Previous metabolomic studies have identified putative blood biomarkers of dietary intake. These biomarkers need to be replicated in other populations and tested for reproducibility over time for the potential use in future epidemiological studies. We conducted a metabolomics analysis among 671 racially/ethnically diverse men and women included in a diet validation study to examine the correlation between >100 food groups/items (101 by a food frequency questionnaire (FFQ), 105 by 24-h diet recalls (24HRs)) with 1141 metabolites measured in fasting plasma sample replicates, six months apart. Diet–metabolite associations were examined by Pearson’s partial correlation analysis. Biomarker reproducibility was assessed using intraclass correlation coefficients (ICCs). A total of 677 diet–metabolite associations were identified after Bonferroni adjustment for multiple comparisons and restricting absolute correlation coefficients to greater than 0.2 (601 associations using the FFQ and 395 using 24HRs). The median ICCs of the 238 putative biomarkers was 0.56 (interquartile range 0.46–0.68). In this study, with repeated FFQs, 24HRs and plasma metabolic profiles, we identified several potentially novel food biomarkers and replicated others found in our previous study. Our findings contribute to the growing literature on food-based biomarkers and provide important information on biomarker reproducibility which could facilitate their utilization in future nutritional epidemiological studies.

Previous cross-sectional metabolomics studies have identified many potential dietary biomarkers, mostly in blood. Few studies examined urine samples although urine is preferred for dietary biomarker discovery. Furthermore, little is known regarding the reproducibility of urinary metabolomic biomarkers over time. We aimed to identify urinary metabolomic biomarkers of diet and assess their reproducibility over time. We conducted a metabolomics analysis among 648 racially/ethnically diverse men and women in the Diet Assessment Sub-study of the Cancer Prevention Study-3 cohort to examine the correlation between >100 food groups/items [101 by a food frequency questionnaire (FFQ), and 105 by repeated 24 h diet recalls (24HRs)] and 1391 metabolites measured in 24 h urine sample replicates, six months apart. Diet–metabolite associations were examined by Pearson’s partial correlation analysis. Biomarkers were evaluated for prediction accuracy assessed using area under the curve (AUC) calculated from the receiver operating characteristic curve and for reproducibility assessed using intraclass correlation coefficients (ICCs). A total of 1708 diet–metabolite associations were identified after Bonferroni correction for multiple comparisons and restricting correlation coefficients to >0.2 or <−0.2 (1570 associations using the FFQ and 933 using 24HRs), 513 unique metabolites correlated with 79 food groups/items. The median ICCs of the 513 putative biomarkers was 0.53 (interquartile range 0.42–0.62). In this study, with comprehensive dietary data and repeated 24 h urinary metabolic profiles, we identified a large number of diet–metabolite correlations and replicated many found in previous studies. Our findings revealed the promise of urine samples for dietary biomarker discovery in a large cohort study and provide important information on biomarker reproducibility, which could facilitate their utilization in future clinical and epidemiological studies.

The objective of this study was to calculate an oxidative balance score (OBS) utilizing diet and lifestyle information collected from 1322 women during the second trimester of pregnancy in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study. An energy-adjusted OBS was calculated using nutrient information from a Food Frequency Questionnaire (FFQ), lifestyle measures, and plasma folate and vitamin D levels. Using the least absolute shrinkage and selection operator method, 91 food items from the FFQ were selected and they accounted for 82% of the variance in the OBS, with cruciferous vegetables, citrus fruits, fruit juice, and coffee being among the highest anti-oxidant predictors, and red meats and alcohol among the highest pro-oxidant contributors. Urinary F₂-isoprostane, an objective indicator of oxidative stress, was lower with increasing OBS quintiles in a stairstep manner (p for trend = 0.0003), suggesting the possible utility of the OBS as an indicator of oxidative stress. The OBS was moderately correlated with the Healthy Eating Index (correlation coefficient = 0.6076), suggesting it provides a distinct measure of a healthy diet. In conclusion, the OBS may serve as a valid reflective indicator of urinary F₂-isoprostanes and an epidemiological tool to inform intervention studies, in order to minimize oxidative stress during pregnancy.

Introduction People with cystic fibrosis (PwCF) are at high risk for developing cystic fibrosis (CF)-related diabetes (CFRD), which worsens morbidity and mortality. Although the pathological events leading to the development of CFRD are complex and not completely understood, dietary factors may play a role. For example, habitual intake of dietary added sugar (i.e., sugar not naturally occurring in foods) has been shown to be increased in PwCF and this excess intake of added sugar could increase the risk of CFRD. Methods and analysis/design The goal of this ongoing double-blind, randomised, parallel-group clinical trial is to recruit approximately 60 clinically stable adults with CF to determine if a low-added sugar intervention improves beta-cell responsiveness and insulin sensitivity (Aim 1), reduces visceral adipose tissue (VAT) and other ectopic fat deposition (Aim 2) and improves plasma redox status (Aim 3) over 8 weeks compared with a typical CF diet. All foods will be provided. Participant selection criteria include confirmed CF diagnosis without CFRD, ≥18 years of age, and baseline estimated daily total added sugar intake >16 tsp. Eligible participants will be randomised to one of two arms: a low-added sugar diet (<5% of kcal from added sugars) or a high-added sugar (≥13% kcal from added sugars) diet. The two diets will be isocaloric and provide 35%–40% kcal from fat. Participants will be seen in the research unit for a screening, baseline/randomisation and 4-week and 8-week follow-up visits. Major study endpoints are changes in beta-cell responsiveness determined by a glucose-potentiated arginine stimulation test (primary endpoint), VAT assessed by magnetic resonance imagin (MRI) and fasted plasma cysteine redox potential. Diet tolerance, body weight and compliance are monitored weekly by phone by an unblinded study dietitian. All analyses will be intention-to-treat. Changes in study endpoints will be assessed with repeated-measures analysis. Models will assess the effects by study arm, time on study, and the interaction between arm and time on study. Ethics and dissemination The National Institutes of Health (NIH) funds this study (R01 DK133523). The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 000004517). Any protocol modifications will be reviewed and approved by the IRB prior to implementation and communicated with the study team and participants, as relevant. We will provide reports of the findings to the NIH and Emory IRB in regular progress reports and post the findings on www.Clinicaltrials.gov. We will inform the findings of the study to the scientific community through presentations and peer-reviewed publications. Authorship for any resulting publications will follow the guidelines established by the International Committee of Medical Journal Editors. Trial registration number This research study is registered at www.Clinicaltrials.gov (NCT05766774).

Introducing grain legumes, i.e., pulses, into any food pattern effectively increases dietary fiber and other bioactive food components of public health concern; however, the impact depends on the amount consumed. Given the convergence of preclinical and clinical data indicating that intake of at least 300 g (1.5 cup) of cooked pulse per day has clinically observable benefit, the feasibility for a typical consumer was demonstrated by creation of a fourteen-day menu plan that met this criterion. This menu plan, named Bean Cuisine, was comprised of a combination of five cooked pulses: dry beans, chickpeas, cowpeas, dry peas, and lentils. As reported herein, the impact of each menu day of the fourteen-day plan on gut microbial composition and predicted function was evaluated in female C57BL/6J mice, a strain commonly used in studies of metabolic dysfunction-associated chronic diseases. We report that pulse-related effects were observed across a wide variety of food item combinations. In comparison to a pulse-free human cuisine, all pulse menu days enriched for a gut ecosystem were associated with changes in predicted metabolic pathways involving amino acids (lysine, tryptophan, cysteine), short-chain fatty acids (butyrate, acetate), and vitamins (B₁, B₆, B₉, B₁₂, K₂) albeit via different combinations of microbiota, according to the PICRUSt2 estimates. The predicted metabolic functions correlating with the various pulses in the menus, indicate the value of a food pattern comprised of all pulse types consumed on a regular basis. This type of multi-pulse food pattern has the potential to enhance the taxonomic and functional diversity of the gut microbiome as a means of strengthening the resilience of the gut ecosystem to the challenges associated with the daily activities of living.