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

Under- and overreporting of energy is related to obesity, lifestyle factors and food group intakes in Jamaican adults

OBJECTIVE: Research in industrialised countries has documented a high prevalence of underreported energy intakes associated with characteristics such as obesity. This paper examines the prevalence, patterns and impact of energy under- and overreporting on diet-obesity relationships in a middle-income developing country. DESIGN: A 70-item food-frequency questionnaire was used. Underreporters had reported energy intakes 2.4 x BMR. Multinomial models were used to identify characteristics associated with implausible reporting. Intakes were compared across reporting groups to assess evidence of bias. Associations between diet and obesity were compared with and without adjustment for implausible reporting. SETTING: Spanish Town, neighbouring the capital city of Kingston, Jamaica. SUBJECTS: Eight hundred and ninety-one Jamaican adults, aged 25-75 years, were randomly recruited. RESULTS: More women than men (38.6% vs. 22.5%) underreported, but more men overreported energy (23.7% vs. 16.0%). Underreporting was positively associated with obesity, special diets, smoking and age; age was inversely associated with overreporting. Underreporters estimated lower energy from potentially socially undesirable food groups (e.g. snacks) and higher intakes of 'healthy' foods (e.g. fruit) than did plausible reporters. For some of these food groups, significant differences in intakes among normal-weight versus obese subjects observed among plausible reporters were absent when implausible reporters were included. In models of food group-obesity associations, adjusting for implausible energy yielded more credible results that more closely resembled findings in plausible reporters. CONCLUSIONS: Energy under- and overreporting are highly prevalent in Jamaica. Adjusting for implausible reporting may help to reduce bias in diet-health outcome associations

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

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

Genetic Variation on Chromosome 6 Influences F Cell Levels in Healthy Individuals of African Descent and HbF Levels in Sickle Cell Patients

Fetal haemoglobin (HbF) is a major ameliorating factor in sickle cell disease. We investigated if a quantitative trait locus on chromosome 6q23 was significantly associated with HbF and F cell levels in individuals of African descent. Single nucleotide polymorphisms (SNPs) in a 24-kb intergenic region, 33-kb upstream of the HBS1L gene and 80-kb upstream of the MYB gene, were typed in 177 healthy Afro-Caribbean subjects (AC) of approximately 7% European admixture, 631 healthy Afro-Germans (AG, a group of African and German descendents located in rural Jamaica with about 20% European admixture), 87 West African and Afro-Caribbean individuals with sickle cell anaemia (HbSS), as well as 75 Northern Europeans, which served as a contrasting population. Association with a tag SNP for the locus was detected in all four groups (AC, P = 0.005, AG, P = 0.002, HbSS patients, P = 0.019, Europeans, P = 1.5×10−7). The association signal varied across the interval in the African-descended groups, while it is more uniform in Europeans. The 6q QTL for HbF traits is present in populations of African origin and is also acting in sickle cell anaemia patients. We have started to distinguish effects originating from European and African ancestral populations in our admixed study populations

Associations between self-reported sleep duration and cardiometabolic risk factors in young African-origin adults from the five-country Modeling the Epidemiologic Transition Study (METS)

To investigate associations between self-reported sleep duration and cardiometabolic (CM) risk factors in African-origin adults residing in five countries spanning the epidemiologic transition. Cross-sectional. Ghanaian (n = 491), South African (n = 503), Jamaican (n = 508), Seychellois (n = 501) and American (n = 480) men and women. Self-reported sleep duration was obtained using questionnaires. Sex- and site-stratified logistic regression analyses investigated relationships between sleep duration, individual CM risk factors and a binary CM risk variable (presence of ≥3 CM risk factors), adjusting for age, physical activity and education. Sleep duration distributions varied by cohort: 44.5%, 41.4%, 35.9%, 16.8% and 2.5% of American, Jamaican, Seychellois, Ghanaian and South African men reported <7 h sleep per night respectively (p < 0.001). Similarly, 42.6%, 28.6%, 25.2%, 12.8% and 1.5% of American, Jamaican, Seychellois, Ghanaian and South African women reported <7 h sleep respectively (p < 0.001). American men reporting ≤6 h sleep were more likely to be in the elevated CM risk group (OR: 2.52, 95%CI: 1.02, 6.22, p = 0.045) and to have a high waist circumference (OR: 2.44, 95%CI: 1.07, 5.57, p = 0.034) compared to those reporting 8 h sleep. Jamaican women reporting ≤6 h sleep (OR: 2.53, 95%CI: 1.19, 5.36, p = 0.016) and American women reporting 7 h sleep (OR: 2.71, 95%CI: 1.17, 6.26, p = 0.002) were more likely to be obese than those reporting 8 h sleep. Associations between short sleep and CM risk factors were only evident in the American men and women and Jamaican women. Future interventions to address CM risk and sleep health may need to be country-specific when targeting high-risk populations

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

Faster rehabilitation weight gain is associated with liver fat in adult survivors of childhood severe acute malnutrition

Background Nutritional rehabilitation during severe acute malnutrition (SAM) aims to quickly restore a healthy body weight, but rapid weight gain has been associated with later cardiovascular risk. We hypothesized that faster weight gain during SAM rehabilitation and post-hospitalization is associated with liver fat in adult survivors. Method Jamaican adult survivors of childhood SAM underwent abdominal CT scan to estimate liver fat as mean liver attenuation (MLA) and liver spleen ratio (L/S). Birth weight (BW) and anthropometry measured during, and post-hospitalization were abstracted from admission records. Results We studied 42 marasmus survivors (MRs) and 40 kwashiorkor survivors (KWs). MRs had a lower mean BW (SD) 2.5 (0.8) vs 3.0 (0.7) kg; p=0.01) and were more wasted (p<0.001) and stunted (p=0.03) than KWs on admission to hospital. MRs and KWs had similar rates of rehabilitation weight gain, which was inversely associated with MLA among all survivors of SM (r=-0.246, p=0.029), but only in MRs when assessed by diagnosis (r= -0.449, p=0.004). The association between rehabilitation weight gain and adult liver fat in MRs was not altered by BW, admission wasting or stunting. In KWs, post-hospitalization height gain was inversely associated with MLA (difference = -0.64, 95%CI: -0.64 to -0.13; p=0.006). Conclusions Faster rehabilitation weight gain is associated with liver fat in adult survivors of childhood severe acute malnutrition. The finding that BW did not influence these outcomes may reflect the timing of the nutritional insult in utero. Target weight gain during nutritional rehabilitation may need to be lowered to optimize long-term outcomes in these children

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