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.

Natural and Synthetic Bioactives for Skin Health, Disease and Management.

The skin is the largest organ of the integumentary system, strategically located at the interface of the body's internal and external environment. [...].

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.

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 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.

A Positive Association of Overactivated Immunity with Metabolic Syndrome Risk and Mitigation of Its Association by a Plant-Based Diet and Physical Activity in a Large Cohort Study.

The association between immunity and metabolic syndrome (MetS) has been studied, but its interaction with lifestyles remains unclear. We studied their association and interactions with lifestyles in 40,768 adults aged over 40 years from a large-scale, hospital-based cohort study collected during 2010-2013. White blood cell counts (WBC) and serum C-reactive protein concentrations (CRP) were used as indexes of immune status. The participants were categorized into four groups by the cutoff points of 6.2 × 109/L WBC(L-WBC) and <0.5 mg/dL CRP(L-CRP): L-WBC+L-CRP(n = 25,604), H-WBC+L-CRP(n = 13,880), L-WBC+H-CRP(n = 464), and H-WBC+H-CRP(n = 820). The participants in the H-WBC+L-CRP were younger and had higher numbers of males than the L-WBC+L-CRP. MetS risk was higher by 1.75- and 1.86-fold in the H-WBC+L-CRP and H-WBC+H-CRP, respectively, than the L-WBC+L-CRP. MetS components, including plasma glucose and triglyceride concentrations, and SBP were elevated in H-WBC+L-CRP and H-WBC+H-CRP compared with L-WBC+L-CR+P. The risk of hyperglycemia and high HbA1c was the highest in the H-WBC+H-CRP among all groups. Areas of WBC counts and serum CRP concentrations were 0.637 and 0.672, respectively, in the receiver operating characteristic curve. Daily intake of energy, carbohydrate, protein, and fat was not significantly different in the groups based on WBC counts and CRP. However, a plant-based diet (PBD), physical activity, and non-smoking were related to lowering WBC counts and CRP, but a Western-style diet was linked to elevating CRP. A high PBD intake and smoking status interacted with immunity to influence MetS risk: a low PBD and current smoking were associated with a higher MetS risk in the H-WBC+H-CRP. In conclusion, overactivated immunity determined by CRP and WBC was associated with MetS risk. Behavior modification with PBD and physical activity might be related to immunity regulation.

Immunonutritional Bioactives from Chenopodium quinoa and Salvia hispanica L. Flour Positively Modulate Insulin Resistance and Preserve Alterations in Peripheral Myeloid Population.

Innate immunity plays a determinant role in high fat diet (HFD)-induced insulin resistance. This study compares the effects of immunonutritional bioactives from Chenopodium quinoa (WQ) or Salvia hispanica L. (Ch) when used to partially replace wheat flour (WB) into bread formulations. These flours were chosen to condition starch and lipid content in the products as well as because their immunonutritional activity. To be administered with different bread formulations, HFD-fed C57BL/6J mice were distributed in different groups: (i) wild type, (ii) displaying inherited disturbances in glucose homeostasis, and (iii) displaying dietary iron-mediated impairment of the innate immune TLR4/TRAM/TRIF pathway. We analyze the effects of the products on glycaemia and insulin resistance (HOMA-IR), plasmatic triglycerides, intestinal and hepatic gene expression and variations of myeloid (MY), and lymphoid (LY) cells population in peripheral blood. Our results show that feeding animals with WQ and Ch formulations influenced the expression of lipogenic and coronary risk markers, thus attaining a better control of hepatic lipid accumulation. WQ and Ch products also improved glucose homeostasis compared to WB, normalizing the HOMA-IR in animals with an altered glucose and lipid metabolism. These positive effects were associated with positive variations in the peripheral myeloid cells population.

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.

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.

Choline: An Essential Nutrient for Skeletal Muscle.

BACKGROUND: Choline is an essential micronutrient with a pivotal role in several metabolic pathways contributing to liver, neurological, and hematological homeostasis. Although choline is commonly administered to improve physical performance, its effects on muscle are still unclear. The aim of this scoping review is to analyze the role of choline on skeletal muscle in terms of biological effects and clinical implications. METHODS: A technical expert panel (TEP) of 6 medical specialists with expertise in muscle physiology and skeletal muscle disorders performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP planned a research on PubMed selecting "choline" as MeSH (Medical Subject Headings) term adding to PubMed Search Builder the terms "skeletal muscle" and "muscle striated". TEP considered for eligibility articles published in the last 30 years, including original researches, particularly in vitro studies, and animal and clinical studies in the English language. RESULTS: From the 1239 studies identified, TEP included 14 studies, 3 in vitro, 9 animal, and 2 clinical studies. CONCLUSIONS: Our scoping review elucidates and summarizes the crucial role of choline in modulating muscle fat metabolism, muscle proteins homeostasis, and the modulation of inflammation and autophagy.

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".

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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.

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.

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.

Cholesterol and Egg Intakes, and Risk of Hypertension in a Large Prospective Cohort of French Women.

Purpose: The relationship between egg and cholesterol intakes, and cardiovascular disease is controversial. Meta-analyses indicate that egg consumption is associated with increased cardiovascular disease and mortality, but reduced incidence of hypertension, a major risk factor for cardiovascular disease. This study aims to investigate the associations between consumption of egg and cholesterol, and hypertension risk in a cohort of French women. Methods: We used data from the E3N cohort study, a French prospective population-based study initiated in 1990. From the women in the study, we included those who completed a detailed diet history questionnaire, and who did not have prevalent hypertension or cardiovascular disease at baseline, resulting in 46,424 women. Hypertension cases were self-reported. Egg and cholesterol intake was estimated from dietary history questionnaires. Cox proportional hazard models with time-updated exposures were used to calculate hazard ratios. Spline regression was used to determine any dose-respondent relationship. Results: During 885,321 person years, 13,161 cases of incident hypertension were identified. Higher cholesterol consumption was associated with an increased risk of hypertension : HRQ1-Q5 = 1.22 [1.14:1.30], with associations similar regarding egg consumption up to seven eggs per week: HR4-7 eggs = 1.14 [1.06:1.18]. Evidence for a non-linear relationship between hypertension and cholesterol intake was observed. Conclusion: Egg and cholesterol intakes were associated with a higher risk of hypertension in French women. These results merit further investigation in other populations.