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1.
Metabolomics ; 16(11): 119, 2020 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-33164148

RESUMO

INTRODUCTION: To date, there has been little effort to develop standards for metabolome-based gut microbiome measurements despite the significant efforts toward standard development for DNA-based microbiome measurements. OBJECTIVES: The National Institute of Standards and Technology (NIST), The BioCollective (TBC), and the North America Branch of the International Life Sciences Institute (ILSI North America) are collaborating to extend NIST's efforts to develop a Human Whole Stool Reference Material for the purpose of method harmonization and eventual quality control. METHODS: The reference material will be rationally designed for adequate quality assurance and quality control (QA/QC) for underlying measurements in the study of the impact of diet and nutrition on functional aspects of the host gut microbiome and relationships of those functions to health. To identify which metabolites deserve priority in their value assignment, NIST, TBC, and ILSI North America jointly conducted a workshop on September 12, 2019 at the NIST campus in Gaithersburg, Maryland. The objective of the workshop was to identify metabolites for which evidence indicates relevance to health and disease and to decide on the appropriate course of action to develop a fit-for-purpose reference material. RESULTS: This document represents the consensus opinions of workshop participants and co-authors of this manuscript, and provides additional supporting information. In addition to developing general criteria for metabolite selection and a preliminary list of proposed metabolites, this paper describes some of the strengths and limitations of this initiative given the current state of microbiome research. CONCLUSIONS: Given the rapidly evolving nature of gut microbiome science and the current state of knowledge, an RM (as opposed to a CRM) measured for multiple metabolites is appropriate at this stage. As the science evolves, the RM can evolve to match the needs of the research community. Ultimately, the stool RM may exist in sequential versions. Beneficial to this evolution will be a clear line of communication between NIST and the stakeholder community to ensure alignment with current scientific understanding and community needs.

2.
Adv Nutr ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200182

RESUMO

In the field of human nutrition, randomized controlled trials (RCTs) are considered the gold standard for establishing causal relations between exposure to nutrients, foods, or dietary patterns and prespecified outcome measures, such as body composition, biomarkers, or event rates. Evidence-based dietary guidance is frequently derived from systematic reviews and meta-analyses of these RCTs. Each decision made during the design and conduct of human nutrition RCTs will affect the utility and generalizability of the study results. Within the context of limited resources, the goal is to maximize the generalizability of the findings while producing the highest quality data and maintaining the highest levels of ethics and scientific integrity. The aim of this document is to discuss critical aspects of conducting human nutrition RCTs, including considerations for study design (parallel, crossover, factorial, cluster), institutional ethics approval (institutional review boards), recruitment and screening, intervention implementation, adherence and retention assessment, and statistical analyses considerations. Additional topics include distinguishing between efficacy and effectiveness, defining the research question(s), monitoring biomarker and outcome measures, and collecting and archiving data. Addressed are specific aspects of planning and conducting human nutrition RCTs, including types of interventions, inclusion/exclusion criteria, participant burden, randomization and blinding, trial initiation and monitoring, and the analysis plan.

3.
Metabolomics ; 16(12): 121, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219392

RESUMO

BACKGROUND: Dietary patterns low in glycemic load are associated with reduced risk of cardiometabolic diseases. Improvements in serum lipid concentrations may play a role in these observed associations. OBJECTIVE: We investigated how dietary patterns differing in glycemic load affect clinical lipid panel measures and plasma lipidomics profiles. METHODS: In a crossover, controlled feeding study, 80 healthy participants (n = 40 men, n = 40 women), 18-45 y were randomized to receive low-glycemic load (LGL) or high glycemic load (HGL) diets for 28 days each with at least a 28-day washout period between controlled diets. Fasting plasma samples were collected at baseline and end of each diet period. Lipids on a clinical panel including total-, VLDL-, LDL-, and HDL-cholesterol and triglycerides were measured using an auto-analyzer. Lipidomics analysis using mass-spectrometry provided the concentrations of 863 species. Linear mixed models and lipid ontology enrichment analysis were implemented. RESULTS: Lipids from the clinical panel were not significantly different between diets. Univariate analysis showed that 67 species on the lipidomics panel, predominantly in the triacylglycerol class, were higher after the LGL diet compared to the HGL (FDR < 0.05). Three species with FA 17:0 were lower after LGL diet with enrichment analysis (FDR < 0.05). CONCLUSION: In the context of controlled eucaloric diets with similar macronutrient distribution, these results suggest that there are relative shifts in lipid species, but the overall pool does not change. Further studies are needed to better understand in which compartment the different lipid species are transported in blood, and how these shifts are related to health outcomes. This trial was registered at clinicaltrials.gov as NCT00622661.

4.
Hepatol Commun ; 4(8): 1112-1123, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32766472

RESUMO

The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population-specific genetic variants associated with liver fat. We conducted a genome-wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population-based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin-like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10-15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10-8) was also observed. Rs7724941 was associated with HOMA-IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high-density lipoprotein (beta = -0.046; P = 0.04), and sex hormone binding globulin (beta = -0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association.

5.
J Nutr ; 150(10): 2764-2771, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-32712658

RESUMO

BACKGROUND: The carbon isotope ratio (CIR) is a proposed biomarker for added sugar (AS) intake in the United States; however, because the CIR is also associated with meat intake in most populations the need for specificity remains. The CIR of amino acids (AAs) has the potential to differentiate sugars from meat intakes, because essential AAs must derive from dietary protein whereas certain nonessential AAs can be synthesized from sugars. OBJECTIVES: We tested whether serum CIR-AAs in combination with participant characteristics could meet a prespecified biomarker criterion for AS intake in the Nutrition and Physical Activity Assessment Study Feeding Study (NPAAS-FS) of the Women's Health Initiative, a population in which the whole-serum CIR was not associated with AS intake. METHODS: Postmenopausal women (n = 145) from Seattle, WA, were provided with individualized diets that approximated their habitual food intakes for 2 wk. Dietary intakes from consumed foods were characterized over the feeding period using the Nutrition Data System for Research. The CIR of 7 AAs-Ala, Gly, Val, Leu, Ile, Pro, and Phe-were measured in fasting serum collected at the end of the 2-wk feeding period, using gas chromatography-combustion isotope ratio mass spectrometry. Biomarker models were evaluated using regression R2 ≥ 0.36 as a major biomarker criterion, based on the benchmark R2 values of well-established recovery biomarkers in the NPAAS-FS. RESULTS: AS intake was associated with CIR-Ala (ρ = 0.32; P < 0.0001). A model of AS intake based on CIR-Ala, CIR-Gly, CIR-Ile, smoking, leisure physical activity, and body weight met the biomarker criterion (R2 = 0.37). Biomarker-estimated AS intake was not associated with meat or animal protein intake. CONCLUSIONS: Results support serum CIR-AAs in combination with participant characteristics as potential biomarkers of AS intake in US populations, including those with low AS intake.The Women's Health Initiative is registered at clinicaltrials.gov (NCT00000611).

6.
J Cancer Prev ; 25(2): 65-69, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32647647

RESUMO

Between 30% to 50% of cancer cases are estimated to be preventable through reduced exposure to tobacco, occupational carcinogens, and infectious agents, and adoption of lifelong healthy eating and a physically active lifestyle. In the past, diet and cancer prevention research has aimed to understand the effects of specific foods and nutrients on cancer-related mechanisms. More recently, there has been a shift in emphasis toward a more holistic focus on patterns of diet, reflecting the goal to understand the impact of adhering to broader public health recommendations. It is increasingly apparent from observational studies that different patterns of diet and physical activity are manifest in a metabolic state that is more, or less, conducive to the acquisition of genetic and epigenetic alterations leading to carcinogenesis. Experimental studies in cell systems, animals and humans have expanded our understanding of the many mechanisms by which specific dietary constituents may modulate inflammation and immune function, carcinogen metabolism, hormone and growth-factor regulation, DNA repair capacity, cell-cycle control, and proliferation and apoptosis. However, few mechanistic studies in animal models have evaluated diets containing the complex mixtures that make up human diets. Overall, more studies are needed across the continuum of prevention research, from basic mechanistic research on the effects of diet patterns on fundamental biologic processes to studies testing the efficacy of implementing lifestyle-directed cancer prevention strategies.

7.
Nutrients ; 12(6)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575611

RESUMO

Plant lignans and their microbial metabolites, e.g., enterolactone (ENL), may affect bile acid (BA) metabolism through interaction with hepatic receptors. We evaluated the effects of a flaxseed lignan extract (50 mg/day secoisolariciresinol diglucoside) compared to a placebo for 60 days each on plasma BA concentrations in 46 healthy men and women (20-45 years) using samples from a completed randomized, crossover intervention. Twenty BA species were measured in fasting plasma using LC-MS. ENL was measured in 24-h urines by GC-MS. We tested for (a) effects of the intervention on BA concentrations overall and stratified by ENL excretion; and (b) cross-sectional associations between plasma BA and ENL. We also explored the overlap in bacterial metabolism at the genus level and conducted in vitro anaerobic incubations of stool with lignan substrate to identify genes that are enriched in response to lignan metabolism. There were no intervention effects, overall or stratified by ENL at FDR < 0.05. In the cross-sectional analysis, irrespective of treatment, five secondary BAs were associated with ENL excretion (FDR < 0.05). In vitro analyses showed positive associations between ENL production and bacterial gene expression of the bile acid-inducible gene cluster and hydroxysteroid dehydrogenases. These data suggest overlap in community bacterial metabolism of secondary BA and ENL.

8.
Microorganisms ; 8(3)2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32156071

RESUMO

Although the gut microbiome has been associated with dietary patterns linked to health, microbial metabolism is not well characterized. This ancillary study was a proof of principle analysis for a novel application of metaproteomics to study microbial protein expression in a controlled dietary intervention. We measured the response of the microbiome to diet in a randomized crossover dietary intervention of a whole-grain, low glycemic load diet (WG) and a refined-grain, high glycemic load diet (RG). Total proteins in stools from 9 participants at the end of each diet period (n = 18) were analyzed by LC MS/MS and proteins were identified using the Human Microbiome Project (HMP) human gut microbiome database and UniProt human protein databases. T-tests, controlling for false discovery rate (FDR) <10%, were used to compare the Gene Ontology (GO) biological processes and bacterial enzymes between the two interventions. Using shotgun proteomics, more than 53,000 unique peptides were identified including microbial (89%) and human peptides (11%). Forty-eight bacterial enzymes were statistically different between the diets, including those implicated in SCFA production and degradation of fatty acids. Enzymes associated with degradation of human mucin were significantly enriched in the RG diet. These results illustrate that the metaproteomic approach is a valuable tool to study the microbial metabolism of diets that may influence host health.

9.
Cancer Epidemiol Biomarkers Prev ; 29(5): 966-973, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32132150

RESUMO

BACKGROUND: Visceral adipose tissue (VAT) may play a greater role than subcutaneous fat in increasing cancer risk but is poorly estimated in epidemiologic studies. METHODS: We developed a VAT prediction score by regression equations averaged across 100 least absolute shrinkage and selection operator models in a cross-sectional study of 1,801 older adults in the Multiethnic Cohort (MEC). The score was then used as proxy for VAT in case-control studies of postmenopausal breast (950 case-control pairs) and colorectal (831 case-control pairs) cancer in an independent sample in MEC. Abdominal MRI-derived VAT; circulating biomarkers of metabolic, hormonal, and inflammation dysfunctions; and ORs for incident cancer adjusted for BMI and other risk factors were assessed. RESULTS: The final score, composed of nine biomarkers, BMI, and height, explained 11% and 15% more of the variance in VAT than BMI alone in men and women, respectively. The area under the receiver operator curve for VAT >150 cm2 was 0.90 in men and 0.86 in women. The VAT score was associated with risk of breast cancer [OR (95% confidence interval [CI]) by increasing tertiles: 1.00, 1.09 (0.86-1.39), 1.48 (1.16-1.89); P trend = 0.002] but not with colorectal cancer (P = 0.84), although an association [1.00, 0.98 (0.68-1.39), 1.24 (0.88-1.76); P trend = 0.08] was suggested for this cancer after excluding cases that occurred within 7 years of blood draw (P heterogeneity = 0.06). CONCLUSIONS: The VAT score predicted risks of postmenopausal breast cancer and can be used for risk assessment in diverse populations. IMPACT: These findings provide specific evidence for a role of VAT in breast cancer.

10.
Am J Clin Nutr ; 112(1): 168-179, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32133498

RESUMO

BACKGROUND: We recently presented associations between serum-based biomarkers of carotenoid and tocopherol intake and chronic disease risk in a Women's Health Initiative (WHI) Measurement Precision subcohort (n = 5488). Questions remain as to whether self-reported dietary data can usefully augment such biomarkers or can be calibrated using biomarkers for reliable disease association estimation in larger WHI cohorts. OBJECTIVES: The aims were to examine the potential of FFQ data to explain intake variation in a WHI Feeding Study and to compare association parameter estimates and their precision from studies based on biomarker-calibrated FFQ intake in larger WHI cohorts, with those previously presented. METHODS: Serum-based intake measures were augmented by using FFQ data in a WHI Feeding Study (n = 153). Corresponding calibration equations were generated, both in a companion Nutritional Biomarker Study (n = 436) and in the previously mentioned subcohort (n = 5488), by regressing these intake measures on dietary data and participant characteristics, for α- and ß-carotene, lutein plus zeaxanthin, and α-tocopherol. The supplemental value of FFQ data was considered by examining the fraction of feeding study intake variation explained by these regression models. Calibrated intake and disease association analyses were evaluated by comparisons with previously reported subcohort results. RESULTS: The inclusion of FFQ data led to some increases in feeding study intake variation explained (total R2 of ∼50%). Calibrated intake estimates explained 25-75% of serum-based intake variation, whether developed using either of the 2 cohort subsamples. Related disease associations for micronutrients were precisely estimated in larger WHI cohorts (n = 76,691) but were often closer to the null compared with previously reported associations. CONCLUSIONS: FFQ data may usefully augment blood concentrations in estimating the intake of carotenoids and tocopherols. Calibrated intake estimates using FFQ, dietary supplement, and participant characteristics only may require further justification to ensure reliable estimation of related disease associations.


Assuntos
Micronutrientes/sangue , Idoso , Biomarcadores/sangue , Carotenoides/sangue , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Micronutrientes/metabolismo , Pessoa de Meia-Idade , Estado Nutricional , Saúde da Mulher , alfa-Tocoferol/sangue , beta Caroteno/sangue
11.
JPEN J Parenter Enteral Nutr ; 44(4): 581-588, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32027044

RESUMO

The 2019 Dudrick Research Symposium, entitled "Targeted Approaches for In Situ Gut Microbiome Manipulation," was held on March 25, 2019, at the American Society for Parenteral and Enteral Nutrition (ASPEN) 2019 Nutrition Science & Practice Conference in Phoenix, AZ. The Dudrick Symposium honors the many pivotal and innovative contributions to the development and advancement of parenteral nutrition (PN) made by Dr Stanley J. Dudrick, physician scientist, academic leader, and a founding member of ASPEN. As the 2018 recipient of the Dudrick award, Dr Gail Cresci organized and chaired the symposium. The symposium addressed the evolving field of nutrition manipulation of the gut microbiome as a means to mitigate disease and support health. Presentations focused on (1) the role of prebiotics as a means to beneficially support gut microbiome composition and function and health; (2) designer synbiotics targeted to support metabolic by-products altered by ethanol exposure and microbial effectors that manipulate host metabolic outcomes; and, lastly, (3) types of intervention designs used to study diet-gut microbiome interactions in humans and a review of findings from recent interventions, which tested the effects of diet on the microbiome and the microbiome's effect on dietary exposures. New molecular techniques and multiomic approaches have improved knowledge of the structure and functional activity of the gut microbiome; however, challenges remain in establishing causal relationships between changes in the gut microbial-community structure and function and health outcomes in humans.

12.
Dig Dis Sci ; 65(3): 840-851, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32006211

RESUMO

Diet is an important risk factor for colorectal cancer (CRC), and several dietary constituents implicated in CRC are modified by gut microbial metabolism. Microbial fermentation of dietary fiber produces short-chain fatty acids, e.g., acetate, propionate, and butyrate. Dietary fiber has been shown to reduce colon tumors in animal models, and, in vitro, butyrate influences cellular pathways important to cancer risk. Furthermore, work from our group suggests that the combined effects of butyrate and omega-3 polyunsaturated fatty acids (n-3 PUFA) may enhance the chemopreventive potential of these dietary constituents. We postulate that the relatively low intakes of n-3 PUFA and fiber in Western populations and the failure to address interactions between these dietary components may explain why chemoprotective effects of n-3 PUFA and fermentable fibers have not been detected consistently in prospective cohort studies. In this review, we summarize the evidence outlining the effects of n-3 long-chain PUFA and highly fermentable fiber with respect to alterations in critical pathways important to CRC prevention, particularly intrinsic mitochondrial-mediated programmed cell death resulting from the accumulation of lipid reactive oxygen species (ferroptosis), and epigenetic programming related to lipid catabolism and beta-oxidation-associated genes.


Assuntos
Apoptose/fisiologia , Neoplasias Colorretais/dietoterapia , Neoplasias Colorretais/microbiologia , Dietoterapia/métodos , Microbioma Gastrointestinal/fisiologia , Animais , Neoplasias Colorretais/patologia , Dieta/métodos , Fibras na Dieta/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Humanos
13.
Am J Clin Nutr ; 111(6): 1226-1234, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32055828

RESUMO

BACKGROUND: Trimethylamine N-oxide (TMAO), a compound derived from diet and metabolism by the gut microbiome, has been associated with several chronic diseases, although the mechanisms of action are not well understood and few human studies have investigated microbes involved in its production. OBJECTIVES: Our study aims were 1) to investigate associations of TMAO and its precursors (choline, carnitine, and betaine) with inflammatory and cardiometabolic risk biomarkers; and 2) to identify fecal microbiome profiles associated with TMAO. METHODS: We conducted a cross-sectional analysis using data collected from 1653 participants (826 men and 827 women, aged 60-77 y) in the Multiethnic Cohort Study. Plasma concentrations of TMAO and its precursors were measured by LC-tandem MS. We also analyzed fasting blood for markers of inflammation, glucose and insulin, cholesterol, and triglycerides (TGs), and further measured blood pressure. Fecal microbiome composition was evaluated by sequencing the 16S ribosomal RNA gene V1-V3 region. Associations of TMAO and its precursors with disease risk biomarkers were assessed by multivariable linear regression, whereas associations between TMAO and the fecal microbiome were assessed by permutational multivariate ANOVA and hurdle regression models using the negative binomial distribution. RESULTS: Median (IQR) concentration of plasma TMAO was 3.05 µmol/L (2.10-4.60 µmol/L). Higher concentrations of TMAO and carnitine, and lower concentrations of betaine, were associated with greater insulin resistance (all P < 0.02). Choline was associated with higher systolic blood pressure, TGs, lipopolysaccharide-binding protein, and lower HDL cholesterol (P ranging from <0.001 to 0.03), reflecting an adverse cardiometabolic risk profile. TMAO was associated with abundance of 13 genera (false discovery rate < 0.05), including Prevotella, Mitsuokella, Fusobacterium, Desulfovibrio, and bacteria belonging to the families Ruminococcaceae and Lachnospiraceae, as well as the methanogen Methanobrevibacter smithii. CONCLUSIONS: Plasma TMAO concentrations were associated with a number of trimethylamine-producing bacterial taxa, and, along with its precursors, may contribute to inflammatory and cardiometabolic risk pathways.


Assuntos
Betaína/sangue , Doenças Cardiovasculares/sangue , Carnitina/sangue , Colina/sangue , Microbioma Gastrointestinal , Metilaminas/sangue , Adiposidade , Idoso , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biomarcadores/sangue , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/microbiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Metilaminas/metabolismo , Pessoa de Meia-Idade
14.
Artigo em Inglês | MEDLINE | ID: mdl-30648524

RESUMO

BACKGROUND: Non-steroidal anti-inflammatory drugs, e.g., celecoxib, are commonly used for inflammatory conditions, but can be associated with adverse effects. Combined glucosamine hydrochloride plus chondroitin sulfate (GH+CS) are commonly used for joint pain and have no known adverse effects. Evidence from in vitro, animal and human studies suggest that GH+CS have anti-inflammatory activity, among other mechanisms of action. OBJECTIVE: We evaluated the effects of GH+CS versus celecoxib on a panel of 20 serum proteins involved in inflammation and other metabolic pathways. METHODS: Samples were from a randomized, parallel, double-blind trial of pharmaceutical grade 1500 mg GH + 1200 mg CS (n=96) versus 200 mg celecoxib daily (n=93) for 6- months in knee osteoarthritis (OA) patients. Linear mixed models adjusted for age, sex, body mass index, baseline serum protein values, and rescue medicine use assessed the intervention effects of each treatment arm adjusting for multiple testing. RESULTS: All serum proteins except WNT16 were lower after treatment with GH+CS, while about half increased after celecoxib. Serum IL-6 was significantly reduced (by 9%, P=0.001) after GH+CS, and satisfied the FDR<0.05 threshold. CCL20, CSF3, and WNT16 increased after celecoxib (by 7%, 9% and 9%, respectively, P<0.05), but these serum proteins were no longer statistically significant after controlling for multiple testing. CONCLUSION: The results of this study using samples from a previously conducted trial in OA patients, demonstrate that GH+CS reduces circulating IL-6, an inflammatory cytokine, but is otherwise comparable to celecoxib with regard to effects on other circulating protein biomarkers.

15.
Adv Nutr ; 11(2): 200-215, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31386148

RESUMO

While conventional nutrition research has yielded biomarkers such as doubly labeled water for energy metabolism and 24-h urinary nitrogen for protein intake, a critical need exists for additional, equally robust biomarkers that allow for objective assessment of specific food intake and dietary exposure. Recent advances in high-throughput MS combined with improved metabolomics techniques and bioinformatic tools provide new opportunities for dietary biomarker development. In September 2018, the NIH organized a 2-d workshop to engage nutrition and omics researchers and explore the potential of multiomics approaches in nutritional biomarker research. The current Perspective summarizes key gaps and challenges identified, as well as the recommendations from the workshop that could serve as a guide for scientists interested in dietary biomarkers research. Topics addressed included study designs for biomarker development, analytical and bioinformatic considerations, and integration of dietary biomarkers with other omics techniques. Several clear needs were identified, including larger controlled feeding studies, testing a variety of foods and dietary patterns across diverse populations, improved reporting standards to support study replication, more chemical standards covering a broader range of food constituents and human metabolites, standardized approaches for biomarker validation, comprehensive and accessible food composition databases, a common ontology for dietary biomarker literature, and methodologic work on statistical procedures for intake biomarker discovery. Multidisciplinary research teams with appropriate expertise are critical to moving forward the field of dietary biomarkers and producing robust, reproducible biomarkers that can be used in public health and clinical research.

16.
Microorganisms ; 7(12)2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31771179

RESUMO

Glucosamine and chondroitin (G&C), typically taken for joint pain, are among the most frequently used specialty supplements by US adults. More recently, G&C have been associated with lower incidence of colorectal cancer in human observational studies and reduced severity of experimentally-induced ulcerative colitis in rodents. However, little is known about their effects on colon-related physiology. G&C are poorly absorbed and therefore metabolized by gut microbiota. G&C have been associated with changes in microbial structure, which may alter host response. We conducted a randomized, double-blind, placebo-controlled crossover trial in ten healthy adults to evaluate the effects of a common dose of G&C compared to placebo for 14 days on gut microbial community structure, measured by 16S rRNA gene sequencing. Linear mixed models were used to evaluate the effect of G&C compared to placebo on fecal microbial alpha and beta diversity, seven phyla, and 137 genera. Nine genera were significantly different between interventions (False Discovery Rate < 0.05). Abundances of four Lachnospiraceae genera, two Prevotellaceae genera, and Desulfovibrio were increased after G&C compared to placebo, while Bifidobacterium and a member of the Christensenellaceae family were decreased. Our results suggest that G&C affect the composition of the gut microbiome which may have implications for therapeutic efficacy.

17.
Am J Clin Nutr ; 110(4): 984-992, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31432072

RESUMO

BACKGROUND: Low-glycemic load dietary patterns, characterized by consumption of whole grains, legumes, fruits, and vegetables, are associated with reduced risk of several chronic diseases. METHODS: Using samples from a randomized, controlled, crossover feeding trial, we evaluated the effects on metabolic profiles of a low-glycemic whole-grain dietary pattern (WG) compared with a dietary pattern high in refined grains and added sugars (RG) for 28 d. LC-MS-based targeted metabolomics analysis was performed on fasting plasma samples from 80 healthy participants (n = 40 men, n = 40 women) aged 18-45 y. Linear mixed models were used to evaluate differences in response between diets for individual metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG)-defined pathways and 2 novel data-driven analyses were conducted to consider differences at the pathway level. RESULTS: There were 121 metabolites with detectable signal in >98% of all plasma samples. Eighteen metabolites were significantly different between diets at day 28 [false discovery rate (FDR) < 0.05]. Inositol, hydroxyphenylpyruvate, citrulline, ornithine, 13-hydroxyoctadecadienoic acid, glutamine, and oxaloacetate were higher after the WG diet than after the RG diet, whereas melatonin, betaine, creatine, acetylcholine, aspartate, hydroxyproline, methylhistidine, tryptophan, cystamine, carnitine, and trimethylamine were lower. Analyses using KEGG-defined pathways revealed statistically significant differences in tryptophan metabolism between diets, with kynurenine and melatonin positively associated with serum C-reactive protein concentrations. Novel data-driven methods at the metabolite and network levels found correlations among metabolites involved in branched-chain amino acid (BCAA) degradation, trimethylamine-N-oxide production, and ß oxidation of fatty acids (FDR < 0.1) that differed between diets, with more favorable metabolic profiles detected after the WG diet. Higher BCAAs and trimethylamine were positively associated with homeostasis model assessment-insulin resistance. CONCLUSIONS: These exploratory metabolomics results support beneficial effects of a low-glycemic load dietary pattern characterized by whole grains, legumes, fruits, and vegetables, compared with a diet high in refined grains and added sugars on inflammation and energy metabolism pathways. This trial was registered at clinicaltrials.gov as NCT00622661.


Assuntos
Dieta , Carga Glicêmica , Inflamação/metabolismo , Metabolômica , Adolescente , Adulto , Biomarcadores/sangue , Metabolismo Energético/fisiologia , Comportamento Alimentar , Feminino , Humanos , Masculino , Metaboloma , Adulto Jovem
18.
Cancer Prev Res (Phila) ; 12(9): 567-578, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31266826

RESUMO

Increased adiposity and diets high in glycemic load (GL) are associated with increased risk of many chronic diseases including cancer. Using plasma from 80 healthy individuals [40 men/40 women, 29 with DXA-derived low fat mass (FM) and 51 with high FM] in a randomized cross-over-controlled feeding trial and arrays populated with 3,504 antibodies, we measured plasma proteins collected at baseline and end of each of two 28-day controlled diets: a low GL diet high in whole grains, legumes, fruits, and vegetables (WG) and a high GL diet high in refined grains and added sugars (RG). Following univariate testing for proteins differing by diet, we evaluated pathway-level involvement. Among all 80 participants, 172 proteins were identified as differing between diets. Stratifying participants by high and low FM identified 221 and 266 proteins, respectively, as differing between diets (unadjusted P < 0.05). These candidate proteins were tested for overrepresentation in Reactome pathways, corresponding to 142 (of 291) pathways in the high-FM group and 72 (of 274) pathways in the low-FM group. We observed that the cancer-related pathways, DNA Repair, DNA Replication, and Cell Cycle, were overrepresented in the high-FM participants while pathways involved in post-translational protein modification were overrepresented in participants with either FM. Although high-GL diets are associated with increased risk of some cancers, our study further suggests that biology associated with consumption of GL diets is variable depending on an individual's adiposity and dietary recommendations related to cancer prevention be made with the additional consideration of an individual's FM.


Assuntos
Adiposidade/fisiologia , Proteínas Sanguíneas/análise , Dieta , Carga Glicêmica/fisiologia , Neoplasias/metabolismo , Proteoma/análise , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adolescente , Adulto , Análise Química do Sangue , Proteínas Sanguíneas/metabolismo , Estudos Cross-Over , Comportamento Alimentar/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Tamanho do Órgão , Proteoma/metabolismo , Proteômica/métodos , Transdução de Sinais/fisiologia , Adulto Jovem
19.
J Nutr ; 149(9): 1575-1584, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31187868

RESUMO

BACKGROUND: Variation in gut microbial community structure is partly attributed to variations in diet. A priori dietary indexes capture diet quality and have been associated with chronic disease risk. OBJECTIVES: The aim of this study was to examine the association of diet quality, as assessed by the Healthy Eating Index, Alternative Healthy Eating Index-2010, alternate Mediterranean Diet, and the Dietary Approaches to Stop Hypertension Trial, with measures of fecal microbial community structure assessed in the Adiposity Phenotype Study (APS), an ethnically diverse study population with varied food intakes. METHODS: Multiethnic Cohort Study members completed a validated quantitative food frequency questionnaire (QFFQ) at cohort entry (1993-1996) and, for the APS subset, at clinic visit (2013-2015), when they also provided a stool sample. DNA was extracted from stool, and the V1-V3 region of the 16S rRNA gene was amplified and sequenced. Dietary index scores were computed based on the QFFQ and an extensive nutritional database. Using linear regression adjusted for relevant covariates, we estimated associations of dietary quality with microbiome measures and computed adjusted mean values of microbial measures by tertiles of dietary index scores. RESULTS: The 858 men and 877 women of white, Japanese American, Latino, Native Hawaiian, and African American ancestry had a mean age of 69.2 years at stool collection. Alpha diversity according to the Shannon index increased by 1-2% across tertiles of all 4 diet indexes measured at clinic visit. The mean relative abundance of the phylum Actinobacteria was 13-19% lower with higher diet quality across all 4 indexes (difference between tertile 3 and tertile 1 divided by tertile 1). Of the 104 bacterial genera tested, 21 (primarily from the phylum Firmicutes) were positively associated with at least 1 index after Bonferroni adjustment. CONCLUSION: Diet quality was strongly associated with fecal microbial alpha diversity and beta diversity and several genera previously associated with human health.


Assuntos
Adiposidade , Dieta , Fezes/microbiologia , Microbioma Gastrointestinal , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
20.
Am J Clin Nutr ; 110(2): 377-390, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31175806

RESUMO

BACKGROUND: Microbial metabolism of lignans from high-fiber plant foods produces bioactive enterolignans, such as enterolactone (ENL) and enterodiol (END). Enterolignan exposure influences cellular pathways important to cancer risk and is associated with reduced colon tumorigenesis in animal models and lower colorectal cancer risk in humans. OBJECTIVES: The aim of this study was to test the effects of a flaxseed lignan supplement (50 mg secoisolariciresinol diglucoside/d) compared with placebo on host gene expression in colon biopsies and exfoliated colonocyte RNA in feces and fecal microbial community composition, and to compare responses in relation to ENL excretion. METHODS: We conducted a 2-period randomized, crossover intervention in 42 healthy men and women (20-45 y). We used RNA-seq to measure differentially expressed (DE) genes in colonic mucosa and fecal exfoliated cells through the use of edgeR and functional analysis with Ingenuity Pathway Analysis. We used 16S ribosomal RNA gene (V1-V3) analysis to characterize the fecal microbiome, and measured END and ENL in 24-h urine samples by gas chromatography-mass spectrometry. RESULTS: We detected 32 DE genes (false discovery rate <0.05) in the exfoliome, but none in the mucosal biopsies, in response to 60 d of lignan supplement compared with placebo. Statistically significant associations were detected between ENL excretion and fecal microbiome measured at baseline and at the end of the intervention periods. Further, we detected DE genes in colonic mucosa and exfoliome between low- and high-ENL excreters. Analysis of biopsy samples indicated that several anti-inflammatory upstream regulators, including transforming growth factor ß and interleukin 10 receptor, were suppressed in low-ENL excreters. Complementary analyses in exfoliated cells also suggested that low-ENL excreters may be predisposed to proinflammatory cellular events due to upregulation of nuclear transcription factor κB and NOS2, and an inhibition of the peroxisome proliferator-activated receptor γ network. CONCLUSIONS: These results suggest that ENL or other activities of the associated gut microbial consortia may modulate response to a dietary lignan intervention. This has important implications for dietary recommendations and chemoprevention strategies. This study was registered at clinicaltrials.gov as NCT01619020.


Assuntos
Fezes/microbiologia , Linho/química , Perfilação da Expressão Gênica , Mucosa Intestinal/efeitos dos fármacos , Lignanas/química , Extratos Vegetais/farmacologia , Adulto , Colo/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Microbioma Gastrointestinal , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mucosa Intestinal/metabolismo , Masculino , Extratos Vegetais/química
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