The current review will examine the field of food intake biomarkers and the potential use of such biomarkers. Biomarkers of food intake have the potential to be objective measures of intake thus addressing some of the limitations associated with self-reported dietary assessment methods. They are typically food-derived biomarkers present in biological samples and distinct from endogenous metabolites. To date, metabolomic profiling has been successful in identifying several putative food intake biomarkers. With respect to food intake biomarkers, there has been a proliferation of publications in this field. However, caution is needed when interpreting these as food intake biomarkers. Many have not been validated thus hampering their use. While much of the focus to date is on discovery of food intake biomarkers there are excellent examples of how to utilise these biomarkers in nutrition research. Applications include but are not limited to: (1) measurement of adherence to diets in intervention studies (2) objectively predicting intake with no reliance on self-reported data and (3) calibrating self-reported data in large epidemiological studies. Examples of these applications will be covered in this review. While significant progress is achieved to date in the food intake biomarkers field there are a number of key challenges that remain. Examples include lack of databases focused on food-derived metabolites thus hindering the discovery of new biomarkers and the need for new statistical approaches to deal with multiple biomarkers for single foods. Addressing these and other key challenges will be key to development of future opportunities.

Ruminant-derived foods, predominantly milk and meat, are globally recognized as staples of a high-quality diet. Despite their widespread popularity, there is a notable deficiency in comprehensive standards addressing the nutritional values and safety of these products. This gap significantly limits both the supply of and demand for premium quality milk and meat. This review endeavors to highlight the benefits of utilizing metabolomics for the evaluation of quality and safety in milk and meat products from ruminants. It identifies critical metabolites, genetic signals, and metabolic pathways related to the synthesis of ruminant-derived milk and meat, proposing their potential as nutritional or regulatory targets and biomarkers. These biomarkers are instrumental in predicting and assessing the quality and safety of dairy and meat products, offering guidance for quality-based pricing and food safety inspections in the market. This review offers a critical overview of current metabolomics-based platforms and tools for interpreting the quality and safety of ruminant foods. The core metabolic biomarkers and biological biosynthetic processes of milk and meat enhance our understanding of the interplay between conventional food production from animals and new synthetic biological technologies.

Prior observational studies have reported the potential protective effect of n-3 fatty acids on the prognosis of acute pancreatitis (AP). However, the causal impact of n-3 fatty acids on AP is unclear. We aimed to investigate further the association of n-3 fatty acids with AP. We performed a meta-analysis and Mendelian randomisation (MR) to explore the association between n-3 fatty acids and the prognosis of AP from clinical observation and genetics perspectives, respectively. Nine randomised controlled trials were included in this study. The result meta-analysis showed that complementary therapy of n-3 fatty acids significantly decreased mortality (Relative Risk (RR): 0·30; 95 % CI 0·14, 0·65, P < 0·05) and infectious complications in AP (RR: 0·45; 95 % CI 0·27, 0·77, P < 0·05). Compared with the control groups, the hospital stays (MD: −1·02; 95 % CI −1·85, −0·20, P < 0·05) in AP patients with n-3 fatty acids treatment were statistically reduced. However, the ICU stay (MD: −0·49; 95 % CI −1·29, −0·31, P > 0·05) between control groups and AP patients with n-3 fatty acids treatment was insignificant. Utilising genetic susceptibility analysis in the MR approach, the MR showed n-3 fatty acids have a significant causal effect on the AP risk (OR, 0·887; 95 % CI 0·797, 0·986, P = 0·027, fixed-effect; OR, 0·887; 95 % CI 0·792, 0·993, P = 0·037, random-effect). n-3 fatty acids complementary therapy may improve the prognosis of AP. Furthermore, genetically predicted serum levels of n-3 fatty acids can significantly lower AP risk.

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.