Nutrition has long been investigated with respect to its influence on human health. With the availability of various omics data, such as metagenomics and metabolomics, novel insights have been obtained into the influence of nutrition, particularly concerning the gut microbiome. The gut microbiome plays an important role in the breakdown of food-derived compounds and in producing essential bioactive metabolites required for human health. However, this wealth of information made the interactions between nutrition and human health increasingly intricate, and unravelling these links is complex. This review covers the concepts of genome-scale metabolic modelling as a tool to understand the links between nutrition, the gut microbiome and human metabolism and its applications. Genome-scale metabolic modelling treats metabolism as a mathematical problem which was used to develop models of human metabolism that incorporate physiology and organ-specific metabolism, known as whole-body metabolic models (WBMs). WBMs can incorporate physiological data, such as sex, weight, and body fat percentage, as well as nutrition in the form of its metabolite constituents. Finally, the gut microbiome can also be incorporated through a mathematical representation of the species present, based on stool metagenomics. WBMs have already been applied to understand gut microbiome–host co-metabolism in various non-communicable diseases. However, challenges remain, as metabolites measured in food items in public databases typically cover only common metabolites, and engagement with end-users such as nutritionists and policymakers is limited. Nevertheless, WBMs represent a promising step towards digital metabolic twins and thus personalised nutrition and medicine.

Given the central role of phosphorus in key metabolic processes, including glucose phosphorylation, ATP synthesis, insulin signalling, and energy metabolism, dietary phosphorus availability may influence postprandial metabolic responses. This systematic review evaluates the effects of inorganic phosphorus supplementation on diet-induced thermogenesis, postprandial glycaemia, and postprandial lipidemia in healthy adults. A systematic search of PubMed, Google Scholar, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted. Only experimental intervention studies assessing phosphorus supplementation as the primary exposure and postprandial metabolic outcomes as primary endpoints were included. Eligible participants were healthy adults aged 18–64 years. Secondary outcomes included changes in body weight, energy intake, and satiety. Ten randomised crossover trials met inclusion criteria, comprising a total of 225 participants. Three out of four studies reported a significant positive association between phosphorus supplementation and diet-induced thermogenesis (P < 0.05). Evidence regarding the effects of phosphorus on postprandial glycaemia and lipidemia was inconsistent. An inverse association was observed between phosphorus intake and weight gain (P < 0.001) and energy intake (P < 0.01), alongside a positive association with satiety (P < 0.05). While these findings indicate potential metabolic benefits of dietary phosphorus, particularly in relation to thermogenesis and energy regulation, interpretation is tempered by the small number of available studies, modest sample sizes, and methodological heterogeneity. These limitations restrict causal inference and generalizability. Further rigorously designed, adequately powered clinical trials are therefore warranted to substantiate these associations and to clarify the effects of phosphorus on postprandial glycaemic and lipid outcomes.

Epidemiological and clinical research has confirmed a link between obesity and depressive symptoms, with inflammation as a potential common mechanism. Given that dietary components modulate inflammation and relate to both conditions, investigating dietary inflammation as a potential underlying pathway is necessary. Herein, we aimed to explore the potential role of the Energy-adjusted Dietary Inflammatory Index (E-DII) in explaining the relationship between obesity and depressive symptoms. We conducted a cross-sectional analysis of the 2007–2018 National Health and Nutrition Examination Survey cohort, enrolling 20 324 participants. Obesity and dietary inflammation were assessed by BMI and E-DII, respectively. Depressive symptoms were evaluated using the nine-item Patient Health Questionnaire-9. We found that obesity and inflammatory diets were positively associated with depressive symptoms (β = 0·50, 95 % CI 0·30, 0·69; β = 0·35, 95 % CI 0·19, 0·50; both P < 0·001), and variations in the association among obesity, pro-inflammatory diets and depressive symptoms were evident across various population subgroups (e.g. sex, age, chronic diseases and smoking status subgroups, Pfor interaction < 0·050). After adjusting for all covariates, E-DII accounted for 4 % of the obesity–depression association. Despite this modest proportion, the finding identifies dietary-induced inflammation as a statistically significant, modifiable pathway. In conclusion, obesity and pro-inflammatory diets are linked to an increased risk of depressive symptoms, with E-DII serving as a modest but significant modifiable pathway. These findings highlight dietary intervention as a potential strategy for mitigating depressive symptoms in individuals with obesity.

The prenatal period, childhood, and adolescence are critical periods of development characterized by high plasticity. As an extension of the Developmental Origins of Health and Disease (DOHaD) paradigm, known as Origins of Paternal Health and Disease (POHaD), recent studies in rodents provide evidence that paternal obesity is associated not only with infertility but also with an increased risk of metabolic disorders in the offspring. In rodents, litter size reduction is used to induce lactational overfeeding by increasing the amount of breast milk to pups, which causes metabolic and reproductive disorders in adulthood. This work evaluated the metabolic and reproductive alterations in the offspring of males raised in normal or small litter (SL) in the prepubertal period and in adult life. The results show that paternal obesity due to early overfeeding affects the offspring in a sex-specific manner. During the prepubertal period, male offspring of SL fathers showed decreased Lee index, tibia length, and HDL plasma levels, and increased weight of gastrocnemius muscle, while female offspring of SL fathers only showed reduced HDL plasma levels. In adulthood, male offspring of overfed males showed glucose intolerance and reduced food intake and triglycerides plasma levels, signs of metabolic dysfunction. Female offspring of overfed males showed delayed puberty onset and higher prevalence of infertile periods in the estrous cycles, indicating a potential susceptibility to reproductive dysfunction. The results of the current study show that paternal obesity due to early overfeeding affects energy balance and reproduction of their offspring in a sex-specific manner.

Magnesium (Mg2+) is essential for plant growth and metabolism, acting as a cofactor in numerous enzymatic and structural processes. This review outlines the main physiological and biochemical functions of Mg2+ and summarizes current knowledge on its transport and homeostatic regulation. We examine how Mg2+ homeostasis intersects with broader signalling networks and metabolic pathways, including its crosstalk with other mineral nutrients, where antagonistic and synergistic interactions influence nutrient acquisition, allocation and stress responses. Emerging evidence further suggests that, beyond its classical roles, Mg2+ may function as a regulatory ion with signalling properties reminiscent of secondary messengers in animal systems. Finally, we highlight recent findings linking Mg2+ dynamics to circadian regulation, suggesting reciprocal interactions between temporal control mechanisms and nutrient fluxes. These insights underscore the central importance of Mg2+ in plant biology and identify key gaps in understanding its regulatory and integrative roles.

The human brain makes up just 2% of body mass but consumes closer to 20% of the body’s energy. Nonetheless, it is significantly more energy-efficient than most modern computers. Although these facts are well-known, models of cognitive capacities rarely account for metabolic factors. In this paper, we argue that metabolic considerations should be integrated into cognitive models. We distinguish two uses of metabolic considerations in modeling. First, metabolic considerations can be used to evaluate models. Evaluative metabolic considerations function as explanatory constraints. Metabolism limits which types of computation are possible in biological brains. Further, it structures and guides the flow of information in neural systems. Second, metabolic considerations can be used to generate new models. They provide: a starting point for inquiry into the relation between brain structure and information processing, a proof-of-concept that metabolic knowledge is relevant to cognitive modeling, and potential explanations of how a particular type of computation is implemented. Evaluative metabolic considerations allow researchers to prune and partition the space of possible models for a given cognitive capacity or neural system, while generative considerations populate that space with new models. Our account suggests cognitive models should be consistent with the brain’s metabolic limits, and modelers should assess how their models fit within these bounds. Our account offers fresh insights into the role of metabolism for cognitive models of mental effort, philosophical views of multiple realization and medium independence, and the comparison of biological and artificial computational systems.

Probiotics represent a promising alternative to antibiotics in livestock production. This study investigated the effects of compound probiotic fermentation (FAM, comprising Lactobacillus acidophilus and Bacillus subtilis) on nitrogen utilization and nutrient digestibility in weaned piglets. A total of 180 piglets (28 days old; initial weight: 8.21 ± 0.67 kg) were allocated to three groups: control (basal diet), FAM (basal diet + 0.1% FAM), and antibiotic (basal diet + 55 mg/kg kitasamycin + 75 mg/kg chlortetracycline). After a 30-day trial, FAM supplementation significantly increased apparent nutrient digestibility of crude protein and ether extract, enhanced duodenal and jejunal digestive enzyme activities, and reduced fecal nitrogen excretion and serum urea nitrogen levels (p < 0.05). Serum metabolomics revealed that FAM upregulated metabolites linked to energy metabolism (e.g., creatine, L-carnosine), which are metabolites of amino acid metabolism, and enriched pathways such as amino acid biosynthesis and protein digestion. These findings demonstrate that FAM improves nitrogen utilization efficiency and gut health in piglets via biosynthesis and metabolism of amino acids, offering a viable alternative to antibiotics.

A Rank Forum was convened to discuss the evidence around food insecurity (FIS), its impact on health, and interventions which could make a difference both at individual and societal level, with a focus on the UK. This paper summarises the proceedings and recommendations. Speakers highlighted the growing issue of FIS due to current economic and social pressures. The health implications of FIS vary geographically since food insecure women in higher income regions tend to be living with overweight or obesity, in contrast to those living in low-to-middle-income countries. This paradox could be due to stress and/or metabolic or behavioural responses to an unpredictable food supply. The gut microbiota may play a role given the negative effects of low fibre diets on bacterial diversity. Solutions to FIS involve individual behavioural change, targeted services and societal/policy change. Obesity-related services are currently difficult to access. Whilst poverty is the root cause of FIS, it cannot be solved solely by making healthy food cheaper due to ingrained beliefs, attitudes and behaviours in target groups. Person-centred models, such as Capability-Opportunity-Motivation Behavioural Change Techniques and Elicit-Provide-Elicit communication techniques, are recommended. Societal change or improved resilience through psychological support may be more equitable ways to address FIS. They can combine with fiscal or food environment policies to shift purchasing towards healthier foods. Policy implementation can be slow to enact due to the need for strong evidence, consultation and political will. Eradicating FIS must involve co-creation of interventions and policies to ensure a consensus on solutions.

Previously, we reported the persistence of the bacterial pathogen Neisseria meningitidis on fomites, indicating a potential route for environmental transmission. The current goal was to identify proteins that vary among strains of meningococci that have differing environmental survival. We carried out a proteomic analysis of two strains that differ in their potential for survival outside the host. The Group B epidemic strain NZ98/254 and Group W carriage strain H34 were cultured either at 36 °C, 5% CO2, and 95% relative humidity (RH) corresponding to host conditions in the nasopharynx, or at lower humidities of 22% or 30% RH at 30 °C, for which there was greater survival on fomites. For NZ98/254, the shift to lower RH and temperature was associated with increased abundance of proteins involved in metabolism, stress responses, and outer membrane components, including pili and porins. In contrast, H34 responded to lower RH by decreasing the abundance of multiple proteins, indicating that the lower viability of H34 may be linked to decreased capacity to mount core protective responses. The results provide a snapshot of bacterial proteins and metabolism that may be related to normal fitness, to the greater environmental persistence of NZ98/254 compared to H34, and potentially to differences in transmission and pathogenicity.

Calcifying macroalgae play a critical role in coastal ecosystems, but rising sea temperatures pose a significant threat to their survival. This study aims to investigate the thermal sensitivity of the three marine macroalgal species Padina boryana, Halimeda opuntia, and H. macroloba. Photosynthetic performance, metabolism, pigment content, and oxidative stress–related parameters were measured at temperatures of 28°C, 32°C, 36°C, and 40°C and the thermal performance curves (TPCs) were determined for Fv/Fm, Fv/F0, ϕPSII, and oxygen production to assess maximum rate (Rmax), optimum temperature (Topt), critical thermal maximum (CTmax), and thermal safety margin (TSM) of these three macroalgal species. The results showed that 40°C had the most negative effect on all three species with P. boryana demonstrating better performance compared to both Halimeda species. TPCs from photosynthetic performance revealed thermal sensitivity variations by species and P. boryana exhibited a broader thermal tolerance range compared to Halimeda. On the other hand, TPCs of oxygen production provided similar CTmax values. Based on TPC projections, all three species might survive future ocean warming and marine heatwaves, though these conditions will have significant effects, with P. boryana showing greater tolerance than both Halimeda species. This study highlights the differential thermal responses and sensitivities of these macroalgae, contributing to understanding their potential resiliencies under future climate change scenarios.

Adverse environmental conditions during early life are known to determine adult metabolic phenotype in laboratory species and human populations. However, less is known about developmental programming of adult metabolic phenotype in livestock, given their size and longevity compared to laboratory animals. As maternal and/or fetal glucocorticoid (GC) concentrations rise in stressful conditions during pregnancy, GCs may act as a common mechanism linking early-life environmental conditions to the subsequent metabolic phenotype. This review examines prenatal and longer-term postnatal programming of metabolism by early-life GC overexposure in livestock species with a particular emphasis on sheep. It examines the effects of both cortisol, the natural glucocorticoid and more potent synthetic GCs used clinically to treat threatened pre-term delivery and other conditions during pregnancy. It considers the effects of early- life GC overexposure on the metabolism of specific feto-placental and adult tissues in relation to changes in the growth trajectory, other metabolic hormones and in the functioning of the hypothalamic–pituitary–adrenal axis itself. It highlights the role of GCs as maturational and environmental signals in programming development of a metabolic phenotype fit for survival at birth and future homeostatic challenges. However, the ensuing metabolic phenotype induced by early GC overexposure may become inappropriate for the prevailing postnatal conditions and lead to metabolic dysfunction as functional reserves decline with age. Further studies are needed in livestock to establish whether the metabolic outcomes of early-life GC overexposure are sex-linked, more pronounced in old age and inherited transgenerationally in these species.

Current evidence points to a research-practice gap in mental health. There is a specific unmet need to identify novel strategies to improve diagnostic criteria, especially when clinical manifestations overlap as in the case of bipolar (BD) and major depressive disorder (MDD). Based on the rapidly evolving notion that affective disorders are characterized by disrupted brain-body communication, current efforts of neuropsychiatric research are converging towards the identification of specific clusters of peripheral interconnected biomarkers. We argue that these can capture the complexity of the disease as they are linked to the fundamental pathophysiological mechanisms underlying BD or MDD, and can thus deliver an unbiased biosignature. Here we provide a critical viewpoint on the promises and challenges of biomarkers to identify reliable biosignatures of affective disorders. Novel methodological insight and relevant biomarkers are discussed with a main focus on immunometabolic derangements and disrupted redox balance. Major advancements are reviewed taking into consideration that an unbiased diagnosis can only derive from a deep understanding of how biological, psychological, and social factors interact ultimately affecting the clinical manifestation of affective disorders.

Rewards are rewarding owing to their hedonic or metabolic value. Individual differences in sensitivity to rewards are predictive of mental health problems but may reflect variation in metabolic types. We have assessed the association of two distinguishable aspects of reward sensitivity, openness to rewards (the striving towards multiple rewards) and insatiability by reward (the strong pursuit and fixation to a particular reward), with measures of metabolism and activity in a longitudinal study of representative birth cohort samples. We used data of the Estonian Children Personality Behaviour and Health Study (original n = 1238) collected at age 15, 18 and 25. Reward sensitivity and physical activity were self-reported during a laboratory visit, when also blood sampling, measurement of blood pressure, height and weight, aerobic exercise testing and the diet interview, after the participants had kept food diary, took place. In the younger cohort, physical activity was also assessed by accelerometry at age 18 and 25. Across adolescence and young adulthood, openness to rewards was positively associated with physical activity and negatively with blood pressure and serum levels of glucose, insulin and cholesterol levels. In contrast, insatiability by reward was positively associated with serum triglyceride levels and negatively with energy intake and cardiorespiratory fitness. In conclusion, the two facets of reward sensitivity have a fairly different association with a variety of metabolic and health-related measures. This may explain the variable findings in literature, and suggests that individual differences in reward sensitivity are part of a complex physiological variability, including energy expenditure profiles.

Nutritional status during the developmental periods leads to predisposition to several diseases and comorbidities, highlighting metabolic and reproductive changes throughout adult life, and in the next generations. One of the experimental models used to induce undernutrition is litter size expansion, which decreases the availability of breast milk to pups and delays development. This work evaluated the effects of maternal undernutrition induced by litter size expansion, a maternal undernutrition preconception model, on the metabolic and reproductive alterations of the offspring. For this, metabolic and reproductive parameters were evaluated in male and female offspring of female rats reared in normal (NL - 10 pups: 5 males and 5 females) and large (LL - 16 pups: 8 males and 8 females) litters. Male and female offspring of LL mothers presented higher food intake than the offspring of NL mothers. Male offspring from undernourished females showed reduced body weight from lactation to adulthood, nasoanal distance in childhood, increased nasoanal distance, and decreased Lee index in adult life, while female offspring showed decreased nasoanal distance in childhood. The male offspring from LL mothers showed increased insulin plasma levels and glucose tolerance, and reduced triglycerides plasma levels, without changes in the female offspring. These results indicate that neonatal undernutrition in females predisposes their male and female offspring to develop metabolic alterations, without reproductive repercussions, and male offspring seems to be more susceptible to present these metabolic changes than females. Thus, there are sexual differences in the metabolic responses of the offspring elicited by maternal preconceptional undernutrition.