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Fecal Metagenomics to Identify Biomarkers of Food Intake in Healthy Adults: Findings from Randomized, Controlled, Nutrition Trials.
Shinn, LM, Mansharamani, A, Baer, DJ, Novotny, JA, Charron, CS, Khan, NA, Zhu, R, Holscher, HD
The Journal of nutrition. 2024;(1):271-283
Abstract
BACKGROUND Undigested components of the human diet affect the composition and function of the microorganisms present in the gastrointestinal tract. Techniques like metagenomic analyses allow researchers to study functional capacity, thus revealing the potential of using metagenomic data for developing objective biomarkers of food intake. OBJECTIVES As a continuation of our previous work using 16S and metabolomic datasets, we aimed to utilize a computationally intensive, multivariate, machine-learning approach to identify fecal KEGG (Kyoto encyclopedia of genes and genomes) Orthology (KO) categories as biomarkers that accurately classify food intake. METHODS Data were aggregated from 5 controlled feeding studies that studied the individual impact of almonds, avocados, broccoli, walnuts, barley, and oats on the adult gastrointestinal microbiota. Deoxyribonucleic acid from preintervention and postintervention fecal samples underwent shotgun genomic sequencing. After preprocessing, sequences were aligned and functionally annotated with Double Index AlignMent Of Next-generation sequencing Data v2.0.11.149 and MEtaGenome ANalyzer v6.12.2, respectively. After the count normalization, the log of the fold change ratio for resulting KOs between pre- and postintervention of the treatment group against its corresponding control was utilized to conduct differential abundance analysis. Differentially abundant KOs were used to train machine-learning models examining potential biomarkers in both single-food and multi-food models. RESULTS We identified differentially abundant KOs in the almond (n = 54), broccoli (n = 2474), and walnut (n = 732) groups (q < 0.20), which demonstrated classification accuracies of 80%, 87%, and 86% for the almond, broccoli, and walnut groups using a random forest model to classify food intake into each food group's respective treatment and control arms, respectively. The mixed-food random forest achieved 81% accuracy. CONCLUSIONS Our findings reveal promise in utilizing fecal metagenomics to objectively complement self-reported measures of food intake. Future research on various foods and dietary patterns will expand these exploratory analyses for eventual use in feeding study compliance and clinical settings.
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Nuts, Energy Balance and Body Weight.
Baer, DJ, Dalton, M, Blundell, J, Finlayson, G, Hu, FB
Nutrients. 2023;(5)
Abstract
Over several decades, the health benefits of consuming nuts have been investigated, resulting in a large body of evidence that nuts can reduce the risk of chronic diseases. The consumption of nuts, being a higher-fat plant food, is restricted by some in order to minimize weight gain. In this review, we discuss several factors related to energy intake from nuts, including food matrix and its impact on digestibility, and the role of nuts in regulating appetite. We review the data from randomized controlled trials and observational studies conducted to examine the relationship between nut intake and body weight or body mass index. Consistently, the evidence from RCTs and observational cohorts indicates that higher nut consumption does not cause greater weight gain; rather, nuts may be beneficial for weight control and prevention of long-term weight gain. Multiple mechanisms likely contribute to these findings, including aspects of nut composition which affect nutrient and energy availability as well as satiety signaling.
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Effect of Nuts on Gastrointestinal Health.
Mandalari, G, Gervasi, T, Rosenberg, DW, Lapsley, KG, Baer, DJ
Nutrients. 2023;(7)
Abstract
Nuts are high nutrient-dense foods containing healthy lipids, dietary fiber, and bioactive phytochemicals, including vitamins and minerals. Although the beneficial effect of nut consumption on different chronic diseases has been well documented, especially in relation to their cardiometabolic benefits, less scientific evidence is available on their possible beneficial effects on gastrointestinal health. In this narrative review, we summarize the most important findings and new research perspectives in relation to the importance of nut consumption on gastrointestinal health. The integrity of the cell wall structure, cell size and particle size after mastication are known to play a crucial role in energy, nutrient and bioactive release from nuts during digestion, therefore affecting bioaccessibility. Other mechanisms, such as cell wall composition, thickness and porosity, as well as stability of the membranes surrounding the oil bodies within the cell, are also important for energy extraction. As the undigested nutrients and phytochemicals are delivered to the colon, effects on gut microbiota composition are predicted. Although the overall effect of nut consumption on microbial alpha- and beta-diversity has been inconsistent, some scientific evidence suggests an increase in fecal butyrate after almond consumption, and a beneficial role of walnuts on the prevention of ulcerative colitis and protection against the development of gastric mucosal lesions.
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Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis.
Fitzgerald, KC, Bhargava, P, Smith, MD, Vizthum, D, Henry-Barron, B, Kornberg, MD, Cassard, SD, Kapogiannis, D, Sullivan, P, Baer, DJ, et al
EBioMedicine. 2022;:104124
Abstract
BACKGROUND Intermittent fasting or calorie restriction (CR) diets provide anti-inflammatory and neuroprotective advantages in models of multiple sclerosis (MS); data in humans are sparse. METHODS We conducted a randomised-controlled feeding study of different CR diets in 36 people with MS over 8 weeks. Participants were randomised to 1 of 3 diets: 1) a control diet, in which the participant received 100% of his or her calorie needs 7 days per week, 2) a daily CR diet, in which the participant received 78% of his or her calorie needs 7 days per week, or 3) an intermittent CR diet, in which the participant received 100% of his or her calorie needs on 5 days per week and 25% of his or her calorie needs 2 days per week (i.e., a "5:2" style diet). Untargeted metabolomics was performed on plasma samples at weeks 0, 4 and 8 at Metabolon Inc (Durham, NC). Flow cytometry of cryopreserved peripheral blood mononuclear cells at weeks 0 and 8 were used to identify CD3+;CD4+ (CD4+) and CD3+;CD4- (as a proxy for CD8+) T cell subsets including effector memory, central memory, and naïve cells. FINDINGS 31 (86%) completed the trial. Over time, individuals randomised to intermittent CR had significant reductions in effector memory (for CD4-EM: -3.82%; 95%CI: -7.44, -0.21; for CD4-: -6.96%; 95%CI: -11.96, -1.97) and Th1 subsets (-4.26%; 95% CI: -7.11, -1.40) and proportional increases in naïve subsets (for CD4-: 10.11%; 95%CI: 3.30, 16.92%). No changes were observed for daily CR or weight-stable diets. Larger within-person changes in lysophospholipid and lysoplasmalogen metabolites in intermittent CR were associated with larger reductions in memory T cell subsets and larger increases in naïve T cell subsets. INTERPRETATION In people with MS, an intermittent CR diet was associated with reduction in memory T cell subsets and certain biologically-relevant lipid markers. FUNDING National MS Society, NIH, Johns Hopkins Catalyst Award.
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Scoping Review and Evidence Map of the Relation between Exposure to Dietary Sweetness and Body Weight-Related Outcomes in Adults.
Higgins, KA, Rawal, R, Baer, DJ, O'Connor, LE, Appleton, KM
Advances in nutrition (Bethesda, Md.). 2022;(6):2341-2356
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Abstract
Numerous governmental and health organizations recommend reduced intake of added sugars due to the health risks associated with excess intake, including the risk of obesity. Some organizations further recommend avoiding dietary sweetness, regardless of the source. A scoping review and evidence map were completed to characterize the research that investigated associations between dietary sweetness and body weight. The aim was to identify and map published studies that have investigated total dietary sweetness, sweet food/beverages, sugar, or sweetener intake, and body weight-related outcomes and/or energy intake. Using preregistered search terms (osf.io/my7pb), 36,779 publications (duplicates removed) were identified from PubMed, Cochrane Library, and Scopus and screened for inclusion. Eligible studies were clinical trials, longitudinal cohorts, case-control studies, cross-sectional studies, and systematic reviews conducted among adults (age ≥18 y), which were performed to investigate associations between dietary sweetness, sweet foods/beverages, sugar, or sweetener (energetic or nonenergetic) intake and body weight, BMI, adiposity, and/or energy intake. A total of 833 eligible publications were identified, detailing 804 studies. Only 7 studies (0.9% of included studies; 2 clinical trials, 4 cross-sectional studies, and 1 with another design type) investigated associations between total dietary sweetness and body weight-related outcome and/or energy intake. An additional 608 (75.6%) studies investigated intakes of sweet foods/beverages, sugar, or sweetener, and body weight-related outcomes and/or energy intake, including 225 clinical trials, 81 longitudinal cohorts, 4 case-control studies, and 280 cross-sectional studies. Most studies (90.6%) did not measure the sweetness of the diet or individual foods consumed. Ninety-two (11.4%) publications reported data from studies on dietary patterns that included sweet foods/beverages alongside other dietary components and 97 (12.1%) systematic reviews addressed different but related research questions. Although there is a breadth of evidence from studies that have investigated associations between intakes of sweet foods and beverages, sugars, and sweeteners and body weight, there is a limited depth of evidence on the association between total dietary sweetness and body weight.
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Perspective: Measuring Sweetness in Foods, Beverages, and Diets: Toward Understanding the Role of Sweetness in Health.
Trumbo, PR, Appleton, KM, de Graaf, K, Hayes, JE, Baer, DJ, Beauchamp, GK, Dwyer, JT, Fernstrom, JD, Klurfeld, DM, Mattes, RD, et al
Advances in nutrition (Bethesda, Md.). 2021;(2):343-354
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Abstract
Various global public health agencies recommend minimizing exposure to sweet-tasting foods or beverages. The underlying rationale is that reducing exposure to the perception of sweet tastes, without regard to the source of sweetness, may reduce preferences for sweetness, added sugar intake, caloric intake, and body weight. However, the veracity of this sequence of outcomes has yet to be documented, as revealed by findings from recent systematic reviews on the topic. Efforts to examine and document the effects of sweetness exposure are needed to support evidence-based recommendations. They require a generally agreed-upon methodology for measuring sweetness in foods, beverages, and the overall diet. Although well-established sensory evaluation techniques exist for individual foods in laboratory settings, they are expensive and time-consuming, and agreement on the optimal approach for measuring the sweetness of the total diet is lacking. If such a measure could be developed, it would permit researchers to combine data from different studies and populations and facilitate the design and conduct of new studies to address unresolved research questions about dietary sweetness. This narrative review includes an overview of available sensory techniques, their strengths and limitations, recent efforts to measure the sweetness of foods and diets across countries and cultures, and a proposed future direction for improving methods for measuring sweetness toward developing the data required to support evidence-based recommendations around dietary sweetness.
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Common Genetic Variations Involved in the Inter-Individual Variability of Circulating Cholesterol Concentrations in Response to Diets: A Narrative Review of Recent Evidence.
Abdullah, MMH, Vazquez-Vidal, I, Baer, DJ, House, JD, Jones, PJH, Desmarchelier, C
Nutrients. 2021;(2)
Abstract
The number of nutrigenetic studies dedicated to the identification of single nucleotide polymorphisms (SNPs) modulating blood lipid profiles in response to dietary interventions has increased considerably over the last decade. However, the robustness of the evidence-based science supporting the area remains to be evaluated. The objective of this review was to present recent findings concerning the effects of interactions between SNPs in genes involved in cholesterol metabolism and transport, and dietary intakes or interventions on circulating cholesterol concentrations, which are causally involved in cardiovascular diseases and established biomarkers of cardiovascular health. We identified recent studies (2014-2020) that reported significant SNP-diet interactions in 14 cholesterol-related genes (NPC1L1, ABCA1, ABCG5, ABCG8, APOA1, APOA2, APOA5, APOB, APOE, CETP, CYP7A1, DHCR7, LPL, and LIPC), and which replicated associations observed in previous studies. Some studies have also shown that combinations of SNPs could explain a higher proportion of variability in response to dietary interventions. Although some findings still need replication, including in larger and more diverse study populations, there is good evidence that some SNPs are consistently associated with differing circulating cholesterol concentrations in response to dietary interventions. These results could help clinicians provide patients with more personalized dietary recommendations, in order to lower their risk for cardiovascular disease.
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Consumption of High-Oleic Soybean Oil Improves Lipid and Lipoprotein Profile in Humans Compared to a Palm Oil Blend: A Randomized Controlled Trial.
Baer, DJ, Henderson, T, Gebauer, SK
Lipids. 2021;(3):313-325
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Partially hydrogenated oils (PHO) have been removed from the food supply due to adverse effects on risk for coronary heart disease (CHD). High-oleic soybean oils (HOSBO) are alternatives that provide functionality for different food applications. The objective of this study was to determine how consumption of diets containing HOSBO compared to other alternative oils, with similar functional properties, modifies LDL cholesterol (LDLc) and other risk factors and biomarkers of CHD. A triple-blind, crossover, randomized controlled trial was conducted in humans (n = 60) with four highly-controlled diets containing (1) HOSBO, (2) 80:20 blend of HOSBO and fully hydrogenated soybean oil (HOSBO+FHSBO), (3) soybean oil (SBO), and (4) 50:50 blend of palm oil and palm kernel oil (PO + PKO). Before and after 29 days of feeding, lipids/lipoproteins, blood pressure, body composition, and markers of inflammation, oxidation, and hemostasis were measured. LDLc, apolipoprotein B (apoB), NonHDL-cholesterol (HDLc), ratios of total cholesterol (TC)-to-HDLc and LDLc-to-HDL cholesterol, and LDL particle number and small LDL particles concentration were lower after HOSBO and HOSBO+FHSBO compared to PO (specific comparisons p < 0.05). Other than TC:HDL, there were no differences in lipid/lipoprotein markers when comparing HOSBO+FHSBO with HOSBO. LDLc and apoB were higher after HOSBO compared to SBO (p < 0.05). PO + PKO increased HDLc (p < 0.001) and apolipoprotein AI (p < 0.03) compared to HOSBO and HOSBO+FHSBO. With the exception of lipid hydroperoxides, dietary treatments did not affect other CHD markers. HOSBO, and blends thereof, is a PHO replacement that results in more favorable lipid/lipoprotein profiles compared to PO + PKO (an alternative fat with similar functional properties).
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Conducting dietary intervention trials in people with multiple sclerosis: Lessons learned and a path forward.
Fitzgerald, KC, Sand, IK, Senders, A, Spain, R, Giesser, B, Sullivan, P, Baer, DJ, LaRocca, N, Zackowski, K, Mowry, EM
Multiple sclerosis and related disorders. 2020;:101478
Abstract
Disease course in people with multiple sclerosis (MS) is heterogeneous. The impact of dietary and nutritional factors on MS prognosis is of interest to both patients and clinicians; differences in diet are hypothesized to contribute to disease evolution over time. However, studying diet, especially in people with MS, introduces methodologic complexity that should be recognized. In this review, we focus on methodological aspects relevant to the conduct of dietary interventions in people with MS, given our experience in leading such studies and the challenges we encountered in the realization of this work. We summarize key aspects of study design and important considerations, regardless of the specifics of the actual study (e.g. the particular diet of interest, target MS population, etc.). We discuss strategies for the design of the intervention as well as the selection of appropriate study endpoints. Finally, we provide an overview of strategies to improve the rigor of conducting dietary studies in people with MS.
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Consumption of cashew nuts does not influence blood lipids or other markers of cardiovascular disease in humans: a randomized controlled trial.
Baer, DJ, Novotny, JA
The American journal of clinical nutrition. 2019;(2):269-275
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BACKGROUND The US Food and Drug Administration (FDA) approved a qualified health claim for tree nuts and reduction of cardiovascular disease. However, cashews are excluded from that claim due to their content of saturated fats, which is predominantly stearic acid. Because stearic acid is neutral with respect to blood lipids, several studies have been conducted to test the effect of cashew nuts on blood lipids, and these studies have produced conflicting results. OBJECTIVES The aim of this study was to conduct a highly controlled intervention to determine the effect of cashews fed at the amount specified in the health claim on risk factors for cardiovascular disease. METHODS A total of 42 adults participated in a controlled-feeding study conducted as a randomized crossover trial with 2 treatment phases. The volunteers were provided the same base diet in both treatment phases, with no additions during the control phase and with the addition of 1.5 servings (42 g) of cashews/d for the cashew nut phase. During the cashew nut phase, the amount of all foods was decreased proportionally to achieve isocaloric overall diets in the 2 phases. After 4 wk of intervention, assessments included blood lipids, blood pressure, central (aortic) pressure, augmentation index, blood glucose, endothelin, proprotein convertase subtilisin/kexin type 9 (PCSK9), adhesion molecules, and clotting and inflammatory factors. RESULTS There were no significant differences in blood lipids, blood pressure, augmentation index, blood glucose, endothelin, adhesion molecules, or clotting factors in this weight-stable cohort. PCSK9 was significantly decreased after cashew consumption, although there was no change in LDL cholesterol. CONCLUSIONS Consumption of 1.5 servings of cashew nuts/d, the amount associated with the FDA qualified health claim for tree nuts and cardiovascular disease, did not positively or adversely affect any of the primary risk factors for cardiovascular disease. This trial was registered at clinicaltrials.gov as NCT02628171.