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Approximately five million children die each year from preventable causes, including respiratory infections, diarrhea, and malaria. Roughly half of those deaths are attributable to undernutrition, including micronutrient deficiencies (MNDs). The influence of infection on micronutrient status is well established: The inflammatory response to pathogens triggers anorexia, while pathogens and the immune response can both alter nutrient absorption and cause nutrient losses. We review the roles of vitamin A, vitamin D, iron, zinc, and selenium in the immune system, which act in the regulation of molecular- or cellular-level host defenses, directly affecting pathogens or protecting against oxidative stress or inflammation. We further summarize high-quality evidence regarding the synergistic or antagonistic interactions between MNDs, pathogens, and morbidity or mortality relevant to child health in low- and middle-income countries. We conclude with a discussion of gaps in the literature and future directions for multidisciplinary research on the interactions of MNDs, infection, and inflammation.
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Micronutrientes , Humanos , Micronutrientes/deficiência , Criança , Saúde da Criança , Infecções/imunologia , Estado Nutricional , Inflamação/imunologia , Zinco/deficiência , Selênio/deficiência , Vitamina A , Pré-EscolarRESUMO
Monocytes are innate immune cells that are continuously produced in bone marrow which enter and circulate the vasculature. In response to nutrient scarcity, monocytes migrate back to bone marrow, where, upon refeeding, they are rereleased back into the bloodstream to replenish the circulation. In humans, the variability in monocyte behavior in response to fasting and refeeding has not been characterized. To investigate monocyte dynamics in humans, we measured blood monocyte fluctuations in 354 clinically healthy individuals after a 12-h overnight fast and at 3 and 6 h after consuming a mixed macronutrient challenge meal. Using cluster analysis, we identified three distinct monocyte behaviors. Group 1 was characterized by relatively low fasting monocyte counts that markedly increased after consuming the test meal. Group 2 was characterized by relatively high fasting monocyte counts that decreased after meal consumption. Group 3, like Group 1, was characterized by lower fasting monocyte counts but increased to a lesser extent after consuming the meal. Although monocyte fluctuations observed in Groups 1 and 3 align with the current paradigm of monocyte dynamics in response to fasting and refeeding, the atypical dynamic observed in Group 2 does not. Although generally younger in age, Group 2 subjects had lower whole body carbohydrate oxidation rates, lower HDL-cholesterol levels, delayed postprandial declines in salivary cortisol, and reduced postprandial peripheral microvascular endothelial function. These unique characteristics were not explained by group differences in age, sex, or body mass index (BMI). Taken together, these results highlight distinct patterns of monocyte responsiveness to natural fluctuations in dietary fuel availability.NEW & NOTEWORTHY Our study composed of adult volunteers revealed that monocyte dynamics exhibit a high degree of individual variation in response to fasting and refeeding. Although circulating monocytes in most volunteers behaved in ways that align with previous reports, many exhibited atypical dynamics demonstrated by elevated fasting blood monocyte counts that sharply decreased after meal consumption. This group was also distinguished by lower HDL levels, reduced postprandial endothelial function, and a delayed postprandial decline in salivary cortisol.
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Jejum , Hidrocortisona , Monócitos , Período Pós-Prandial , Humanos , Período Pós-Prandial/fisiologia , Jejum/fisiologia , Masculino , Feminino , Adulto , Monócitos/metabolismo , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Pessoa de Meia-Idade , Adulto Jovem , Voluntários Saudáveis , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Idoso , Contagem de Leucócitos , Lipoproteínas HDL/sangue , Lipoproteínas HDL/metabolismoRESUMO
BACKGROUND: Higher diet quality has been associated with lower risk of developing inflammatory bowel disease, but associations between diet and gastrointestinal (GI) inflammation in healthy adults prior to disease onset are understudied. OBJECTIVES: The purpose of this project was to examine associations between reported dietary intake and markers of GI inflammation in a healthy adult human cohort. METHODS: In a cross-sectional observational trial of 358 healthy adults, participants completed ≤3 unannounced 24-h dietary recalls using the Automated Self-Administered Dietary Assessment Tool and a Block 2014 Food Frequency Questionnaire to assess recent and habitual intake, respectively. Those who provided a stool sample were included in this analysis. Inflammation markers from stool, including calprotectin, neopterin, and myeloperoxidase, were measured by ELISA along with LPS-binding protein from plasma. RESULTS: Recent and habitual fiber intake was negatively correlated with fecal calprotectin concentrations (n = 295, P = 0.011, 0.009). Habitual soluble fiber intake was also negatively correlated with calprotectin (P = 0.01). Recent and habitual legume and vegetable intake was negatively correlated with calprotectin (P = 0.013, 0.026, 0.01, 0.009). We observed an inverse correlation between recent Healthy Eating Index (HEI) scores and calprotectin concentrations (n = 295, P = 0.026). Dietary Inflammatory Index scores were calculated and positively correlated with neopterin for recent intake (n = 289, P = 0.015). When participants with clinically elevated calprotectin were excluded, recent and habitual fiber, legume, vegetable, and fruit intake were negatively correlated with calprotectin (n = 253, P = 0.00001, 0.0002, 0.045, 0.001, 0.009, 0.001, 0.004, 0.014). Recent total HEI score was inversely correlated with subclinical calprotectin (P = 0.003). CONCLUSIONS: Higher diet quality may be protective against GI inflammation even in healthy adults. This trial was registered at clinicaltrials.gov as NCT02367287.
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Dieta , Frutas , Adulto , Humanos , Estados Unidos , Estudos Transversais , Neopterina , Verduras , Inflamação , Complexo Antígeno L1 LeucocitárioRESUMO
BACKGROUND: Gut microbes produce short-chain fatty acids (SCFAs), which are associated with broad health benefits. However, it is not fully known how diet and/or the gut microbiome could be modulated to improve SCFA production. OBJECTIVES: The objective of this study was to identify dietary, inflammatory, and/or microbiome predictors of SCFAs in a cohort of healthy adults. METHODS: SCFAs were measured in fecal and plasma samples from 359 healthy adults in the United States Department of Agriculture Nutritional Phenotyping Study. Habitual and recent diet was assessed using a food frequency questionnaire and automated self-administered 24-h dietary assessment tool dietary recalls. Markers of systemic and gut inflammation were measured in fecal and plasma samples. The gut microbiome was assessed using shotgun metagenomics. Using statistics and machine learning, we determined how the abundance and composition of SCFAs varied with measures of diet, inflammation, and the gut microbiome. RESULTS: We show that fecal pH may be a good proxy for fecal SCFA abundance. A higher healthy eating index for a habitual diet was associated with a compositional increase in fecal butyrate relative to acetate and propionate. SCFAs were associated with markers of subclinical GI inflammation. Fecal SCFA abundance was inversely related to plasma lipopolysaccharide-binding protein. When we analyzed hierarchically organized diet and microbiome data with taxonomy-aware algorithms, we observed that diet and microbiome features were far more predictive of fecal SCFA abundances compared to plasma SCFA abundances. The top diet and microbiome predictors of fecal butyrate included potatoes and the thiamine biosynthesis pathway, respectively. CONCLUSIONS: These results suggest that resistant starch in the form of potatoes and microbially produced thiamine provide a substrate and essential cofactor, respectively, for butyrate synthesis. Thiamine may be a rate-limiting nutrient for butyrate production in adults. Overall, these findings illustrate the complex biology underpinning SCFA production in the gut. This trial was registered at clinicaltrials.gov as NCT02367287.
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BACKGROUND: Polyphenols are dietary bioactive compounds, many of which have anti-inflammatory properties. However, information on the intake of dietary polyphenols at the class and compound levels and their associations with gastrointestinal (GI) and systemic inflammation is lacking. OBJECTIVES: Estimate dietary polyphenol intake in healthy adults and examine its relationship with GI and systemic inflammation markers. METHODS: Healthy adults (n = 350) completed the United States Department of Agriculture Nutritional Phenotyping Study, an observational, cross-sectional study balanced for age, sex, and body mass index. Dietary intake, assessed via multiple 24-h recalls, was ingredientized and mapped to FooDB, a comprehensive food composition database. Dietary polyphenol intake (total, class, compound) was estimated and examined for its relationship to GI and systemic inflammation markers using linear models and random forest regressions. RESULTS: Mean total polyphenol intake was â¼914 mg/1000 kcal/d with flavonoids as the greatest class contributor (495 mg/1000 kcal/d). Tea, coffee, and fruits were among the largest food contributors to polyphenol intake. Total polyphenol intake was negatively associated with the GI inflammation marker, fecal calprotectin (ß = -0.004, P = 0.04). At the class level, polyphenols were categorized as prenol lipids (ß = -0.94, P < 0.01) and phenylpropanoic acids (ß = -0.92, P < 0.01) were negatively associated with plasma lipopolysaccharide-binding protein, a proxy for GI permeability. Food sources of these 2 classes included mainly olive products. We further detected a positive association between C-reactive protein and polyphenols in the "cinnamic acids and derivatives" class using hierarchical feature engineering and random forest modeling. CONCLUSIONS: Even in healthy adults, dietary polyphenol intake was negatively associated with GI inflammation and intake of prenol lipids and phenylpropanoic acids was negatively associated with GI permeability. Relationships between polyphenol intake and inflammatory outcomes varied with the resolution-total, class, compound-of polyphenol intake, suggesting a nuanced impact of polyphenols on GI and systemic inflammation. This trial was registered at clinicaltrials.gov as NCT02367287.
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During adolescence, growth and development are transformative and have profound consequences on an individual's health in later life, as well as the health of any potential children. The current generation of adolescents is growing up at a time of unprecedented change in food environments, whereby nutritional problems of micronutrient deficiency and food insecurity persist, and overweight and obesity are burgeoning. In a context of pervasive policy neglect, research on nutrition during adolescence specifically has been underinvested, compared with such research in other age groups, which has inhibited the development of adolescent-responsive nutritional policies. One consequence has been the absence of an integrated perspective on adolescent growth and development, and the role that nutrition plays. Through late childhood and early adolescence, nutrition has a formative role in the timing and pattern of puberty, with consequences for adult height, muscle, and fat mass accrual, as well as risk of non-communicable diseases in later life. Nutritional effects in adolescent development extend beyond musculoskeletal growth, to cardiorespiratory fitness, neurodevelopment, and immunity. High rates of early adolescent pregnancy in many countries continue to jeopardise the growth and nutrition of female adolescents, with consequences that extend to the next generation. Adolescence is a nutrition-sensitive phase for growth, in which the benefits of good nutrition extend to many other physiological systems.
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Desenvolvimento do Adolescente/fisiologia , Desnutrição/epidemiologia , Estado Nutricional/fisiologia , Sobrepeso/epidemiologia , Adolescente , Saúde do Adolescente , Insegurança Alimentar , Saúde Global , Humanos , Desnutrição/fisiopatologia , Micronutrientes/deficiência , Política Nutricional , Sobrepeso/fisiopatologiaRESUMO
BACKGROUND: Lactase persistence (LP) is a heritable trait in which lactose can be digested throughout adulthood. Lactase nonpersistent (LNP) individuals who consume lactose may experience microbial adaptations in response to undigested lactose. OBJECTIVES: The objective of the study was to estimate lactose from foods reported in the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) and determine the interaction between lactose consumption, LP genotype, and gut microbiome in an observational cross-sectional study of healthy adults in the United States (US). METHODS: Average daily lactose consumption was estimated for 279 healthy US adults, genotyped for the lactase gene -13910G>A polymorphism (rs4988235) by matching ASA24-reported foods to foods in the Nutrition Coordinating Center Food and Nutrient Database. Analysis of covariance was used to identify whether the A genotype (LP) influenced lactose and total dairy consumption, with total energy intake and weight as covariates. The 16S rRNA V4/V5 region, amplified from bacterial DNA extracted from each frozen stool sample, was sequenced using Illumina MiSeq (300 bp paired-end) and analyzed using Quantitative Insights Into Microbial Ecology (QIIME)2 (version 2019.10). Differential abundances of bacterial taxa were analyzed using DESeq2 likelihood ratio tests. RESULTS: Across a diverse set of ethnicities, LP subjects consumed more lactose than LNP subjects. Lactobacillaceae abundance was highest in LNP subjects who consumed more than 12.46 g/d (upper tercile). Within Caucasians and Hispanics, family Lachnospiraceae was significantly enriched in the gut microbiota of LNP individuals consuming the upper tercile of lactose across both sexes. CONCLUSIONS: Elevated lactose consumption in individuals with the LNP genotype is associated with increased abundance of family Lactobacillaceae and Lachnospriaceae, taxa that contain multiple genera capable of utilizing lactose. This trial was registered on clinicaltrials.gov as NCT02367287.
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Microbioma Gastrointestinal , Intolerância à Lactose , Masculino , Feminino , Humanos , Adulto , Estados Unidos , Lactose , Intolerância à Lactose/genética , Microbioma Gastrointestinal/genética , Estudos Transversais , RNA Ribossômico 16S/genética , Laticínios , Lactase/genética , GenótipoRESUMO
BACKGROUND: Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. Deeper characterization of food carbohydrate composition can serve to strengthen the link between diet and gastrointestinal health outcomes. OBJECTIVES: The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. METHODS: This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. Dietary recalls were mapped to the Davis Food Glycopedia to estimate monosaccharide intake. Participants with >75% of carbohydrate intake mappable to the glycopedia were included (N = 180). RESULTS: Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). CONCLUSIONS: Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. This trial is registered at www. CLINICALTRIALS: gov as NCT02367287.
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Microbioma Gastrointestinal , Masculino , Feminino , Adulto , Humanos , Monossacarídeos , Estudos Transversais , Fibras na Dieta , Ingestão de Alimentos , Dieta , Fezes/química , InflamaçãoRESUMO
BACKGROUND: Progressive age-associated change in frequencies and functional capacities of immune cells is known as immunosenescence. Despite data linking chronic environmental, physiological, and psychosocial stressors with accelerated aging, how stress contributes to immunosenesence is not well characterized. OBJECTIVE: To help delineate the contribution of cumulative physiological stress on immunosensence we assessed relationships between a composite measurement of cumulative physiological stress, reflecting the functioning of the hypothalamic-pituitary-adrenal axis, sympathetic nervous system, cardiovascular system, and metabolic processes, and lymphocyte changes typically affiliated with aging in a cohort of healthy volunteers ranging from 18 to 66 y. RESULTS: Physiological stress load positively correlated with subject age in the study cohort and was significantly higher in adults 50-66 y compared to adults 18-33 y and 34-49 y. Using physiological stress load, we identified a significant age-dependent association between stress load and frequencies of circulating regulatory T lymphocytes (Tregs). Frequencies were higher in younger participants, but only in participants exhibiting low physiological stress load. As stress load increased, frequencies of Tregs decreased in young participants but were unchanged with increasing stress load in middle and older age individuals. Follow-up analysis of stress load components indicated lower circulating DHEA-S and higher urinary norepinephrine as the primary contributors to the effects of total stress load on Tregs. In addition, we identified age-independent inverse associations between stress load and frequencies of naïve Tregs and naïve CD4 T cells and positive associations between stress load and frequencies of memory Tregs and memory CD4 T cells. These associations were primarily driven by stress load components waist circumference, systolic and diastolic blood pressure, CRP, and HbA1c. In summary, our study results suggest that, in younger people, physiological stress load may diminish regulatory T cell frequencies to levels seen in older persons. Furthermore, independent of age, stress load may contribute to contraction of the naïve Treg pool and accumulation of memory Treg cells. CLINICAL TRIAL: Registered on ClincialTrials.gov (Identifier: NCT02367287).
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Plasma trimethylamine n-oxide (TMAO) concentration increases in responses to feeding TMAO, choline, phosphatidylcholine, L-carnitine, and betaine but it is unknown whether concentrations change following a mixed macronutrient tolerance test (MMTT) with limited amounts of TMAO precursors. In this proof-of-concept study, we provided healthy female and male adults (n = 97) ranging in age (18-65 years) and BMI (18-44 kg/m2) a MMTT (60% fat, 25% sucrose; 42% of a standard 2000 kilo calorie diet) and recorded their metabolic response at fasting and at 30 min, 3 h, and 6 h postprandially. We quantified total exposure to TMAO (AUC-TMAO) and classified individuals by the blood draw at which they experienced their maximal TMAO concentration (TMAO-response groups). We related AUC-TMAO to the 16S rRNA microbiome, to two SNPs in the exons of the FMO3 gene (rs2266782, G>A, p.Glu158Lys; and rs2266780, A>G, p.Glu308Gly), and to a priori plasma metabolites. We observed varying TMAO responses (timing and magnitude) and identified a sex by age interaction such that AUC-TMAO increased with age in females but not in males (p-value = 0.0112). Few relationships between AUC-TMAO and the fecal microbiome and FMO3 genotype were identified. We observed a strong correlation between AUC-TMAO and TNF-α that depended on TMAO-response group. These findings promote precision nutrition and have important ramifications for the eating behavior of adults who could benefit from reducing TMAO exposure, and for understanding factors that generate plasma TMAO.
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Betaína , Colina , Humanos , Masculino , Adulto , Feminino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , RNA Ribossômico 16S , Colina/metabolismo , Metilaminas/metabolismo , NutrientesRESUMO
BACKGROUND: Diet patterns are a significant and modifiable contributing factor to the composition of the human gut microbiota. OBJECTIVES: We set out to identify reproducible relationships between diet and gut microbial community composition in a diverse, healthy US adult cohort. METHODS: We collected 2 to 3 automated self-administered 24-hour dietary recalls over 10-14 days, together with a single stool sample, from 343 healthy adults in a cross-sectional phenotyping study. This study examined a multi-ethnic cohort balanced for age (18-65 years), sex, and BMI (18.5-45 kg/m2). Dietary data were edited to a tree format according to published methods. The tree structure was annotated with the average total grams of dry weight, fat, protein, carbohydrate, or fiber from each food item reported. The alpha and beta diversity measurements, calculated using the tree structure, were analyzed relative to the microbial community diversity, determined by a Quantitative Insights Into Microbial Ecology (QIIME) 2 analysis of the bacterial 16S ribosomal RNA V4 region, sequenced from stool samples. K-means clustering was used to form groups of individuals consuming similar diets, and gut microbial communities were compared among groups using differential expression analysis for sequence count data. RESULTS: The alpha diversity of diet dry weight was significantly correlated with the gut microbial community alpha diversity (r = 0.171). The correlation improved when diet was characterized using grams of carbohydrates (r = 0.186) or fiber (r = 0.213). Bifidobacterium was enriched with diets containing higher levels of total carbohydrate from cooked grains. Lachnospira, was enriched with diet patterns containing high consumption of fiber from fruits excluding berries. CONCLUSIONS: The tree structure, annotated with grams of carbohydrate, is a robust analysis method for comparing self-reported diet to the gut microbial community composition. This method identified consumption of fiber from fruit robustly associated with an abundance of pectinolytic bacterial genus, Lachnospira, in the guts of healthy adults. This trial was registered at clinicaltrials.gov as NCT02367287.
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Microbioma Gastrointestinal , Adolescente , Adulto , Idoso , Estudos Transversais , Dieta , Fibras na Dieta/análise , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Pessoa de Meia-Idade , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/genética , Adulto JovemRESUMO
BACKGROUND: Monocytes are a heterogenous population of immune cells whose subsets and functions become substantially dysregulated with advanced age. Although much of our current understanding of the age-related changes in monocytes is derived from fasting blood samples, most people are predominately in the postprandial state during waking hours. As hormonal, metabolic, and immunological changes in response to the consumption of a meal are manifested in postprandial blood, it's unclear how age-dependent changes in peripheral monocytes at fasting are impacted by a dietary challenge. OBJECTIVE: We investigated the impact of age and meal consumption on circulating monocyte frequencies and subsets defined as classical (CD14 + CD16-), intermediate (CD14 + CD16 +), or non-classical (CD14dim CD16 +) in a cohort of 349 healthy adult volunteers grouped into categories based on their age: young adults (18-33 y, n = 123), middle adults (34-49 y, n = 115), and older adults (50-66 y, n = 111). RESULTS: Following 12-h fast total monocyte counts inversely correlated with subject age. Older adults had significantly fewer circulating monocytes along with elevated levels of TGs, cholesterol, glucose, IL-6, IL-8, TNF, neopterin, and CCL2 compared with young adults. Circulating monocyte pools in older adults consisted of smaller proportions of classical but larger proportions of intermediate and non-classical monocytes. Proportions of classical monocytes were inversely correlated with plasma TNF, IL-8, and neopterin while intermediate monocytes were positively correlated with plasma IL-6, TNF, and neopterin. Three hours after consuming a fat-containing meal postprandial monocyte counts increased in all age groups. Despite age-dependent differences in monocyte subsets at fasting, consumption of a meal induced similar changes in the proportions of classical and non-classical monocytes across age groups. Within the circulating postprandial monocyte pool, percentages of classical monocytes decreased while non-classical monocytes increased. However no change in precursory intermediate monocytes were detected. Our study confirms that ageing is associated with changes in monocyte frequencies and subsets and shows that consuming a fat-containing meal induces temporal changes in monocyte frequency and subsets independently of subject age. CLINICAL TRIAL: Registered on ClincialTrials.gov (Identifier: NCT02367287).
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BACKGROUND: A variety of modifiable and nonmodifiable factors such as ethnicity, age, and diet have been shown to influence bone health. Previous studies are usually limited to analyses focused on the association of a few a priori variables or on a specific subset of the population. OBJECTIVE: Dietary, physiological, and lifestyle data were used to identify directly modifiable and nonmodifiable variables predictive of bone mineral content (BMC) and bone mineral density (BMD) in healthy US men and women using machine-learning models. METHODS: Ridge, lasso, elastic net, and random forest models were used to predict whole-body, femoral neck, and spine BMC and BMD in healthy US men and women ages 18-66 y, with a BMI (kg/m2) of 18-44 (n = 313), using nonmodifiable anthropometric, physiological, and demographic variables; directly modifiable lifestyle (physical activity, tobacco use) and dietary (via FFQ) variables; and variables approximating directly modifiable behavior (circulating 25-hydroxycholecalciferol and stool pH). RESULTS: Machine-learning models using nonmodifiable variables explained more variation in BMC and BMD (highest R2 = 0.75) compared with when using only directly modifiable variables (highest R2 = 0.11). Machine-learning models had better performance compared with multivariate linear regression, which had lower predictive value (highest R2 = 0.06) when using directly modifiable variables only. BMI, body fat percentage, height, and menstruation history were predictors of BMC and BMD. For directly modifiable features, betaine, cholesterol, hydroxyproline, menaquinone-4, dihydrophylloquinone, eggs, cheese, cured meat, refined grains, fruit juice, and alcohol consumption were predictors of BMC and BMD. Low stool pH, a proxy for fermentable fiber intake, was also predictive of higher BMC and BMD. CONCLUSIONS: Modifiable factors, such as diet, explained less variation in the data compared with nonmodifiable factors, such as age, sex, and ethnicity, in healthy US men and women. Low stool pH predicted higher BMC and BMD. This trial was registered at www.clinicaltrials.gov as NCT02367287.
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Densidade Óssea , Colo do Fêmur , Absorciometria de Fóton , Adolescente , Adulto , Idoso , Antropometria , Feminino , Humanos , Concentração de Íons de Hidrogênio , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Prior studies of adults with constipation or diarrhea suggest that dietary intake, physical activity, and stress may affect stool consistency. However, the influence of these factors is unresolved and has not been investigated in healthy adults. OBJECTIVES: We assessed the relations of technician-scored stool consistency in healthy adults with self-reported diet, objectively monitored physical activity, and quantifiable markers of stress. METHODS: Stool consistency was scored by an independent technician using the Bristol Stool Form Scale (BSFS) to analyze samples provided by healthy adults, aged 18-65 y, BMI 18-44 kg/m2, in the USDA Nutritional Phenotyping Study (n = 364). A subset of participants (n = 109) were also asked to rate their sample using the BSFS. Dietary intake was assessed with two to three 24-h recalls completed at home and energy expenditure from physical activity was monitored using an accelerometer in the 7-d period preceding the stool collection. Stress was measured using the Wheaton Chronic Stress Inventory and allostatic load (AL). Statistical and machine learning analyses were conducted to determine which dietary, physiological, lifestyle, and stress factors differed by stool form. RESULTS: Technician-scored BSFS scores were significantly further (P = 0.003) from the central score (mean ± SEM distance: 1.41 ± 0.089) than the self-reported score (1.06 ± 0.086). Hard stool was associated with higher (P = 0.005) intake of saturated fat (13.8 ± 0.40 g/1000 kcal) than was normal stool (12.5 ± 0.30 g/1000 kcal). AL scores were lower for normal stool (2.49 ± 0.15) than for hard (3.07 ± 0.18) (P = 0.009) or soft stool (2.89 ± 0.18) (P = 0.049). Machine learning analyses revealed that various dietary components, physiological characteristics, and stress hormones predicted stool consistency. CONCLUSIONS: Technician-scored stool consistency differed by dietary intake and stress hormones, but not by physical activity, in healthy adults.This trial was registered at clincialtrials.gov as NCT02367287.
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Dieta , Fezes , Estresse Psicológico/epidemiologia , Adulto , Constipação Intestinal , Estudos Transversais , Diarreia , Exercício Físico , Hormônios , Humanos , Aprendizado de Máquina , Estados UnidosRESUMO
BACKGROUND: Bifidobacterium longum subsp. infantis (B. infantis) is a commensal bacterium that colonizes the gastrointestinal tract of breast-fed infants. B. infantis can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence. We hypothesized that metabolites from B. infantis grown on HMO produce a beneficial effect on the host. RESULTS: In a previous study, we demonstrated that B. infantis routinely dominated the fecal microbiota of a breast fed Bangladeshi infant cohort (1). Characterization of the fecal metabolome of binned samples representing high and low B. infantis populations from this cohort revealed higher amounts of the tryptophan metabolite indole-3-lactic acid (ILA) in feces with high levels of B. infantis. Further in vitro analysis confirmed that B. infantis produced significantly greater quantities of the ILA when grown on HMO versus lactose, suggesting a growth substrate relationship to ILA production. The direct effects of ILA were assessed in a macrophage cell line and intestinal epithelial cell lines. ILA (1-10 mM) significantly attenuated lipopolysaccharide (LPS)-induced activation of NF-kB in macrophages. ILA significantly attenuated TNF-α- and LPS-induced increase in the pro-inflammatory cytokine IL-8 in intestinal epithelial cells. ILA increased mRNA expression of the aryl hydrogen receptor (AhR)-target gene CYP1A1 and nuclear factor erythroid 2-related factor 2 (Nrf2)-targeted genes glutathione reductase 2 (GPX2), superoxide dismutase 2 (SOD2), and NAD(P) H dehydrogenase (NQO1). Pretreatment with either the AhR antagonist or Nrf-2 antagonist inhibited the response of ILA on downstream effectors. CONCLUSIONS: These findings suggest that ILA, a predominant metabolite from B. infantis grown on HMO and elevated in infant stool high in B. infantis, and protects gut epithelial cells in culture via activation of the AhR and Nrf2 pathway.
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Anti-Inflamatórios/farmacologia , Bifidobacterium/fisiologia , Indóis/farmacologia , Microbiota , Animais , Anti-Inflamatórios/análise , Bifidobacterium/metabolismo , Linhagem Celular , Endotoxinas/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fezes/química , Fezes/microbiologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Humanos , Indóis/análise , Lactente , Interleucina-8/metabolismo , Lactose/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Camundongos , Leite Humano/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Oligossacarídeos/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Vitamin A (VA) stores are low in early infancy and may impair development of the immune system. OBJECTIVE: This study determined if neonatal VA supplementation (VAS) affects the following: 1) development of regulatory T (Treg) cells; 2) chemokine receptor 9 (CCR9) expression, which directs mucosal targeting of immune cells; and 3) systemic endotoxin exposure as indicated by changed plasma concentrations of soluble CD14 (sCD14). Secondarily, VA status, growth, and systemic inflammation were investigated. METHODS: In total, 306 Bangladeshi infants were randomly assigned to receive 50,000 IU VA or placebo (PL) within 48 h of birth, and immune function was assessed at 6 wk, 15 wk, and 2 y. Primary outcomes included the following: 1) peripheral blood Treg cells; 2) percentage of Treg, T, and B cells expressing CCR9; and 3) plasma sCD14. Secondary outcomes included the following: 4) VA status measured using the modified relative dose-response (MRDR) test and plasma retinol; 5) infant growth; and 6) plasma C-reactive protein (CRP). Statistical analysis identified group differences and interactions with sex and birthweight. RESULTS: VAS increased (P = 0.004) the percentage of CCR9+ Treg cells (13.2 ± 1.37%) relative to PL (9.17 ± 1.15%) in children below the median birthweight but had the opposite effect (P = 0.04) in those with higher birthweight (VA, 9.13 ± 0.89; PL, 12.1 ± 1.31%) at 6 and 15 wk (values are combined mean ± SE). VAS decreased (P = 0.003) plasma sCD14 (1.56 ± 0.025 mg/L) relative to PL (1.67 ± 0.032 mg/L) and decreased (P = 0.034) the prevalence of VA deficiency (2.3%) relative to PL (9.2%) at 2 y. CONCLUSIONS: Neonatal VAS enhanced mucosal targeting of Treg cells in low-birthweight infants. The decreased systemic exposure to endotoxin and improved VA status at 2 y may have been due to VA-mediated improvements in gut development resulting in improved barrier function and nutrient absorption. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.
Assuntos
Receptores CCR/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Deficiência de Vitamina A/prevenção & controle , Vitamina A/administração & dosagem , Bangladesh/epidemiologia , Peso ao Nascer , Pré-Escolar , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Feminino , Humanos , Recém-Nascido , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Receptores CCR/genética , Linfócitos T Reguladores/metabolismo , Deficiência de Vitamina A/epidemiologiaRESUMO
BACKGROUND: Vitamin A deficiency (VAD) impairs T-cell-mediated immunity. In regions where VAD is prevalent, vitamin A supplementation (VAS) reduces child mortality, perhaps by improving immune function. OBJECTIVE: Our objective was to determine if neonatal VAS would improve thymic function in Bangladeshi infants, and to determine if such effects differed by sex or nutritional status (i.e., birth weight above/below the median). METHODS: Three hundred and six infants were randomly assigned to 50,000 IU vitamin A (VA) or placebo (PL) within 48 h of birth. Primary outcomes were measured at multiple ages and included 1) thymic index (TI) at 1, 6, 10, and 15 wk; 2) T-cell receptor excision circles (TREC), an index of thymic output of naïve T cells; and 3) total/naïve T cells in peripheral blood at 6 wk, 15 wk, and 2 y. A mixed linear model for repeated measures was used to assess group differences at each age and identify interactions with sex and birth weight. RESULTS: VAS did not significantly (P = 0.21) affect TI overall (i.e., at all ages) but decreased TI by 7.8% (P = 0.029) at 6 wk: adjusted TI means for the PL and VA groups at 1, 6, 10, and 15 wk were 4.09 compared with 3.80 cm2, 7.78 compared with 7.18 cm2, 8.11 compared with 7.84 cm2, and 7.91 compared with 7.97 cm2, respectively. VAS did not significantly (P = 0.25) affect TREC overall but decreased TREC by 19% (P = 0.029) at 15 wk: adjusted TREC means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 13.6 compared with 16.1 copies/pg DNA, 19.4 compared with 15.7 copies/pg DNA, and 11.8 compared with 10.0 copies/pg DNA, respectively. VAS did not significantly affect overall total (P = 0.10) or naïve (P = 0.092) T cells: adjusted naïve T-cell means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 3259 compared with 3109 cells/µL, 3771 compared with 3487 cells/µL, and 1976 compared with 1898 cells/µL, respectively. CONCLUSION: In contrast to our hypothesis, VAS decreased thymic function early in infancy but health effects are presumably negligible owing to the transience and small magnitude of this effect. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.
Assuntos
Timo/efeitos dos fármacos , Deficiência de Vitamina A/tratamento farmacológico , Vitamina A/administração & dosagem , Suplementos Nutricionais , Feminino , Humanos , Recém-Nascido , Masculino , Estado Nutricional , Linfócitos T/fisiologiaRESUMO
BACKGROUND: Zinc deficiency impairs immune function and is common among children in South-East Asia. OBJECTIVES: The effect of zinc supplementation on immune function in young Laotian children was investigated. METHODS: Children (n = 512) aged 6-23 mo received daily preventive zinc tablets (PZ; 7 mg Zn/d), daily multiple micronutrient powder (MNP; 10 mg Zn/d, 6 mg Fe/d, plus 13 other micronutrients), therapeutic dispersible zinc tablets only in association with diarrhea episodes (TZ; 20 mg Zn/d for 10 d after an episode), or daily placebo powder (control). These interventions continued for 9 mo. Cytokine production from whole blood cultures, the concentrations of T-cell populations, and a complete blood count with differential leukocyte count were measured at baseline and endline. Endline means were compared via ANCOVA, controlling for the baseline value of the outcome, child age and sex, district, month of enrollment, and baseline zinc status (below, or above or equal to, the median plasma zinc concentration). RESULTS: T-cell cytokines (IL-2, IFN-γ, IL-13, IL-17), LPS-stimulated cytokines (IL-1ß, IL-6, TNF-α, and IL-10), and T-cell concentrations at endline did not differ between intervention groups, nor was there an interaction with baseline zinc status. However, mean ± SE endline lymphocyte concentrations were significantly lower in the PZ than in the control group (5018 ± 158 compared with 5640 ± 160 cells/µL, P = 0.032). Interactions with baseline zinc status were seen for eosinophils (Pixn = 0.0036), basophils (Pixn = 0.023), and monocytes (P = 0.086) but a significant subgroup difference was seen only for eosinophils, where concentrations were significantly lower in the PZ than in the control group among children with baseline plasma zinc concentrations below the overall median (524 ± 44 compared with 600 ± 41 cells/µL, P = 0.012). CONCLUSIONS: Zinc supplementation of rural Laotian children had no effect on cytokines or T-cell concentrations, although zinc supplementation affected lymphocyte and eosinophil concentrations. These cell subsets may be useful as indicators of response to zinc supplementation.This trial was registered at clinicaltrials.gov as NCT02428647.
Assuntos
Suplementos Nutricionais , Eosinófilos , Linfócitos , Zinco/administração & dosagem , Zinco/deficiência , Deficiências Nutricionais/sangue , Deficiências Nutricionais/epidemiologia , Deficiências Nutricionais/prevenção & controle , Humanos , Lactente , Laos/epidemiologia , Prevalência , População RuralRESUMO
BACKGROUND: Infancy is a crucial period for establishing the intestinal microbiome. This process may be influenced by vitamin A (VA) status because VA affects intestinal immunity and epithelial integrity, factors that can, in turn, modulate microbiome development. OBJECTIVES: The aim of this study was to determine if neonatal VA supplementation (VAS) affected the abundance of Bifidobacterium, a beneficial commensal, or of Proteobacteria, a phylum containing enteric pathogens, in early (6-15 wk) or late (2 y) infancy. Secondary objectives were to determine if VAS affected the abundance of other bacterial taxa, and to determine if VA status assessed by measuring plasma retinol was associated with bacterial abundance. METHODS: Three hundred and six Bangladeshi infants were randomized by sex and birthweight status (above/below median) to receive 1 VA dose (50,000 IU) or placebo within 48 h of birth. Relative abundance at the genus level and above was assessed by 16S rRNA gene sequencing. A terminal restriction fragment-length polymorphism assay was used to identify Bifidobacterium species and subspecies at 6 wk. RESULTS: Linear regression showed that Bifidobacterium abundance in early infancy was lower in boys (median, 1st/3rd quartiles; 0.67, 0.52/0.78) than girls (0.73, 0.60/0.80; P = 0.003) but that boys receiving VAS (0.69, 0.55/0.78) had higher abundance than boys receiving placebo (0.65, 0.44/0.77; P = 0.039). However this difference was not seen in girls (VAS 0.71, 0.54/0.80; placebo 0.75, 0.63/0.81; P = 0.25). VAS did not affect Proteobacteria abundance. Sex-specific associations were also seen for VA status, including positive associations of plasma retinol with Actinobacteria (the phylum containing Bifidobacterium) and Akkermansia, another commensal with possible health benefits, for girls in late infancy. CONCLUSIONS: Better VA status in infancy may influence health both in infancy and later in life by promoting the establishment of a healthy microbiota. This postulated effect of VA may differ between boys and girls. This trial was registered at clinicaltrials.gov as NCT02027610.
Assuntos
Suplementos Nutricionais , Microbioma Gastrointestinal , Vitamina A/administração & dosagem , Bangladesh , Bifidobacterium/efeitos dos fármacos , Bifidobacterium/isolamento & purificação , Pré-Escolar , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Estado Nutricional , Proteobactérias/efeitos dos fármacos , Proteobactérias/isolamento & purificação , Vitamina A/sangueRESUMO
Stress can impair T cell-mediated immunity. To determine if infants with high stress responses had deficits in T-cell mediated immunity, we examined the association of pain-induced cortisol responsiveness with thymic function and vaccine responses in infants. This study was performed among 306 (male = 153 and female = 153) participants of a randomized, controlled trial examining the effect of neonatal vitamin A supplementation on immune function in Bangladesh (NCT01583972). Salivary cortisol was measured before and 20 min after a needle stick (vaccination) at 6 weeks of age. The thymic index (TI) was determined by ultrasonography at 1, 6, 10 and 15 weeks. T-cell receptor excision circle and blood T-cell concentrations were measured at 6 and 15 weeks. Responses to Bacillus Calmette-Guérin (BCG), tetanus toxoid, hepatitis B virus and oral poliovirus vaccination were assayed at 6 and 15 weeks. Cortisol responsiveness was negatively associated with TI at all ages (p < .01) in boys only, was negatively associated with naïve helper T-cell concentrations in both sexes at both 6 (p = .0035) and 15 weeks (p = .0083), and was negatively associated with the delayed-type hypersensitivity (DTH) skin test response to BCG vaccination at 15 weeks (p = .034) in both sexes. Infants with a higher cortisol response to pain have differences in the T-cell compartment and a lower DTH response to vaccination. Sex differences in the immune system were seen as early as 6 weeks of age in these healthy infants.