Betaine Levels Research Articles

Changes in Trimethylamine-N-oxide Levels in Obese Patients following Laparoscopic Roux-en-Y Gastric Bypass or Sleeve Gastrectomy in a Korean Obesity Surgical Treatment Study (KOBESS).

Trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite, has been implicated as a novel risk factor for cardiovascular events related to obesity and type 2 diabetes mellitus (T2DM). The aim of the study was to test the hypothesis if TMAO is associated with the reduction of cardiovascular disease in the Korean obese patients who underwent bariatric surgery. From a subgroup of a multicenter, nonrandomized, controlled trial, titled KOBESS, 38 obese patients, 18 with and 20 without T2DM, who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were investigated. Bariatric surgery is indicated for Korean patients with a body mass index (BMI) ≥ 35 kg/m2 or for Korean patients with a BMI ≥ 30 kg/m2 who have comorbidities. Serum levels of TMAO and its precursors, betaine, carnitine, and choline were measured before and six months after bariatric surgery. The levels of TMAO and its precursors did not differ between obese patients with T2DM and non-T2DM at baseline. However, TMAO increased more than twofold in patients with T2DM after RYGB surgery, but not in patients without T2DM. Choline levels were decreased by half in all patients after RYGB. In patients with T2DM who underwent SG, TMAO, betaine, and carnitine levels did not change after the surgery. Furthermore, in obese patients who underwent bariatric surgery, increased TMAO levels were associated with both T2DM and RYGB, while reduced choline levels were associated with RYGB. These associations need to be further elucidated in follow-up studies to gain further insights into the relationship between TMAO levels and bariatric surgery outcomes.

Gut Microbiome-Dependent Metabolic Pathways and Risk of Lethal Prostate Cancer: Prospective Analysis of a PLCO Cancer Screening Trial Cohort.

Diet and the gut microbiome have a complex interaction that generates metabolites with an unclear effect on lethal prostate cancer risk. Identification of modifiable risk factors for lethal prostate cancer is challenging given the long natural history of this disease and difficulty of prospectively identifying lethal cancers. Mass spectrometry was performed on baseline serum samples collected from 173 lethal prostate cancer cases and 519 controls enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial. Baseline serum levels of choline, carnitine, betaine, γ-butyrobetaine, crotonobetaine, phenylacetylglutamine, hippuric acid, and p-cresol sulfate were quantified and analyzed by quartile. Conditional multivariable logistic regression analysis associated analyte levels with lethal prostate cancer incidence after adjusting for body mass index and PSA. The Cochran-Armitage test evaluated analyte level trends across quartiles. Relative to those in the first quartile, cases with the highest baseline levels of choline (Q4 OR: 2.19; 95% CI, 1.23-3.90; P-trend: 0.005) and betaine (Q4 OR: 1.86; 95% CI, 1.05-3.30; P-trend: 0.11) exhibited increased odds of developing lethal prostate cancer. Higher baseline serum levels of phenylacetylglutamine (Q4 OR: 2.55; 95% CI, 1.40-4.64; P-trend: 0.003), a gut microbiome metabolite of phenylalanine with adrenergic activity, were also associated with lethal prostate cancer. Baseline serum levels of one-carbon methyl donors and adrenergic compounds resulting from human and gut microbiota-mediated metabolism are associated with increased lethal prostate cancer risk. Dietary composition, circulating metabolite levels, and downstream signaling pathways may represent modifiable risk factors associated with incident lethal prostate cancer. Beta-adrenergic blockade represents an additional target for oncologic risk reduction.

Assessment of betaine content in commercial cow and goat milk

Betaine is a cytoplasmic osmolyte and a methyl group donor in many biochemical pathways. It exhibits numerous beneficial biological effects and has shown health benefits against some common chronic metabolic and degenerative diseases. In humans, it is obtained mostly from the diet, but it can also be endogenously synthesised by choline oxidation. Although betaine is a valuable human nutrient, information concerning its concentration in milk is still limited. Therefore, the aim of the present work was to quantify and compare the betaine content in commercial cow and goat milk. The betaine content was estimated using a simple isocratic HPLC-UV method following derivatisation with 4-bromophenacyl bromide. The sample pre-treatment included deproteinisation with 0.3% trifluoroacetic acid in acetonitrile. Betaine concentrations in cow milk ranged from 5.56 mg/L in milk with 0.5% fat, to 8.14 mg/L in milk with 2.8% fat. A positive but not significant relationship between fat and the betaine content in milk (r = 0.43) was observed. The average betaine concentration in commercial cow milk (7.21 mg/L) was in line with the results of previous studies. On the other hand, the average level of betaine in commercial goat milk was three times greater (22.82 mg/L). As far as the authors are aware, there are no published results of the betaine content in goat milk, and the present work is the first in this field. The present work demonstrated that the application of a simple and efficient sample pre-treatment and the HPLC-UV method for betaine determination allows for its successful quantification in milk.

Grading of endometrial cancer using 1H HR-MAS NMR-based metabolomics

The tissue metabolomic characteristics associated with endometrial cancer (EC) at different grades were studied using high resolution (400 MHz) magic angle spinning (HR-MAS) proton spectroscopy. The metabolic profiles were obtained from 64 patients (14 with grade 1 (G1), 33 with grade 2 (G2) and 17 with grade 3 (G3) tumors) and compared with the profile acquired from 10 patients with the benign disorders. OPLS-DA revealed increased valine, isoleucine, leucine, hypotaurine, serine, lysine, ethanolamine, choline and decreased creatine, creatinine, glutathione, ascorbate, glutamate, phosphoethanolamine and scyllo-inositol in all EC grades in reference to the non-transformed tissue. The increased levels of taurine was additionally detected in the G1 and G2 tumors in comparison to the control tissue, while the elevated glycine, N-acetyl compound and lactate—in the G1 and G3 tumors. The metabolic features typical for the G1 tumors are the increased dimethyl sulfone, phosphocholine, and decreased glycerophosphocholine and glutamine levels, while the decreased myo-inositol level is characteristic for the G2 and G3 tumors. The elevated 3-hydroxybutyrate, alanine and betaine levels were observed in the G3 tumors. The differences between the grade G1 and G3 malignances were mainly related to the perturbations of phosphoethanolamine and phosphocholine biosynthesis, inositol, betaine, serine and glycine metabolism. The statistical significance of the OPLS-DA modeling was also verified by an univariate analysis. HR-MAS NMR based metabolomics provides an useful insight into the metabolic reprogramming in endometrial cancer.

Drought Stress Alleviation by Potassium-Nitrate-Containing Chitosan/Montmorillonite Microparticles Confers Changes in Spinacia oleracea L.

Drought and low amounts of mineral nutrients in the soil are the two leading global constraints in arid and semiarid regions. Their detrimental effects on soils and crops can be alleviated by applying controlled release and biodegradable fertilizers to better and sustain the crops. On a global scale, spinach (Spinacia oleracea L.) is an essential leafy green vegetable that is biologically considered a reliable source of essential nutrients and minerals for human health. A comprehensive approach is needed to manage water stress to mitigate the impacts of stress-caused damage and to examine this for better and increased plant production. An experiment was conducted using potassium-nitrate-containing chitosan/montmorillonite microparticles (150 mg) under mild and severe drought stress (MDS: 50% and SDS: 35% FC, respectively). The treatments include control (no KNO3 and 70% FC as normal irrigation (NI)), KNO3 + NI, 50% FC as mild drought stress (MDS), KNO3 + MDS, 35% FC as severe drought stress (SDS) and KNO3 + SDS. Results revealed that drought stress decreased all studied physiological parameters and increased oxidative stress indicators in spinach. Applying KN significantly increased root (122%) and shoot length (4%), shoot fresh weight (32%) and shoot dry weight (71%), chlorophyll a (88%), carotenoids (39%), total soluble proteins (50%), soluble sugars (51%), potassium (80%), and phosphorous (32%) concentrations over No KN at severe drought. While stress indicators, like glycine betaine, malondialdehyde, hydrogen peroxide, electrolyte leakage, peroxidase, superoxide dismutase, and ascorbic acid levels, were increased in stress. Treatment KN was proved efficient and effective in improving spinach physiological status in both MDS and SDS.

Dietary supplementation of betaine promotes lipolysis by regulating fatty acid metabolism in geese

Supplementation of betaine in the diet appears to regulate fatty acid metabolism and decrease fat deposition. This study aims to identify the effects of dietary supplementation of betaine on zootechnical performance, fatty acid synthesis, abdominal fat deposition, and morphology. Three hundred healthy, male, one-day-old Jiangnan White geese of similar body weight were randomly divided into 5 groups, with 6 replicates per treatment and 10 geese per replicate, and given the following amounts of supplementary betaine: 0 (group A), 600 mg/kg (group B), 1,200 mg/kg (group C), 1,800 mg/kg (group D), or 2,400 mg/kg (group E). Feed intake (FI), body weight (BW), abdominal fat and sebum thickness, clinical blood parameters, hepatic enzyme activity, and abdominal fat morphology were monitored during the experiment. All geese had free access to feed and water throughout the study. Our results indicate that supplementation of betaine increased zootechnical performance at 21 and 42 d of age. The percentage of abdominal fat and sebum thickness of geese at 63 d of age decreased linearly with the addition of betaine (P < 0.05). The triglyceride (TG) and total cholesterol (TCHOL) content of serum decreased with the increased level of betaine when measured at 63 d of age (P<0.05). Hormone sensitive lipase (HSL) increased with the level of betaine (P<0.05). However, dietary betaine appeared to decrease the activity of fatty acid synthase (FAS) in the geese at 42 d and 63 d of age (P<0.05). The percentage of total area of lipid droplet decreased with the increased level of betaine supplementation. In conclusion, dietary supplementation of betaine increased lipolysis and decreased fat deposition in the finishing period of geese via reducing feed intake. However, the precise mode-of–action is yet unclear and warrants further research.

Dietary Intake Adequacy and Food Sources of Nutrients Involved in the Methionine-Methylation Cycle in Women of Childbearing Age from the ANIBES Spanish Population.

Growing evidence confirms choline as a critical perinatal nutrient. However, intake levels of choline and betaine among the Spanish fertile population remain unknown. Given their role in one-carbon metabolism with potential epigenetic effects, the aim of the present study was to evaluate the dietary intakes, their adequacy to existing guidelines and the main food sources together with other micronutrients involved in the methylation-methionine cycle (vitamin B6, folates and vitamin B12) in women of childbearing age. The ANIBES study, a cross-sectional study of a representative sample of women of childbearing age (18–45 years, n = 641) resident in Spain, was used. The sample was divided into younger women (18–30 years, n = 251) and older women (31–45 years, n = 390). Dietary intake was assessed by a three-day dietary record by using a tablet device. Total median intakes for the total sample were 303.9 mg/d for choline; 122.6 mg/d for betaine; 1.3 mg/d for vitamin B6; 140.8 μg/d for folates, and 3.8 μg/d for vitamin B12. The older subgroup showed significantly higher choline (p < 0.05), betaine (p < 0.001) and folates (p < 0.05) intakes than younger women. Main food sources for the whole sample were meat and meat products for choline (28.3%), vitamin B6 (25.7%) and vitamin B12 (22.8%); cereals and derivatives (79.9%) for betaine; vegetables (20.0%) for folates. Overall intake adequacy was only observed for vitamin B12, with a very limited number of participants showing adequate intakes for all the other micronutrients. These results illustrate there is a relevant need to raise awareness about optimizing the status of the methionine cycle-related vitamins and cofactors in this potentially vulnerable population.

Resistant Starch Type-2 Supplementation Does Not Decrease Trimethylamine N-Oxide (TMAO) Plasma Level in Hemodialysis Patients

Purpose: Dysbiosis is recognized as a new cardiovascular disease (CVD) risk factor in hemodialysis (HD) patients because it is linked to increased generation in the gut of uremic toxins such as trimethylamine N-Oxide (TMAO) from dietary precursors (choline, betaine, or L-carnitine). Nutritional strategies have been proposed to modulate the gut microbiota and reduce the production of these toxins. This study aimed to evaluate the effect of amylose-resistant starch (RS) supplementation on TMAO plasma levels in HD patients. Methods: We conducted a randomized, double-blind, placebo-controlled trial (NCT02706808) with patients undergoing HD enrolled in a previous pilot study. The participants were allocated to RS or placebo groups to receive 16 g/d of RS or placebo for 4 weeks. Plasma TMAO, choline, and betaine levels were measured with LC-MS/MS. Fecal microbiome composition was evaluated by 16S ribosomal RNA sequencing, followed by a search for TMA-associated taxa. Anthropometric, routine biochemical parameters, and food intake were evaluated. Results: Twenty-five participants finished the study, 13 in the RS group, and 12 in the placebo group. RS supplementation did not reduce TMAO plasma levels. Moreover, no significant alterations were observed in choline, betaine, anthropometric, biochemical parameters, or food intake in both groups. Likewise, RS was not found to exert any influence on the proportion of potential TMA-producing bacterial taxa in fecal matter. Conclusion: RS supplementation did not influence plasma TMAO, choline, betaine, or fecal taxa potentially linked to TMAO. Thus, RS does not seem to modify the TMA-associated bacterial taxa, precursors of TMAO. Supplemental data for this article is available online at https://doi.org/10.1080/07315724.2021.1967814 .

Unraveling the hepatoprotective effects of blueberries in a hypercaloric diet-induced rat model of prediabetes by metabolomic and transcriptomic approaches

Abstract Background We previously described protective effects of blueberry juice (BJ) against hepatic steatosis evolution in a hypercaloric diet-induced rat model of prediabetes; however, the underlying mechanisms, are still scarcely explored. Herein, we aim to elucidate the molecular pathways underpinning BJ hepatoprotection on the dysmetabolism evolution in a rat model of prediabetes. Methods A rat model of evolutive prediabetes [Male Wistar rats, 8 weeks old] was developed by ingestion of a high-sucrose (HSu, 35%) diet for 9 weeks (W9), supplemented with a high-fat diet (HF, 60%) for further 14 weeks (HSuHF, W23), vs control with standard diet. Half of the animals (n = 10/group) daily received BJ (25g/Kg BW, orally) between W9 and W23. Along with metabolic characterization, BJ effects on serum and hepatic metabolic surrogates were elucidated using a 1H NMR based metabolomic approach. Moreover, the liver expression of genes (RT-PCR) involved in insulin signaling, lipid metabolism, inflammatory response and mitochondrial respiration was also explored. Values are means ± S.E.M (ANOVA followed by post-hoc tests). Results HSuHF+BJ rats restored hepatic levels of betaine and tend to recover the depletion of glutathione content found in HSuHF animals’ livers. Moreover, BJ positively affected the hepatic mRNA expression of key enzymes and mediators involved in fatty acid oxidation, insulin signalling, inflammatory response, as well as mitochondrial respiratory chain-related genes, which were all downregulated (P &amp;lt; 0.05) in HSuHF animals’ livers. Conclusions Altogether, these molecular findings contribute to explain the mechanisms by which BJ elicits protection against hepatic steatosis and mitochondrial dysfunction induced by hypercaloric diets in the frame of prediabetes evolution.

Differential metabolism of choline supplements in adult volunteers

BackgroundAdequate intake of choline is essential for growth and homeostasis, but its supply does often not meet requirements. Choline deficiency decreases phosphatidylcholine (PC) and betaine synthesis, resulting in organ pathology, especially of liver, lung, and brain. This is of particular clinical importance in preterm infants and cystic fibrosis patients. We compared four different choline supplements for their impact on plasma concentration and kinetics of choline, betaine as a methyl donor and trimethylamine oxide (TMAO) as a marker of bacterial degradation prior to absorption.MethodsProspective randomized cross-over study (1/2020–4/2020) in six healthy adult men. Participants received a single dose of 550 mg/d choline equivalent in the form of choline chloride, choline bitartrate, α-glycerophosphocholine (GPC), and egg-PC in randomized sequence at least 1 week apart. Blood was taken from t = − 0.1–6 h after supplement intake. Choline, betaine, TMAO, and total PC concentrations were analyzed by tandem mass spectrometry. Results are shown as medians and interquartile range.ResultsThere was no difference in the AUC of choline plasma concentrations after intake of the different supplements. Individual plasma kinetics of choline and betaine differed and concentrations peaked latest for PC (at ≈3 h). All supplements similarly increased plasma betaine. All water-soluble supplements rapidly increased TMAO, whereas egg-PC did not.ConclusionAll supplements tested rapidly increased choline and betaine levels to a similar extent, with egg-PC showing the latest peak. Assuming that TMAO may have undesirable effects, egg-PC might be best suited for choline supplementation in adults.Study registrationThis study was registered at “Deutsches Register Klinischer Studien” (DRKS) (German Register for Clinical Studies), 17.01.2020, DRKS00020454.

Integration of FGF21 Signaling and Metabolomics in High-Fat Diet-Induced Obesity.

Sex differences in obesity have been well established, but the metabolic mechanism underlying these differences remains unclear. In the present study, we determined the expression levels of endogenous fibroblast growth factor 21 (FGF21) and its related receptors in male and female mice that were fed a high-fat diet (HFD) for 12 weeks. We also analyzed the metabolic changes in serum and livers using a nuclear magnetic resonance-based metabolomics approach. Reverse transcription polymerase chain reaction and western blotting results revealed that the levels of FGFR1, FGFR2, and co-factor β-klotho were upregulated in female mice to alleviate FGF21 resistance induced by HFD. The metabolomics results demonstrated that the serum and liver metabolic patterns of HFD-fed male mice were significantly separated from those of the female HFD-fed group and the normal diet group. Furthermore, low-density lipoprotein/very low density lipoprotein and betaine levels were associated with the resistance of exogenous HFD in female mice. These findings imply that sex-based differences in metabolism and susceptibility to obesity might be mediated by the FGF21 signaling pathway.

Comparison of Associations between One-Carbon Metabolism, Lipid Metabolism, and Fatty Liver Markers in Normal-Weight and Overweight People Aged 20–40 Years

The aim of the present study was to compare biomarkers of one-carbon metabolism (OCM), lipid metabolism, and fatty liver in people with normal and increased body weight. The study was performed on 421 participants, aged 20–40 years, enrolled in Poznan, Poland, in 2016–2018. Choline and betaine intakes were assessed. DNA samples were genotyped for polymorphisms of phosphatidylethanolamine N-methyltransferase (PEMT; rs7946 and rs12325817), methylene tetrahydrofolate reductase (MTHFR; rs180113), methylenetetrahydrofolate dehydrogenase (MTHFD1; rs2236225), and dihydrofolate reductase (DHFR; rs70991108). To assess the associations between blood metabolites (choline, betaine, folate, L-carnitine, o-acetyl-L-carnitine, and trimethylamine N-oxide]), circulating lipids, and fatty liver indices, multiple logistic regression analyses were performed. Overweight/obese participants had 5.8% higher choline (p < 0.05) and 10% higher L-carnitine (p < 0.001) levels than normal-weight subjects. Serum folate and betaine levels were associated with lower total cholesterol (p < 0.001 and p < 0.05), low-density lipoprotein (LDL) cholesterol (p < 0.001 and p < 0.05, respectively), triacylglycerols (p < 0.01 and p < 0.001), and triglyceride glucose index (p < 0.001 and p < 0.01, respectively), though only in overweight/obese people. The PEMT rs12325817 CC genotype was associated with higher levels of high-density lipoprotein (HDL) cholesterol (p < 0.01) in overweight/obese people. The associations between OCM markers, fatty liver indices, and blood lipids differ in subjects with normal and excessive body weight.

UPLC-MS/MS-based profiling of 31 neurochemicals in the mouse brain after treatment with the antidepressant nefazodone

Depression, typically understood as a mental disorder, is characterized by monoamine neurotransmitter deficiencies in the central nervous system (CNS). A majority of antidepressants have been developed to increase endogenous levels of monoamine neurotransmitters, such as dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in brain tissue. Increasingly, the critical effects of a variety of neurotransmitters, including those of the dopaminergic, serotonergic, kynurenergic, cholinergic, histaminergic, and GABAergic systems, as well as several amino acids, have been spotlighted as neuromodulators over the years in various behavioral and emotional responses. In the present study, we developed a simple method for simultaneous analysis of 31 neurochemicals in mouse whole brain tissue using liquid chromatography tandem mass spectrometry (LC-MS/MS). Our neurochemical profiles were classified into seven categories according to metabolic pathways composed of neurotransmitters and their precursors or metabolites. The analytical method was validated by intra- and inter-day precision, accuracy, sensitivity, and selectivity, and finally applied for neurochemical profiling in the mouse brain following nefazodone treatment. In this study, the modulation of 5-HT and DA by nefazodone was confirmed in the mouse brain, as previously reported. Interestingly, nefazodone-induced broad-spectrum neurochemical changes could suggest that nefazodone has novel anti-depressive and anti-cholinesterase potency via increasing endogenous levels of betaine and acetylcholine in the mouse brain. This neurochemical profiling approach may represent a meaningful tool for better understanding brain neurochemistry and neurotoxicity in discovery and development of CNS drugs.

Dietary Betaine Mitigates Hepatic Steatosis and Inflammation Induced by a High-Fat-Diet by Modulating the Sirt1/Srebp-1/Pparɑ Pathway in Juvenile Black Seabream (Acanthopagrus schlegelii).

The present study aimed to elucidate the mechanism of dietary betaine, as a lipid-lowering substance, on the regulation of lipid metabolism and inflammation in juvenile black seabream (Acanthopagrus schlegelii) fed a high fat diet. An 8-week feeding trial was conducted in black seabream with an initial weight of 8.39 ± 0.01g fed four isonitrogenous diets including Control, medium-fat diet (11%); HFD, high-fat diet (17%); and HFD supplemented with two levels (10 and 20 g/kg) of betaine, HFD+B1 and HFD+B2, respectively. SGR and FE in fish fed HFD+B2 were significantly higher than in fish fed HFD. Liver histology revealed that vacuolar fat droplets were smaller and fewer in bream fed HFD supplemented with betaine compared to fish fed HFD. Betaine promoted the mRNA and protein expression levels of silent information regulator 1 (Sirt1), up-regulated mRNA expression and protein content of lipid peroxisome proliferator-activated receptor alpha (pparα), and down-regulated mRNA expression and protein content of sterol regulatory element-binding protein-1(srebp-1). Furthermore, the mRNA expression levels of anti-inflammatory cytokines in liver and intestine were up-regulated, while nuclear factor kB (nf-kb) and pro-inflammatory cytokines were down-regulated by dietary betaine supplementation. Likewise, in fish that received lipopolysaccharide (LPS) to stimulate inflammatory responses, the expression levels of mRNAs of anti-inflammatory cytokines in liver, intestine and kidney were up-regulated in fish fed HFD supplemented with betaine compared with fish fed HFD, while nf-kb and pro-inflammatory cytokines were down-regulated. This is the first report to suggest that dietary betaine could be an effective feed additive to alleviate hepatic steatosis and attenuate inflammatory responses in black seabream fed a high fat diet by modulating the Sirt1/Srebp-1/Pparɑ pathway.

Socioeconomic position links circulatory microbiota differences with biological age

Imbalanced nutrition is associated with accelerated ageing, possibly mediated by microbiota. An analysis of the circulatory microbiota obtained from the leukocytes of participants in the MRC Twenty-07 general population cohort was performed. We now report that in this cohort, the most biologically aged exhibit a significantly higher abundance of circulatory pathogenic bacteria, including Neisseria, Rothia and Porphyromonas, while those less biologically aged possess more circulatory salutogenic (defined as being supportive of human health and wellbeing) bacteria, including Lactobacillus, Lachnospiraceae UCG-004 and Kocuria. The presence of these salutogenic bactreria is consistent with a capacity to metabolise and produce Nrf2 agonists. We also demonstrate that associated one carbon metabolism, notably betaine levels, did not vary with chronological age, but displayed a difference with socioeconomic position (SEP). Those at lower SEP possessed significantly lower betaine levels indicative of a poorer diet and poorer health span and consistent with reduced global DNA methylation levels in this group. Our data suggest a clear route to improving age related health and resilience based on dietary modulation of the microbiota.

Urine NMR Metabolomics Profile of Preterm Infants With Necrotizing Enterocolitis Over the First Two Months of Life: A Pilot Longitudinal Case-Control Study.

Objective: To investigate changes in the urine metabolome of very low birth weight preterm newborns with necrotizing enterocolitis (NEC) and feed intolerance, we conducted a longitudinal study over the first 2 months of life. The metabolome of NEC newborns was compared with two control groups that did not develop NEC: the first one included preterm babies with feed intolerance, while the second one preterm babies with good feed tolerance. Methods: Newborns developing NEC within the 3 weeks of life were identified as early onset NEC, while the remaining as late onset NEC. Case-control matching was done according to the gestational age (±1 week), birth weight (± 200 g), and postnatal age. A total of 96 urine samples were collected and analyzed. In newborns with NEC, samples were collected before, during and after the diagnosis over the first 2 months of life, while in controls samples were collected as close as possible to the postnatal age of newborns with NEC. Proton nuclear magnetic resonance (1H NMR) spectroscopy was used for metabolomic analysis. Data were analyzed by univariate and multivariate statistical analysis. Results: In all the preterm newborns, urine levels of betaine, glycine, succinate, and citrate positively correlated with postnatal age. Suberate and lactate correlated with postnatal age in preterms with NEC and in controls with food intolerance, while N,N-dimethylglycine (N,N-DMG) correlated only in controls with good digestive tolerance. Preterm controls with feed intolerance showed a progressive significant decrease of N-methylnicotinamide and carnitine. Lactate, betaine, myo-inositol, urea, creatinine, and N,N-dimethylglycine discriminated late-onset NEC from controls with good feed tolerance. Conclusion: Our findings are discussed in terms of contributions from nutritional and clinical managements of patients and gut microbiota.

Maternal Plasma Betaine in Middle Pregnancy Was Associated with Decreased Risk of GDM in Twin Pregnancy: A Cohort Study.

PurposeAlthough previous studies have shown that choline-related metabolites in one carbon metabolism (OCM) were related to gestational diabetes mellitus (GDM) risk in singleton pregnancy, their role in twin gestations remains unclear. We aimed to investigate the associations between choline, betaine, methionine, dimethylglycine (DMG), trimethylamine N-oxide (TMAO) and GDM risk among women with twin gestations.Patients and MethodsThis hospital-based cohort study included 187 women with dichorionic twin gestations. Blood samples were collected during pregnancy at a median of 16.1 weeks of gestation (IQR: 13.9 −17.9). Concentrations of plasma metabolites were measured by HPLC-triple quadrupole MS. Log-binomial regression models were applied to estimate the associations between plasma metabolites and the risk of GDM.ResultsA total of 57 (30.5%) GDM cases were diagnosed over the study follow-up. Eighty-seven percent of women conceived through ART. Plasma betaine had an inverse association with GDM risk, and the adjusted RR of GDM comparing the highest tertile with the lowest tertile was 0.41 (95% CI: 0.19–0.86, Ptrend=0.015). Women with a high betaine/choline ratio or a low DMG/betaine ratio were at decreased GDM risk (Ptrend=0.031 or 0.001, respectively). Plasma choline, methionine, DMG and TMAO were not associated with GDM risk.ConclusionAmong women with dichorionic twin gestations, higher plasma level of betaine in the second trimester was associated with lower risk of GDM. This finding needs further confirmation.

Maize Grain Extract Enriched with Polyamines Alleviates Drought Stress in Triticum aestivum through Up-Regulation of the Ascorbate–Glutathione Cycle, Glyoxalase System, and Polyamine Gene Expression

The potential protective role of priming wheat seeds with maize green extract (MGE) against the stress effects of drought was studied. Pretreatment using MGE, MGE enriched with polyamines (MGEPA), and drought treatments (irrigation deficit of 30% (severe drought) or 60% (moderate drought) versus 90% relative water content of soil as a control) were applied in a factorial completely randomized design. Under moderate drought, pretreatment with MGEPA outperformed MGE and control, while severely stressed plants died even with pretreatments. Both extracts enhanced normal plant growth and yield and mitigated the deleterious effect of moderately stressed plants. Application of both extracts markedly increased photosynthetic efficiency, membrane stability, relative water content, and accumulation of antioxidants, osmoprotectants, trans- and cis-zeatin, polyamines, and their gene expressions, while levels of superoxide (O2•−) and hydrogen peroxide (H2O2), lipid peroxidation, and electrolyte leakage were decreased. Enzymatic antioxidants and glyoxalase system activities were improved in moderately stressed plants and were further improved with pretreatment with both extracts, thus protecting plants from oxidative damage by up-regulation of the ascorbate–glutathione cycle. Glycine betaine, soluble sugars, and proline levels were greatly increased in pretreated plants, thus maintaining membrane stability and photosynthetic efficiency. The interaction between drought and pretreatment using MGEPA was significant in growing wheat plants in dry environments with 60% relative water content of soil.

Microbiome-Metabolomics Analysis Reveals the Protection Mechanism of α-Ketoacid on Adenine-Induced Chronic Kidney Disease in Rats.

Objectives: As nitrogen-free precursors of corresponding essential amino, α-ketoacid have been widely prescribed to end-stage renal disease patients together with a low protein diet However, the impact of α-ketoacid on intestinal microbiota in chronic kidney disease (CKD) individuals is unknown. The study aims at investigating the variation in the intestinal microbiota and metabolic profile in response to α-ketoacid treatment in an adenine-induced CKD rat model. Design: Rats in the treatment groups were given solution of compound α-ketoacid tablets. At the end of the study, blood, feces, colon tissues and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses. Results: α-Ketoacid treatment reduced serum creatinine, blood urea nitrogen and 24 h urine protein, and alleviated tubular atrophy, glomerulosclerosis and interstitial fibrosis in adenine-induced CKD rats. Moreover, α-ketoacid significantly improved intestinal barrier and increased the abundance of Methanobrevibacter, Akkermansia, Blautia and Anaerositipes while reduced the abundance of Anaerovorax and Coprococcus_3 at the genus level. In addition, our results also demonstrated that α-ketoacid significantly reduced the concentrations of indoxyl sulfate, betaine, choline and cholesterol. Spearman’s correlation analysis revealed that the abundance of Coprococcus_3 was positively correlated with serum level of betaine, trimethylamine N-oxide, indoxyl sulfate, cholic acid and deoxycholic acid. Conclusion: α-Ketoacid has a reno-protective effect against adenine-induced CKD, which may be mediated regulation of serum metabolic profiles via affecting intestinal microbial community.

Understanding the Relationship between Intrinsic Cardiorespiratory Fitness and Serum and Skeletal Muscle Metabolomics Profile.

Intrinsic cardiorespiratory fitness (iCRF) indicates the CRF level in the sedentary state. However, even among sedentary individuals, a wide interindividual variability is observed in the iCRF levels, whose associated molecular characteristics are little understood. This study aimed to investigate whether serum and skeletal muscle metabolomics profiles are associated with iCRF, measured by maximal power output (MPO). Seventy sedentary young adults were submitted to venous blood sampling, a biopsy of the vastus lateralis muscle and iCRF assessment. Blood serum and muscle tissue samples were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy. Metabolites related to iCRF were those supported by three levels of evidence: (1) correlation with iCRF, (2) significant difference between individuals with low and high iCRF, and (3) metabolite contribution to significant pathways associated with iCRF. From 43 serum and 70 skeletal muscle analyzed metabolites, iCRF was positively associated with levels of betaine, threonine, proline, ornithine, and glutamine in serum and lactate, fumarate, NADP+, and formate in skeletal muscle. Serum betaine and ornithine and skeletal muscle lactate metabolites explained 31.2 and 16.8%, respectively, of the iCRF variability in addition to body mass. The results suggest that iCRF in young adults is positively associated with serum and skeletal muscle metabolic levels, indicative of the amino acid and carbohydrate metabolism.