Dietary microRNAs (miRNAs) constitute a novel nexus among nutrition, gene regulation, and human health. Accumulating evidence indicates that miRNAs ingested with food can traverse the gastrointestinal barrier, enter systemic circulation, and modulate gene expression through gene-silencing mechanisms in critical metabolic pathways of mammals. These observations have driven growing interest in elucidating their bioavailability, molecular stability, and physiological relevance. In this review, we provide a systematic analysis of dietary miRNAs, with particular emphasis on plant-derived species and those present in breast milk, evaluating controversies and their potential implications for human health and disease. Breast milk is highlighted as a key vehicle for miRNA-mediated communication in early life, integrating maternal, environmental, and infant signals. Drawing on these insights, we identify major challenges in dietary miRNA research and propose strategies to address them, establishing a structured framework to guide future studies. Finally, we highlight the biotechnological potential of dietary miRNAs in promoting nutritional approaches to advance human health.

Growing evidence suggests that dietary interventions can influence cancer progression and patient outcomes. Here, we discuss mechanistic links between diet and cancer biology including those related to systemic hormone signaling, modulation of nutrient availability within the tumor microenvironment, and interactions with the immune system and microbiome, while highlighting their interconnectedness. Further, we review preclinical and clinical data evaluating specific diets, including their use with cancer therapies. Given the interest in diet as an adjunct to cancer care, it is essential to establish evidence-based dietary strategies for optimizing patient outcomes and quality of life.

Severe nutrient deficiency in utero has been associated with elevated type 2 diabetes (T2D) odds across the life span. Optimal early-life nutrition interventions that mitigate T2D in adulthood remain unclear, largely due to limited understanding of the underlying biologic pathways. In this review, we summarize recent evidence of physiologic mechanisms by which early-life nutrition could influence T2D pathophysiology in adulthood. We focus on studies evaluating genes as effect modifiers as well as epigenetic reprogramming of gene expression, structural development of key tissues and organs, and accelerated biological aging as causal mediators. We present evidence regarding biologic alterations that are nutrition sensitive during the first 1,000 days of life and could persistently impact glucose-insulin homeostasis across decades. This review emphasizes studies published from 2015 to 2025, with large-scale biological data generated from high-throughput technologies.

Glucagon-like peptide-1 (GLP-1)-based obesity pharmacotherapies have revolutionized obesity treatment. In this review, we discuss the discovery of GLP-1 and evaluate the efficacy of marketed and investigational GLP-1 receptor (GLP-1R) agonists (GLP-1RAs), most notably semaglutide, as well as their potential central mechanism of action. We highlight the GLP-1R/glucose-dependent insulinotropic polypeptide receptor (GIPR) dual agonist tirzepatide and the GLP-1RA/GIPR antagonist maridebart cafraglutide, discussing how both methods of GIPR targeting can produce beneficial metabolic effects. The lack of evidence for the anorectic effects of GIPR agonism or antagonism alone in humans is noted, and the review concludes with an evaluation of other reasons for the greater efficacy of GIPR/GLP-1R dual targeting compounds over semaglutide.

Preterm birth disrupts nutrient-responsive signaling pathways critical for skeletal muscle growth and long-term metabolic health. Despite improvements in neonatal care, preterm infants often experience postnatal growth failure marked by impaired lean mass accretion. This review examines how prematurity intrinsically alters insulin and amino acid signaling to mechanistic target of rapamycin complex 1 (mTORC1), a central regulator of translation initiation and protein synthesis. Evidence from translational models reveals blunted activation of mTORC1 and its downstream effectors, independent of birth weight or comorbidities. Defects in insulin-PDK1/mTORC2-Akt signaling and amino acid sensing, particularly leucine sensing, contribute to impaired mTORC1-dependent translation initiation and reduced muscle protein synthesis. Feeding strategies that mimic physiological nutrient pulsatility, including intermittent bolus feeding and pulsatile leucine supplementation during continuous feeding, show promise in restoring anabolic signaling. Understanding these molecular impairments provides a foundation for targeted nutritional and therapeutic interventions to improve muscle growth and mitigate long-term health risks in individuals born preterm.

Due to its unique chemical nature, zinc is indispensable to diverse functional roles in protein structure, catalysis, and the dynamic regulation of metabolic processes. In support of zinc-dependent metabolic functions, the zinc content of peripheral blood plasma turns over in exchange with cells on the order of 100-fold daily. Although zinc deficiency is well-known for its effects in reducing child growth and impairing immune function, a growing body of evidence has implicated zinc intake and plasma zinc concentration in the complex etiological web of metabolic disease. In turn, stresses linked with the progression of metabolic disease interfere with protein-zinc binding and accelerate zinc loss from the body. We summarize evidence connecting zinc with metabolic disease, discuss the effects of metabolic disease on zinc homeostasis, and suggest areas for future research to integrate knowledge of zinc metabolism with efforts to prevent and treat metabolic disease.

Spatial metabolomics has emerged as a transformative approach for understanding how metabolism is organized within tissues and how nutritional factors influence health and disease. By preserving the spatial context of metabolites within intact tissue architecture, techniques such as MALDI and DESI imaging mass spectrometry reveal metabolic heterogeneity that bulk analyses cannot capture. This review examines how spatial metabolomics advances nutrition research across multiple domains: from mapping nutrient distributions in foods to understanding how diet reshapes tissue metabolism in disease states. We highlight recent innovations, including single-cell-resolution imaging, 3D metabolome reconstruction, stable isotope tracing, and multiomics integration. Key applications demonstrate how dietary patterns drive glycogen accumulation in cancer, alter lipid zonation in fatty liver disease, and modulate brain metabolism through the gut-brain axis. These spatially resolved insights establish direct mechanistic links between nutrition, tissue metabolism, and disease pathogenesis.

Ultraprocessed foods (UPFs), which feature reductions in naturally occurring food components (fiber, phytochemicals) as well as the addition of fat, sugar, salt, and artificial food components (colorings, preservatives) are consumed in large quantities globally. Although a growing body of research has suggested that higher levels of UPF consumption are associated with poorer cardiometabolic outcomes, literature synthesizing the evidence that UPF consumption has negative effects on the aging brain has been scarce. This review provides a comprehensive view of the evidence connecting UPF consumption to downstream consequences for the brain in aging, including proposed mechanisms of action, evidence supporting those mechanisms from basic science studies, and clinical evidence. We then survey current challenges and opportunities in the study of brain aging effects of UPF consumption and provide recommendations for researchers and policymakers.

This article presents a nuanced analysis of current evidence regarding the role of emotions as understudied mediators of the effectiveness of type 2 diabetes (T2D) prevention and management programs. It reviews empirical literature on how indicators of poor mental health, as well as positive affective functioning, are relevant to health behaviors that contribute to T2D risk, such as compliance with recommended diets and improved nutrition. Addressing these emotional aspects of diabetes may be an effective means of improving uptake, and ultimately efficacy, of efforts to reduce the burden of T2D. This article also discusses examples of diabetes self-management efforts that aim to simultaneously address diabetes care and emotional health needs across clinical and community settings, including the collaborative care model, peer-led programs, and community health educators. Finally, this article considers what centering the emotional side of diabetes means for innovative health promotion efforts for people with T2D.

Obesity is a chronic disease driven by complex neurohormonal and behavioral mechanisms that regulate adipocyte mass by impacting appetite, food reward, and ingestive patterns. This review synthesizes evidence from objective, rather than verbal report-based, methodologies examining how bariatric surgery and obesity medicines modify human eating behavior. Roux-en-Y gastric bypass and sleeve gastrectomy consistently reduce total energy intake through sustained reductions in meal size and eating rate, without systematic changes in meal initiation or macronutrient selection. In small cohorts where food choices did shift, alterations were associated with greater weight loss, highlighting interindividual variability. GLP-1-based therapy similarly reduces energy intake and improves appetitive behavior through strengthened gut-brain signaling, whereas naltrexone/bupropion primarily targets central reward circuits. Overall, bariatric surgery leads to reduced intake without altering food choices, suggesting a benefit from eating "less of the same," whereas equivalent conclusions for obesity medicines remain premature due to limited direct evidence.

This review provides a comprehensive overview of dietary plant bioactive intake among populations. Plant-based diets are rich in bioactive phytochemicals such as (poly)phenols, carotenoids, alkaloids, glucosinolates, and many other molecules scarcely assessed. Despite the recognized health benefits attributed to most phytochemicals, there is a considerable lack of information on the intake of these food bioactives across different populations. When available, data indicate that the intake of plant bioactives may be influenced by factors such as dietary habits, age, sex/gender, ethnicity, and cultural practices. Most information available regards (poly)phenols and carotenoids, as well as some specific compounds of interest because of commercial or safety aspects. This work represents a pioneering effort to compile comprehensive data on the intake of dietary plant bioactives, thereby contributing to the body of scientific knowledge and informing future research on these dietary components of nutritional interest.

Time-restricted feeding (TRF), which confines food intake to a defined daily window, has emerged as a promising nonpharmacological strategy to improve health by aligning behavior and physiology with the endogenous circadian clock. Preclinical research has expanded substantially, now spanning both nocturnal and diurnal species, diverse dietary regimens, varying intervention durations, and examinations of sex-specific responses. These consistently show that synchronizing feeding-fasting cycles with the natural active phase of an organism's circadian rhythm enhances rhythmic gene expression across tissues. Concomitantly, this mitigates metabolic dysfunction, reduces inflammation, and lowers disease risk, often without reducing caloric intake. While findings in animal models are robust, human outcomes have been more modest and variable, influenced by the timing and duration of feeding window, metabolic state, and sex. This review synthesizes current insights into the relationship between TRF and circadian rhythms, highlighting recent discoveries and the challenges that remain for translation to humans.

2-Oxo acid dehydrogenase complexes include four members to oxidatively decarboxylate pyruvate, 2-oxoglutarate, 2-oxoadipate, and branched-chain 2-oxo acids. The complexes produce CO2, acyl-coenzyme As (acyl-CoAs), and NADH through consecutive action of three enzymes with their coenzymes: 2-oxo acid dehydrogenase with thiamine diphosphate, dihydrolipoyllysine-residue acyltransferase with the lipoyllysine prosthetic group, and dihydrolipoyl dehydrogenase with FAD. Some of the complexes include additional regulatory proteins. Producing energy in the form of NADH and acyl-CoAs, which are feedback inhibitors, the complexes mediate the Ca2+ activation of mitochondrial function, couple metabolism of glucose and amino acids, are essential for biosynthesis of the signaling molecules acetylcholine and glutamate, regulate metabolism through posttranslational acylations including histones acylations, and sense the metabolic imbalance as nonoptimal ratios of their substrates and products. The complexes signal the imbalance by the generation of reactive species: O2*-, thiyl radicals, thiamine-dependent carbon radicals, and/or peracids, potentially involved in DNA damage and development of diseases.

The advent of oral vaccines (OVs) in the mid-twentieth century led to dramatic reductions in the global burden of gut and gut-acquired infectious diseases such as polio, rotavirus, cholera, and typhoid. Paradoxically, OVs have been less effective in low- and middle-income countries (LMICs) where morbidity and mortality from these diseases are highest. This so-called tropical barrier does not reflect intrinsic defects of OV platforms but rather the influence of adverse host and environmental conditions more prevalent in LMIC settings. Among these, nutritional status stands out as a key modifiable determinant of OV performance. The collision of undernutrition and poor sanitation in LMIC contexts fosters repeated exposure to enteropathogens via contaminated food, water, and living environments; proinflammatory gut microbiota; disrupted intestinal mucosal architecture and barrier function; and profoundly altered immune development. Together, these factors hinder the replication and take of OVs. Micronutrient deficiencies-particularly in zinc, vitamin A, vitamin D, and iron-further compromise intestinal epithelial homeostasis, antigen presentation, and antibody responses to undermine OV efficacy. This review synthesizes recent advances in our understanding of how human nutrition shapes OV immunogenicity. By integrating epidemiologic evidence, field interventions, and mechanistic insights, we outline pathways linking diet, gut health, and vaccine response and strategies to close global gaps in OV performance.

I never expected to be a nutritional scientist. I developed an interest in ingestive behavior as an undergraduate in biology when mentors included me in research activities and directed me toward studies of the physiology of thirst for my PhD degree. While conducting basic studies on drinking behavior, my primary interests emerged. I wanted to study eating behavior to find effective strategies to improve food choices and manage overconsumption leading to obesity. Those studies started with animal models of obesity, but my interest in practical approaches to weight management led to studies in humans, the most difficult species to understand. With collaboration from colleagues, students, and staff, my team has characterized food properties that drive intake, including variety, energy density, and portion size. Studies aimed at understanding properties of food that influence eating behavior are now recognized as integral to nutrition, and I have found a natural home in this field.