Control of immunity via nutritional interventions.

Nutrition affects all physiological processes including those linked to the development and function of our immune system. Here, we discuss recent evidence and emerging concepts supporting the idea that our newfound relationship with nutrition in industrialized countries has fundamentally altered the way in which our immune system is wired. This will be examined through the lens of studies showing that mild or transient reductions in dietary intake can enhance protective immunity while also limiting aberrant inflammatory responses. We will further discuss how trade-offs and priorities begin to emerge in the context of severe nutritional stress. In those settings, specific immunological functions are heightened to re-enforce processes and tissue sites most critical to survival. Altogether, these examples will emphasize the profound influence nutrition has over the immune system and highlight how a mechanistic exploration of this cross talk could ultimately lead to the design of novel therapeutic approaches that prevent and treat disease.

Metabolic pressure and the breach of immunological self-tolerance.

The prevalence of autoimmune disorders in affluent countries has reached epidemic proportions. Over the past 50 years, a reverse trend between the frequency of infectious diseases and the incidence of autoimmune and allergic diseases led to the so-called 'hygiene hypothesis'. Given the epidemiological evidence and recent experimental data, we propose that this concept should also include metabolic pressure secondary to exposure to excessive daily caloric intake and overnutrition. We discuss how metabolic workload can modulate immunological tolerance and review the molecular mechanisms and the state of the art of the field. We also critically evaluate possibilities for restoring immunological homeostasis under conditions of metabolic pressure.

Nutritional Modulation of the Microbiome and Immune Response.

The evolution of the immune system, diet, and the microbiome are interconnected. Dietary metabolites modulate the cells of the immune system both directly and indirectly via shifts in the composition of the intestinal microbiota and its products. As a result, overconsumption and malnutrition can have substantial effects on immune responses and inflammation. In resource-rich nations, diets high in processed foods, fat, and sugar can contribute to chronic inflammatory conditions, which are on the rise worldwide. Conversely, in resource-poor countries, malnutrition associated with food insecurity can lead to immunodeficiencies and shifts in the microbiome that drive intestinal inflammation. Developing a deeper understanding of the relationship between diet, microbiota, and the immune system is of huge importance, given its impact on inflammatory diseases and its potential as an easily modifiable mediator of immunomodulation.

Personalized Nutrition 2020: Proceedings from the American Nutrition Association's 61st Annual Summit.

The American Nutrition Association's 61st annual summit, Personalized Nutrition 2020, convened thought leaders and stakeholders to discuss innovations in personalized nutrition (PN) technology, science, and practice. Evolutions in PN science and technology are enabling novel inroads and applications, leading the ANA to launch a new component of its annual gathering, the Personalized Nutrition Business Leaders Forum. In light of renewed global interest in immune health during the COVID-19 pandemic, the flagship Science and Practice Conference focused on the topic of immune resilience. Presentations highlighted emerging research suggesting that individuals may have unique immunological responses to exogenous insults and that immune system resilience can be optimized by the application of nutritional factors that regulate immune function. Thus, PN tools and services may uniquely enhance immune preparedness by optimizing immune system function and status. Furthermore, PN practitioners trained to utilize emerging techniques and services can help prepare society to meet our modern immune challenges.HighlightsIn order to be effectively implemented, personalized nutrition requires ongoing research, innovative tools and services, and a specialized health care workforcePersonalized nutrition will continue to grow as an economic driver as consumer and patient interest surgeThere has been increased interest in the role of nutrition in immune function in light of COVID-19 and its comorbidities.

Immunodeficiency and inborn disorders of vitamin B12 and folate metabolism.

PURPOSE OF REVIEW: Immune dysfunction, including severe combined immunodeficiency, has been described in genetic disorders affecting the metabolism of the vitamins cobalamin (vitamin B12) and folate. We have reviewed reports of clinical findings in patients with a number of inborn errors of cobalamin or folate metabolism, specifically looking for immune problems. RECENT FINDINGS: There is little evidence that immune function is affected in most of the disorders. Exceptions are Imerslund-Gräsbeck syndrome and hereditary folate malabsorption (affecting intestinal absorption of cobalamin and folate, respectively), transcobalamin deficiency (affecting transport of cobalamin in blood and cellular cobalamin uptake), and methylenetetrahydrofolate dehydrogenase 1 deficiency (catalyzing cytoplasmic interconversion of reduced folate coenzyme derivatives). SUMMARY: Although some inborn errors of cobalamin or folate can be associated with immune dysfunction, the degree and type of immune dysfunction vary with no obvious pattern.

Covid-19 and dietary socioecology: Risk minimisation.

Pandemics have shaped humanity over and over again, but the coronavirus outbreak of 2019-2020 is in a world at the tipping point of catastrophic climate change. Its origins and distinction derive from over-population with inequity and an industrial revolution since the 17th century which has exploited fossil fuels as a globalised energy source, a period now described as the anthropocene. Asymptotic ecosystem loss and dysfunction, for people whose being is socioecological, makes ultimate survival tenuous. Microbial forms of life jump species when habitats are destroyed, or their host misused. Our innate immunity depends on our general health and fitness- social, mental, physical, and nutritional, in step with nature and its rhythms through walking in it, enjoying sunlight and sleep. Biodiversity and the associated benefit of food variety, after being breast-fed, is the key descriptor of a healthful, sustainable, accessible, and acceptable way of eating. How this pattern might contribute to our resilience in the face of a highly transmissible and biologically evasive virus is becoming clear. It may also be possible to compliment usefully preventive vaccination and therapeutic healthcare and rehabilitation through a greater understanding of our nutritional biology.

Immunological aspects of sport nutrition.

Prolonged bouts of exercise and heavy training regimens are associated with depression of immune system functions that can increase the risk of picking up opportunistic infections such as the common cold and influenza. Some common sport nutrition practices including high-carbohydrate diets and carbohydrate ingestion during exercise, training with low-glycogen stores, intentional dieting for weight loss, ingestion of high-dose antioxidant supplements and protein ingestion post exercise may influence immune system status in athletes. In order to maintain robust immunity, athletes need to consume a well-balanced diet that is sufficient to meet their requirements for energy, carbohydrate, protein and micronutrients. Dietary deficiencies of protein and specific micronutrients are well known to be potential causes of immune dysfunction and an adequate intake of some essential minerals including iron and zinc and the vitamins A, D, E, B6 and B12 are important to maintain a healthy immune function. Vitamin D may be a particular concern as recent studies have emphasised its importance in limiting infection episode incidence and duration in both the general population and in athletes and many individuals exhibit inadequate vitamin D status during the winter months. There is only limited evidence that individual amino acids, ß-glucans, herbal extracts and zinc are capable of boosting immunity or reducing infection risk in athletes. The ingestion of carbohydrate during exercise and daily consumption of probiotics, vitamin D3, bovine colostrum and plant polyphenol containing supplements or foodstuffs currently offer the best chance of success, particularly for those individuals who are prone to illness.

Translating nutritional immunology into drug development for inflammatory bowel disease.

PURPOSE OF REVIEW: To highlight recent advances in the understanding of nutritional immunology and in the development of novel therapeutics for inflammatory bowel disease (IBD). RECENT FINDINGS: We highlight the variety of factors that contribute to the interaction of the immune system and nutrition including the microbiome and the nervous system stimulation of the gut. We describe the potential for therapeutic development in IBD. Further, we review the cellular metabolic effects on immune activation and promising therapeutic targets. Finally, we show how the progression of understanding the role of lanthionine synthetase C-like 2 has encompassed both nutritional and therapeutic advances and led to the development of novel oral small molecule therapeutics for IBD. SUMMARY: Nutritional immunology and drug development research centered around immunoregulatory pathways can provide safer and more effective drugs while accelerating the path to cures.

Sensing of nutrients and microbes in the gut.

PURPOSE OF REVIEW: Sensing of nutrients and microbes in the gut are fundamental processes necessary for life. This review aims to provide an overview of the basic background and new data on cellular nutrient, energy, and microbe sensors. RECENT FINDINGS: The nutrient sensors 5' adenosine monophosphate-activated protein kinase, activating transcription factor 4 and mechanistic target of rapamycin (mTOR) are critical in control of the cell cycle. Recent data demonstrate their role in metabolic syndrome, in cell growth, and as therapeutic targets. Regulation of mTOR by the amino acids is the subject of intense investigation. Recent studies have further elucidated the exact mechanism of amino acid-dependent mTOR regulation. Pathogen recognition receptors (PRRs) are receptors that recognize conserved microbial molecules. New data demonstrate how lymphocyte-specific PRRs are necessary to maintain homeostasis. Moreover, new studies explore the role of PRRs in controlling the gut bacterial and fungal microbiome. SUMMARY: Nutrient sensing molecules are central to cell growth and metabolism and are implicated in cancer and the metabolic syndrome. Regulation of nutrient sensors is complex, and may be amenable to therapeutic targeting. Microbial sensors play critical roles in homeostasis and maintenance of the gut fungal and bacterial microbiome.

Nutritional immunology: function of natural killer cells and their modulation by resveratrol for cancer prevention and treatment.

Natural killer (NK) cells as part of the innate immune system represent the first line of defence against (virus-) infected and malignantly transformed cells. The emerging field of nutritional immunology focuses on compounds featuring immune-modulating activities in particular on NK cells, which e.g. can be exploited for cancer prevention and treatment. The plant-based nutrition resveratrol is a ternary hydroxylated stilbene, which is present in many foods and beverages, respectively. In humans it comprises a large variety of distinct biological activities. Interestingly, resveratrol strongly modulates the immune response including the activity of NK cells. This review will give an overview on NK cell functions and summarize the resveratrol-mediated modulation thereof.

Prebiotics, probiotics, synbiotics, and the immune system: experimental data and clinical evidence.

PURPOSE OF REVIEW: The intestinal immune system is constantly exposed to foreign antigens, which for the most part should be tolerated. Certain probiotics, prebiotics, and synbiotics are able to influence immune responses. In this review, we highlight the recent publications (within the last 2 years) that have substantially progressed this field. RECENT FINDINGS: The immunological mechanisms underpinning probiotics, prebiotics, and synbiotics effects continue to be better defined with novel mechanisms being described for dendritic cells, epithelial cells, T regulatory cells, effector lymphocytes, natural killer T cells, and B cells. Many of the mechanisms being described are bacterial strain or metabolite specific, and should not be extrapolated to other probiotics or prebiotics. In addition, the timing of intervention seems to be important, with potentially the greatest effects being observed early in life. SUMMARY: In this review, we discuss the recent findings relating to probiotics, prebiotics, and synbiotics, specifically their effects on immunological functions.

Reciprocal interaction of diet and microbiome in inflammatory bowel diseases.

PURPOSE OF REVIEW: Diet is an emerging but poorly defined disease modulator in inflammatory bowel diseases (IBDs). Dietary factors exert direct effects on epithelial and immune cells and indirectly modulate immune homeostasis by shaping the intestinal microbiota. RECENT FINDINGS: The increase in IBD prevalence in industrialized countries is associated with lifestyle changes including diets rich in energy, saturated fats, meat and sugar. Despite the fact that the intestinal ecosystem shows high stability and resilience to short-term perturbations, long-term dietary habits have profound effects on composition and function eventually leading to dysbiosis, that is changes in microbial composition associated with deleterious effects to the host. High-throughput sequencing data generated deeper insights of the intestinal ecosystems related to health and disease. However, the available cohort-studies establish associative relationships between microbiota changes and disease, rather than causality. New mouse models of intestinal inflammation and the possibility to transfer disease-associated microbial consortia state an essential tool to unravel the potential of diet-induced microbial shifts. SUMMARY: This review will discuss new insights of how nutrition or single dietary factors shape the intestinal ecosystem. Furthermore, we want to provide perspectives for clinical translation of this knowledge to treat or prevent IBD.

Evidence of the effect of immunonutrition on the prevention of surgical site infection.

Surgical candidates are often immunosuppressed patients. Immunodeficiency associated with malnutrition are risk factors for developing postoperative SSI. The term "immunonutrition" refers to the addition of omega-3 fatty acids, glutamine and arginine to liquid nutritional supplements. Diverse studies have shown a reduction in septic complications after perioperative use of immunonutrition, but these results could not be confirmed by other authors. In this issue, we will review the actual evidence about the effect of immunonutrition on the prevention of SSI.

Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases.

Nutrients and foods for the primary prevention of asthma and allergy: systematic review and meta-analysis.

BACKGROUND: Epidemiologic studies suggest that deficiencies of the nutrients selenium; zinc; vitamins A, C, D, and E; and low fruit and vegetable intake may be associated with the development of asthma and allergic disorders. OBJECTIVES: To investigate the evidence that nutrient and food intake modifies the risk of children developing allergy. METHODS: We systematically searched 11 databases. Studies were critically appraised, and meta-analyses were undertaken. RESULTS: We identified 62 eligible reports. There were no randomized controlled trials. Studies used cohort (n = 21), case-control (n = 15), or cross-sectional (n = 26) designs. All studies were judged to be at moderate to substantial risk of bias. Meta-analysis revealed that serum vitamin A was lower in children with asthma compared with controls (odds ratio [OR], 0.25; 95% CI, 0.10-0.40). Meta-analyses also showed that high maternal dietary vitamin D and E intakes during pregnancy were protective for the development of wheezing outcomes (OR, 0.56, 95% CI, 0.42-0.73; and OR, 0.68, 95% CI, 0.52-0.88, respectively). Adherence to a Mediterranean diet was protective for persistent wheeze (OR, 0.22; 95% CI, 0.08-0.58) and atopy (OR, 0.55; 95% CI, 0.31-0.97). Seventeen of 22 fruit and vegetable studies reported beneficial associations with asthma and allergic outcomes. Results were not supportive for other allergic outcomes for these vitamins or nutrients, or for any outcomes in relation to vitamin C and selenium. CONCLUSION: The available epidemiologic evidence is weak but nonetheless supportive with respect to vitamins A, D, and E; zinc; fruits and vegetables; and a Mediterranean diet for the prevention of asthma. Experimental studies of these exposures are now warranted.

[Immune dysfunction in highly skilled athletes and nutritional rehabilitation].

The present review examines the effects of strenuous and moderate exercise on various components of the immune system including humoral and cell immunity. Acute exercise have been found to affect lymphocyte subsets, immunoglobulin levels, the activity of mononuclear phagocytic system, polymorphonuclear leukocytes and cytokine levels, especially IL-1, IL-2, IL-6 and TNF. The extreme type of immune deficiency in sportsmen, in which there are not determine different isotypes of immunoglobulins, there are described as phenomenon of Ig disappearance. The immune suppression is associated with an increased risk of subclinical and clinical infection in athletes. The mechanisms immunodeficiency are multifactorial and include neuroendocrinologocal and metabolic disorders. The immunosuppression in sportsmen may be prevented by use of special diets. Although athletes need to eat a well-balanced basic diet, there are several nutritional factors that are difficult to obtain at a sufficient level from a normal diet since athletes require more nutrients than the recommended daily allowances. Thus, appropriate nutrition enrichment of special products and food supplements containing proteins, amino acids, carbohydrates, vitamins, minerals, antioxidants, probiotics is an essential prerequisite for effective improvement of athletic performance, recovery from fatigue after exercise and ward off immunodeficiency.

A Link between Chronic Kidney Disease and Gut Microbiota in Immunological and Nutritional Aspects.

Chronic kidney disease (CKD) is generally progressive and irreversible, structural or functional renal impairment for 3 or more months affecting multiple metabolic pathways. Recently, the composition, dynamics, and stability of a patient's microbiota has been noted to play a significant role during disease onset or progression. Increasing urea concentration during CKD can lead to an acceleration of the process of kidney injury leading to alterations in the intestinal microbiota that can increase the production of gut-derived toxins and alter the intestinal epithelial barrier. A detailed analysis of the relationship between the role of intestinal microbiota and the development of inflammation within the symbiotic and dysbiotic intestinal microbiota showed significant changes in kidney dysfunction. Several recent studies have determined that dietary factors can significantly influence the activation of immune cells and their mediators. Moreover, dietary changes can profoundly affect the balance of gut microbiota. The aim of this review is to present the importance and factors influencing the differentiation of the human microbiota in the progression of kidney diseases, such as CKD, IgA nephropathy, idiopatic nephropathy, and diabetic kidney disease, with particular emphasis on the role of the immune system. Moreover, the effects of nutrients, bioactive compounds on the immune system in development of chronic kidney disease were reviewed.

The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies.

Infectious diseases and infections remain a leading cause of death in low-income countries and a major risk to vulnerable groups, such as infants and the elderly. The immune system plays a crucial role in the susceptibility, persistence, and clearance of these infections. With 70-80% of immune cells being present in the gut, there is an intricate interplay between the intestinal microbiota, the intestinal epithelial layer, and the local mucosal immune system. In addition to the local mucosal immune responses in the gut, it is increasingly recognized that the gut microbiome also affects systemic immunity. Clinicians are more and more using the increased knowledge about these complex interactions between the immune system, the gut microbiome, and human pathogens. The now well-recognized impact of nutrition on the composition of the gut microbiota and the immune system elucidates the role nutrition can play in improving health. This review describes the mechanisms involved in maintaining the intricate balance between the microbiota, gut health, the local immune response, and systemic immunity, linking this to infectious diseases throughout life, and highlights the impact of nutrition in infectious disease prevention and treatment.

The Complex Interplay between Immunonutrition, Mast Cells, and Histamine Signaling in COVID-19.

There is an ongoing need for new therapeutic modalities against SARS-CoV-2 infection. Mast cell histamine has been implicated in the pathophysiology of COVID-19 as a regulator of proinflammatory, fibrotic, and thrombogenic processes. Consequently, mast cell histamine and its receptors represent promising pharmacological targets. At the same time, nutritional modulation of immune system function has been proposed and is being investigated for the prevention of COVID-19 or as an adjunctive strategy combined with conventional therapy. Several studies indicate that several immunonutrients can regulate mast cell activity to reduce the de novo synthesis and/or release of histamine and other mediators that are considered to mediate, at least in part, the complex pathophysiology present in COVID-19. This review summarizes the effects on mast cell histamine of common immunonutrients that have been investigated for use in COVID-19.

Molecular Immune-Inflammatory Connections between Dietary Fats and Atherosclerotic Cardiovascular Disease: Which Translation into Clinics?

Current guidelines recommend reducing the daily intake of dietary fats for the prevention of ischemic cardiovascular diseases (CVDs). Avoiding saturated fats while increasing the intake of mono- or polyunsaturated fatty acids has been for long time the cornerstone of dietary approaches in cardiovascular prevention, mainly due to the metabolic effects of these molecules. However, recently, this approach has been critically revised. The experimental evidence, in fact, supports the concept that the pro- or anti-inflammatory potential of different dietary fats contributes to atherogenic or anti-atherogenic cellular and molecular processes beyond (or in addition to) their metabolic effects. All these aspects are hardly translatable into clinics when trying to find connections between the pro-/anti-inflammatory potential of dietary lipids and their effects on CVD outcomes. Interventional trials, although providing stronger potential for causal inference, are typically small sample-sized, and they have short follow-up, noncompliance, and high attrition rates. Besides, observational studies are confounded by a number of variables and the quantification of dietary intakes is far from optimal. A better understanding of the anatomic and physiological barriers for the absorption and the players involved in the metabolism of dietary lipids (e.g., gut microbiota) might be an alternative strategy in the attempt to provide a first step towards a personalized dietary approach in CVD prevention.