Gut microbial features can predict host phenotype response to protein deficiency.

Malnutrition remains a major health problem in low- and middle-income countries. During low protein intake, <0.67 g/kg/day, there is a loss of nitrogen (N2 ) balance, due to the unavailability of amino acid for metabolism and unbalanced protein catabolism results. However, there are individuals, who consume the same low protein intake, and preserve N2 balance for unknown reasons. A novel factor, the gut microbiota, may account for these N2 balance differences. To investigate this, we correlated gut microbial profiles with the growth of four murine strains (C57Bl6/J, CD-1, FVB, and NIH-Swiss) on protein deficient (PD) diet. Results show that a PD diet exerts a strain-dependent impact on growth and N2 balance as determined through analysis of urinary urea, ammonia and creatinine excretion. Bacterial alpha diversity was significantly (P < 0.05, FDR) lower across all strains on a PD diet compared to normal chow (NC). Multi-group analyses of the composition of microbiomes (ANCOM) revealed significantly differential microbial signatures between the four strains independent of diet. However, mice on a PD diet demonstrated differential enrichment of bacterial genera including, Allobaculum (C57Bl6/J), Parabacteroides (CD-1), Turicibacter (FVB), and Mucispirillum (NIH-Swiss) relative to NC. For instance, selective comparison of the CD-1 (gained weight) and C57Bl6/J (did not gain weight) strains on PD diet also demonstrated significant pathway enrichment of dihydroorodate dehydrogenase, rRNA methyltransferases, and RNA splicing ligase in the CD-1 strains compared to C57Bl6/J strains; which might account in their ability to retain growth despite a protein deficient diet. Taken together, these results suggest a potential relationship between the specific gut microbiota, N2 balance and animal response to malnutrition

Prenatal factors contribute to the emergence of kwoshiorkor or marasmus in severe undernutrition: evidence for the predictive adaptation model

Severe acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor) and non-oedematous (marasmus) syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity

Emergence of Western diseases in the tropical world: The experience with chronic cardiovascular diseases

Our knowledge of the disease burden components of tropical populations is fragmentary. Historically, the infectious diseases have been emphasized but, as some populations have undergone socio-economic changes, vital statistics have described a change in the pattern of disease. The picture is of a decline in infectious and a rise in chronic non-communicable disease. We focus here on the emergence of chronic cardiovascular diseases, and use hypertension as the paradigmic example. Early blood pressure surveys showed a virtual absence of hypertension among rural Africans and moderate prevalences in the Caribbean. Prevalence was highest among US and UK blacks. In a recent comparative study of blood pressure and its determinants in Nigeria, Jamaica and the US there was a steep gradient in prevalence from 15% through 26% to 33%. Body mass index and salt intake were the major determinants, accounting for 70% of the variance in hypertension prevalence. Additional information on mechanism comes from the exploration of the renin-angiotensin system across these populations. Angiotensinogen levels rise steadily from Africa to the US and are modestly associated with body mass index (BMI), and even more modestly with polymorphisms of the angiotensinogen gene. 30% of the variation in angiotensin-converting enzyme levels is attributable to the insertion/deletion polymorphism, and angiotensin-converting enzyme levels are modestly related to BMI and blood pressure. Thus, the steep gradient in prevalence is not attributable to the genetics as manifested in the renin-angiotensin system. The usefulness of these and other data on cardiovascular diseases include planning for primordial prevention in Africa and amelioration of existing epidemics in the Caribbean, the US and the UK. Additional long term surveillance data to define the burden and distribution of causes are necessary in Africa. Lastly, education and advocacy to transfer the information to policy makers and planners is required

Limitations of fasting indices in the measurement of insulin sensitivity in Afro-Caribbean adults

In young Afro-Caribbean adults, HOMA-IR compared poorly with other measures of insulin sensitivity. It remains important to determine whether similar findings occur in a more insulin resistant population. However, HOMA-IR correlated with clinical measures of insulin sensitivity (i.e. adiposity), so it may still be useful in epidemiological studies

Developmental contributions to macronutrient selection: A randomized controlled trial in adult survivors of malnutrition

Background and objectives: Birthweight differences between kwashiorkor and marasmus suggest that intrauterine factors influence the development of these syndromes of malnutrition and may modulate risk of obesity through dietary intake. We tested the hypotheses that the target protein intake in adulthood is associated with birthweight, and that protein leveraging to maintain this target protein intake would influence energy intake (EI) and body weight in adult survivors of malnutrition.Methodology: Sixty-three adult survivors of marasmus and kwashiorkor could freely compose a diet from foods containing 10, 15 and 25 percentage energy from protein (percentage of energy derived from protein (PEP); Phase 1) for 3 days. Participants were then randomized in Phase 2 (5 days) to diets with PEP fixed at 10%, 15% or 25%.Results: Self-selected PEP was similar in both groups. In the groups combined, selected PEP was 14.7, which differed significantly (P < 0.0001) from the null expectation (16.7%) of no selection. Self-selected PEP was inversely related to birthweight, the effect disappearing after adjusting for sex and current body weight. In Phase 2, PEP correlated inversely with EI (P = 0.002) and weight change from Phase 1 to 2 (P = 0.002). Protein intake increased with increasing PEP, but to a lesser extent than energy increased with decreasing PEP.Conclusions and implications: Macronutrient intakes were not independently related to birthweight or diagnosis. In a free-choice situation (Phase 1), subjects selected a dietary PEP significantly lower than random. Lower PEP diets induce increased energy and decreased protein intake, and are associated with weight gain

Distribution of metals exposure and associations with cardiometabolic risk factors in the “Modeling the Epidemiologic Transition Study”

Background: Metals are known endocrine disruptors and have been linked to cardiometabolic diseases via multiple potential mechanisms, yet few human studies have both the exposure variability and biologically-relevant phenotype data available. We sought to examine the distribution of metals exposure and potential associations with cardiometabolic risk factors in the “Modeling the Epidemiologic Transition Study” (METS), a prospective cohort study designed to assess energy balance and change in body weight, diabetes and cardiovascular disease risk in five countries at different stages of social and economic development. Methods: Young adults (25–45 years) of African descent were enrolled (N = 500 from each site) in: Ghana, South Africa, Seychelles, Jamaica and the U.S.A. We randomly selected 150 blood samples (N = 30 from each site) to determine concentrations of selected metals (arsenic, cadmium, lead, mercury) in a subset of participants at baseline and to examine associations with cardiometabolic risk factors. Results: Median (interquartile range) metal concentrations (μg/L) were: arsenic 8.5 (7.7); cadmium 0.01 (0.8); lead 16.6 (16.1); and mercury 1.5 (5.0). There were significant differences in metals concentrations by: site location, paid employment status, education, marital status, smoking, alcohol use, and fish intake. After adjusting for these covariates plus age and sex, arsenic (OR 4.1, 95% C.I. 1.2, 14.6) and lead (OR 4.0, 95% C.I. 1.6, 9.6) above the median values were significantly associated with elevated fasting glucose. These associations increased when models were further adjusted for percent body fat: arsenic (OR 5.6, 95% C.I. 1.5, 21.2) and lead (OR 5.0, 95% C.I. 2.0, 12.7). Cadmium and mercury were also related with increased odds of elevated fasting glucose, but the associations were not statistically significant. Arsenic was significantly associated with increased odds of low HDL cholesterol both with (OR 8.0, 95% C.I. 1.8, 35.0) and without (OR 5.9, 95% C.I. 1.5, 23.1) adjustment for percent body fat. Conclusions: While not consistent for all cardiometabolic disease markers, these results are suggestive of potentially important associations between metals exposure and cardiometabolic risk. Future studies will examine these associations in the larger cohort over time

Protocol for the modeling the epidemiologic transition study: a longitudinal observational study of energy balance and change in body weight, diabetes and cardiovascular disease risk.

BACKGROUND: The prevalence of obesity has increased in societies of all socio-cultural backgrounds. To date, guidelines set forward to prevent obesity have universally emphasized optimal levels of physical activity. However there are few empirical data to support the assertion that low levels of energy expenditure in activity is a causal factor in the current obesity epidemic are very limited. METHODS/DESIGN: The Modeling the Epidemiologic Transition Study (METS) is a cohort study designed to assess the association between physical activity levels and relative weight, weight gain and diabetes and cardiovascular disease risk in five population-based samples at different stages of economic development. Twenty-five hundred young adults, ages 25-45, were enrolled in the study; 500 from sites in Ghana, South Africa, Seychelles, Jamaica and the United States. At baseline, physical activity levels were assessed using accelerometry and a questionnaire in all participants and by doubly labeled water in a subsample of 75 per site. We assessed dietary intake using two separate 24-hour recalls, body composition using bioelectrical impedance analysis, and health history, social and economic indicators by questionnaire. Blood pressure was measured and blood samples collected for measurement of lipids, glucose, insulin and adipokines. Full examination including physical activity using accelerometry, anthropometric data and fasting glucose will take place at 12 and 24 months. The distribution of the main variables and the associations between physical activity, independent of energy intake, glucose metabolism and anthropometric measures will be assessed using cross-section and longitudinal analysis within and between sites. DISCUSSION: METS will provide insight on the relative contribution of physical activity and diet to excess weight, age-related weight gain and incident glucose impairment in five populations' samples of young adults at different stages of economic development. These data should be useful for the development of empirically-based public health policy aimed at the prevention of obesity and associated chronic diseases.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Association between Blood Pressure and Resting Energy Expenditure Independent of Body Size

Obesity is an important risk factor for hypertension; however, the pathway through which it raises blood pressure (BP) is poorly understood. Body size is also the primary determinant of energy expenditure, and we therefore examined the joint relationship of energy expenditure and body size to blood pressure. Resting energy expenditure (REE) was measured using respiratory gas exchange in population-based samples of 997 Nigerians and 452 African Americans. In a third sample of 118 individuals, nonresting energy expenditure (ie, physical activity) was measured in addition to REE. The univariate correlation between REE and BP ranged from 0.10 to 0.22 in the 3 samples (P\u3c0.001). In multivariate models, adiposity, whether defined by body mass, fat mass, or leptin, was no longer associated with BP, while REE remained highly significant (P\u3c0.001). The REE-BP association also persisted after adjustment for physical activity measured with doubly labeled water. The odds ratio for hypertension among persons in the highest quartile versus the lowest quartile of REE, after adjustment for body size, was 1.7. This relationship was not the result of hypertension among the obese, because it did not vary across the range of BMI and was the same in lean Nigerians as in obese Americans. These data suggest that metabolic processes represented by REE may mediate the effect of body size on BP. The interrelationship of REE with sympathetic tone, transmembrane ion exchange, or other metabolic processes that determine energy costs at rest could provide physiological explanations for this observation

Predicting incident diabetes in Jamaica: The role of anthropometry

Objective: To evaluate the performance of the body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHTR) in predicting incident diabetes in Jamaica. Research Methods and Procedures: A cohort of 728 non-diabetic adults (290 men and 438 women), ages 25 to 74 years and residents of Spanish Town, Jamaica, were followed for a mean of 4 years. Participants had fasting and 2-hour postchallenge glucose concentrations measured at baseline and follow-up. Results: There were 51 cases of incident diabetes (17 men and 34 women). All indices were independent predictors of diabetes, and none was clearly superior. The area under the receiver operating characteristics curves (95% confidence interval) for BMI was 0.74 (0.59 to 0.88) for men and 0.62 (0.51 to 0.72) for women. For waist circumference, these values were 0.78 (0.65 to 0.91) in men and 0.61 (0.50 to 0.71) in women. Similar results were obtained for WHR and WHTR. Optimal cut-off points for BMI were 24.8 kg/m2 (men) and 29.3 kg/m2 (women). For waist circumference, these were 88 cm and 84.5 cm for men and women, respectively. Corresponding values for WHR were 0.87 and 0.80 and for WHTR were 0.51 and 0.54, respectively. Discussion: Cut-off points for waist circumference and WHR were similar to those proposed in developed countries for women but lower in men. Waist circumference could be useful in health promotion as an alternative to BMI

An international comparative study of blood pressure in populations of European vs. African descent

Background: The consistent finding of higher prevalence of hypertension in US blacks compared to whites has led to speculation that African-origin populations are particularly susceptible to this condition. Large surveys now provide new information on this issue. Methods: Using a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants). Results: The range in hypertension prevalence was from 27 to 55% for whites and 14 to 44% for blacks. Conclusions: These data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated