Precision Nutrition relies heavily on multimodal data to account for factors that drive variability in response to nutrition and develop more precise dietary recommendations. Despite the promising potential to improve the overall health of individuals, its implementation is not without ethical and practical challenges. To realize its potential, Precision Nutrition must be paired with measures that foster responsible innovation. Building on this premise, we present a normative yet practical roadmap that emphasizes the central role of high-dimensional, multimodal, and harmonized data in enabling Precision Nutrition initiatives, structured around 5 phases: 1) data acquisition, 2) data modeling, 3) data translation, 4) data communication, and 5) data evaluation. For each phase of this roadmap, we identify core challenges and propose initial strategies to address such challenges. We expect this roadmap to serve as a reference for researchers, practitioners, and policymakers, as well as a blueprint for future research and governance.

BACKGROUND:Despite the growing availability of plant protein ingredients on the market, data on their digestibility and metabolic effects in humans are limited. OBJECTIVES:This study aimed to examine the effects of differently processed pea proteins on postprandial metabolism and compare them with those of whey protein (WP). METHODS:In a randomized crossover trial, healthy males and females (n = 20, aged 24 ± 3 y, body mass index = 21.6 ± 1.8 kg/m2) consumed 4 test meals each containing 25 g protein from 1) pea protein concentrate (PC), 2) pea protein isolate (PI), 3) pea protein extrudate (PE), or 4) WP. Acetaminophen was administered with each test meal as a marker for gastric emptying. Venous blood samples were obtained in the fasting state and at multiple time points postprandially (15-300 min). Samples were analyzed for the concentration of plasma amino acids (primary outcome), serum urea, plasma glucose, serum insulin, and uric acid. Satiety was assessed using visual analog scales. All data were analyzed using linear mixed models. RESULTS:Plasma essential amino acid (EAA) concentrations increased after ingestion of all test meals. Compared with WP, meals containing PC, PI, and PE resulted in lower plasma EAA concentrations [incremental area under the curve (iAUC)0-300, P < 0.001] without any significant difference between the 3 degrees of processing. The PE meal showed a delayed increase in EAA compared with PC, PI, and WP (iAUC0-120P = 0.008, 0.016, <0.001, and time to reach the maximum plasma concentration P < 0.001). After the WP meal, uric acid decreased but increased after the PC, PI, and PE meals (P < 0.001). No meal effect was observed for postprandial urea, glucose, insulin, and acetaminophen concentrations or satiety ratings. CONCLUSIONS:In healthy young adults, pea protein elicits a lower postprandial EAA response than WP, independent of processing degree. Comparisons across processing degrees indicate a delayed EAA response after PE consumption. Other metabolic parameters and satiety responses are comparable between pea and WP. This trial was registered at clinicaltrials.gov as NCT06155656.

Values can influence various aspects of scientific research, including research questions, methodologies, interpretations, and applications of scientific knowledge. Instead of pursuing value-free science, the scientific community recognizes the importance of value-aware science, which acknowledges the role of values in scientific inquiry but emphasizes transparency and accountability. Conflicts of interest statements often focus only on financial ties. We argue for the inclusion of positionality statements in nutrition science, similar to practices in the social sciences and humanities. Positionality statements highlight the influence of the researcher’s position, background, and values on scientific inquiry, promoting transparency, reflexivity, and dialogue within the scientific community. We advocate for a shift towards a perspectival epistemology that recognizes the value of diverse perspectives and contributes to a more robust and reliable scientific knowledge. We include case studies demonstrating different styles of positionality statements and addresses potential critiques of positionality, including concerns about subjectivity and equating individuals with their social identities. Overall, we conclude that embracing value-awareness and positionality can lead to a more credible and socially engaged nutrition science.

The diversification of Nutrition Sciences (NS) in recent decades has highlighted the need to review current practices in relation to funding, communication and interaction with stakeholders. The Federation of European Nutrition Societies (FENS) Presidential Activity “Improving standards in the science of nutrition” established three working groups to develop consensus documents. This paper is part of Working Group 2 (WG2) “Organisation, Capabilities and Funding” and aims at describing the European Nutrition Research Landscape, addressing its diversity, challenges and future perspectives. WG2 developed two rounds of questionnaires designed to map the current funding architecture in FENS member countries. Questionnaires were administered to representatives of national NS member societies in 2022 and desk research was carried out to describe the main European Union (EU) sources of funding. Qualitative data analysis was performed on questionnaire data collected and agreed and approved by WG2. 42

Personalised nutrition (PN) as a new endeavour emerged in the background of the human genome project with the ease to analyse genetic heterogeneity. First commercial offers with recommendations for diet and lifestyle changes, usually based on a few polymorphisms, entered markets soon after the presentation of the human genome blueprint. Although PN has seen many attempts, meanwhile, with the inclusion of other biomedical measures such as microbiome and/or continuous glucose monitoring, scientific assessments of such approaches in various settings revealed limited success. Although personalisation improved general compliance over generic advice, particular benefits in referring to biomedical measures and individual risks did, in most cases, not provide any significant advantage. Moreover, scholars criticised such approaches as of limited impact from a public health perspective by attracting mainly technology-open individuals of high social status and proper financial capabilities. Based on these experiences, new avenues for personalising dietary advice are developed, and those are going beyond pure biomedical data by assessing the entire food environment of the individual with its capabilities and constraints in the given life setting. Embedded into digital environments for data collection but also for bidirectional communication, new possibilities emerge. Artificial intelligence methods allow for the multitude of input data and highly complex decision trees to be derived to customize advice. And that can be delivered on the spot and in time in any language whenever decisions are made on what to buy or what to eat. But systems can also be employed to increase physical activity levels and for the adoption of a more healthy lifestyle in general.

Personalized nutrition (PN) represents an approach aimed at delivering tailored dietary recommendations, products, or services to support both prevention and treatment of nutrition-related conditions and to improve individual health using genetic, phenotypic, medical, nutritional, and other pertinent information. However, current approaches have yielded limited scientific success in improving diets or in mitigating diet-related conditions. In addition, PN currently caters to a specific subgroup of the population rather than having a widespread impact on diet and health at a population level. Addressing these challenges requires integrating traditional biomedical and dietary assessment methods with psycho-behavioral, and novel digital and diagnostic methods for comprehensive data collection, which holds considerable promise in alleviating present PN shortcomings. This comprehensive approach not only allows for deriving personalized goals ("what should be achieved") but also customizing behavioral change processes ("how to bring about change"). We herein outline and discuss the concept of "Adaptive Personalized Nutrition Advice Systems," which blends data from 3 assessment domains: 1) biomedical/health phenotyping; 2) stable and dynamic behavioral signatures; and 3) food environment data. Personalized goals and behavior change processes are envisaged to no longer be based solely on static data but will adapt dynamically in-time and in-situ based on individual-specific data. To successfully integrate biomedical, behavioral, and environmental data for personalized dietary guidance, advanced digital tools (e.g., sensors) and artificial intelligence-based methods will be essential. In conclusion, the integration of both established and novel static and dynamic assessment paradigms holds great potential for transitioning PN from its current focus on elite nutrition to a widely accessible tool that delivers meaningful health benefits to the general population.

Nutrients serve physiological functions in a dose-dependent manner and that needs to be recognized in risk assessment. An example of the consequences of not properly considering this can be seen in a recent assessment by the European Food Safety Authority (EFSA). EFSA concluded in 2022 that the intake of added and free sugars should be “as low as possible in the context of a nutritionally adequate diet”. That conclusion of EFSA is based on the effects on two surrogate endpoints for an adverse effect found in randomized controlled trials with high sugars intake levels: fasting glucose and fasting triglycerides. The lowest intake levels in these trials were around 10 energy% and at this intake level there were no adverse effects on the two outcomes. This indicates that the adverse effects of sugars have an observable threshold value for these two endpoints. The most appropriate interpretation from the vast amount of data is that currently no definitive conclusion can be drawn on the tolerable upper intake level for dietary sugars. Therefore, EFSA's own guidance would lead to the conclusion that the available data do not allow the setting of an upper limit for added sugars and hence, that more robust data are required to identify the threshold value for intake of sugars.

The rapid growth of product sectors for plant-based meat and dairy alternatives has raised significant scientific interest in their nutritional and ecological benefits. Here, it outlines the fractionation of plant-based raw materials and describes the technologies applied in the production of meat and dairy substitutes. Moreover, the study describes the effects of these new products on human nutrient supply and metabolic responses. Examples of meat-like products produced by extrusion technology and dairy alternatives are provided, addressing production challenges and the effects of processing on nutrient digestibility and bioavailability. In contrast to animal-based products, plant-based protein ingredients can contain many compounds produced by plants for defense or symbiotic interactions, such as lectins, phytates, and a wide range of secondary metabolites. The intake of these compounds as part of a plant-based diet can influence the digestion, bioaccessibility, and bioavailability of essential nutrients such as minerals and trace elements but also of amino acids. This is a critical factor, especially in regions with limited plant species for human consumption and inadequate technologies to eliminate these compounds. To fully understand these impacts and ensure that plant-based diets meet human nutritional needs, well-controlled human studies are needed.

IntroductionWe previously showed enteric nerve activation after application of colonic mucosal biopsy supernatants from patients with irritable bowel syndrome (IBS). The question remains whether this is a region-specific or a generalized sensitization. We tested the nerve-activating properties of supernatants from large and small intestinal regions of IBS patients with diarrhea (IBS-D) in comparison to those from mastocytosis patients with diarrhea (MC-D) or non-IBS/non-MC patients with GI-complaints. MC-D patients were included to test samples from patients with an established, severe mast cell disorder, because mast cells are suggested to play a role in IBS.MethodsVoltage-sensitive dye imaging was used to record the effects of mucosal biopsy supernatants from IBS-D, MC-D, and non-IBS/non-MC on guinea pig submucous neurons. Mast cell density and histamine concentrations were measured in all samples.ResultsThe median neuroindex (spike frequency × % responding neurons in Hz × %) was significantly (all p < 0.001) increased for IBS-D (duodenum and colon, proximal and distal each, 49.3; 50.5; 63.7; 71.9, respectively) compared to non-IBS/non-MC (duodenum and colon, proximal and distal each, 8.7; 4.9; 6.9; 5.4, respectively) or MC-D supernatants (duodenum and colon, proximal and distal each, 9.4; 11.9; 0.0; 7.9, respectively). Nerve activation by MC-D and non-IBS/non-MC supernatants was comparable (p>0.05). Mast cell density or histamine concentrations were not different between IBS-D, MC-D, and non-IBS/non-MC samples.DiscussionNerve activation by biopsy supernatants is an IBS hallmark that occurs throughout the gut, unrelated to mast cell density or histamine concentration. At least as important is our finding that GI complaints per se were not associated with biopsy supernatant-induced nerve activation, which further stresses the relevance of altered nerve behavior in IBS.

Because of the indispensable amino acids dietary proteins are the most important macronutrients. Proper growth and body maintenance depends on the quantity and quality of protein intake and proteins have thus been most crucial throughout evolution with hominins living in quite diverse food ecosystems. Developments in agriculture and food science have increased availability and diversity of food including protein for a rapidly growing world population while nutrient deficiencies resulting in stunting in children for example have been reduced. Nevertheless, the developing world and growing population needs more protein of high quality – with around 400 million tons per annum estimated for 2050. In contrary, protein consumption in all developed countries exceeds meanwhile the recommended intakes considerably with consequences for health and the environment. There is a growing interest in dietary proteins driven by the quest for more sustainable diets and the increasing food demand for a growing world population. This brings new and novel sources such as algae, yeast, insects or bacteria into play in delivering the biomass but also new technologies such as precision fermentation or in vitro meat/fish or dairy. What needs to be considered when such new protein sources are explored is that proteins need to provide not only the required amino acids but also functionality in the food produced thereof. This review considers human physiology and metabolism in the context of protein intake from an evolutionary perspective and prospects on future protein production.

Metabolism oscillates between catabolic and anabolic states depending on food intake, exercise, or stresses that change a multitude of metabolic pathways simultaneously. We present the HuMet Repository for exploring dynamic metabolic responses to oral glucose/lipid loads, mixed meals, 36-h fasting, exercise, and cold stress in healthy subjects. Metabolomics data from blood, urine, and breath of 15 young, healthy men at up to 56 time points are integrated and embedded within an interactive web application, enabling researchers with and without computational expertise to search, visualize, analyze, and contextualize the dynamic metabolite profiles of 2,656 metabolites acquired on multiple platforms. With examples, we demonstrate the utility of the resource for research into the dynamics of human metabolism, highlighting differences and similarities in systemic metabolic responses across challenges and the complementarity of metabolomics platforms. The repository, providing a reference for healthy metabolite changes to six standardized physiological challenges, is freely accessible through a web portal.

Solute carrier (SLC) transport proteins are fundamental for the translocation of endogenous compounds and drugs across membranes, thus playing a critical role in disease susceptibility and drug response. Because only a limited number of transporter substrates are currently known, the function of a large number of SLC transporters is elusive. Here, we describe the proof-of-concept of a novel strategy to identify SLC transporter substrates exemplarily for the proton-coupled peptide transporter (PEPT) 2 (SLC15A2) and multidrug and toxin extrusion (MATE) 1 transporter (SLC47A1), which are important renal transporters of drug reabsorption and excretion, respectively. By combining metabolomic profiling of mice with genetically-disrupted transporters, in silico ligand screening and in vitro transport studies for experimental validation, we identified nucleobases and nucleosidederived anticancer and antiviral agents (flucytosine, cytarabine, gemcitabine, capecitabine) as novel drug substrates of the MATE1 transporter. Our data confirms the successful applicability of this new approach for the identification of transporter substrates in general, which may prove particularly relevant in drug research.

Background: The capacity of an individual to respond to changes in food intake so that postprandial metabolic perturbations are resolved, and metabolism returns to its pre-prandial state, is called phenotypic flexibility. This ability may be a more important indicator of current health status than metabolic markers in a fasting state.Aim: In this parallel randomized controlled trial study, an energy-restricted healthy diet and 2 dietary challenges were used to assess the effect of weight loss on phenotypic flexibility.Methods: Seventy-two volunteers with overweight and obesity underwent a 12-wk dietary intervention. The participants were randomized to a weight loss group (WLG) with 20% less energy intake or a weight-maintenance group (WMG). At weeks 1 and 12, participants were assessed for body composition by MRI. Concurrently, markers of metabolism and insulin sensitivity were obtained from the analysis of plasma metabolome during 2 different dietary challenges-an oral glucose tolerance test (OGTT) and a mixed-meal tolerance test.Results: Intended weight loss was achieved in the WLG (-5.6 kg, P < 0.0001) and induced a significant reduction in total and regional adipose tissue as well as ectopic fat in the liver. Amino acid-based markers of insulin action and resistance such as leucine and glutamate were reduced in the postprandial phase of the OGTT in the WLG by 11.5% and 28%, respectively, after body weight reduction. Weight loss correlated with the magnitude of changes in metabolic responses to dietary challenges. Large interindividual variation in metabolic responses to weight loss was observed.Conclusion: Application of dietary challenges increased sensitivity to detect metabolic response to weight loss intervention. Large interindividual variation was observed across a wide range of measurements allowing the identification of distinct responses to the weight loss intervention and mechanistic insight into the metabolic response to weight loss.

Nearly all approaches to personalized nutrition (PN) use information such as the gene variants of individuals to deliver advice that is more beneficial than a generic “1-size-fits-all” recommendation. Despite great enthusiasm and the increased availability of commercial services, thus far, scientific studies have only revealed small to negligible effects on the efficacy and effectiveness of personalized dietary recommendations, even when using genetic or other individual information. In addition, from a public health perspective, scholars are critical of PN because it primarily targets socially privileged groups rather than the general population, thereby potentially widening health inequality. Therefore, in this perspective, we propose to extend current PN approaches by creating adaptive personalized nutrition advice systems (APNASs) that are tailored to the type and timing of personalized advice for individual needs, capacities, and receptivity in real-life food environments. These systems encompass a broadening of current PN goals (i.e., what should be achieved) to incorporate “individual goal preferences” beyond currently advocated biomedical targets (e.g., making sustainable food choices). Moreover, they cover the “personalization processes of behavior change” by providing in situ, “just-in-time” information in real-life environments (how and when to change), which accounts for individual capacities and constraints (e.g., economic resources). Finally, they are concerned with a “participatory dialog between individuals and experts” (e.g., actual or virtual dieticians, nutritionists, and advisors) when setting goals and deriving measures of adaption. Within this framework, emerging digital nutrition ecosystems enable continuous, real-time monitoring, advice, and support in food environments from exposure to consumption. We present this vision of a novel PN framework along with scenarios and arguments that describe its potential to efficiently address individual and population needs and target groups that would benefit most from its implementation.

Insulin secretion following ingestion of a carbohydrate load affects a multitude of metabolic pathways that simultaneously change direction and quantity of interorgan fluxes of sugars, lipids and amino acids. In the present study, we aimed at identifying markers associated with differential responses to an OGTT a population of healthy adults. By use of three metabolite profiling platforms, we assessed these postprandial responses of a total of 202 metabolites in plasma of 72 healthy volunteers undergoing comprehensive phenotyping and of which half enrolled into a weight-loss program over a three-month period. A standard oral glucose tolerance test (OGTT) served as dietary challenge test to identify changes in postprandial metabolite profiles. Despite classified as healthy according to WHO criteria, two discrete clusters (A and B) were identified based on the postprandial glucose profiles with a balanced distribution of volunteers based on gender and other measures. Cluster A individuals displayed 26% higher postprandial glucose levels, delayed glucose clearance and increased fasting plasma concentrations of more than 20 known biomarkers of insulin resistance and diabetes previously identified in large cohort studies. The volunteers identified by canonical postprandial responses that form cluster A may be called pre-pre-diabetics and defined as "at risk" for development of insulin resistance. Moreover, postprandial changes in selected fatty acids and complex lipids, bile acids, amino acids, acylcarnitines and sugars like mannose revealed marked differences in the responses seen in cluster A and cluster B individuals that sustained over the entire challenge test period of 240 min. Almost all metabolites, including glucose and insulin, returned to baseline values at the end of the test (at 240 min), except a variety of amino acids and here those that have been linked to diabetes development. Analysis of the corresponding metabolite profile in a fasting blood sample may therefore allow for early identification of these subjects at risk for insulin resistance without the need to undergo an OGTT.

In the last decades, dietary phosphate intake has increased due to a higher consumption of ultraprocessed food. This higher intake has an impact on body composition and health state. Recently, this study finds that a high chronic phosphate diet leads to no major renal alterations, but negatively affects parameters of bone health probably due to the chronic acid load. Here the effect of high phosphate consumption on parameters of energy metabolism is assessed. Healthy mature adult mice are fed for 1 year or 4 months with either a standard (0.6 % w/w) or a high phosphate (1.2 % w/w) diet. Males and females of two different genetic backgrounds are investigated. Mice feed the high phosphate diet show an attenuated body-weight gain, lower respiratory exchange ratio, decreased body fat mass, and increased lean-to-fat mass ratio. Moreover, the high phosphate diet leads to fasting hypoglycemia with no differences in the glucose response to an oral glucose tolerance test. Triglycerides and cholesterol in blood are similar independently of dietary phosphate content. However, 1-methylhistidine is lower in animals feed a chronic high phosphate intake. High phosphate diet attenuates body weight gain, but induces hypoglycemia and may alter muscle homeostasis.

With the presentation of the blueprint of the first human genome in 2001 and the advent of technologies for high-throughput genetic analysis, personalized nutrition (PN) becomes a new scientific field and the first commercial offerings of genotype-based nutrition advice emerge at the same time. Here, the state of evidence for the effect of genetic and epigenetic factors in the development of obesity, the metabolic syndrome, and resulting illnesses such as non-insulin-dependent diabetes mellitus and cardiovascular diseases is summarized. This study also critically value the concepts of PN that are built around the new genetic avenue from both the academic and a commercial perspective and their effectiveness in causing sustained changes in diet, lifestyle, and for improving health. Despite almost 20 years of research and commercial direct-to-consumer offerings, evidence for the success of gene-based dietary recommendations is still generally lacking. This calls for new concepts of future PN solutions that incorporate more phenotypic measures and provide a panel of instruments (e.g., self- and bio-monitoring tools, feedback systems, algorithms based on artificial intelligence) that increases compliance based on the individual´s physical and social environment and value system.

In recent years, bile acids (BA) have received great interest due to their pleiotropic biological activity and the presence of plasma membrane-bound and nuclear receptors. Moreover, BA in blood have been identified by metabolite screening approaches as biomarkers that are associated with various diseases and even with a human longevity phenotype. With the growing interest in the microbiota contribution to the health-disease trajectory, BA that undergo deconjugation and other modifications by bacteria in the large intestine have become a prime target as a microbiome diversity modifier. We here profiled BA by a quantitative and a semiquantitative approach in 15 healthy and phenotypically very similar young individuals for over a 36-h fasting period, an oral glucose tolerance test (OGTT), and an oral lipid tolerance test (OLTT). We demonstrate a remarkable heterogeneity of the responses and describe the different dynamics of the plasma changes that likely originate from different routes by which BA enters the peripheral blood, and that may represent a direct secretion from the liver into the blood and a route that reaches the blood as a spill-over after passing from the gallbladder through the intestine and the portal system. We discuss the finding that an individual transport process involved in the passage of BA could be a critical determinant in the kinetics of plasma appearance and the overall phenotypic variability found.

Research on the gut microbiome has gained high popularity and almost every disease has meanwhile been linked to alterations in microbiome composition. Typically assessed via stool samples, the microbiome displays a huge diversity with a multitude of environmental parameters already identified as contributing to its character. Despite impressive scientific progress, normal microbiome diversity remains largely unexplained and it is tempting to speculate some of the yet unexplained variance is hidden in normal gut physiology. Although a few genome/phenome-wide associations studies have recently highlighted physiological parameters such as stool frequency, known as contributing to microbiome diversity, there is a large knowledge base from decades of basic research on gut functions that can be explored for possible links to stool features and microbiome characteristics. And, when extrapolating findings from faecal samples to the biology in the intestinal lumen or the mucosal microenvironment, gut anatomy and physiology features need to be considered. Similarly, differences in anatomy and physiology between rodents and humans need attention when discussing findings in animals in relation to human physiology and nutrition.