To improve the interpretation and utilisation of blood lipids, ketones and acylcarnitine concentrations as biomarkers in clinical assessments, more information is needed on their dynamic alterations in response to dietary intake and fasting. The aim of this intervention study was to characterise the changes in serum lipid, ketone and acylcarnitine concentrations 24 h after a standardised breakfast meal. Thirty-four healthy subjects (eighteen males and sixteen females) aged 20–30 years were served a breakfast meal (∼500 kcal, 36 E% fat, 46 E% carbohydrates, 16 E% protein, 2E% fibre), after which they consumed only water for 24 h. Blood samples were drawn before and at thirteen standardised timepoints after the meal. Metabolite concentrations were plotted as a function of time since the completion of the breakfast meal. Results demonstrated that concentrations of HDL-cholesterol and LDL-cholesterol decreased until ∼2 h (–4 % for both), while TAG concentrations peaked at 3 h (+27 %). Acetoacetate and β-hydroxybutyrate were highest 24 h after the meal (+433 and +633 %, respectively). Acetylcarnitine, butyrylcarnitine, hexanoylcarnitine, octanoylcarnitine, decanoylcarnitine and dodecanoylcarnitine reached the lowest values at 60 min (decreases ranging from –47 to –70 %), before increasing and peaking at 24 h after the meal (increases ranging from +86 to +120 %). Our findings suggest that distinguishing between fasting and non-fasting blood samples falls short of capturing the dynamics in lipid, ketone, carnitine and acylcarnitine concentrations. To enhance the utility of serum acylcarnitine analyses, we strongly recommend accounting for the specific time since the last meal at the time of blood sampling.

Deficiency of vitamin B12 (B12 or cobalamin), an essential water-soluble vitamin, leads to neurological damage, which can be irreversible and anaemia, and is sometimes associated with chronic disorders such as osteoporosis and cardiovascular diseases. Clinical tests to detect B12 deficiency lack specificity and sensitivity. Delays in detecting B12 deficiency pose a major threat because the progressive decline in organ functions may go unnoticed until the damage is advanced or irreversible. Here, using targeted unbiased metabolomic profiling in the sera of subjects with low B12 levels v control individuals, we set out to identify biomarker(s) of B12 insufficiency. Metabolomic profiling identified seventy-seven metabolites, and partial least squares discriminant analysis and hierarchical clustering analysis showed a differential abundance of taurine, xanthine, hypoxanthine, chenodeoxycholic acid, neopterin and glycocholic acid in subjects with low B12 levels. Random forest multivariate analysis identified a taurine/chenodeoxycholic acid ratio, with an AUC score of 1, to be the best biomarker to predict low B12 levels. Mechanistic studies using a mouse model of B12 deficiency showed that B12 deficiency reshaped the transcriptomic and metabolomic landscape of the cell, identifying a downregulation of methionine, taurine, urea cycle and nucleotide metabolism and an upregulation of Krebs cycle. Thus, we propose taurine/chenodeoxycholic acid ratio in serum as a potential biomarker of low B12 levels in humans and elucidate using a mouse model of cellular metabolic pathways regulated by B12 deficiency.

Newborn calf diarrhea has led to widespread overuse of antibiotics. Therefore, it is crucial to find effective solutions for calf diarrhea. In this study, we aimed to evaluate the impact of the synthetic organic zinc-chelating-peptide glycine-glutamine-Zn (GQ-Zn) on the microbiota and metabolites in the gut of calves with diarrhea. The results showed that GQ-Zn alleviated diarrhea in calves. Additionally, 16S rDNA sequencing and metabolomic analysis revealed that GQ-Zn improved antioxidant capacity, relieved inflammation, altered the gut microbiota by decreasing the number of harmful bacteria Prevotella denticola, Fusobacterium necrophorum and influenced metabolomic profiles via the linoleic acid metabolic pathway in calves. In conclusion, GQ-Zn supplementation alleviated diarrhea through regulating the gut microbiota and metabolites in pre-weaning Holstein calves.

Fetuses undergo major surgical stress as well as fluid shifts secondary to both twin-twin transfusion (TTTS) as well as the fetoscopic surgery for treatment of TTTS. While the pathophysiology of TTTS is understood, the acute metabolic changes that fetuses experience from fetoscopic surgery are not. We sought to evaluate the changes in recipient metabolomic profile secondary to TTTS surgery. Amniotic fluid was collected at the beginning and end of four TTTS surgical cases performed from 12/2022−2/2023. Samples were immediately processed and evaluated via NMR-based Metabolomics Facility protocol. In univariate analysis, 12 metabolites (glucose, lactate, and 10 key amino acids) showed statistically significant changes between the beginning and end of the surgery. Among these, 11 metabolites decreased at the end, while only lactate increased. Supervised oPLS-DA modeling revealed pyruvate and lactate as the two metabolites most impact on the variance between cases, and that 40% of metabolomic changes could be attributed directly to the timing that the sample was taken (i.e., if pre- or postoperatively). These results indicate significant metabolic changes in the recipient twin during fetoscopic surgery for TTTS. These findings of decreased glucose, increased lactate, and decreased amnio acids would indicate increased catabolism during surgery. This study raises questions regarding optimal maternal and fetal nutrition during surgery and if nutritional status could be optimized to further improve twin survival during fetoscopic surgery.

Gut microbiome changed dramatically during pregnancy and played important roles in metabolic status and reproductive endocrinology in mammals. However, investigating the functional microbiota and metabolites to improve the reproductive performance and understanding the host–microbiota interaction are still arduous tasks. This study aims to reveal the dominant strains and metabolites that improve the reproductive performance. We analyzed the fecal microbiota composition and metabolic status of higher yield Chinese pig breed Meishan (MS) sows and lower yield but widespread raised hybrid pig breed Landrace × Yorkshire (L × Y) sows on days 28 and 100 of gestation. Results showed that MS sows had higher litter sizes and steroid hormone level but lower short-chain fatty acid level in feces. Fecal metabolomic analysis revealed that MS sows showed a different metabolic status compared with L × Y sows both at early and late pregnancy, which enriched with phenylpropanoid biosynthesis, bile secretion, steroid hormone biosynthesis, and plant secondary metabolite biosynthesis. In addition, 16S rDNA and internal transcribed spacer sequencing indicated that MS sows showed different structures of microbiota community and exhibited an increased bacterial α-diversity but non-differential fungal α-diversity than L × Y sows. Moreover, we found that the litter sizes and bacteria including Sphaerochaeta, Solibacillus, Oscillospira, Escherichia–Shigella, Prevotellaceae_UCG-001, dgA-11_gut_group, and Bacteroides, as well as fungi including Penicillium, Fusarium, Microascus, Elutherascus, and Heydenia both have positive association to the significant metabolites at the early pregnancy. Our findings revealed significant correlation between reproductive performance and gut microbiome and provided microbial and metabolic perspective to improve litter sizes and steroid hormones of sows.

Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analysed 1928 patients with suspected stable angina pectoris (geometric mean age 61), representing elevated CVD risk, to assess associations between dietary macronutrient composition (FFQ) and plasma one-carbon metabolites and related B-vitamin status markers (GC–MS/MS, LC–MS/MS or microbiological assay). Diet-metabolite associations were modelled on the continuous scale, adjusted for age, sex, BMI, smoking, alcohol and total energy intake. Average (geometric mean (95 % prediction interval)) intake was forty-nine (38, 63) energy percent (E%) from carbohydrate, thirty-one (22, 45) E% from fat and seventeen (12, 22) E% from protein. The strongest associations were seen for higher protein intake, i.e. with higher plasma pyridoxal 5’-phosphate (PLP) (% change (95 % CI) 3·1 (2·1, 4·1)), cobalamin (2·9 (2·1, 3·7)), riboflavin (2·4 (1·1, 3·7)) and folate (2·1 (1·2, 3·1)) and lower total homocysteine (tHcy) (–1·4 (–1·9, −0·9)) and methylmalonic acid (MMA) (–1·4 (–2·0, −0·8)). Substitution analyses replacing MUFA or PUFA with SFA demonstrated higher plasma concentrations of riboflavin (5·0 (0·9, 9·3) and 3·3 (1·1, 5·6)), tHcy (2·3 (0·7, 3·8) and 1·3 (0·5, 2·2)) and MMA (2·0 (0·2, 3·9) and 1·7 (0·7, 2·7)) and lower PLP (–2·5 (–5·3, 0·3) and −2·7 (–4·2, −1·2)). In conclusion, a higher protein intake and replacing saturated with MUFA and PUFA were associated with a more favourable metabolic phenotype regarding metabolites associated with CVD risk.

Metabolomics has been utilised in epidemiological studies to investigate biomarkers of nutritional status and metabolism in relation to non-communicable diseases. However, little is known about the effect of prandial status on several biomarker concentrations. Therefore, the aim of this intervention study was to investigate the effect of a standardised breakfast meal followed by food abstinence for 24 h on serum concentrations of amino acids, one-carbon metabolites and B-vitamin biomarkers. Thirty-four healthy subjects (eighteen males and sixteen females) aged 20–30 years were served a breakfast meal (∼500 kcal) after which they consumed only water for 24 h. Blood samples were drawn before and at thirteen standardised timepoints after the meal. Circulating concentrations of most amino acids and metabolites linked to one-carbon metabolism peaked within the first 3 h after the meal. The branched-chain amino acids steadily increased from 6 or 8 hours after the meal, while proline decreased in the same period. Homocysteine and cysteine concentrations immediately decreased after the meal but steadily increased from 3 and 4 hours until 24 h. FMN and riboflavin fluctuated immediately after the meal but increased from 6 h, while folate increased immediately after the meal and remained elevated during the 24 h. Our findings indicate that accurate reporting of time since last meal is crucial when investigating concentrations of certain amino acids and one-carbon metabolites. Our results suggest a need for caution when interpretating studies, which utilise such biomarkers, but do not strictly control for time since the last meal.

Ulcerative colitis (UC) is an immune-mediated inflammation of the colonic mucosa. Gut microbiota dysbiosis may play a significant role in disease pathogenesis by causing shifts in metabolomic profiles within the gut. To identify differences and trends in the metabolomic profile of paediatric UC patients pre- and post-faecal microbiota transplants (FMT). Forty-six paediatric patients with mild-to-moderate UC and 30 healthy paediatric patients were enrolled in this study. Baseline stool samples were collected prior to FMT initiation and at months 1, 3, 6, and 12 post-FMT. Pediatric Ulcerative Colitis Activity Index (PUCAI) scores were calculated at baseline and months 1, 3, 6, and 12 after FMT. The average Bray–Curtis dissimilarities to healthy subjects decreased after FMT. In principal coordinate analysis plots, UC patients’ centroids drew nearer to healthy individuals. The variance explained by phenotype (Healthy versus UC) reduced and remained significant. From 1 to 3 months after FMT, PUCAI trends were statistically significant and decreasing. PUCAI scores remain flat starting 6 months after FMT. This study concludes that paediatric UC patients have a significantly different baseline metabolite profile than healthy controls. Although being time limited, FMT significantly altered these metabolite profiles and shifted them towards that of healthy controls.

The overall aim of precision nutrition is to replace the ‘one size fits all’ approach to dietary advice with recommendations that are more specific to the individual in order to improve the prevention or management of chronic disease. Interest in precision nutrition has grown with advancements in technologies such as genomics, proteomics, metabolomics and measurement of the gut microbiome. Precision nutrition initiatives have three major applications in precision medicine. First, they aim to provide more ‘precision’ dietary assessments through artificial intelligence, wearable devices or by employing omic technologies to characterise diet more precisely. Secondly, precision nutrition allows us to understand the underlying mechanisms of how diet influences disease risk and identify individuals who are more susceptible to disease due to gene–diet or microbiota–diet interactions. Third, precision nutrition can be used for ‘personalised nutrition’ advice where machine-learning algorithms can integrate data from omic profiles with other personal and clinical measures to improve disease risk. Proteomics and metabolomics especially provide the ability to discover new biomarkers of food or nutrient intake, proteomic or metabolomic signatures of diet and disease, and discover potential mechanisms of diet–disease interactions. Although there are several challenges that must be overcome to improve the reproducibility, cost-effectiveness and efficacy of these approaches, precision nutrition methodologies have great potential for nutrition research and clinical application.

Mobilisation of seed storage reserves is important for seedling establishment in Arabidopsis. In this process, sucrose is synthesised from triacylglycerol via core metabolic processes. Mutants with defects in triacylglycerol-to-sucrose conversion display short etiolated seedlings. We found that whereas sucrose content in the indole-3-butyric acid response 10 (ibr10) mutant was significantly reduced, hypocotyl elongation in the dark was unaffected, questioning the role of IBR10 in this process. To dissect the metabolic complexity behind cell elongation, a quantitative-based phenotypic analysis combined with a multi-platform metabolomics approach was applied. We revealed that triacylglycerol and diacylglycerol breakdown were disrupted in ibr10, resulting in low sugar content and poor photosynthetic ability. Importantly, batch-learning self-organised map clustering revealed that threonine level was correlated with hypocotyl length. Consistently, exogenous threonine supply stimulated hypocotyl elongation, indicating that sucrose levels are not always correlated with etiolated seedling length, suggesting the contribution of amino acids in this process.

Despite extensive research into the toxicology of the herbicide glyphosate, there are still major unknowns regarding its effects on the human gut microbiome. We describe the effects of glyphosate and a Roundup glyphosate-based herbicide on infant gut microbiota using SHIME technology. SHIME microbiota culture was undertaken in the presence of a concentration of 100-mg/L glyphosate and the same glyphosate equivalent concentration of Roundup. Roundup and to a lesser extent glyphosate caused an increase in fermentation activity, resulting in acidification of the microbial environment. This was also reflected by an increase in lactate and acetate production concomitant to a decrease in the levels of propionate, valerate, caproate and butyrate. Ammonium production reflecting proteolytic activities was increased by Roundup exposure. Global metabolomics revealed large-scale disturbances, including an increased abundance of long-chain polyunsaturated fatty acids. Changes in bacterial composition measured by qPCR and 16S rRNA suggested that lactobacilli had their growth stimulated as a result of microenvironment acidification. Co-treatment with the spore-based probiotic formulation MegaSporeBiotic reverted some of the changes in short-chain fatty acid levels. Altogether, our results suggest that glyphosate can exert effects on human gut microbiota.

Preterm birth (PTB) is one of the leading causes of deaths in infants under the age of five. Known risk factors of PTB include genetic factors, lifestyle choices or infection. Identification of omic biomarkers associated with PTB could aid clinical management of women at high risk of early labour and thereby reduce neonatal morbidity. This systematic literature review aimed to identify and summarise maternal omic and multi-omic (genomics, transcriptomics, proteomics and metabolites) biomarker studies of PTB. Original research articles were retrieved from three databases: PubMed, Web of Science and Science Direct, using specified search terms for each omic discipline. PTB studies investigating genomics, transcriptomics, proteomics or metabolomics biomarkers prior to onset of labour were included. Data were collected and reviewed independently. Pathway analyses were completed on the biomarkers from non-targeted omic studies using Reactome pathway analysis tool. A total of 149 omic studies were identified; most of the literature investigated proteomic biomarkers. Pathway analysis identified several cellular processes associated with the omic biomarkers reported in the literature. Study heterogeneity was observed across the research articles, including the use of different gestation cut-offs to define PTB. Infection/inflammatory biomarkers were identified across majority of papers using a range of targeted and non-targeted approaches.

Prolonged parturition duration has been widely demonstrated to be a risk factor for incidence of stillbirth. This study evaluated the supply of dietary fibre on the parturition duration, gut microbiota and metabolome using sows as a model. A total of 40 Yorkshire sows were randomly given diet containing normal level of dietary fibre (NDF, 17·5 % dietary fibre) or high level of dietary fibre (HDF, 33·5 % dietary fibre). Faecal microbiota profiled with 16S rRNA amplicon sequencing, SCFA and metabolome in the faeces and plasma around parturition were compared between the dietary groups. Correlation analysis was conducted to further explore the potential associations between specific bacterial taxa and metabolites. Results showed that HDF diet significantly improved the parturition process as presented by the shorter parturition duration. HDF diet increased the abundance of the phyla Bacteroidetes and Synergistetes and multiple genera. Except for butyrate, SCFA levels in the faeces and plasma of sows at parturition were elevated in HDF group. The abundances of fifteen and twelve metabolites in the faeces and plasma, respectively, markedly differ between HDF and NDF sows. These metabolites are involved in energy metabolism and bacterial metabolism. Correlation analysis also showed associations between specific bacteria taxa and metabolites. Collectively, our study indicates that the improvement of parturition duration by high fibre intake in late gestation is associated with gut microbiota, production of SCFA and other metabolites, potentially serving for energy metabolism.

Tart Montmorency cherries (MC) are a particularly rich source of anthocyanins and other polyphenols that have been shown to elicit antioxidant, anti-inflammatory and vasomodulatory actions. The current study aimed to determine the influence of chronic MC supplementation on cognitive function and mood. In a 3-month double-blinded, placebo-controlled parallel study, middle-aged adults (mean ± sd: 48 ± 6 years) were randomly assigned to either 30 ml twice daily of MC (n 25) or the same amount of an isoenergetic placebo (n 25). Cognitive function and mood were assessed before and after supplementation using a computerised cognitive task battery and visual analogue scales. Cerebral blood flow was also monitored by near-infrared spectroscopy during the task battery, and questionnaires were administered to determine subjective sleep and health status and plasma metabolomics were analysed before and after supplementation. After 3 months, the MC resulted in higher accuracy in digit vigilance (mean difference: 3·3, 95 % CI: 0·2, 6·4 %) with lower number of false alarms (mean difference: −1·2, 95 % CI: −2·0, −0·4) compared with the placebo. There was also a treatment effect for higher alertness (mean difference: 5·9, 95 % CI: 1·3, 10·5 %) and lower mental fatigue ratings (mean difference −9·5, 95 % CI: −16·5, −2·5 %) with MC. Plasma metabolomics revealed an increase in a number of amino acids in response to MC intake, but not placebo. These data suggest an anti-fatiguing effect of MC supplementation as well as the ability to improve sustained attention during times of high cognitive demand, this could be related to changes in amino acid metabolism.

Urinary O-desmethylangolensin (ODMA) concentrations provide a functional gut microbiome marker of dietary isoflavone daidzein metabolism to ODMA. Individuals who do not have gut microbial environments that produce ODMA have less favourable cardiometabolic and cancer risk profiles. Urinary metabolomics profiles were evaluated in relation to ODMA metabotypes within and between individuals over time. Secondary analysis of data was conducted from the BEAN2 trial, which was a cross-over study of premenopausal women consuming 6 months on a high and a low soya diet, each separated by a 1-month washout period. In all of the 672 samples in the study, sixty-six of the eighty-four women had the same ODMA metabotype at seven or all eight time points. Two or four urine samples per woman were selected based on temporal metabotypes in order to compare within and across individuals. Metabolomics assays for primary metabolism and biogenic amines were conducted in sixty urine samples from twenty women. Partial least-squares discriminant analysis was used to compare metabolomics profiles. For the same ODMA metabotype across different time points, no profile differences were detected. For changes in metabotype within individuals and across individuals with different metabotypes, distinct metabolomes emerged. Influential metabolites (variables importance in projection score > 2) included several phenolic compounds, carnitine and derivatives, fatty acid and amino acid metabolites and some medications. Based on the distinct metabolomes of producers v. non-producers, the ODMA metabotype may be a marker of gut microbiome functionality broadly involved in nutrient and bioactive metabolism and should be evaluated for relevance to precision nutrition initiatives.

The aetiology of inflammatory bowel disease (IBD) is multifactorial, with diet and gut microbiota playing an important role. Nonetheless, there are very few studies, particularly clinical research, which have explored the interaction between diet and gut microbiota. In the current review, we summarise the evidence from clinical trials exploring the interactions between the gut microbiota and diet in the management of IBD. Data from the effect of exclusive enteral nutrition (EEN) on the gut microbiota of children with active Crohn's disease (CD), receiving induction treatment, offer opportunities to understand the role of gut microbiota in underlying disease pathogenesis and develop novel dietary and pharmacological microbial therapeutics. In contrast, the evidence which links the effectiveness of food-based dietary therapies for IBD with mechanisms involving the gut microbiota is far less convincing. The microbial signals arising from these dietary therapies are inconsistent and vary compared to the effects of effective treatment with EEN in CD.

To understand why Procapra przewalskii does not show the same white myopathy as sheep in Se-deficient regions and to provide reference for feeding nutrition level of artificial population and selection of wild reintroduction areas in the later period, a Se-deficient model was established. The mineral elements content, physiological and biochemical parameters in blood and serum metabonomics were determined. In the Se-deficient group compared with the control group, the Se content was highly significantly lower (P < 0·01), and the Cu content was significantly higher (P < 0·05). The activity of glutathione peroxidase was significantly lower (P < 0·05), but total superoxide dismutase was significantly higher (P < 0·05). By matching the mass spectrum data of compounds with the Kyoto Encyclopedia of Genes and Genomes (KEGG database), eighty-six types of differential metabolites in the serum were identified. The main metabolic pathways included secondary bile acid biosynthesis, biosynthesis of unsaturated fatty acids and pyrimidine metabolism. Further analysis showed that there were seven different metabolites in pyrimidine metabolism pathway between the two groups. And there was no significant difference in erythrocyte, Hb and total antioxidant capacity between the two groups (P > 0·05). The above results showed that the differential metabolism of substances exhibited complementary functions, thus alleviating some adverse effects and resulting normal activities of P. przewalskii can be carried out under the condition of dietary Se content lower than 0·05 mg/kg.