eBioMedicine

Background/ObjectivesHuman lactoferrin (hLF) is glycoprotein of commercial interest as a food ingredient for gut health. Here, we report an exploratory analysis evaluating the effects of Helaina hLF (effera(R)), produced by Komagataella phaffii, on the adult gut microbiome and fecal metabolites in comparison to bovine LF (bLF). MethodsIn a randomized, double-blind, parallel-arm, controlled trial, 66 healthy adults received either high-dose (HD) effera(R) (3.4 g/day), low-dose (LD) effera(R) (0....

BackgroundHuman milk (HM) bioactive components can have immune modulatory functions, impact the gut microbiome, and may result in functional benefits when added to infant formula (IF). In this single-arm, prospective, intervention study, we tested the effectiveness of an IF with a whey protein concentrate co-enriched in -lactalbumin, milk fat globule membrane (MFGM), and Sn-2 palmitate resulting in protein and lipid profiles observed in HM. The outcomes tested were feeding tolerance, Bifidobacte...

BackgroundLong-term fasting is a promising strategy for improving human health and reducing cardiometabolic risk. Emerging evidence suggests that the gut microbiome may mediate many of these benefits, but the role of its viral component, dominated by bacteriophages, remains poorly understood. MethodsUsing shotgun metagenomic data from a single-arm, monocentric fasting intervention, this study profiled the gut virome (n=89 individuals, n=241 samples) before and after 9.8 days of fasting ([~]250 ...

Iron deficiency (ID) in children caused by dietary deprivation can be alleviated in [~]40% cases with iron-fortified nutritional solutions. Devising more effective nutritional solutions requires a quantitative understanding of iron homeostasis, which is lacking. Here, we developed a physiologically-based mathematical model of paediatric iron homeostasis that recapitulates ID due to dietary deprivation and its alleviation using nutritional solutions. The model integrates key cellular and systemic...

BackgroundCaloric restriction (CR) improves markers of biological aging, yet long-term effects on the human metabolome remain unclear. ObjectiveThis study examined the effects of CR (2 years) in healthy adults without obesity on circulating metabolites linked to aging and metabolic adaptations. MethodsUntargeted metabolomics was performed using fasted plasma samples collected at baseline, 12, and 24 months (BL, 12M, 24M) from CALERIE participants randomized to CR or ad libitum (AL) control. A ...

The gut microbiota has been implicated in regulating body composition, insulin resistance, and energy metabolism through microbial metabolites, including short-chain fatty acids (SCFAs) and amino acids. However, evidence in adolescents, particularly regarding sex-specific differences and lifestyle such as alcohol intake, remains limited. Characterizing sex-specific metabolic signatures in adolescence may improve early identification of metabolic risk. To address this gap, we investigated associ...

BackgroundPrediabetes is associated with an increased risk of progression to type 2 diabetes. While dietary interventions in prediabetes traditionally primary focus on energy and macronutrient intake, the role of eating timing has recently been highlighted. This study aimed to examine the relationships between components of eating timing patterns and glycaemic parameters in prediabetes. MethodsIn 297 individuals with prediabetes, i.e. impaired fasting glucose or impaired glucose tolerance (age ...

Poor sleep is linked to consumption of sugary foods/beverages and high neural responsivity to palatable food cues. Yet, whether hedonic liking for sweet taste explains these associations remains unclear. We examined cross-sectional associations of five sleep traits (chronotype, sleep duration, insomnia frequency, snoring, daytime dozing) and a composite sleep score with sweet food liking, and total and free sugar intake in 76,734 UK Biobank participants (39-72 years, 56.3% female). Models adjust...

Human milk oligosaccharides (HMOs) are bioactive components in human milk that influence infant health, yet their role in growth trajectories remains unclear. This study examined associations between concentrations of individual HMOs and child growth outcomes: length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) z-scores--at 24 months of age in a population-based cohort from Leon, Nicaragua. Data were analyzed from 295 mother-infant dyads. HMO concentrations in human milk coll...

IntroductionFiber intake is the most common nutritional inadequacy in the Western diet, with most adults consuming less than half of the recommended intake with only 5% of adults meeting the RDI. A novel, short-chain beta-glucan derived from oats (scOat Fiber), with improved solubility, low viscosity and enhanced palatability, compared to conventional oat fibers, was investigated for its benefits as a source of fiber supplementation. MethodsA 14-day pilot study evaluated the gastrointestinal to...

Seasonality of inflammatory and infectious diseases is associated with several factors, including serum vitamin D fluctuations and immunological state. We longitudinally investigated peripheral blood mononuclear cell (PBMC) methylomes of healthy South African adults in summer, winter, and after high-dose winter vitamin D3 supplementation to determine whether vitamin D3 modulates seasonal epigenetic variations and whether these underpin reported seasonal transcriptional oscillations. PBMC DNA met...

The biomarker MetaboHealth represents a novel indicator of overall health in middle age and may potentially be suitable as actionable health check in prevention strategies. MetaboHealth is a blood-based metabolomic composite score that predicts a wide range of age-related conditions and mortality in large European cohorts. Here, we investigated whether MetaboHealth can be personalised and limited to clinically validated metabolomic markers. Next, we assessed whether the updated MetaboHealth scor...

Cancer is among the leading causes of death worldwide; however, with incidence rising, there is a requirement to identify novel risk factors and biomarkers to prevent and diagnose cancer earlier. Previous work has implicated a role of the gut microbiome in cancer aetiology; however, its causal relevance is not clear. Whilst Mendelian randomisation (MR) is increasingly being applied to assess the causal role of the gut microbiome on several health outcomes, the complexities and limitations of the...

South Asian populations remain underrepresented in cancer genomics, despite elevated risk for certain malignancies and distinct clinical profiles. This gap is especially pronounced for British Bangladeshi and Pakistani communities. We analysed data from 57,416 individuals of Bangladeshi and Pakistani ancestry in the UK-based Genes & Health cohort, integrating electronic health records, cancer registry data, and whole-exome sequencing (n=43,462). Among them, 2,782 (4.8%) had cancer, with earlier ...

Aging is accompanied by molecular changes across multiple biological systems that contribute to functional decline and increased disease risk, but the underlying mechanisms and inter-individual variation remain poorly understood. We investigated whether multi-omics integration can reveal coordinated molecular processes associated with accelerated PhenoAge, a clinical biomarker-based estimate of biological aging. Using UK Biobank data from [~]20,000 participants, we integrated plasma proteomics a...

Early-life gut microbiome development is shaped by complex maternal and nutritional influences, yet the temporal and directional structure of these interactions remains unclear. In a longitudinal study of 152 mother-infant dyads in rural Burkina Faso, we examined how maternal gut and milk microbiomes, alongside milk components, influence infant gut microbiome development during the first six months. At 1-2 months, the infant gut microbiome clustered into three types: Escherichia-dominated, Bifid...

Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, an...

BackgroundObservational studies have linked high adherence to the "Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay" (MIND) diet to improved cognitive functions in older adults. The underlying peripheral and central mechanisms of this association remain poorly understood, although multiple nutrients in the MIND diet are known for their anti-inflammatory effects. Therefore, we explored the cross-sectional relation between MIND diet adherence (Dutch ve...

Recent methodological advances have enabled minimally invasive, convenient self-assessment of central circadian phase in home-based settings [1]. In this report, we describe salivary melatonin onset secretion profiles in 261 participants (36% male; age range, 9-83 years) who were recruited from 18 clinics in North America or by self-referral. All participants received a standardized, at-home central circadian phase assessment kit by mail or directly through their provider, along with written and...

BackgroundTime-restricted eating (TRE) has gained popularity for weight loss and metabolic health. While some evidence suggests greater benefits when TRE aligns with circadian rhythms--characterized by early daytime eating and avoidance of nighttime intake, often referred to as early TRE (eTRE), other studies report no meaningful differences between eTRE, other TRE approaches with or without exercise, or calorie restriction (CR), and robust comparative evidence remains limited. AimTherefore, th...