Microbiome epidemiology and association studies in human health.

Studies of the human microbiome share both technical and conceptual similarities with genome-wide association studies and genetic epidemiology. However, the microbiome has many features that differ from genomes, such as its temporal and spatial variability, highly distinct genetic architecture and person-to-person variation. Moreover, there are various potential mechanisms by which distinct aspects of the human microbiome can relate to health outcomes. Recent advances, including next-generation sequencing and the proliferation of multi-omic data types, have enabled the exploration of the mechanisms that connect microbial communities to human health. Here, we review the ways in which features of the microbiome at various body sites can influence health outcomes, and we describe emerging opportunities and future directions for advanced microbiome epidemiology.

Evidence for root adaptation to a spatially discontinuous water availability in the absence of external water potential gradients.

We hereby show that root systems adapt to a spatially discontinuous pattern of water availability even when the gradients of water potential across them are vanishingly small. A paper microfluidic approach allowed us to expose the entire root system of Brassica rapa plants to a square array of water sources, separated by dry areas. Gradients in the concentration of water vapor across the root system were as small as 10-4⋅mM⋅m-1 (∼4 orders of magnitude smaller than in conventional hydrotropism assays). Despite such minuscule gradients (which greatly limit the possible influence of the well-understood gradient-driven hydrotropic response), our results show that 1) individual roots as well as the root system as a whole adapt to the pattern of water availability to maximize access to water, and that 2) this adaptation increases as water sources become more rare. These results suggest that either plant roots are more sensitive to water gradients than humanmade water sensors by 3-5 orders of magnitude, or they might have developed, like other organisms, mechanisms for water foraging that allow them to find water in the absence of an external gradient in water potential.

Alcohol consumption and sleep quality: a community-based study.

OBJECTIVE: To assess the association between total alcohol intake, specific alcoholic beverages and sleep quality in a community-based cohort. DESIGN: A cross-sectional study. SETTING: The Kailuan community, China. PARTICIPANTS: Included were 11 905 participants who were free of a history of CVD, cancer, Parkinson's disease, dementia and head injury in or prior to 2012. Alcohol consumption (amount and frequency intake) and alcoholic beverage type were collected in 2006 (baseline) and 2012. Participants were grouped into non-, light- (women: 0-0·4 serving/d; men: 0-0·9 serving/d), moderate- (women: 0·5-1·0 serving/d; men: 1·0-2·0 servings/d) and heavy- (women: >1·0 servings/d; men: >2·0 servings/d) drinkers. Overall sleep quality was measured in 2012 and included four sleep parameters (insomnia, daytime sleepiness, sleep duration, snoring/obstructive sleep apnoea). RESULTS: We observed a dose-response association between higher alcohol consumption in 2006 and worse sleep quality in 2012 (Ptrend < 0·001), after adjusting for age, sex, socio-economic status, smoking status, physical activity, obesity, plasma lipid profiles, diabetes and hypertension. A similar association was observed when alcohol consumption in 2012 was used as exposure. Alcohol was associated with higher odds of having short sleep duration (adjusted OR for heavy- v. non-drinkers = 1·31; 95 % CI: 1·09, 1·57) and snoring (adjusted OR for heavy- v. non-drinkers: 1·38; 95 % CI: 1·22, 1·57). Consumption of hard liquor, but not beer or wine, was significantly associated with poor sleep quality. CONCLUSIONS: Higher alcohol consumption was associated with poorer sleep quality and higher odds of having snoring and short sleep duration.

Habitually skipping breakfast is associated with chronic inflammation: a cross-sectional study.

OBJECTIVE: We examined whether breakfast frequency was associated with chronic inflammatory, as assessed by high-sensitivity C-reactive protein (CRP) concentration. DESIGN: Cross-sectional study. SETTING: Kailuan community, China. PARTICIPANTS: Included were 70 092 Chinese adults without CVD and cancer in 2014 with CRP concentrations <10 mg/l, when breakfast frequency was assessed via a questionnaire, and plasma CRP concentration was measured. RESULTS: Breakfast frequency was associated with CRP concentration (P-trend < 0·001). The adjusted mean CRP was 1·33 mg/l (95 % CI 1·23, 1·44) for the 'no breakfast' group and 1·07 mg/l (95 % CI 1·0, 1·14) for the 'breakfast everyday' group (P-difference < 0·001), adjusting for age, sex, diet quality, total energy, obesity, education, occupation, marital status, smoking, alcohol consumption, blood pressure, sleep parameters, fasting blood glucose and lipid profiles. Consistently, the adjusted OR for CRP ≥ 1·0 mg/l and CRP ≥ 3·0 mg/l were 1·86 (95 % CI 1·73, 2·00) and 1·27 (95 % CI 1·15, 1·40), respectively, when comparing these two breakfast consumption groups (P-trend < 0·001 for both). The associations were more pronounced among older adults, relative to those who were younger (P-interaction < 0·001). Significant association between breakfast skipping and elevated CRP concentration was observed in those with poor diet quality, but not those with good diet quality. CONCLUSIONS: Habitually skipping breakfast is associated with elevated concentrations of CRP. Future prospective studies including repeated assessment of inflammatory biomarkers and a collection of detailed information on type and amount of breakfast foods are warranted.

Linking the Gut Microbiota to Bone Health in Anorexia Nervosa.

PURPOSE OF REVIEW: The purpose of this review is to examine the anorexia nervosa-microbiota-bone relationship, offering a compilation of the relevant human and animal studies that may contribute to a more comprehensive understanding of potential mechanisms involved. RECENT FINDINGS: Recent studies have implicated fermentation by-products of the gut microbiota in bone metabolism. Compromised bone health often accompanies anorexia nervosa due to energy deficiency and hypoestrogenism. The gut microbiome has been implicated as a link between these conditions and impaired bone growth phenotypes. Current research supports decrements in Firmicutes and short-chain fatty acids with increases in Methanobrevibacter smithii and Proteobacteria in anorexia nervosa. A potential mechanism for microbiome-regulated bone growth is through modulation of insulin-like growth factor-1. Future research should aim to examine short-chain fatty acids, probiotics, and prebiotics as alternative therapies to treat low bone density in anorexia nervosa.

The impact of avocado intake on anthropometric measures among Hispanic/Latino children and adolescents: A cluster randomized controlled trial.

BACKGROUND/OBJECTIVE: While the association between avocado consumption and low metabolic risk has been shown in some studies conducted in adults, little is known about the potential effects of avocado consumption on health outcomes in children and adolescents. Thus, we investigated the impact of two levels of avocado allotment, plus a standard nutrition education, on measures of adiposity in children and adolescents (<18 years old). METHODS: Children (aged 5-12, n = 58) and adolescents (aged 13-17, n = 32) in seventy-two families that self-identified as Hispanic, with at least 3 members over the age of 5 that resided in the same home, were free of severe chronic disease, and not on specific diets, were randomized to one of two levels of avocado allotment plus bi-weekly nutrition education sessions. Low allotment families received 3 avocados per week, while high allotment families received 14 avocados per week for 6 months. We performed an intention-to-treat analysis, using unpaired, 2-sided t-tests to test the mean changes in anthropometric measures of adiposity (body mass index (BMI), waist circumference, hip circumference, and weight) between children and adolescents from high and low allotment families after the 6-month intervention. RESULTS: At six months, there were no significant differences in body mass index, waist circumference, hip circumference, or waist circumference to weight ratio by avocado allotment group. In children, there was a significant difference in weight (difference in means: 1.10, 95% CI: 0.09, 2.10, p-value = 0.03) and waist circumference to height ratio (difference in means: 0.27, 95% CI: 0.12, 0.41, p-value <0.01) between the avocado allotment groups at six months, but these did not remain significant after sensitivity analyses including per-protocol analyses. In adolescents only, there was a significant reduction in waist to hip circumference ratio in the high allotment group compared to the low allotment group after 6 months (difference in means: -0.05, 95% CI: -0.08, 0.00, p-value = 0.04) that persisted after multiple sensitivity analyses. CONCLUSIONS: Different levels of avocado availability among children and adolescents does not appear to result in significant changes in anthropometric measures. Further study is needed to determine whether avocado consumption promotes metabolic health in this age group.

Low-Density Lipoprotein Cholesterol and the Risk of Rheumatoid Arthritis: A Prospective Study in a Chinese Cohort.

Objective: This study aimed to investigate whether low-density lipoprotein cholesterol (LDL-C) concentration was associated with the risk of rheumatoid arthritis (RA) in Chinese adults. Methods: The study included the 97,411 participants in the Kailuan Study without RA, with complete baseline LDL-C data, and who did not use lipid-lowering medications at baseline or during follow-up. We used Cox proportional hazards modeling to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of RA according to baseline LDL-C tertiles, adjusting for age, sex, body mass index, HDL-C, triglycerides, diabetes, hypertension, alcohol consumption, and smoking. We also calculated the HR and 95% CI of RA using updated LDL-C measurements prior to the end of follow-up, adjusting for covariates. Results: We identified 97 incident RA cases between 2006 and 2018. After adjusting for potential confounders, updated LDL-C concentration­rather than baseline LDL-C­was inversely associated with RA risk. The adjusted HR of RA was 0.64 (95% CI: 0.38, 1.09; p-trend = 0.10) comparing the two extreme baseline LDL-C tertiles, and 0.38 (95% CI: 0.22, 0.64; p-trend < 0.01) comparing the two extreme tertiles of the updated LDL-C concentrations. Conclusions: In this prospective study, high LDL-C concentrations, when measured closest to RA diagnosis or the end of follow-up, were associated with a low risk of RA. These findings highlight the changes in LDL-C prior to RA diagnosis, and the importance of including lipid analyses into studies of the pathogenesis of RA.

The Role of Prunes in Modulating Inflammatory Pathways to Improve Bone Health in Postmenopausal Women.

The prevalence of osteoporosis among women aged 50 y and older is expected to reach 13.6 million by 2030. Alternative nonpharmaceutical agents for osteoporosis, including nutritional interventions, are becoming increasingly popular. Prunes (dried plums; Prunus domestica L.) have been studied as a potential whole-food dietary intervention to mitigate bone loss in preclinical models of osteoporosis and in osteopenic postmenopausal women. Sixteen preclinical studies using in vivo rodent models of osteopenia or osteoporosis have established that dietary supplementation with prunes confers osteoprotective effects both by preventing and reversing bone loss. Increasing evidence from 10 studies suggests that, in addition to antiresorptive effects, prunes exert anti-inflammatory and antioxidant effects. Ten preclinical studies have found that prunes and/or their polyphenol extracts decrease malondialdehyde and NO secretion, increase antioxidant enzyme expression, or suppress NF-κB activation and proinflammatory cytokine production. Two clinical trials have investigated the impact of dried plum consumption (50-100 g/d for 6-12 mo) on bone health in postmenopausal women and demonstrated promising effects on bone mineral density and bone biomarkers. However, less is known about the impact of prune consumption on oxidative stress and inflammatory mediators in humans and their possible role in modulating bone outcomes. In this review, the current state of knowledge on the relation between inflammation and bone health is outlined. Findings from preclinical and clinical studies that have assessed the effect of prunes on oxidative stress, inflammatory mediators, and bone outcomes are summarized, and evidence supporting a potential role of prunes in modulating inflammatory and immune pathways is highlighted. Key future directions to bridge the knowledge gap in the field are proposed.

Maternal consumption of ultra-processed foods and subsequent risk of offspring overweight or obesity: results from three prospective cohort studies.

OBJECTIVE: To assess whether maternal ultra-processed food intake during peripregnancy and during the child rearing period is associated with offspring risk of overweight or obesity during childhood and adolescence. DESIGN: Population based prospective cohort study. SETTING: The Nurses' Health Study II (NHSII) and the Growing Up Today Study (GUTS I and II) in the United States. PARTICIPANTS: 19 958 mother-child (45% boys, aged 7-17 years at study enrollment) pairs with a median follow-up of 4 years (interquartile range 2-5 years) until age 18 or the onset of overweight or obesity, including a subsample of 2925 mother-child pairs with information on peripregnancy diet. MAIN OUTCOME MEASURES: Multivariable adjusted, log binomial models with generalized estimating equations and an exchangeable correlation structure were used to account for correlations between siblings and to estimate the relative risk of offspring overweight or obesity defined by the International Obesity Task Force. RESULTS: 2471 (12.4%) offspring developed overweight or obesity in the full analytic cohort. After adjusting for established maternal risk factors and offspring's ultra-processed food intake, physical activity, and sedentary time, maternal consumption of ultra-processed foods during the child rearing period was associated with overweight or obesity in offspring, with a 26% higher risk in the group with the highest maternal ultra-processed food consumption (group 5) versus the lowest consumption group (group 1; relative risk 1.26, 95% confidence interval 1.08 to 1.47, P for trend<0.001). In the subsample with information on peripregnancy diet, while rates were higher, peripregnancy ultra-processed food intake was not significantly associated with an increased risk of offspring overweight or obesity (n=845 (28.9%); group 5 v group 1: relative risk 1.17, 95% confidence interval 0.89 to 1.53, P fortrend=0.07). These associations were not modified by age, sex, birth weight, and gestational age of offspring or maternal body weight. CONCLUSIONS: Maternal consumption of ultra-processed food during the child rearing period was associated with an increased risk of overweight or obesity in offspring, independent of maternal and offspring lifestyle risk factors. Further study is needed to confirm these findings and to understand the underlying biological mechanisms and environmental determinants. These data support the importance of refining dietary recommendations and the development of programs to improve nutrition for women of reproductive age to promote offspring health.

Alcohol Consumption and Risk of Rheumatoid Arthritis among Chinese Adults: A Prospective Study.

Alcohol consumption may be associated with the risk of rheumatoid arthritis (RA), but potential sex-related differences in this association have not been explored. Thus, we utilized 87,118 participants in the Kailuan Study, a prospective cohort initiated in 2006 to study the risk factors of cardiovascular disease in a Chinese population. We included those that did not have RA at baseline (2006), and performed cox proportional hazard modeling to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of RA according to the levels of alcohol consumption (never or past, light or moderate (<1 serving/day for women, <2 servings/day for men), and heavy (>1 serving/day for women, >2 servings/day for men), adjusting for age, sex, body mass index, and smoking. Diagnoses of RA were confirmed via medical record review by rheumatologists. From 2006 to 2018, we identified 87 incident RA cases. After adjusting for potential confounders, the HR of RA was 1.26 (95% CI: 0.62, 2.56) for participants with light or moderate alcohol consumption and 1.98 (95% CI: 0.93, 4.22) for participants with heavy alcohol consumption) versus non-drinkers. The HR of each 10 g increase in alcohol consumption was 1.11 (95% CI: 0.98, 1.26) (p-trend = 0.09). A significant association between alcohol consumption and RA risk was observed in women, but not in men (p for interaction = 0.06). Among women, each 10 g increase in alcohol consumption was significantly associated with a high risk of RA (HR: 1.56; 95% CI: 1.06, 2.29). In contrast, each 10 g increase in alcohol consumption was not significantly associated with the risk of RA in men (HR: 1.10; 95% CI: 0.97, 1.25). Excluding past drinkers generated similar results. In this prospective Chinese cohort, increasing alcohol consumption was associated with an elevated risk of RA among women, but not in men. These findings highlight the importance of incorporating analysis of sex differences into future studies of alcohol consumption and RA risk.

In Utero and Early Life Exposure to the Great Chinese Famine and Risk of Rheumatoid Arthritis in Adulthood.

OBJECTIVE: To investigate whether early life exposure to the Great Chinese Famine of 1959-1961 is associated with the risk of RA development in adulthood. METHODS: This study included 101,510 participants who were enrolled in the Kailuan Study in 2006. RA cases were confirmed by medical record review. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) for RA according to famine exposure status (exposed in utero or between ages 0 and 3 years, between ages 3 and 6 years, or at age 6 years or older), in comparison to participants born after 1961 who were not exposed to famine. RESULTS: During 12 years of follow-up (2006-2018), we identified 187 RA cases. Individuals exposed to famine in utero or between ages 0 and 3 years had a higher prevalence of RA relative to other groups (0.2-0.35% versus 0.08-0.20%). After adjustment for potential confounders, the OR for RA was 2.95 (95% CI 1.55-5.59) for individuals exposed in utero, 4.53 (95% CI 2.72-7.54) for those exposed between ages 0 and 3 years, 2.55 (95% CI 1.43-4.57) for those exposed between ages 3 and 6 years, and 2.72 (95% CI 1.70-4.36) for those exposed at age 6 years or older versus individuals born after 1961. Similar associations with the risk of RA were observed for men and women when subjects were stratified by sex (P for interaction = 0.89). CONCLUSION: Individuals exposed to famine in utero or in early childhood (between ages 0 and 3 years) were more likely to develop RA in adulthood, highlighting the importance of early life as a vulnerable developmental period.

A simple and versatile 2-dimensional platform to study plant germination and growth under controlled humidity.

We describe a simple, inexpensive, but remarkably versatile and controlled growth environment for the observation of plant germination and seedling root growth on a flat, horizontal surface over periods of weeks. The setup provides to each plant a controlled humidity (between 56% and 91% RH), and contact with both nutrients and atmosphere. The flat and horizontal geometry of the surface supporting the roots eliminates the gravitropic bias on their development and facilitates the imaging of the entire root system. Experiments can be setup under sterile conditions and then transferred to a non-sterile environment. The system can be assembled in 1-2 minutes, costs approximately 8.78$ per plant, is almost entirely reusable (0.43$ per experiment in disposables), and is easily scalable to a variety of plants. We demonstrate the performance of the system by germinating, growing, and imaging Wheat (Triticum aestivum), Corn (Zea mays), and Wisconsin Fast Plants (Brassica rapa). Germination rates were close to those expected for optimal conditions.