Publications by authors named "Kari Wong"

Introduction: There is a lack of biomarkers of clinically important diets, such as the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet.

Objectives: Our study explored serum metabolites associated with adherence to the MIND diet.

Methods: In 3,908 Atherosclerosis Risk in Communities (ARIC) study participants, we calculated a modified MIND diet score based on a 66-item self-reported food frequency questionnaire (FFQ).

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  • The increasing consumption of artificially sweetened beverages has raised concerns about their potential negative health effects, creating a need for reliable biomarkers to better assess dietary intake and understand their metabolic impacts.
  • The study aimed to identify serum metabolites linked to the consumption of these beverages by analyzing fasting serum samples from participants in the Atherosclerosis Risk in Communities (ARIC) study, categorized by their level of beverage consumption.
  • Results revealed that 11 specific serum metabolites were significantly associated with artificially sweetened beverage intake, with heavier drinkers showing higher levels of most metabolites and lower levels of glycocholenate sulfate.
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  • Circulating metabolite levels are indicators of human health and can be influenced by genetic factors; however, most research has focused on European populations.
  • The study utilized metabolomics data from 25,058 diverse individuals, identifying 1,778 gene loci linked to 667 metabolites and providing methods for data analysis and handling.
  • Notably, the research uncovered new genetic associations, including 108 novel gene-metabolite pairs, and highlighted sex differences in metabolism, enhancing the understanding of genetic influences on human health.
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Background: Vitamin A is essential for physiological processes like vision and immunity. Vitamin A's effect on gut microbiome composition, which affects absorption and metabolism of other vitamins, is still unknown. Here we examined the relationship between gut metagenome composition and six vitamin A-related metabolites (two retinoid: -retinol, 4 oxoretinoic acid (oxoRA) and four carotenoid metabolites, including beta-cryptoxanthin and three carotene diols).

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  • - Metabolomics research assessed the effects of prebiotic fiber (inulin) and omega-3 fatty acids on 64 healthy adults over a 6-week trial by profiling 534 stool and 799 serum metabolites.
  • - Significant metabolites were identified that could distinguish between the two supplements: indoleproprionate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoate for omega-3, and eicosapentaenoate for fiber, with high accuracy (AUC scores of 0.87 and 0.86).
  • - Changes in indoleproprionate levels from fiber were linked to shifts in gut microbiome composition, suggesting a connection between dietary fiber
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Rationale & Objective: While urine excretion of nitrogen estimates the total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of 6 protein-rich foods and to examine whether dietary protein-related metabolites are associated with incident chronic kidney disease (CKD).

Study Design: Prospective cohort study.

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  • * A study involving 1,453 participants from TwinsUK found a positive link between DAL and early-stage CKD, identifying various metabolites connected to both.
  • * Certain metabolites, particularly from stool samples, showed a relationship with gut microbial species, highlighting the potential for gut microbiota interventions to mitigate the effects of DAL on CKD progression; however, further research is needed to confirm causality.
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Background: Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults.

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Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs.

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Unlabelled: Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings.

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Background: Dairy consumption is related to chronic disease risk; however, the measurement of dairy consumption has largely relied upon self-report. Untargeted metabolomics allows for the identification of objective markers of dietary intake.

Objectives: We aimed to identify associations between dietary dairy intake (total dairy, low-fat dairy, and high-fat dairy) and serum metabolites in 2 independent study populations of United States adults.

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Short-chain fatty acids (SCFA) are involved in immune system and inflammatory responses. We comprehensively assessed the host genetic and gut microbial contribution to a panel of eight serum and stool SCFAs in two cohorts (TwinsUK,  = 2507; ZOE PREDICT-1,  = 328), examined their postprandial changes and explored their links with chronic and acute inflammatory responses in healthy individuals and trauma patients. We report low concordance between circulating and fecal SCFAs, significant postprandial changes in most circulating SCFAs, and a heritable genetic component (average : serum = 14%(SD = 14%); stool = 12%(SD = 6%)).

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Background: Dietary consumption has traditionally been studied through food intake questionnaires. Metabolomics can be used to identify blood markers of dietary protein that may complement existing dietary assessment tools.

Objectives: We aimed to identify associations between 3 dietary protein sources (total protein, animal protein, and plant protein) and serum metabolites using data from the Atherosclerosis Risk in Communities Study.

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Biologics address a range of unmet clinical needs, but the occurrence of biologics-induced liver injury remains a major challenge. Development of cimaglermin alfa (GGF2) was terminated due to transient elevations in serum aminotransferases and total bilirubin. Tocilizumab has been reported to induce transient aminotransferase elevations, requiring frequent monitoring.

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Article Synopsis
  • Circulating metabolite levels can indicate health status, but the genetics behind them are not completely understood.
  • A study involving whole-genome sequencing analyzed data from 11,840 multi-ethnic participants and identified 1,985 new variant-metabolite associations, validating 761 known associations.
  • Further analysis showed links between metabolites and tissues, causal relationships with diseases, and potential regulation by plasma proteins, enhancing our understanding of the genetic factors in human metabolism and disease.
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Background: The DASH (Dietary Approaches to Stop Hypertension) diets reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. We identified metabolites associated with systolic BP or diastolic BP (DBP) changes induced by dietary interventions (DASH versus control arms) in 2 randomized controlled feeding studies-the DASH and DASH-Sodium trials.

Methods: Metabolomic profiling was conducted in serum and urine samples collected at the end of diet interventions: DASH (n=219) and DASH-Sodium (n=395).

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Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool.

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Background: High ultra-processed food consumption is associated with higher risk of CKD. However, there is no biomarker for ultra-processed food, and the mechanism through which ultra-processed food is associated with CKD is not clear. Metabolomics can provide objective biomarkers of ultra-processed food and provide important insights into the mechanisms by which ultra-processed food is associated with risk of incident CKD.

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Gut microbiome studies have documented depletion of butyrate-producing taxa in type 2 diabetes. We analyzed associations between butyrate-producing taxa and detailed measures of insulin homeostasis, whose dysfunction underlies diabetes in 224 non-Hispanic Whites and 129 African Americans, all of whom completed an oral glucose tolerance test. Stool microbiome was assessed by whole-metagenome shotgun sequencing with taxonomic profiling.

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Background: Greater adherence to plant-based diets is associated with a lower risk of incident chronic kidney disease (CKD). Metabolomics can help identify blood biomarkers of plant-based diets and enhance understanding of underlying mechanisms.

Objectives: Using untargeted metabolomics, we aimed to identify metabolites associated with 4 plant-based diet indices (PDIs) (overall PDI, provegetarian diet, healthful PDI, and unhealthful PDI) and incident CKD in 2 subgroups within the Atherosclerosis Risk in Communities study.

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Scope: Lack of biomarkers is a challenge for the accurate assessment of protein intake and interpretation of observational study data. The study aims to identify biomarkers of a protein-rich dietary pattern.

Methods And Results: The Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart) trial is a randomized cross-over feeding study which tested three dietary patterns with varied macronutrient content (carbohydrate-rich; protein-rich with about half from plant sources; and unsaturated fat-rich).

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Scope: Serum metabolomic markers of the Dietary Approaches to Stop Hypertension (DASH) diet are previously reported. In an independent study, the similarity of urine metabolomic markers are investigated.

Methods And Results: In the DASH-Sodium trial, participants are randomly assigned to the DASH diet or control diet, and received three sodium interventions (high, intermediate, low) within each randomized diet group in random order for 30 days each.

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