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.

Narrative Review of n-3 Polyunsaturated Fatty Acid Supplementation upon Immune Functions, Resolution Molecules and Lipid Peroxidation.

Fish oil supplementation is commonplace in human nutrition and is being used in both enteral and parenteral formulations during the treatment of patients with a large variety of diseases and immune status. The biological effects of fish oil are believed to result from their content of n-3 polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). These fatty acids are known to have numerous effects upon immune functions and are described as immunomodulatory. However, immunomodulatory is a nondescript term that encompasses immunostimulation and immunosuppression. The primary goal of this review is to better describe the immune effects of n-3 PUFA as they relate to immunostimulatory vs. immunosuppressive effects. One mechanism proposed for the immune effects of n-3 PUFA relates to the production of specialized pro-resolving mediators (SPMs). A second goal of this review is to evaluate the effects of n-3 PUFA supplementation upon production of SPMs. Although n-3 PUFA are stated to possess anti-oxidative properties, these molecules are highly oxidizable due to multiple double bonds and may increase oxidative stress. Thus, the third goal of this review is to evaluate the effects of n-3 PUFA upon lipid oxidation. We conclude, based upon current scientific evidence, that n-3 PUFA suppress inflammatory responses and most cellular immune responses such as chemotaxis, transmigration, antigen presentation, and lymphocyte functions and should be considered immunosuppressive. n-3 PUFA induced production of resolution molecules is inconsistent with many resolution molecules failing to respond to n-3 PUFA supplementation. n-3 PUFA supplementation is associated with increased lipid peroxidation in most studies. Vitamin E co-administration is unreliable for prevention of the lipid peroxidation. These effects should be considered when administering n-3 PUFA to patients that may be immunosuppressed or under high oxidative stress due to illness or other treatments.

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.

Chenopodium Quinoa and Salvia Hispanica Provide Immunonutritional Agonists to Ameliorate Hepatocarcinoma Severity under a High-Fat Diet.

Complex interactions between immunonutritional agonist and high fat intake (HFD), the immune system and finally gut microbiota are important determinants of hepatocarcinoma (HCC) severity. The ability of immunonutritional agonists to modulate major aspects such as liver innate immunity and inflammation and alterations in major lipids profile as well as gut microbiota during HCC development is poorly understood. 1H NMR has been employed to assess imbalances in saturated fatty acids, MUFA and PUFA, which were associated to variations in iron homeostasis. These effects were dependent on the botanical nature (Chenopodium quinoa vs. Salvia hispanica L.) of the compounds. The results showed that immunonutritional agonists' promoted resistance to hepatocarcinogenesis under pro-tumorigenic inflammation reflected, at a different extent, in increased proportions of F4/80+ cells in injured livers as well as positive trends of accumulated immune mediators (CD68/CD206 ratio) in intestinal tissue. Administration of all immunonutritional agonists caused similar variations of fecal microbiota, towards a lower obesity-inducing potential than animals only fed a HFD. Modulation of Firmicutes to Bacteroidetes contents restored the induction of microbial metabolites to improve epithelial barrier function, showing an association with liver saturated fatty acids and the MUFA and PUFA fractions. Collectively, these data provide novel findings supporting beneficial immunometabolic effects targeting hepatocarcinogenesis, influencing innate immunity within the gut-liver axis, and providing novel insights into their immunomodulatory activity.

Sex-Specific Differences in the Gut Microbiome in Response to Dietary Fiber Supplementation in IL-10-Deficient Mice.

There is growing interest in studying dietary fiber to stimulate microbiome changes that might prevent or alleviate inflammatory bowel disease (IBD). However, dietary fiber effects have shown varying degrees of efficacy, for reasons that are unclear. This study examined whether the effects of isomaltodextrin on gut microbiota and IBD were dependent on dose or host sex, using an Interleukin (IL)-10 deficient murine colitis model. After 12 weeks, colonic IL-12p70 was depressed in male mice receiving high-dose isomaltodextrin supplementation compared to the control group (p = 0.04). Male mice receiving high-dose isomaltodextrin exhibited changes in microbial alpha-diversity, including enhanced richness and evenness (p = 0.01) and limited reduction in the relative abundance of Coprococcus (q = 0.08), compared to the control group. These microbial compositional changes were negatively associated with IL-12p70 levels in the male group (rs ≤ -0.51, q ≤ 0.08). In contrast, female mice receiving isomaltodextrin displayed a reduction in alpha-diversity and Coprococcus abundance and a high level of IL-12p70, as did the control group. Together, these results indicate that isomaltodextrin altered the gut microbial composition linking specific immune-regulatory cytokine responses, while the interactions among fiber, microbiota and immune response were dose dependent and largely sex specific. The results further indicate that interactions between environmental and host factors can affect microbiome manipulation in the host.

Reply: "Comment on "Consumption of Cooked Black Beans Stimulates a Cluster of Some Clostridia Class Bacteria Decreasing Inflammatory Response and Improving Insulin Sensitivity." Nutrients 2020, 12(4), 1182".

We appreciate the interest of Dr [...].

Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005-2016 NHANES.

A well-functioning immune system is essential for human health and well-being. Micronutrients such as vitamins A, C, D, E, and zinc have several functions throughout the immune system, yet inadequate nutrient intakes are pervasive in the US population. A large body of research shows that nutrient inadequacies can impair immune function and weaken the immune response. Here, we present a new analysis of micronutrient usual intake estimates based on nationally representative data in 26,282 adults (>19 years) from the 2005-2016 National Health and Nutrition Examination Surveys (NHANES). Overall, the prevalence of inadequacy (% of population below estimated average requirement [EAR]) in four out of five key immune nutrients is substantial. Specifically, 45% of the U.S. population had a prevalence of inadequacy for vitamin A, 46% for vitamin C, 95% for vitamin D, 84% for vitamin E, and 15% for zinc. Dietary supplements can help address nutrient inadequacy for these immune-support nutrients, demonstrated by a lower prevalence of individuals below the EAR. Given the long-term presence and widening of nutrient gaps in the U.S.-specifically in critical nutrients that support immune health-public health measures should adopt guidelines to ensure an adequate intake of these micronutrients. Future research is needed to better understand the interactions and complexities of multiple nutrient shortfalls on immune health and assess and identify optimal levels of intake in at-risk populations.

Specific Dietary (Poly)phenols Are Associated with Sleep Quality in a Cohort of Italian Adults.

BACKGROUND: Diet has been the major focus of attention as a leading risk factor for non-communicable diseases, including mental health disorders. A large body of literature supports the hypothesis that there is a bidirectional association between sleep and diet quality, possibly via the modulation of neuro-inflammation, adult neurogenesis and synaptic and neuronal plasticity. In the present study, the association between dietary total, subclasses of and individual (poly)phenols and sleep quality was explored in a cohort of Italian adults. METHODS: The demographic and dietary characteristics of 1936 adults living in southern Italy were analyzed. Food frequency questionnaires (FFQs) were used to assess dietary intake. Data on the (poly)phenol content in foods were retrieved from the Phenol-Explorer database. The Pittsburg Sleep Quality Index was used to measure sleep quality. Multivariate logistic regression analyses were used to test the associations. RESULTS: A significant inverse association between a higher dietary intake of lignans and inadequate sleep quality was found. Additionally, individuals with the highest quartile of hydroxycinnamic acid intake were less likely to have inadequate sleep quality. When individual compounds were taken into consideration, an association with sleep quality was observed for naringenin and apigenin among flavonoids, and for matairesinol among lignans. A secondary analysis was conducted, stratifying the population into normal weight and overweight/obese individuals. The findings in normal weight individuals showed a stronger association between certain classes of, subclasses of and individual compounds and sleep quality. Notably, nearly all individual compounds belonging to the lignan class were inversely associated with inadequate sleep quality. In the overweight/obese individuals, there were no associations between any dietary (poly)phenol class and sleep quality. CONCLUSIONS: The results of this study suggest that a higher dietary intake of certain (poly)phenols may be associated with better sleep quality among adult individuals.

Nutritional immunology: Diversification and diet-dependent expression of antimicrobial peptides in the black soldier fly Hermetia illucens.

The black soldier fly Hermetia illucens is used for the bioconversion of organic waste into feed for livestock and aquaculture, and is economically among the most important farmed insects in the world. The larvae can be fed on agricultural waste and even liquid manure, resulting in highly unpredictable pathogen levels and dietary conditions. Here we show that H. illucens larvae express a remarkably expanded spectrum of antimicrobial peptides (AMPs), many of which are induced by feeding on a diet containing high bacterial loads. The addition of sulfonated lignin, cellulose, chitin, brewer's grains or sunflower oil revealed the diet-dependent expression profiles of AMPs in the larvae. The highest number of AMPs and the highest levels of AMP expression were induced by feeding larvae on diets supplemented with protein or sunflower oil. Strikingly, the diet-dependent expression of AMPs translated into diet-dependent profiles of inhibitory activities against a spectrum of bacteria, providing an intriguing example for the emerging field of nutritional immunology. We postulate that the fine-tuned expression of the expanded AMP repertoire mediates the adaptation of the gut microbiota to the digestion of unusual diets, and this feature could facilitate the use of H. illucens for the bioconversion of organic waste.

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.

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.

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.

[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.

Imunonutrição em pacientes com sepse?: [revisão] / Immunonutrition in patients with sepsis?: [review]

Objetivos: revisar os conhecimentos atuais sobre o uso de imunonutrientes em pacientes críticos, especialmente naqueles com sepse.Fonte de dados: foi realizada uma revisão narrativa da literatura, utilizando as bases de dados Medline/Pubmed. Os artigos pesquisados compreendem publicações entre 2000 e 2011. Foram incluídos também artigos obtidos em referências bibliográficas dos artigos com maior relevância. Foram selecionados trabalhos referentes a indivíduos humanos adultos.Síntese dos dados: os estudos utilizaram diferentes fórmulas contendo imunonutrientes, nem sempre com os mesmos imunomoduladores. A quantidade administrada também variou de acordo com o tipo de fórmula, a tolerância do paciente e a via de administração. Efeitos favoráveis e desfavoráveis resultaram da administração de dietas enriquecidas com nutrientes imunomoduladores em pacientes com sepse.Conclusões: a literatura é bastante controversa em relação à recomendação do uso de imunonutrientes em pacientes críticos, sobretudo naqueles com sepse. Ainda não há resultados consistentes sobre a eficiência e a segurança da imunonutrição nesses pacientes. São necessários estudos com desenho metodológico e população mais homogêneos, utilizando imunonutrientes isolados e com quantidades definidas.

Aims: To review the current knowledge on the use of immunonutrients in critically ill patients, especially those with sepsis.Source of data: A narrative review of the literature was conducted, using the Medline/Pubmed data bases. The selected articles included publications between 2000 and 2011. Articles cited in reference lists of articles with the highest relevance were also included. Works on adult human individuals were selected.Summary of findings: Studies used different formulas containing immunonutrients, not always with the same immunomodulators. The given amount varied according to the type of formula, the patient?s tolerance and the route of administration. Favorable and unfavorable effects appeared as a result of administration of diets enriched with immunomodulator nutrients in patients with sepsis.Conclusions: Literature is controversial regarding the recommendation to use immunonutrients in critically ill patients, especially those with sepsis. There is currently no evidence to define the efficiency and safety of immunonutrition in these patients. For more consistent results, studies should be conducted with more homogeneous methodological design and population, using isolated immunonutrients in defined dosis.

The 2008 ESPEN Sir David Cuthbertson Lecture: Fatty acids and inflammation--from the membrane to the nucleus and from the laboratory bench to the clinic.

Many chronic conditions involve excessive inflammation that is damaging to host tissues. Excessive or inappropriate inflammation and immunosuppression are components of the response to surgery, trauma, injury and infection in some individuals and these can lead, progressively, to sepsis and septic shock. Hyperinflammation is characterised by the production of inflammatory cytokines, eicosanoids and other inflammatory mediators, while the immunosuppression is characterised by impairment of antigen presentation and of certain T cell responses. N-6 fatty acids may contribute to the hyperinflamed and immunosuppressed states. N-3 fatty acids from fish oil decrease the production of inflammatory cytokines and eicosanoids. They act both directly (by replacing arachidonic acid as an eicosanoid precursor) and indirectly (by altering the expression of inflammatory genes through effects on transcription factor activation). Thus, these fatty acids are potentially useful anti-inflammatory agents and may be of benefit in patients with chronic inflammatory diseases or at risk of hyperinflammation and sepsis. An emerging application of n-3 fatty acids is in surgical or critically ill patients where they may be added to parenteral or enteral formulas. Studies to date are suggestive of clinical benefits from these approaches, although more robust data are needed especially in critically ill patients.

Nutrition, immunology, and genetics: future perspectives.

This review surveys some of the areas in which nutrients have been shown to have an impact on specific immune functions, the use of molecular and genetic tools to study molecular responses to dietary factors,and the metabolic consequences of food. It also explores the relationships between nutrient molecules, genetic polymorphisms, and the biological system as a whole, while providing a short introduction to nutrition immunology, nutrient-gene interactions and the novel technologies employed in nutrigenomics and nutrigenetics research.

Enteral nutrition in the cardiothoracic intensive care unit: challenges and considerations.

Cardiovascular disease is a common preexisting condition among hospitalized patients. Acute myocardial infarction and cardiac surgery account for 2 of the most common reasons patients are admitted to the intensive care unit. Determining how and when to feed these patients is a constant challenge presented to nutrition support practitioners. Enteral nutrition has emerged as the preferred route of feeding particularly in critical illness. By providing enteral nutrition instead of parenteral nutrition, the natural physiologic pathway is being followed and gut immunity preserved. However, obstacles such as upper gastrointestinal intolerance, hypoperfusion vasopressor support, and glycemic control make the task of initiating feeds a challenge. Once a patient has successfully tolerated feeds, the nutrition support clinician must still determine how much to feed and if specialty formulas such as those containing omega-3 fatty acids are beneficial for their patient. The purpose of this review is to present recent research on the feeding challenges in the critical care population with a focus on the cardiothoracic population and an emphasis on improving patient outcomes.

Nutritional modulation of exercise-induced immunodepression in athletes: a systematic review and meta-analysis.

BACKGROUND: Heavy exercise induces marked immunodepression that is multifactorial in origin. Nutrition can modulate normal immune function. OBJECTIVE: To assess the efficacy of nutritional supplements in exercise-induced immunodepression in athletes. DESIGN: Systematic review. REVIEW METHODS: Randomised and/or controlled trials of athletes undertaking nutritional supplements to minimise the immunodepression after exercise were retrieved. The primary outcome measure was incidence of upper respiratory tract (URT) illness symptoms after exercise, and secondary outcomes included cortisol, cell counts, plasma cytokine concentration, cell proliferative response, oxidative burst, natural killer cell activity and immunoglobulins. When data were available for a pooled estimate of the effect of intervention, meta-analyses were conducted for direct comparisons. RESULTS: Forty-five studies were included (1603 subjects). The studies were heterogeneous in terms of exercise interventions, selection of athletes, settings and outcomes. The overall methodological quality of most of the trials was poor. Twenty studies addressed carbohydrate supplementation, eight glutamine, 13 vitamin C and four others interventions. Three trials assessed the effect of intervention on prevention of URT infections. The pooled rate ratio for URT infections after vitamin C supplementation against placebo was 0.49 (0.34-0.71). Carbohydrate supplementation attenuated the increase in cortisol and neutrophils after exercise; vitamin C attenuated the decrease in lymphocytes after exercise. No other interventions had significant or consistent effect on any of the studied outcomes. CONCLUSIONS: Although the prevention of URT infections by vitamin C was supported by two trials, further studies are needed. The available evidence failed to support a role for other nutritional supplements in preventing exercise-induced immune suppression. Larger trials with clinically relevant and uniform end points are necessary to clarify the role of these nutritional interventions.

Influencia de la dieta en la salud ósea / Influence of diet on bone health

En conclusión, es difícil determinar en qué medida la dieta es responsable del mantenimiento de la salud de la población. Las recomendaciones nutricionales pretenden prevenir el desarrollo de enfermedades crónicas y degenerativas, con el fin de promocionar la salud de los individuos. En este contexto nace la idea de dieta sana para el mantenimiento, entre otros, de la salud ósea. Hasta la fecha no existe una evidencia científica definitiva para establecer recomendaciones firmes en la relación dieta y salud ósea, con la excepción del calcio y la vitamina D. En el caso del calcio, se deben recomendar suplementos del mineral en poblaciones con ingesta inferior a 400-500 mg/día. Por el momento, se necesitan más estudios para establecer si el aumento de la ingesta de calcio en individuos con dietas suficientes y en poblaciones con bajo riesgo de fractura supone un beneficio adicional para el hueso. Con respecto a la vitamina D, la evidencia demuestra que los individuos a riesgo de presentar déficit, como son los ancianos que viven en residencias, deben recibir suplementos orales de esta vitamina. Sin embargo, se desconoce en el momento actual si mejorar el estado de esta vitamina en estos grupos vulnerables es una estrategia poblacional eficaz para prevenir la osteoporosis en el futuro. Para el resto de los componentes de la dieta, su relación con la salud ósea permanece en discusión. Las recomendaciones de dieta adecuada para promocionar la salud y evitar las enfermedades crónicas también son válidas para la osteoporosis. Estas medidas incluyen el consumo habitual de fruta, verdura y productos lácteos, sustituir la carne por productos de granja, pescado y legumbres, y reducir el contenido de sal, café y alcohol de la dieta(AU)

In conclusion, it is difficult to determine to what degree diet is responsible for health maintenance of the population. Nutritional recommendations aim to prevent the development of chronic and degenerative diseases in order to promote the individual's health. The idea of a healthy diet for maintenance, among others, of bone health arises in this context. Up to now, there is no definitive scientific evidence to establish firm recommendations on the diet and bone health relationship, except for calcium and vitamin D. In the case of calcium, mineral supplements should be recommended in populations with intake less than 400-500 mg/day. At present, more studies are needed to establish if the increase of calcium intake in individuals with sufficient diets and in populations with low risk of fracture mean an additional benefit for the bone. In regards to vitamin D, the evidence demonstrates that individuals at risk of having a deficit, as the elderly who live in residences, should receive oral supplements of this vitamin. However, at present, it is unknown if improving the state of this vitamin in these vulnerable groups is an effective populational strategy to prevent osteoporosis in the future. For the rest of the diet components, their relationship with bone health is still under debate. Recommendations of adequate diet to promote health and avoid chronic diseases are also valid for osteoporosis. These measures include usual intake of fruit, vegetables and lactic products, substitute mean with farm products, fish and pod vegetables and reducing salt content, coffee and alcohol in the diet(AU)