scholarly journals Nurturing the Early Life Gut Microbiome and Immune Maturation for Long Term Health

2021 ◽  
Vol 9 (10) ◽  
pp. 2110
Author(s):  
Shaillay Dogra ◽  
Kwong Cheong ◽  
Dantong Wang ◽  
Olga Sakwinska ◽  
Sara Colombo Mottaz ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Early Life ◽  
Maternal Diet ◽  
Head Turning ◽  
Great Opportunity ◽  
Increased Risk ◽  
Age Appropriate ◽  
Functional Features ◽  
Microbiome Development

Early life is characterized by developmental milestones such as holding up the head, turning over, sitting up and walking that are typically achieved sequentially in specific time windows. Similarly, the early gut microbiome maturation can be characterized by specific temporal microorganism acquisition, colonization and selection with differential functional features over time. This orchestrated microbial sequence occurs from birth during the first years of age before the microbiome reaches an adult-like composition and function between 3 and 5 years of age. Increasingly, these different steps of microbiome development are recognized as crucial windows of opportunity for long term health, primarily linked to appropriate immune and metabolic development. For instance, microbiome disruptors such as preterm and Cesarean-section birth, malnutrition and antibiotic use are associated with increased risk to negatively affect long-term immune and metabolic health. Different age discriminant microbiome taxa and functionalities are used to describe age-appropriate microbiome development, and advanced modelling techniques enable an understanding and visualization of an optimal microbiome maturation trajectory. Specific microbiome features can be related to later health conditions, however, whether such features have a causal relationship is the topic of intense research. Early life nutrition is an important microbiome modulator, and ‘Mother Nature’ provides the model with breast milk as the sole source of nutrition for the early postnatal period, while dietary choices during the prenatal and weaning period are to a large extent guided by tradition and culture. Increasing evidence suggests prenatal maternal diet and infant and child nutrition impact the infant microbiome trajectory and immune competence development. The lack of a universal feeding reference for such phases represents a knowledge gap, but also a great opportunity to provide adequate nutritional guidance to maintain an age-appropriate microbiome for long term health. Here, we provide a narrative review and perspective on our current understanding of age-appropriate microbiome maturation, its relation to long term health and how nutrition shapes and influences this relationship.

scholarly journals The neonatal microbiome in utero and beyond: perinatal influences and long-term impacts

2021 ◽  
Vol 45 (6) ◽  
pp. 275-291
Author(s):  
Lee Hill ◽  
Ruchika Sharma ◽  
Lara Hart ◽  
Jelena Popov ◽  
Michal Moshkovich ◽  
...  
Keyword(s):  
Risk Factors ◽  
Human Health ◽  
Early Life ◽  
Inflammatory Diseases ◽  
In Utero ◽  
Current Evidence ◽  
Chronic Inflammatory Diseases ◽  
Health And Disease ◽  
Microbiome Development

Abstract The neonatal microbiome offers a valuable model for studying the origins of human health and disease. As the field of metagenomics expands, we also increase our understanding of early life influences on its development. In this review we will describe common techniques used to define and measure the microbiome. We will review in utero influences, normal perinatal development, and known risk factors for abnormal neonatal microbiome development. Finally, we will summarize current evidence that links early life microbial impacts on the development of chronic inflammatory diseases, obesity, and atopy.

scholarly journals Long-Term Burden of Increased Body Mass Index from Childhood on Adult Dyslipidemia: The i3C Consortium Study

2019 ◽  
Vol 8 (10) ◽  
pp. 1725 ◽  
Author(s):  
Yinkun Yan ◽  
Lydia A. Bazzano ◽  
Markus Juonala ◽  
Olli T. Raitakari ◽  
Jorma S. A. Viikari ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Early Life ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Lowering ◽  
Lipid Levels ◽  
Increased Risk ◽  
The Impact

Background: Data are limited regarding the association of cumulative burden and trajectory of body mass index (BMI) from early life with adult lipid disorders. Methods: The study cohort consisted of 5195 adults who had BMI repeatedly measured 4 to 21 times from childhood and had blood lipid measurements of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and information on lipid-lowering medications in the last adult survey. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI. Results: Participants with dyslipidemia, high LDL-C, low HDL-C and high TG had consistently and significantly higher BMI levels from childhood to adulthood compared to those with normal lipid levels. After adjusting for age, race, sex, and cohort, increased risk of adult dyslipidemia was significantly associated with higher values of childhood BMI, adulthood BMI, total AUC and incremental AUC, with odds ratio (95% confidence interval) = 1.22 (1.15–1.29), 1.85 (1.74–1.97), 1.61 (1.52–1.71), and 1.59 (1.50–1.69), respectively, and p < 0.001 for all. The association patterns were similar in most race–sex subgroups. Conclusions: Adults with dyslipidemia versus normal lipid levels have consistently higher levels and distinct life-course trajectories of BMI, suggesting that the impact of excessive body weight on dyslipidemia originates in early life.

scholarly journals HIV-1 Persistence in Children during Suppressive ART

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1134
Author(s):  
Mary Grace Katusiime ◽  
Gert U. Van Zyl ◽  
Mark F. Cotton ◽  
Mary F. Kearney
Keyword(s):  
Antiretroviral Therapy ◽  
Early Life ◽  
Clonal Expansion ◽  
Hiv Cure ◽  
Major Barrier ◽  
Hiv Persistence ◽  
Increased Risk ◽  
Infected Cells ◽  
Hiv 1

There is a growing number of perinatally HIV-1-infected children worldwide who must maintain life-long ART. In early life, HIV-1 infection is established in an immunologically inexperienced environment in which maternal ART and immune dynamics during pregnancy play a role in reservoir establishment. Children that initiated early antiretroviral therapy (ART) and maintained long-term suppression of viremia have smaller and less diverse HIV reservoirs than adults, although their proviral landscape during ART is reported to be similar to that of adults. The ability of these early infected cells to persist long-term through clonal expansion poses a major barrier to finding a cure. Furthermore, the effects of life-long HIV persistence and ART are yet to be understood, but growing evidence suggests that these individuals are at an increased risk for developing non-AIDS-related comorbidities, which underscores the need for an HIV cure.

scholarly journals Nutritional adversity, sex and reproduction: 30 years of DOHaD and what have we learned?

2019 ◽  
Vol 242 (1) ◽  
pp. T51-T68 ◽  
Author(s):  
Patrycja A Jazwiec ◽  
Deborah M Sloboda
Keyword(s):  
Germ Cells ◽  
Early Life ◽  
Disease Risk ◽  
Primordial Germ Cells ◽  
Reproductive Function ◽  
Postnatal Life ◽  
Early Life Adversity ◽  
Increased Risk ◽  
Health And Disease

It is well established that early life environmental signals, including nutrition, set the stage for long-term health and disease risk – effects that span multiple generations. This relationship begins early, in the periconceptional period and extends into embryonic, fetal and early infant phases of life. Now known as the Developmental Origins of Health and Disease (DOHaD), this concept describes the adaptations that a developing organism makes in response to early life cues, resulting in adjustments in homeostatic systems that may prove maladaptive in postnatal life, leading to an increased risk of chronic disease and/or the inheritance of risk factors across generations. Reproductive maturation and function is similarly influenced by early life events. This should not be surprising, since primordial germ cells are established early in life and thus vulnerable to early life adversity. A multitude of ‘modifying’ cues inducing developmental adaptations have been identified that result in changes in reproductive development and impairments in reproductive function. Many types of nutritional challenges including caloric restriction, macronutrient excess and micronutrient insufficiencies have been shown to induce early life adaptations that produce long-term reproductive dysfunction. Many pathways have been suggested to underpin these associations, including epigenetic reprogramming of germ cells. While the mechanisms still remain to be fully investigated, it is clear that a lifecourse approach to understanding lifetime reproductive function is necessary. Furthermore, investigations of the impacts of early life adversity must be extended to include the paternal environment, especially in epidemiological and clinical studies of offspring reproductive function.

scholarly journals Maternal Separation Induces Long-Term Alterations in the Cardiac Oxytocin Receptor and Cystathionine γ-Lyase Expression in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Daniela C. Wigger ◽  
Nicole Gröger ◽  
Alexandra Lesse ◽  
Sabrina Krause ◽  
Tamara Merz ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Chest Trauma ◽  
Maternal Separation ◽  
Expression Patterns ◽  
Early Life Stress ◽  
Oxytocin Receptor ◽  
Increased Risk ◽  
Genetic Deletion

We recently showed that blunt chest trauma reduced the expression of the myocardial oxytocin receptor (Oxtr), which was further aggravated by genetic deletion of the H2S-producing enzyme cystathionine γ-lyase (CSE). Exogenous H2S supplementation restored myocardial Oxtr expression under these conditions. Early life stress (ELS) is a risk factor for cardiovascular disease by affecting vascular and heart structures. Therefore, we tested the hypotheses that (i) ELS affects cardiac Oxtr and CSE expressions and (ii) Oxtr and CSE expression patterns depend on the duration of stress exposure. Thus, two stress paradigms were compared: long- and short-term separation stress (LTSS and STSS, respectively). Cardiac Oxtr expression was differentially affected by the two stress paradigms with a significant reduction after LTSS and a significant increase after STSS. CSE expression, which was significantly reduced in Oxtr-/- knockout hearts, was downregulated and directly related to Oxtr expression in LTSS hearts (r=0.657, p=0.012). In contrast, CSE expression was not related to Oxtr upregulation in STSS. Plasma Oxt levels were not affected by either ELS paradigm. The coincidence of LTSS-induced reduction of cardiac Oxtr and reduced CSE expression may suggest a novel pathophysiological link between early life adversities and increased risk for the development of cardiovascular disorders in adulthood.

scholarly journals Leptin partially mediates the association between early-life nutritional supplementation and long-term glycemic status among women in a Guatemalan longitudinal cohort

2020 ◽  
Vol 111 (4) ◽  
pp. 804-813 ◽  
Author(s):  
Siran He ◽  
Ngoc-Anh Le ◽  
Manuel Ramirez-Zea ◽  
Reynaldo Martorell ◽  
K M Venkat Narayan ◽  
...  
Keyword(s):  
Early Life ◽  
Cell Function ◽  
Fasting Glucose ◽  
Mediation Effect ◽  
Glycemic Status ◽  
Glucose Lowering ◽  
Obesity And Diabetes ◽  
Increased Risk

ABSTRACT Background Early-life exposure to improved nutrition is associated with decreased risk of diabetes but increased risk of obesity. Leptin positively correlates with adiposity and has glucose-lowering effects, thus it may mediate the association of early-life nutrition and long-term glycemic status. Objectives We aimed to investigate the role of leptin in the differential association between early-life nutrition and the risks of obesity and diabetes. Methods We analyzed data from a Guatemalan cohort who were randomly assigned at the village level to receive nutritional supplements as children. We conducted mediation analysis to examine the role of leptin in the associations of early-life nutrition and adult cardiometabolic outcomes. Results Among 1112 study participants aged (mean ± SD) 44.1 ± 4.2 y, 60.6% were women. Cardiometabolic conditions were common: 40.2% of women and 19.4% of men were obese, and 53.1% of women and 41.0% of men were hyperglycemic or diabetic. Median (IQR) leptin concentration was 15.2 ng/mL (10.2–17.3 ng/mL) in women and 2.7 ng/mL (1.3–5.3 ng/mL) in men. Leptin was positively correlated with BMI (Spearman's ρ was 0.6 in women, 0.7 in men). Women exposed to improved nutrition in early life had 2.8-ng/mL (95% CI: 0.3, 5.3 ng/mL) higher leptin and tended to have lower fasting glucose (–0.8 mmol/L; –1.8, 0.2 mmol/L, nonsignificant) than unexposed women. There were no significant differences in leptin (–0.7 ng/mL; –2.1, 0.8 ng/mL) or fasting glucose (0.2 mmol/L; –0.5, 0.9 mmol/L) in men exposed to improved nutrition in early life compared with unexposed men. Leptin mediated 34.9% of the pathway between early-life nutrition and fasting glucose in women. The mediation in women was driven by improved pancreatic β-cell function. We did not observe the mediation effect in men. Conclusions Leptin mediated the glucose-lowering effect of early-life nutrition in women but not in men.

Skeletal muscle and fetal alcohol spectrum disorder

2018 ◽  
Vol 96 (2) ◽  
pp. 222-229 ◽  
Author(s):  
Semone B. Myrie ◽  
Mark A. Pinder
Keyword(s):  
Skeletal Muscle ◽  
Alcohol Exposure ◽  
Limited Information ◽  
Functional Impairments ◽  
Fetal Alcohol ◽  
Skeletal Abnormalities ◽  
Increased Risk ◽  
Functional Features ◽  
And Function

Skeletal muscle is critical for mobility and many metabolic functions integral to survival and long-term health. Alcohol can affect skeletal muscle physiology and metabolism, which will have immediate and long-term consequences on health. While skeletal muscle abnormalities, including morphological, biochemical, and functional impairments, are well-documented in adults that excessively consume alcohol, there is a scarcity of information about the skeletal muscle in the offspring prenatally exposed to alcohol (“prenatal alcohol exposure”; PAE). This minireview examines the available studies addressing skeletal muscle abnormalities due to PAE. Growth restriction, fetal alcohol myopathy, and abnormalities in the neuromuscular system, which contribute to deficits in locomotion, are some direct, immediate consequences of PAE on skeletal muscle morphology and function. Long-term health consequences of PAE-related skeletal abnormalities include impaired glucose metabolism in the skeletal muscle, resulting in glucose intolerance and insulin resistance, leading to an increased risk of type 2 diabetes. In general, there is limited information on the morphological, biochemical, and functional features of skeletal abnormalities in PAE offspring. There is a need to understand how PAE affects muscle growth and function at the cellular level during early development to improve the immediate and long-term health of offspring suffering from PAE.

scholarly journals Early-life exposure to the Chinese famine of 1959–61 and risk of Hyperuricemia: results from the China health and retirement longitudinal study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wenqiang Zhang ◽  
Rongsheng Luan
Keyword(s):  
Early Childhood ◽  
Uric Acid ◽  
Longitudinal Study ◽  
Serum Uric Acid ◽  
Early Life ◽  
Early Life Exposure ◽  
Long Term Effect ◽  
Increased Risk ◽  
Famine Exposure

Abstract Background Short-term starvation has been related to hyperuricemia. However, little is known about the long-term effect of early-life exposure to famine on hyperuricemia risk in adulthood. Methods The analysis included 2383 participants from the China Health and Retirement Longitudinal Study in 2015. Hyperuricemia was diagnosed as serum uric acid ≥7 mg/dL in men and serum uric acid ≥6 mg/dL in women. Famine exposure subgroups were defined as unexposed (born between October 1, 1962, and September 30, 1964), fetal-exposed (born between October 1, 1959, and September 30, 1961), and early-childhood exposed (born between October 1, 1956, and September 1, 1958). The association between early-life famine exposure and hyperuricemia risk was assessed using multivariate logistic regression. Results The prevalence of hyperuricemia in the unexposed, fetal-exposed, and early-childhood exposed participants was 10.7, 14.1, 11.1%, respectively. Compared with unexposed and early-childhood exposed participants combined as an age-balanced control, fetal-exposed participants showed an increased risk of hyperuricemia in adulthood (OR = 1.41; 95% CI: 1.06–1.88), after adjusting for gender, marital status, famine severity, residence, smoking, drinking, BMI, hypertension, and diabetes. The famine effect on hyperuricemia was accentuated by overweight or obesity (P for interaction = 0.042). Compared with unexposed and BMI < 24 kg/m2 participants, the OR (95%CI) of hyperuricemia was 3.66 (2.13–6.30) for fetal-exposed and overweight/obesity participants. However, combined unexposed and early-childhood exposed participants as an age-balanced control, the interaction of famine exposure and BMI was not statistically significant (P for interaction = 0.054). Conclusion Famine exposure in the fetal stage was associated with an increased risk of hyperuricemia in adulthood.

scholarly journals Early nutrition programming of long-term health

2012 ◽  
Vol 71 (3) ◽  
pp. 371-378 ◽  
Author(s):  
Berthold Koletzko ◽  
Brigitte Brands ◽  
Lucilla Poston ◽  
Keith Godfrey ◽  
Hans Demmelmair
Keyword(s):  
Weight Gain ◽  
Early Life ◽  
Adverse Outcomes ◽  
Postnatal Life ◽  
Long Term Effects ◽  
Public Health Importance ◽  
Rapid Weight Gain ◽  
Early Nutrition ◽  
Increased Risk

Increasing evidence from the EU Project EARNEST and many other investigators demonstrates that early nutrition and lifestyle have long-term effects on later health and the risk of common non-communicable diseases (known as ‘developmental programming’). Because of the increasing public health importance and the transgenerational nature of the problem, obesity and associated disorders are the focus of the new EU funded project ‘EarlyNutrition’. Currently, three key hypotheses have been defined: the fuel mediated ‘in utero’ hypothesis suggests that intrauterine exposure to an excess of fuels, most notably glucose, causes permanent changes of the fetus that lead to obesity in postnatal life; the accelerated postnatal weight gain hypothesis proposes an association between rapid weight gain in infancy and an increased risk of later obesity and adverse outcomes; and the mismatch hypothesis suggests that experiencing a developmental ‘mismatch’ between a sub-optimal perinatal and an obesogenic childhood environment is related to a particular predisposition to obesity and corresponding co-morbidities. Using existing cohort studies, ongoing and novel intervention studies and a basic science programme to investigate those key hypotheses, project EarlyNutrition will provide the scientific foundations for evidence-based recommendations for optimal nutrition considering long-term health outcomes, with a focus on obesity and related disorders. Scientific and technical expertise in placental biology, epigenetics and metabolomics will provide understanding at the cellular and molecular level of the relationships between early life nutritional status and the risk of later adiposity. This will help refine strategies for intervention in early life to prevent obesity.

scholarly journals Maternal High-Fiber Diet Protects Offspring against Type 2 Diabetes

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 94
Author(s):  
Huishi Toh ◽  
James A. Thomson ◽  
Peng Jiang
Keyword(s):  
Type 2 Diabetes ◽  
Early Life ◽  
Maternal Diet ◽  
Later Life ◽  
High Fiber ◽  
Early Life Environment ◽  
Fiber Diet ◽  
Increased Risk ◽  
High Fiber Diet

Previous studies have reported that maternal malnutrition is linked to increased risk of developing type 2 diabetes in adulthood. Although several diabetic risk factors associated with early-life environment have been identified, protective factors remain elusive. Here, we conducted a longitudinal study with 671 Nile rats whereby we examined the interplay between early-life environment (maternal diet) and later-life environment (offspring diet) using opposing diets that induce or prevent diet-induced diabetes. Specifically, we modulated the early-life environment throughout oogenesis, pregnancy, and nursing by feeding Nile rat dams a lifelong high-fiber diet to investigate whether the offspring are protected from type 2 diabetes. We found that exposure to a high-fiber maternal diet prior to weaning significantly lowered the risk of diet-induced diabetes in the offspring. Interestingly, offspring consuming a high-fiber diet after weaning did not develop diet-induced diabetes, even when exposed to a diabetogenic maternal diet. Here, we provide the first evidence that the protective effect of a high-fiber diet can be transmitted to the offspring through the maternal diet, which has important implications in diabetes prevention.

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