cows. This suggests that local inflammation of the uterus impairs maintenance of pregnancy in dairy cows following ET.

Discovery of different metabotypes in overconditioned dairy cows by means of machine learning

Using data from targeted metabolomics in serum in combination with machine learning (ML) approaches, we aimed at (1) identifying divergent metabotypes in overconditioned cows and at (2) exploring how metabotypes are associated with lactation performance, blood metabolites, and hormones. In a previously established animal model, 38 pregnant multiparous Holstein cows were assigned to 2 groups that were fed differently to reach either high (HBCS) or normal (NBCS) body condition score (BCS) and backfat thickness (BFT) until dryoff at -49 d before calving [NBCS: BCS < 3.5 (3.02 ± 0.24) and BFT < 1.2 cm (0.92 ± 0.21), mean ± SD; HBCS: BCS > 3.75 (3.82 ± 0.33) and BFT > 1.4 cm (2.36 ± 0.35)]. Cows were then fed the same diets during the dry period and the subsequent lactation, and maintained the differences in BFT and BCS throughout the study. Blood samples were collected weekly from 7 wk antepartum (ap) to 12 wk postpartum (pp) to assess serum concentrations of metabolites (by targeted metabolomics and by classical analyses) and metabolic hormones. Metabolic clustering by applying 4 supervised ML-based classifiers [sequential minimal optimization (SMO), random forest (RF), alternating decision tree (ADTree), and naïve Bayes-updatable (NB)] on the changes (d 21 pp minus d 49 ap) in concentrations of 170 serum metabolites resulted in 4 distinct metabolic clusters: HBCS predicted HBCS (HBCS-PH, n = 13), HBCS predicted NBCS (HBCS-PN, n = 6), NBCS predicted NBCS (NBCS-PN, n = 15), and NBCS predicted HBCS (NBCS-PH, n = 4). The accuracies of SMO, RF, ADTree, and NB classifiers were >70%. Because the number of NBCS-PH cows was low, we did not consider this group for further comparisons. Dry matter intake (kg/d and percentage of body weight) and energy intake were greater in HBCS-PN than in HBCS-PH in early lactation, and HBCS-PN also reached a positive energy balance earlier than did HBCS-PH. Milk yield was not different between groups, but milk protein percentage was greater in HBCS-PN than in HBCS-PH cows. The circulating concentrations of fatty acids (FA) increased during early lactation in both groups, but HBCS-PN cows had lower concentrations of β-hydroxybutyrate, indicating lower ketogenesis compared with HBCS-PH cows. The concentrations of insulin, insulin-like growth factor 1, leptin, adiponectin, haptoglobin, glucose, and revised quantitative insulin sensitivity check index did not differ between the groups, whereas serum concentrations of glycerophospholipids were lower before calving in HBCS-PH than in HBCS-PN cows. Glycine was the only amino acid that had higher concentration after calving in HBCS-PH than in HBCS-PN cows. The circulating concentrations of some short- (C2, C3, and C4) and long-chain (C12, C16:0, C18:0, and C18:1) acylcarnitines on d 21 pp were greater in HBCS-PH than in HBCS-PN cows, indicating incomplete FA oxidation. In conclusion, the use of ML approaches involving data from targeted metabolomics in serum is a promising method for differentiating divergent metabotypes from apparently similar BCS phenotypes. Further investigations, using larger numbers of cows and farms, are warranted for confirmation of this finding.

Exploration of n-6 and n-3 Polyunsaturated Fatty Acids Metabolites Associated with Nutritional Levels in Patients with Severe Stable Chronic Obstructive Pulmonary Disease.

Background and ObjectiveSevere chronic obstructive pulmonary disease (COPD) is the terminal stage of the disease characterized by declined lung function, malnutrition, and poor prognosis. Such patients cannot tolerate long-time sports rehabilitation owing to dyspnea and fail to achieve the desired therapeutic effect; therefore, increasing nutritional support will be an important strategy for them. The present study applied metabolomics technology to evaluate the correlation between serum concentrations of polyunsaturated fatty acid (PUFA) metabolites, nutritional status, and lung function in patients with COPD to provide a theoretical basis for accurate nutritional support.Materials and MethodsWe enrolled 82 patients with stable severe COPD in our hospital. The general characteristics including height, weight, and lung function were recorded. Metabolomics was used to detect the concentrations of serum metabolites of n-3 and n-6 at baseline and at 24 and 52 weeks after enrollment. The correlations between nutrition level and pulmonary function and clinical indicators were evaluated.ResultsThe concentrations of n-3 and n-6 increased over time along with the progression of COPD. Body mass index (BMI) and percent of ideal body weight (IBW%) decreased with disease development, and BMI was found to be significantly correlated with FEV1% predicted and FEV1/FVC. Serum levels of n-6 metabolites such as linoleic acid (LA), γ-linoleic acid (GLA), and arachidonic acid (ARA) (all P < 0.01) and the n-3 metabolites such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (all P < 0.05) showed significant correlations with BMI and were closely correlated with FEV1% predicted and FEV1/FVC of lung function (all P< 0.05).ConclusionThis study demonstrates that malnutrition in patients with severe COPD is progressive and is positively correlated with n-3 and n-6 polyunsaturated fatty acids and lung function.

Effects of beta-1,3-glucan supplementation on concentrations of serum metabolites in transition Holstein cows

Objectives of this study were to evaluate the alleviating effects of a commercial beta-1,3-glucan product (Aleta, containing 50% beta-1,3-glucan, Kemin Industries) on metabolic stress in transition Holstein cows as reflected by circulating metabolites and enzymes. Fifty-four multiparous Holstein cows were randomly allocated to three groups with 18 cows each. Cows in each group received a commercial basal diet or the basal diet supplemented with Aleta calculated to supply 5 or 10 g of Aleta per cow per day. Blood samples were collected at day −21, 1, and 21 relative to calving for determination of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDLC), very low density lipoprotein (VLDL), glucose, insulin, β-hydroxybutyric acid (BHBA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyl transpeptidase (GGT), and non-esterified fatty acid (NEFA). Supplementation with Aleta markedly elevated serum concentrations of TG, TC, HDLC, LDL-C and VLDL, implying its positive effect on lipid metabolism in transition dairy cows. Aleta treatment significantly decreased the serum concentrations of NEFA and BHBA, but markedly elevated the serum concentrations of glucose and insulin. Also, Aleta treatment significantly elevated the dry matter intake and milk production in postpartum cows, indicating the alleviating effect of Aleta on negative energy balance in transition cows. Moreover, Aleta treatment significantly reduced the serum activities of AST, ALT and GGT, indicating its hepatoprotective effect on transition cows. These results suggest that Aleta supplementation may help to improve fat metabolism disorder initiated by negative energy balance in transition dairy cows.

Serum and fecal profiles of aromatic microbial metabolites reflect gut microbiota disruption in critically ill patients: a prospective observational pilot study

BackgroundHigh serum levels of certain aromatic microbial metabolites (AMM) are associated with severity and mortality in critically ill patients. Omics-based studies suggest gut dysbiosis and reduced microbiome diversity in critical conditions. However, the landscape of gut microbial metabolites is still to be outlined, not to mention the interplay correlation between the metabolome and gut microbiome in critically ill patients. The aim of this study was to analyze the association between serum and fecal levels of AMM and compare them with the composition of gut microbiota in critically ill patients in the acute and chronic stages.MethodsIn this prospective observational pilot study, we analyzed the temporal dynamics of the gut microbiome and the AMM spectrum across two distinct subgroups—acute critical ill (ACI) patients with nosocomial pneumonia and chronically critically ill (CCI) patients (9 subjects each group)—as well as performed comparison with 23 healthy volunteers. The AMM levels for each patient were measured using GC-MS in simultaneously taken serum and fecal samples (SFS). These parameters were compared with 16S rRNA fecal microbiome profiles.ResultsThe observed proportions of bacterial taxa suggest a significant gut dysbiosis in the ACI and the CCI patients. Stronger imbalance in microbiome composition and dynamics observed in the ACI patients compared to the CCI ones resonates with a higher severity in the former group. The total levels of AMM in serum samples were higher for the ACI patients than for the CCI patients (3.7 (1.4–6.3) and 1.1 (1.0–1.6) μM, respectively; p = 0.0003). The qualitative composition of the SFS was also altered. We discovered significant associations between gut microbial taxa levels and metabolite concentrations in blood serum as well as in feces in each of the ACI and the CCI patients.ConclusionsAromatic microbial metabolite profiles in the gut and the serum are interlinked and reflect a disruption of the gut microbial community in critically ill patients.

Personalized Nutrition Recommendations Improve Plasma Metabolite Concentrations Related to Dietary Intake

Abstract Objectives The objectives of our proof-of-concept study was to assess the efficacy of personalized nutrition interventions on diet and chronic disease risk. Methods Fasting plasma samples were collected at day 1 and day 100 of a cohort of 148 adults (aged 23–65y) volunteers with a median (range) BMI of 25.8 (17.2–48.3). At both time points 119 metabolites were quantitated using LC-MS/MS. Based on their metabolite concentrations and dietary preferences, each participant received their own personalized nutrition recommendations through an AI-assisted online platform and were advised to follow the recommendations for 100 days. Plasma metabolite concentrations from Day 1 and Day 100 were compared using a paired t-test with Holm-Bonferroni correction (P &amp;lt; 0.05). Results After 100 days, statistically significant changes in acylcarnitine, phosphatidylcholine and amino acid concentrations indicated participants had increased their intakes of omega-3 fats and whole grains and decreased their intakes of saturated fat. For example, Betaine, a biomarker of whole grain intake, increased significantly in concentration from Day 1 to Day 100 [mean (SD): 34.3 (13.2) to 45.3 (15.6) umol/l]. Overall, 55 of the analyzed 119 metabolites’ (46%) concentrations had previously been linked to dietary intake according to a systematic literature search that was used to generate evidence-based personalized nutrition recommendations. Concentrations of 33 (60%) of these 55 metabolites changed significantly. The majority [26 (79%)] of the metabolite concentrations changed in a predicted manner consistent with the literature, particularly those metabolites associated to chronic disease risk. For example, a significant decrease in asymmetric dimethylarginine concentration [mean (SD): 0.54 (0.15) to 0.48 (0.12) umol/L] which is understood to result in a decreased cardiovascular disease risk. Conclusions Adherence with an evidence-based personalized nutrition plan based on a panel of serum metabolomic data can significantly modify serum metabolite concentrations in a direction that can reduce the risk of chronic disease. Further analysis in how these changes relate to chronic disease risk is warranted. Funding Sources This study was supported by Mitacs and Molecular You.

Metabolomics in endometrial cancer diagnosis: A systematic review.

Endometrial cancer (EC) is the most common gynecological malignancy in the developed world. The prognosis of EC strongly depends on tumor stage, hence the importance of improving diagnosis. Metabolomics has recently appeared as a promising test for a non-invasive diagnosis of several diseases. Nevertheless, no metabolic marker has been approved for use in the routine practice. We aimed to provide an overview of metabolomics findings in the diagnosis of EC. A systematic review was performed by searching eight electronic databases from their inception to October 2019 for studies assessing metabolomics in EC diagnosis. Extracted data included characteristics of patients and EC, serum concentration of metabolites in women with and without EC and its association with EC diagnosis, tumor behavior and pathological characteristics. Six studies with 732 women (356 cases and 376 controls) were included. Several metabolites were found able to predict the presence of EC, tumor behavior (progression and recurrence) and pathological characteristics (histotype, myometrial invasion and lymph vascular space invasion). Metabolomics might be suitable for a non-invasive diagnosis and screening of EC, offering the possibility to predict tumor behavior and pathological characteristics. Further studies are necessary to validate these results.

Relationships between early postpartum nutritional and metabolic profiles and subsequent reproductive performance of lactating dairy cows

The objective of this study was to examine the relationship between early postpartum nutritional and metabolic profiles in lactating dairy cows and subsequent pregnancy to first artificial insemination (AI), pregnancy by 150 d in milk (DIM) and pregnancy loss after first AI. A blood sample was collected between 2 and 14 (median = 9) DIM from 869 lactating Holstein cows to determine serum concentrations of metabolites, minerals, and liver enzymes. Associations between analytes and fertility were determined using an adjusted odds ratio (OR). Overall, pregnancy to first AI, pregnancy by 150 DIM and pregnancy loss after first AI were 37.9, 65.8 and 11.2%, respectively. Compared to cows pregnant to first AI, non-pregnant cows had higher (P < 0.05) serum concentrations of aspartate aminotransferase (AST; 92.3 ± 1.6 vs. 84.6 ± 2.0 U/L), non-esterified fatty acid (NEFA; 0.73 ± 0.02 vs. 0.54 ± 0.02 mmol/L), and haptoglobin (0.77 ± 0.04 vs. 0.60 ± 0.05 g/L), and lower (P < 0.05) serum concentrations of Mg (0.86 ± 0.02 vs. 0.89 ± 0.02 mmol/L) and cholesterol (2.1 ± 0.03 vs. 2.4 ± 0.04 mmol/L). Cows non-pregnant by 150 DIM had lower (P < 0.05) serum concentration of Mg (0.86 ± 0.02 vs. 0.88 ± 0.02 mmol/L) and higher serum concentration of haptoglobin (0.82 ± 0.1 vs. 0.63 ± 0.09 g/L) than cows pregnant by 150 DIM. Cows that lost their pregnancy after first AI had greater serum concentrations of haptoglobin than those that did not undergo pregnancy loss (1.1 ± 0.09 vs. 0.5 ± 0.05 g/L; P < 0.01). The odds of pregnancy to first AI (OR; 95% confidence interval [CI]) decreased with increased serum concentrations of AST (OR = 0.99; 95% CI = 0.98–1.00), NEFA (OR = 0.54; 95% CI = 0.37–0.79) and haptoglobin (OR = 0.80; 85% CI = 0.66–0.96) and increased with inreased concentrations of Mg (OR = 3.24; 95% CI = 1.09–9.62) and cholesterol (OR = 1.24; 95% CI = 1.02–1.54). Increased serum concentrations of Mg (OR = 3.06; 95% CI = 1.02–9.20) and haptoglobin (OR = 0.92; 95% CI = 0.69–0.97) were associated with greater and lower odds of pregnancy by 150 DIM, respectively. Only increased concentrations of haptoglobin (OR = 1.58; 95% CI = 1.13–2.20) were associated with increased odds of pregnancy loss after the first AI. In summary, greater early postpartum serum concentrations of AST, NEFA and haptoglobin were associated with reduced fertility, but the opposite was observed for serum concentrations of Mg and cholesterol. In addition, serum concentrations of haptoglobin were positively associated with pregnancy loss.

Blood Metabolite Signatures of Metabolic Syndrome in Two Cross-Cultural Older Adult Cohorts.

Metabolic syndrome (MetS) affects an increasing number of older adults worldwide. Cross-cultural comparisons can provide insight into how factors, including genetic, environmental, and lifestyle, may influence MetS prevalence. Metabolomics, which measures the biochemical products of cell processes, can be used to enhance a mechanistic understanding of how biological factors influence metabolic outcomes. In this study we examined associations between serum metabolite concentrations, representing a range of biochemical pathways and metabolic syndrome in two older adult cohorts: The Tsuruoka Metabolomics Cohort Study (TMCS) from Japan (n = 104) and the Baltimore Longitudinal Study of Aging (BLSA) from the United States (n = 146). We used logistic regression to model associations between MetS and metabolite concentrations. We found that metabolites from the phosphatidylcholines-acyl-alkyl, sphingomyelin, and hexose classes were significantly associated with MetS and risk factor outcomes in both cohorts. In BLSA, metabolites across all classes were uniquely associated with all outcomes. In TMCS, metabolites from the amino acid, biogenic amines, and free fatty acid classes were uniquely associated with MetS, and metabolites from the sphingomyelin class were uniquely associated with elevated triglycerides. The metabolites and metabolite classes we identified may be relevant for future studies exploring disease mechanisms and identifying novel precision therapy targets for individualized medicine.

1H NMR Based Metabolomics in Human Sepsis and Healthy Serum.

Early diagnosis is essential but challenging in severe sepsis. Quantifying and comparing metabolite concentrations in serum has been suggested as a new diagnostic tool. Here we used proton nuclear magnetic resonance spectroscopy (1H NMR) based metabolomics to analyze the possible differences in metabolite concentrations between sera taken from septic patients and healthy controls, as well as between sera of surviving and non-surviving sepsis patients. We took serum samples from 44 sepsis patients when the first sepsis induced organ dysfunction was found. Serum samples were also collected from 14 age and gender matched healthy controls. The samples were analyzed by quantitative 1H NMR spectroscopy for non-lipid metabolites. We found that the serum levels of glucose, glycine, 3-hydroxybutyrate, creatinine and glycoprotein acetyls (mostly alpha-1-acid glycoprotein, AGP) were significantly (p < 0.05) higher in sepsis compared to healthy sera, whereas citrate and histidine were significantly (p < 0.05) lower in sepsis patients compared to healthy controls. We found statistically significantly higher serum lactate and citrate concentrations in non-survivors compared to 30-day survivors. According to our study, 3-hydroxybutyrate, citrate, glycine, histidine, and AGP are candidates for further studies to enable identification of phenotype association in the early stages of sepsis.

The study of tryptophan metabolite concentrations in blood serum and fecal extracts from obese children

We found that changes in the concentrations of tryptophan metabolites in the blood serum and in the intestinal contents are one of the mechanisms for the formation of metabolic coupling in the system "macroorganism-intestinal microbiota", which undergoes significant changes in the development of obesity. Although blood kynurenine remained basically unchanged in obese children we found an increase in some of its serum metabolites: anthranilic, kynurenic and xanthurenic acids. It is noteworthy that in the analysis of fecal matter in obese children, revealed a 2-fold increase in the level of kynurenine while the concentration of kynurenine pathway metabolites corresponded to the level of the group of healthy children. This may indicate the metabolic activation of the microbiota associated with the intestinal mucosa. This is also supported by the absence of statistically significant differences in the concentration of indole in healthy children and in obese children in fecal analyses, and a significant increase in the concentration of indole-3-lactate and indole-3-acetate in the blood serum of obese children.

METHOTREXATE METABOLISM AND BILIRUBIN LEVELS AS PREDICTORS OF ORAL MUCOSITIS IN PEDIATRIC ONCOLOGIC PATIENTS

Objective To evaluate the relation of oral mucositis (OM) with time of methotrexate (MTX) metabolism and levels of bilirubin (BB). Study Design 146 cycles of chemotherapy with MTX in high doses (>1.0 g/m2) were evaluated in patients aged 0 to 18 years. Several information were collected such as dose of MTX infused, OM grade from D1 to D15, total BB levels and MTX serum metabolite concentration. Pearson multiple comparisons correlation test and Spearman test adjusted for the correlations between the times were used. Results Patients who received doses above 8 g/m2 of MTX presented more than 72 hours to metabolize it (P = .003). In addition, longer time to metabolize MTX was associated with ulcerated lesions of OM (P = .017). A relation between BB increasing and higher severity of OM (grade 3 and 4) was observed (P = .004). Conclusions Serum metabolite concentration of MTX and BB should be monitored as relative predictors of higher OM risk. To evaluate the relation of oral mucositis (OM) with time of methotrexate (MTX) metabolism and levels of bilirubin (BB). 146 cycles of chemotherapy with MTX in high doses (>1.0 g/m2) were evaluated in patients aged 0 to 18 years. Several information were collected such as dose of MTX infused, OM grade from D1 to D15, total BB levels and MTX serum metabolite concentration. Pearson multiple comparisons correlation test and Spearman test adjusted for the correlations between the times were used. Patients who received doses above 8 g/m2 of MTX presented more than 72 hours to metabolize it (P = .003). In addition, longer time to metabolize MTX was associated with ulcerated lesions of OM (P = .017). A relation between BB increasing and higher severity of OM (grade 3 and 4) was observed (P = .004). Serum metabolite concentration of MTX and BB should be monitored as relative predictors of higher OM risk.

Alcohol consumption and serum metabolite concentrations in young women.

Alcohol consumption is an established breast cancer risk factor, though further research is needed to advance our understanding of the mechanism underlying the association. We used global metabolomics profiling to identify serum metabolites and metabolic pathways that could potentially mediate the alcohol-breast cancer association. A cross-sectional analysis of reported alcohol consumption and serum metabolite concentrations was conducted among 211 healthy women 25-29years old who participated in the Dietary Intervention Study in Children 2006 Follow-Up Study (DISC06). Alcohol-metabolite associations were evaluated using multivariable linear mixed-effects regression. Alcohol was significantly (FDR p < 0.05) associated with several serum metabolites after adjustment for diet composition and other potential confounders. The amino acid sarcosine, the omega-3 fatty acid eicosapentaenoate, and the steroid 4-androsten-3beta,17beta-diol monosulfate were positively associated with alcohol intake, while the gamma-tocopherol metabolite gamma-carboxyethyl hydroxychroman (CEHC) was inversely associated. Positive associations of alcohol with 2-methylcitrate and 4-androsten-3beta,17beta-diol disulfate were borderline significant (FDR p < 0.10). Metabolite set enrichment analysis identified steroids and the glycine pathway as having more members associated with alcohol consumption than expected by chance. Most of the metabolites associated with alcohol in the current analysis participate in pathways hypothesized to mediate the alcohol-breast cancer association including hormonal, one-carbon metabolism, and oxidative stress pathways, but they could also affect risk via alternative pathways. Independent replication of alcohol-metabolite associations and prospective evaluation of confirmed associations with breast cancer risk are needed.

PSIII-40 Dietary effects on food intake, body weight, body composition and metabolism of adult female cats after spay surgery

Abstract Spay and neuter surgeries are common procedures to control the pet population, but have been associated with increased risk for obesity due to changes in appetite, decreased metabolic rate, and decreased energy expenditure. Dietary management post-spay could help decrease obesity risk, but few research studies have been conducted on cats following spay surgery. Therefore, the objective of this study was to evaluate the effects of a high-protein, high-fiber diet (HPHF) vs. a moderate-protein, moderate-fiber diet (MPMF) in female cats following spay surgery. Twenty healthy female cats (9.5±0.1 months old) were used. After a 5-wk baseline phase with cats fed MPMF to maintain BW, 16 cats were spayed and randomly allotted to MPMF (n = 8) or HPHF (n = 8), with the remaining cats being sham-operated and fed MPMF (n = 4). Cats were fed to maintain BW for 12 wk, then fed up to twice that amount during the subsequent 12 wk of study. Daily food intake, twice weekly BW and twice weekly BCS were assessed. Body composition using DEXA, serum metabolite concentrations, and voluntary physical activity levels were measured prior to spay (wk 0) and every 6 wk post-spay. A treatment*time effect was observed for food intake (g/d), but not caloric intake (kcal ME/d). Caloric intake was affected by time and treatment effects, being reduced over the first 12 wk and reduced at higher amounts in HPHF and MPMF cats vs. sham cats. BW, BCS and body fat percentage were affected over time. A treatment*time effect was observed for blood urea nitrogen, ALP, and fructosamine, while blood triglycerides, total cholesterol, creatinine, total protein, phosphorus, and bicarbonate were affected by time. Physical activity was also reduced over time. Our results demonstrate that spay surgery affects food intake, BW, metabolism, and physical activity in cats. Dietary intervention in this study, however, led to minor changes.

PSII-13 Effects of antibiotics on serum metabolomic profiles in weanling pigs experimentally infected with a pathogenic E. coli

Abstract Our previous studies have shown that exposure to low-dose antibiotic growth promoter (AGP) may exacerbate the negative effects of Escherichia coli (E. coli) infection on weaned pigs. The objective of this experiment was to investigate the effects of low-dose AGP on serum metabolomic profiles of weaned pigs experimentally infected with F18 E. coli. Thirty-four pigs (6.88 ± 1.03 kg BW) were individually housed in disease containment rooms and randomly allotted to one of three treatments with 9–13 replicate pigs per treatment. The three dietary treatments were control diet (control) and 2 additional diets supplemented with 0.5 or 50 mg/kg of AGP (carbadox), respectively. The experiment lasted 18 d [7 d before and 11 d after first inoculation (d 0)]. The F18 E. coli inoculum was orally provided to all pigs with the dose of 1010 cfu/3 mL for 3 consecutive days. Blood samples were collected on d 0 before E. coli inoculation and on d 5 and 11 post-inoculation (PI). Serum metabolomics were analyzed for untargeted metabolomics by gas chromatography-time of flight-mass spectrometer (GC-TOF-MS). All processed data were statistically analyzed and evaluated by online MetaboAnalyst tool. No significant differences were observed in serum metabolites between control and low-dose AGP throughout the experiment. Supplementation of high-dose AGP changed the concentrations of several serum metabolites (P &amp;lt; 0.05; arabitol, guanine, and xylitol) compared with control pigs on d 5 PI. Further metabolic pathway enrichment analysis showed that low-dose AGP modified (P &amp;lt; 0.05) pentose phosphate pathway, DNA synthesis in T and B lymphocytes, bile acid metabolism, and amino acid metabolism in E. coli infected pigs, compared with high-dose AGP. In conclusion, the modification of serum metabolites and metabolic pathways by low-dose AGP may be involved in reduced growth performance, exacerbated diarrhea and systemic inflammation of weaned pigs induced by E. coli infection.

The effect of an organic rumen-protected fat supplement on performance, metabolic status, and health of dairy cows

BackgroundNegative energy balance during the transition period is a concern for both conventional and certified organic dairy systems. During early lactation, supplemental strategies are used to cope with nutrient deficiencies that are associated with impaired health, production, and reproduction. As organic certified dairies in the United States face restricted access to dietary supplements, the evaluation of products especially formulated for organic production is needed. Our objective was to assess the effect of supplementing 0.45 kg/d of an organic rumen-protected fat (RPF) on health, metabolic status, and productive and reproductive performance of organic certified Holstein cows from 1 to 150 days in milk (DIM). Two-hundred and two cows were enrolled in a randomized blocked controlled trial conducted from January to July 2017 in a certified organic dairy located in Northern Colorado (USA). Two groups were randomly assigned to be individually supplemented with organic RPF (ORG; n = 100) or control pellets (CON; n = 102) once per day, in addition to the total mixed ration (TMR). Outcomes of interest included milk yield (kg/d) and milk components, serum concentration of glucose, and non-esterified fatty acids (NEFA), resumption of cyclicity, time-to-first artificial insemination (AI), conception at first AI, and conception within 150 DIM, disease occurrence, culling, mortality.ResultsA significant effect for the inclusion of RPF was found in daily milk yield; RPF supplemented cows had greater milk yield (1.6 kg/d) compared to CON cows up to 150 DIM (P = 0.03). During grazing, multiparous (MP) ORG cows had greater milk yield compared to MP CON cows, whereas no effect was found in primiparous (PP) cows. Health outcomes, serum metabolite concentrations, and reproductive performance were not affected by the inclusion of RPF. Body condition loss was smaller in the ORG group up to 80 DIM; however, there was no effect on body condition during the grazing season and in the overall study period.ConclusionsThese results indicate that supplementation of RPF increased daily milk yield and prevented body condition loss during at 90 DIM. However, RPF supplementation did not affect health, serum metabolite concentration, milk components, and reproductive outcomes.

The Relationship between Uterine, Fecal, Bedding, and Airborne Dust Microbiota from Dairy Cows and Their Environment: A Pilot Study.

Simple SummaryAfter calving, dairy cows face the risk of negative energy balance, inflammation, and immunosuppression, which may result in bacterial infection and disruption of the normal microbiota, thus encouraging the development of metritis and endometritis. This study characterized uterine, fecal, bedding, and airborne dust microbiota from postpartum dairy cows and their environment during summer and winter. The results clarify the importance of microbiota in cowshed environments, i.e., bedding and airborne dust, in understanding the postpartum uterine microbiota of dairy cows. The aim of this study was to characterize uterine, fecal, bedding, and airborne dust microbiota from postpartum dairy cows and their environment. The cows were managed by the free-stall housing system, and samples for microbiota and serum metabolite assessment were collected during summer and winter when the cows were at one and two months postpartum. Uterine microbiota varied between seasons; the five most prevalent taxa were Enterobacteriaceae, Moraxellaceae, Ruminococcaceae, Staphylococcaceae, and Lactobacillaceae during summer, and Ruminococcaceae, Lachnospiraceae, Bacteroidaceae, Moraxellaceae, and Clostridiaceae during winter. Although Actinomycetaceae and Mycoplasmataceae were detected at high abundance in several uterine samples, the relationship between the uterine microbiota and serum metabolite concentrations was unclear. The fecal microbiota was stable regardless of the season, whereas bedding and airborne dust microbiota varied between summer and winter. With regards to uterine, bedding, and airborne dust microbiota, Enterobacteriaceae, Moraxellaceae, Staphylococcaceae, and Lactobacillaceae were more abundant during summer, and Ruminococcaceae, Lachnospiraceae, Bacteroidaceae, and Clostridiaceae were more abundant during winter. Canonical analysis of principal coordinates confirmed the relationship between uterine and cowshed microbiota. These results indicated that the uterine microbiota may vary when the microbiota in cowshed environments changes.

Concentrations of Blood Serum and Urinal Ellagitannin Metabolites Depend Largely on the Post-Intake Time and Duration of Strawberry Phenolics Ingestion in Rats

Concentrations of Blood Serum and Urinal Ellagitannin Metabolites Depend Largely on the Post-Intake Time and Duration of Strawberry Phenolics Ingestion in Rats