Body size and immune responses

Nutritional deficiencies are associated with altered immune responses and increased susceptibility to infection. The changes are most marked in severe deficits of nutrient intake and some nutrients are more critical than others in influencing immunity. Similarly, there is a correlation between body size and immunocompetence. Both protein-energy malnutrition and obesity are associated with changes in selected parameters of immunity. Very little is known about changes in immune responses in stunting. These effects of nutritional status and of body size and composition may be mediated through changes in hormones, cytokines and/or cell number and function.     

Epigenetic Effects of Human Breast Milk

A current aim of nutrigenetics is to personalize nutritional practices according to genetic variations that influence the way of digestion and metabolism of nutrients introduced with the diet. Nutritional epigenetics concerns knowledge about the effects of nutrients on gene expression. Nutrition in early life or in critical periods of development, may have a role in modulating gene expression, and, therefore, have later effects on health. Human breast milk is well-known for its ability in preventing several acute and chronic diseases. Indeed, breastfed children may have lower risk of neonatal necrotizing enterocolitis, infectious diseases, and also of non-communicable diseases, such as obesity and related-disorders. Beneficial effects of human breast milk on health may be associated in part with its peculiar components, possible also via epigenetic processes. This paper discusses about presumed epigenetic effects of human breast milk and components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are still unclear. Studies have to be conducted to clarify the actual role of human breast milk on genetic expression, in particular when linked to the risk of non-communicable diseases, to potentially benefit the infant’s health and his later life.     

Obesity,Nutrients and the Immune System in the Era of COVID-19

The past year has shown that obesity is a risk factor for severe complications of SARS-CoV-2 infection. Excess fat mass during obesity is known to be a risk factor for chronic diseases but also for severe infections and infectious complications. We have focused here on the elements responsible for this particular susceptibility to infections and more specifically to COVID-19. Excess fat is, in itself, responsible for alterations of the immune system by disrupting the production and function of immune cells. Indeed, hypertrophic adipocytes produce more pro-inflammatory adipokines (including cytokines). The increase in their apoptosis induces a release of pro-inflammatory compounds into the circulation and a recruitment of pro-inflammatory macrophages into the adipose tissue. A chronic systemic inflammatory state is then observed. In addition, diet, apart from its role in the development of adipose tissue, can also affect the immune system, with excess simple sugars and saturated fats exerting pro-inflammatory effects. This inflammation, the adipokines released by the adipocytes, and the infiltration of lipids into the lymphoid organs affects the production of immune cells and, directly, the functions of these cells. The alteration of the immune system increases the risk of infection as well as complications, including secondary bacterial infections and septic states, and increases infection-related mortality. During COVID-19, the chronic inflammatory state promotes the cytokine shock, characteristic of severe forms, caused in particular by excessive activation of the NLRP3 inflammasome. Furthermore, in obese subjects, the already present endothelial dysfunction will render endothelial inflammation (endotheliitis) due to viral infiltration all the more severe. Added to this is a state of hypercoagulability and a decrease in respiratory capacity, leading to a risk of severe COVID-19 with cardiovascular complications, acute respiratory distress syndrome, and disseminated intravascular coagulation, which can lead to multiple organ failure and even death.     

The weight of obesity on the human immune response to vaccination

Despite the high success of protection against several infectious diseases through effective vaccines, some sub-populations have been observed to respond poorly to vaccines, putting them at increased risk for vaccine-preventable diseases. In particular, the limited data concerning the effect of obesity on vaccine immunogenicity and efficacy suggests that obesity is a factor that increases the likelihood of a poor vaccine-induced immune response. Obesity occurs through the deposition of excess lipids into adipose tissue through the production of adipocytes, and is defined as a body-mass index (BMI) ≥ 30 kg/m². The immune system is adversely affected by obesity, and these “immune consequences” raise concern for the lack of vaccine-induced immunity in the obese patient requiring discussion of how this sub-population might be better protected.     

Immunosénescence et infections,mythe ou réalité ?

The susceptibility of elderly people to infectious diseases is usually associated to increasing risk factors found in young adults. However, the role of immune function ageing is associated with the decline of immune function but this decline is not homogenous. Some functions such as the cellular immune system are altered but others are enhanced such as innate immunity. The important events of immune ageing are modifications of lymphocyte subsets with accumulation of memory cells, decrease in proliferative response, and a chronic inflammatory state. The chronic antigenic load throughout life is responsible for gaps in the antigenic system with a greater sensitivity to new antigens. These immune system changes are all the more important that diseases are severe and that denutrition is associated. These diseases will speed up the ageing process. The interaction between immunosenescence and pathology is an important phenomenon to consider. This review outlines the immune system changes due to ageing, their relationship with diseases of the aged patient, and the consequences of these modifications on vaccination effectiveness.     

Nutrition and immunity in the elderly

Immune function declines with age, leading to increased infection and cancer rates in aged individuals. In fact, recent progress in the study of immune ageing has introduced the idea that rather than a general decline in the functions of the immune system with age, immune ageing is mainly characterized by a progressive appearance of immune dysregulation throughout life. Changes appear earlier in life for cell-mediated immunity than for humoral immunity. Thus, age-related modifications in cell-mediated immunity, i.e. changes in naive : memory T-cells, mature : immature T-cells, T-helper 1 : T-helper 2 cells are more important in the elderly than changes in humoral immunity, i.e. CD5 : CD5+ cells or length of antibody responses. Such evolution of the immune system has been linked to declining thymus function and to accumulative antigenic influence over the lifespan. In contrast, innate immunity (macrophage functions) is preserved or even increased during the ageing process. This finding shows that the 'primitive' immune system is less affected by the ageing process than the sophisticated specific immune system. The present review focuses on innate and cell-mediated immune changes with ageing. It provides evidence that primary changes (intrinsic modifications in the immune system) and secondary changes (resulting from environmental influences during the lifespan) exert different influences on the immune system. Primary changes, occurring in healthy individuals, seem less important nowadays than they were considered to be previously. For example, interleukin 2 secretion in some very healthy aged individuals is comparable with that in younger adults. Primary immune changes may not explain the increased incidence and severity of infections observed in the elderly population. Secondary immunological changes are far more frequent and are certainly responsible for most of the immune modifications observed in the elderly population. Environmental factors leading to secondary immune dysfunctions include not only antigenic influence, which is a reflection of diseases experienced over the lifespan, but also many other factors such as drug intake, physical activity and diet; factors for which important changes occur in the elderly population. Nutritional factors play a major role in the immune responses of aged individuals and the present review shows that nutritional influences on immune responses are of great consequence in aged individuals, even in the very healthy elderly.     

Exercise and immune function: effect of ageing and nutrition

Strenuous exercise is followed by lymphopenia, neutrophilia, impaired natural immunity, decreased lymphocyte proliferative responses to mitogens, a low level of secretory immunoglobulin A in saliva, but high circulating levels of pro- and anti-inflammatory cytokines. These exercise-induced immune changes may provide the physiological basis of altered resistance to infections. The mechanisms underlying exercise-induced immune changes are multifactorial and include neuroendocrinological and metabolic mechanisms. Nutritional supplementation with glutamine abolishes the exercise-induced decline in plasma glutamine, but does not influence post-exercise immune impairment. However, carbohydrate loading diminishes most exercise effects of cytokines, lymphocyte and neutrophils. The diminished neutrophilia and elastase (EC 3.4.21.37) responses to eccentric exercise in elderly subjects were enhanced to levels comparable with those of young subjects by fish oil or vitamin E supplements. However, although vitamin C supplementation may diminish the risk of contracting an infection after strenuous exercise, it is not obvious that this effect is linked to an effect of vitamin C on exercise-induced immune changes. In conclusion, it is premature to make recommendations regarding nutritional supplementation to avoid post-exercise impairment of the immune system.     

儿童血清维生素D水平、自噬、免疫调节及机体各系统疾病的相关性综述

维生素D对人体作用广泛且复杂,是一种与特异性受体相结合而发挥作用的一类脂溶性类固醇激素,其受体在多种组织细胞中都有分布,含量最多的器官为小肠、肾脏、甲状旁腺及骨骼,此外,心血管、胃肠道、中枢神经系统等其他脏器也有维生素D受体的表达。血清维生素D水平异常时,机体会出现相应的病理改变,如:呼吸道疾病、消化道疾病、泌尿系统疾病、风湿免疫疾病、自身免疫性疾病、肥胖等疾病,本文就维生素D水平、自噬、免疫调节及各系统疾病的相关性进行综述。     

Health Benefits of Plant-Based Nutrition: Focus on Beans in Cardiometabolic Diseases

Cardiovascular disease (CVD) is the leading cause of death worldwide, claiming over 650,000 American lives annually. Typically not a singular disease, CVD often coexists with dyslipidemia, hypertension, type-2 diabetes (T2D), chronic system-wide inflammation, and obesity. Obesity, an independent risk factor for both CVD and T2D, further worsens the problem, with over 42% of adults and 18.5% of youth in the U.S. categorized as such. Dietary behavior is a most important modifiable risk factor for controlling the onset and progression of obesity and related disease conditions. Plant-based eating patterns that include beans and legumes support health and disease mitigation through nutritional profile and bioactive compounds including phytochemical. This review focuses on the characteristics of beans and ability to improve obesity-related diseases and associated factors including excess body weight, gut microbiome environment, and low-grade inflammation. Additionally, there are growing data that link obesity to compromised immune response and elevated risk for complications from immune-related diseases. Body weight management and nutritional status may improve immune function and possibly prevent disease severity. Inclusion of beans as part of a plant-based dietary strategy imparts cardiovascular, metabolic, and colon protective effects; improves obesity, low-grade inflammation, and may play a role in immune-related disease risk management.     

Immunonutrition support for athletes

Multiple components of the immune systems in athletes exhibit transient dysfunction after prolonged, heavy exertion. During this "open window" of impaired immunity, pathogens may gain a foothold, increasing infection risk. Nutritional supplements have been studied as countermeasures to exercise-induced immune changes and infection risk. This review focuses on findings from recent exercise-based studies with macro- and micronutrient supplements, and "advanced" immunonutrition supplements including beta-glucan, curcumin, and quercetin. Results from these studies indicate that immunonutrition supplements have the potential to lessen the magnitude of exercise-induced perturbations in immune function and to reduce the risk of upper respiratory tract infections.     

Assessing immune function changes in exercise and diet intervention studies

PURPOSE OF REVIEW: To discuss the advantages and limitations of the methods currently available to assess changes in human immune function in response to interventions such as changes in diet or exercise. RECENT FINDINGS: Much recent research has focused on the effect of regular moderate exercise and the role of foods or specific food components in enhancing immune system responsiveness to challenge and thereby improving health and reducing disease risk. The present review summarizes the issues in experimental design that need to be considered in human intervention studies, the immune function variables commonly used as markers in such studies and the biological relevance (e.g. known correlation with clinically relevant endpoints) of the markers. In-vivo markers appear to be the best. Markers of peripheral blood leukocyte function are also of value since they may provide information on the mechanism(s) of change caused by an intervention. SUMMARY: Currently, no single marker of human immune function is available to predict the outcome of an exercise or dietary intervention on the resistance to infection or to other immune system-related diseases. There is too little evidence at present that correlates individual markers with global health improvement and therefore assessing changes of immune function requires a thorough methodological approach targeting a large spectrum of parameters.     

Political changes and trends in cardiovascular risk factors in the Czech Republic, 1985-92.

BACKGROUND: Mortality from cardiovascular diseases is substantially higher in central and eastern Europe than in the west. After the fall of communism, these countries have undergone radical changes in their political, social, and economic environments but little is known about the impact of these changes on health behaviours or risk factors. Data from the Czech Republic, a country whose mortality rates from cardiovascular diseases are among the highest, were analysed in this report. OBJECTIVES: To examine the trends in cardiovascular risk factors in Czech population over the last decade during which a major and sudden change of the political and social system occurred in 1989, and whether the trends differed in relation to age and educational group. DESIGN AND SETTING: Data from three cross sectional surveys conducted in 1985, 1988, and 1992 as a part of the MONICA project were analysed. The surveys examined random samples of men and women aged 25-64 in six Czech districts and measured the following risk factors: smoking, blood pressure, body mass index (BMI), and total and high density lipoprotein (HDL) cholesterol. RESULTS: The numbers of subjects (response rate) examined were 2573 (84%) in 1985, 2769 (87%) in 1988, and 2353 (73%) in 1992. Total cholesterol and body mass index increased between 1985 and 1988 and decreased between 1988 and 1992. The prevalence of smoking was declining slightly in men between 1985 and 1992 but remained stable in women. There were only small changes in blood pressure. The decline in cholesterol and BMI in 1988-92 may be related to changes in foods consumption after the price deregulation in 1991. An improvement in risk profile was more pronounced in younger age groups, and the declines in cholesterol and obesity were substantially larger in men and women with higher education. By contrast, there was an increase in smoking in women educated only to primary level. CONCLUSION: Substantial changes in cholesterol, obesity, and women's smoking occurred in the Czech population after the political changes in 1989. Although a causal association cannot be claimed, national trends in foods consumption are consistent with changes in blood lipids and obesity. Further monitoring of trends is required to confirm these trends.     

Perinatal immunotoxicity: why adult exposure assessment fails to predict risk

Recent research has pointed to the developing immune system as a remarkably sensitive toxicologic target for environmental chemicals and drugs. In fact, the perinatal period before and just after birth is replete with dynamic immune changes, many of which do not occur in adults. These include not only the basic maturation and distribution of immune cell types and selection against autoreactive lymphocytes but also changes designed specifically to protect the pregnancy against immune-mediated miscarriage. The newborn is then faced with critical immune maturational adjustments to achieve an immune balance necessary to combat myriad childhood and later-life diseases. All these processes set the fetus and neonate completely apart from the adult regarding immunotoxicologic risk. Yet for decades, safety evaluation has relied almost exclusively upon exposure of the adult immune system to predict perinatal immune risk. Recent workshops and forums have suggested a benefit in employing alternative exposures that include exposure throughout early life stages. However, issues remain concerning when and where such applications might be required. In this review we discuss the reasons why immunotoxic assessment is important for current childhood diseases and why adult exposure assessment cannot predict the effect of xenobiotics on the developing immune system. It also provides examples of developmental immunotoxicants where age-based risk appears to differ. Finally, it stresses the need to replace adult exposure assessment for immune evaluation with protocols that can protect the developing immune system.     

Metabolic diseases and pro- and prebiotics: Mechanistic insights

ABSTRACT: Metabolic diseases, such as obesity and type 2 diabetes, are world-wide health problems. The prevalence of metabolic diseases is associated with dynamic changes in dietary macronutrient intake during the past decades. Based on national statistics and from a public health viewpoint, traditional approaches, such as diet and physical activity, have been unsuccessful in decreasing the prevalence of metabolic diseases. Since the approaches strongly rely on individual's behavior and motivation, novel science-based strategies should be considered for prevention and therapy for the diseases. Metabolism and immune system are linked. Both overnutrition and infection result in inflammation through nutrient and pathogen sensing systems which recognize compounds with structural similarities. Dietary macronutrients (fats and sugars) can induce inflammation through activation of an innate immune receptor, Toll-like receptor 4 (TLR4). Long-term intake of diets high in fats and meats appear to induce chronic systemic low-grade inflammation, endotoxicity, and metabolic diseases. Recent investigations support the idea of the involvement of intestinal bacteria in host metabolism and preventative and therapeutic potentials of probiotic and prebiotic interventions for metabolic diseases. Specific intestinal bacteria seem to serve as lipopolysaccharide (LPS) sources through LPS and/or bacterial translocation into the circulation due to a vulnerable microbial barrier and increased intestinal permeability and to play a role in systemic inflammation and progression of metabolic diseases. This review focuses on mechanistic links between metabolic diseases (mainly obesity and type 2 diabetes), chronic systemic low-grade inflammation, intestinal environment, and nutrition and prospective views of probiotic and prebiotic interventions for the diseases.     

Beneficial role of dietary phytoestrogens in obesity and diabetes

Evidence is emerging that dietary phytoestrogens play a beneficial role in obesity and diabetes. Nutritional intervention studies performed in animals and humans suggest that the ingestion of soy protein associated with isoflavones and flaxseed rich in lignans improves glucose control and insulin resistance. In animal models of obesity and diabetes, soy protein has been shown to reduce serum insulin and insulin resistance. In studies of human subjects with or without diabetes, soy protein also appears to moderate hyperglycemia and reduce body weight, hyperlipidemia, and hyperinsulinemia, supporting its beneficial effects on obesity and diabetes. However, most of these clinical trials were relatively short and involved a small number of patients. Furthermore, it is not clear whether the beneficial effects of soy protein and flaxseed are due to isoflavones (daidzein and genistein), lignans (matairesinol and secoisolariciresinol), or some other component. Isoflavones and lignans appear to act through various mechanisms that modulate pancreatic insulin secretion or through antioxidative actions. They may also act via estrogen receptor-mediated mechanisms. Some of these actions have been shown in vitro, but the relevance of these studies to in vivo disease is not known. The diversity of cellular actions of isoflavones and lignans supports their possible beneficial effects on various chronic diseases. Further investigations are needed to evaluate the long-term effects of phytoestrogens on obesity and diabetes mellitus and their associated possible complications.     

Obesity and immunocompetence

The increasing worldwide prevalence of obesity is a major health problem since excessive body weight constitutes a risk factor in a number of chronic diseases. It has been reported that obese individuals are more susceptible to infection than lean subjects; however, the underlying factors are not fully understood. Limited and often controversial information exists comparing immunocompetence in obese and nonobese subjects as well as the cellular and molecular mechanisms involved, although much evidence supports a link between adipose tissue metabolism and immunocompetent cell functions. The complexity and heterogeneity of nutritional status and immune system interactions require an integral study of the immunocompetent cells, their subsets and products, as well as specific and non-specific inducer/regulatory systems in situations of human obesity. Additional research is needed to determine the clinical implications of these alterations on immunity and whether various interventions such as weight loss, exercise or nutrient supplementation could help to ameliorate them.     

Nutritional form for the elderly is a reliable and valid instrument for the determination of undernutrition risk,and it is associated with health-related quality of life

Undernutrition is a common problem associated with clinical complications such as impaired immune response, reduced muscle strength, impaired wound healing, and susceptibility to infections; therefore, it is an important treatment target to reduce morbidity and mortality associated with chronic diseases and aging. The aim of the present study was to apply a reliable and valid instrument for the determination of undernutrition risk in an in-hospital patient population and to describe possible associations between risk of undernutrition and some aspects of health-related quality of life in patients with chronic diseases. Fifty-six adult patients with different chronic diseases were interviewed with NUFFE questionnaire and the EQ-5D. Anthropometric measurements were performed. Reliability and validity of the NUFFE instrument was tested, and its correlation with EQ-5D was calculated. Euro-Qol scores correlated significantly with the total NUFFE scores and with the items constructing the most important factor of the instrument, explaining 53.74% of its variance. Nutritional form for the elderly was shown to be a reliable instrument in the study group because its internal consistency measured by Cronbach α was 0.62, and the item-total score correlations were significant for the half of the items. Criterion-related validity, concurrent validity, and construct validity of NUFFE were established. We have shown that impaired level of health-related quality of life is an important determinant of risk for undernutrition. Nutritional form for the elderly is an appropriate instrument to estimate undernutrition risk in a general, in-hospital patient population with various chronic diseases and to identify “at risk” patients who may benefit from professional dietary interventions to reduce undernutrition-related complications.     

基层综合性医院住院患者临床营养支持状况分析

目的：调查基层综合医院住院患者入院和人院2周（或出院）时营养风险、营养不足、超重、肥胖和营养支持的状况。方法：采用定点连续抽样，选择2008年10月至2009年10月在衢州市人民医院住院的年轻患者进行营养风险筛查，使用营养风险筛查2002（NRS2002）于患者入院和入院2周（或出院）时实施，并调查患者2周内（或至出院时）的营养支持状况，分析营养风险和营养支持之间的关系。NRS2002≥3分为有营养风险，体重指数（BMI）〈18．5kg／m。并结合患者临床情况判定为营养不足。结果：1618例入选者完成筛查。人院时总营养风险发生率为35．0％。营养不足、超重和肥胖的发生率分别为8．0％、33．3％和17．9％。存在营养风险和无营养风险患者的营养支持率分别为20．1％和9．0％。结论：目前基层综合医院患者营养风险评估和营养支持应用尚不规范，应推广和使用NRS2002营养评定方法和肠外肠内营养指南以改善此状况。     

The impact of obesity on the immune response to infection

There is strong evidence indicating that excess adiposity negatively impacts immune function and host defence in obese individuals. This is a review of research findings concerning the impact of obesity on the immune response to infection, including a discussion of possible mechanisms. Obesity is characterised by a state of low-grade, chronic inflammation in addition to disturbed levels of circulating nutrients and metabolic hormones. The impact of these metabolic abnormalities on obesity-related comorbidities has undergone intense scrutiny over the past decade. However, relatively little is known of how the immune system and host defence are influenced by the pro-inflammatory and excess energy milieu of the obese. Epidemiological data suggest obese human subjects are at greater risk for nosocomial infections, especially following surgery. Additionally, the significance of altered immunity in obese human subjects is emphasised by recent studies reporting obesity to be an independent risk factor for increased morbidity and mortality following infection with the 2009 pandemic influenza A (H1N1) virus. Rodent models offer important insight into how metabolic abnormalities associated with excess body weight can impair immunity. However, more research is necessary to understand the specific aspects of immunity that are impaired and what factors are contributing to reduced immunocompetence in the obese. Additionally, special consideration of how infection in this at-risk population is managed is required, given that this population may not respond optimally to antimicrobial drugs and vaccination. Obesity impacts millions globally, and greater understanding of its associated physiological disturbances is a key public health concern.     

Early nutrition programming of long-term health

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.