1 2835 126 FOOD AS MEDICINE: TARGETING THE URAEMIC PHENOTYPE IN CHRONIC KIDNEY DISEASE. THE OBSERVATION THAT UNHEALTHY DIETS (THOSE THAT ARE LOW IN WHOLE GRAINS, FRUITS AND VEGETABLES, AND HIGH IN SUGAR, SALT, SATURATED FAT AND ULTRA-PROCESSED FOODS) ARE A MAJOR RISK FACTOR FOR POOR HEALTH OUTCOMES HAS BOOSTED INTEREST IN THE CONCEPT OF 'FOOD AS MEDICINE'. THIS CONCEPT IS ESPECIALLY RELEVANT TO METABOLIC DISEASES, SUCH AS CHRONIC KIDNEY DISEASE (CKD), IN WHICH DIETARY APPROACHES ARE ALREADY USED TO AMELIORATE METABOLIC AND NUTRITIONAL COMPLICATIONS. INCREASED AWARENESS THAT TOXIC URAEMIC METABOLITES ORIGINATE NOT ONLY FROM INTERMEDIARY METABOLISM BUT ALSO FROM GUT MICROBIAL METABOLISM, WHICH IS DIRECTLY INFLUENCED BY DIET, HAS FUELLED INTEREST IN THE POTENTIAL OF 'FOOD AS MEDICINE' APPROACHES IN CKD BEYOND THE CURRENT STRATEGIES OF PROTEIN, SODIUM AND PHOSPHATE RESTRICTION. BIOACTIVE NUTRIENTS CAN ALTER THE COMPOSITION AND METABOLISM OF THE MICROBIOTA, ACT AS MODULATORS OF TRANSCRIPTION FACTORS INVOLVED IN INFLAMMATION AND OXIDATIVE STRESS, MITIGATE MITOCHONDRIAL DYSFUNCTION, ACT AS SENOLYTICS AND IMPACT THE EPIGENOME BY ALTERING ONE-CARBON METABOLISM. AS GUT DYSBIOSIS, INFLAMMATION, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, PREMATURE AGEING AND EPIGENETIC CHANGES ARE COMMON FEATURES OF CKD, THESE FINDINGS SUGGEST THAT TAILORED, HEALTHY DIETS THAT INCLUDE BIOACTIVE NUTRIENTS AS PART OF THE FOODOME COULD POTENTIALLY BE USED TO PREVENT AND TREAT CKD AND ITS COMPLICATIONS. 2021 2 2855 44 FROM INFLAMMAGING TO HEALTHY AGING BY DIETARY LIFESTYLE CHOICES: IS EPIGENETICS THE KEY TO PERSONALIZED NUTRITION? THE PROGRESSIVELY OLDER POPULATION IN DEVELOPED COUNTRIES IS REFLECTED IN AN INCREASE IN THE NUMBER OF PEOPLE SUFFERING FROM AGE-RELATED CHRONIC INFLAMMATORY DISEASES SUCH AS METABOLIC SYNDROME, DIABETES, HEART AND LUNG DISEASES, CANCER, OSTEOPOROSIS, ARTHRITIS, AND DEMENTIA. THE HETEROGENEITY IN BIOLOGICAL AGING, CHRONOLOGICAL AGE, AND AGING-ASSOCIATED DISORDERS IN HUMANS HAVE BEEN ASCRIBED TO DIFFERENT GENETIC AND ENVIRONMENTAL FACTORS (I.E., DIET, POLLUTION, STRESS) THAT ARE CLOSELY LINKED TO SOCIOECONOMIC FACTORS. THE COMMON DENOMINATOR OF THESE FACTORS IS THE INFLAMMATORY RESPONSE. CHRONIC LOW-GRADE SYSTEMIC INFLAMMATION DURING PHYSIOLOGICAL AGING AND IMMUNOSENESCENCE ARE INTERTWINED IN THE PATHOGENESIS OF PREMATURE AGING ALSO DEFINED AS 'INFLAMMAGING.' THE LATTER HAS BEEN ASSOCIATED WITH FRAILTY, MORBIDITY, AND MORTALITY IN ELDERLY SUBJECTS. HOWEVER, IT IS UNKNOWN TO WHAT EXTENT INFLAMMAGING OR LONGEVITY IS CONTROLLED BY EPIGENETIC EVENTS IN EARLY LIFE. TODAY, HUMAN DIET IS BELIEVED TO HAVE A MAJOR INFLUENCE ON BOTH THE DEVELOPMENT AND PREVENTION OF AGE-RELATED DISEASES. MOST PLANT-DERIVED DIETARY PHYTOCHEMICALS AND MACRO- AND MICRONUTRIENTS MODULATE OXIDATIVE STRESS AND INFLAMMATORY SIGNALING AND REGULATE METABOLIC PATHWAYS AND BIOENERGETICS THAT CAN BE TRANSLATED INTO STABLE EPIGENETIC PATTERNS OF GENE EXPRESSION. THEREFORE, DIET INTERVENTIONS DESIGNED FOR HEALTHY AGING HAVE BECOME A HOT TOPIC IN NUTRITIONAL EPIGENOMIC RESEARCH. INCREASING EVIDENCE HAS REVEALED THAT COMPLEX INTERACTIONS BETWEEN FOOD COMPONENTS AND HISTONE MODIFICATIONS, DNA METHYLATION, NON-CODING RNA EXPRESSION, AND CHROMATIN REMODELING FACTORS INFLUENCE THE INFLAMMAGING PHENOTYPE AND AS SUCH MAY PROTECT OR PREDISPOSE AN INDIVIDUAL TO MANY AGE-RELATED DISEASES. REMARKABLY, HUMANS PRESENT A BROAD RANGE OF RESPONSES TO SIMILAR DIETARY CHALLENGES DUE TO BOTH GENETIC AND EPIGENETIC MODULATIONS OF THE EXPRESSION OF TARGET PROTEINS AND KEY GENES INVOLVED IN THE METABOLISM AND DISTRIBUTION OF THE DIETARY CONSTITUENTS. HERE, WE WILL SUMMARIZE THE EPIGENETIC ACTIONS OF DIETARY COMPONENTS, INCLUDING PHYTOCHEMICALS, AND MACRO- AND MICRONUTRIENTS AS WELL AS METABOLITES, THAT CAN ATTENUATE INFLAMMAGING. WE WILL DISCUSS THE CHALLENGES FACING PERSONALIZED NUTRITION TO TRANSLATE HIGHLY VARIABLE INTERINDIVIDUAL EPIGENETIC DIET RESPONSES TO POTENTIAL INDIVIDUAL HEALTH BENEFITS/RISKS RELATED TO AGING DISEASE. 2015 3 2930 28 GENES AND DIET IN THE PREVENTION OF CHRONIC DISEASES IN FUTURE GENERATIONS. NUTRITION IS A MODIFIABLE KEY FACTOR THAT IS ABLE TO INTERACT WITH BOTH THE GENOME AND EPIGENOME TO INFLUENCE HUMAN HEALTH AND FERTILITY. IN PARTICULAR, SPECIFIC GENETIC VARIANTS CAN INFLUENCE THE RESPONSE TO DIETARY COMPONENTS AND NUTRIENT REQUIREMENTS, AND CONVERSELY, THE DIET ITSELF IS ABLE TO MODULATE GENE EXPRESSION. IN THIS CONTEXT AND THE ERA OF PRECISION MEDICINE, NUTRIGENETIC AND NUTRIGENOMIC STUDIES OFFER SIGNIFICANT OPPORTUNITIES TO IMPROVE THE PREVENTION OF METABOLIC DISTURBANCES, SUCH AS TYPE 2 DIABETES, GESTATIONAL DIABETES, HYPERTENSION, AND CARDIOVASCULAR DISEASES, EVEN WITH TRANSGENERATIONAL EFFECTS. THE PRESENT REVIEW TAKES INTO ACCOUNT THE INTERACTIONS BETWEEN DIET, GENES AND HUMAN HEALTH, AND PROVIDES AN OVERVIEW OF THE ROLE OF NUTRIGENETICS, NUTRIGENOMICS AND EPIGENETICS IN THE PREVENTION OF NON-COMMUNICABLE DISEASES. MOREOVER, WE FOCUS OUR ATTENTION ON THE MECHANISM OF INTERGENERATIONAL OR TRANSGENERATIONAL TRANSMISSION OF THE SUSCEPTIBILITY TO METABOLIC DISTURBANCES, AND UNDERLINE THAT THE REVERSIBILITY OF EPIGENETIC MODIFICATIONS THROUGH DIETARY INTERVENTION COULD COUNTERACT PERTURBATIONS INDUCED BY LIFESTYLE AND ENVIRONMENTAL FACTORS. 2020 4 5821 34 STRESS IN OBESITY AND ASSOCIATED METABOLIC AND CARDIOVASCULAR DISORDERS. OBESITY HAS SIGNIFICANT IMPLICATIONS FOR HEALTHCARE, SINCE IT IS A MAJOR RISK FACTOR FOR BOTH TYPE 2 DIABETES AND THE METABOLIC SYNDROME. THIS SYNDROME IS A COMMON AND COMPLEX DISORDER COMBINING OBESITY, DYSLIPIDEMIA, HYPERTENSION, AND INSULIN RESISTANCE. IT IS ASSOCIATED WITH HIGH ATHEROSCLEROTIC CARDIOVASCULAR RISK, WHICH CAN ONLY PARTIALLY BE EXPLAINED BY ITS COMPONENTS. THEREFORE, TO EXPLAIN HOW OBESITY CONTRIBUTES TO THE DEVELOPMENT OF METABOLIC AND CARDIOVASCULAR DISORDERS, MORE AND BETTER INSIGHT IS REQUIRED INTO THE EFFECTS OF PERSONAL AND ENVIRONMENTAL STRESS ON DISEASE PROCESSES. IN THIS PAPER, WE SHOW THAT OBESITY IS A CHRONIC INFLAMMATORY DISEASE, WHICH HAS MANY MOLECULAR MECHANISMS IN COMMON WITH ATHEROSCLEROSIS. FURTHERMORE, WE FOCUS ON THE ROLE OF OXIDATIVE STRESS ASSOCIATED WITH OBESITY IN THE DEVELOPMENT OF THE METABOLIC SYNDROME. WE DISCUSS HOW SEVERAL STRESS CONDITIONS ARE RELATED TO INFLAMMATION AND OXIDATIVE STRESS IN ASSOCIATION WITH OBESITY AND ITS COMPLICATIONS. WE ALSO EMPHASIZE THE RELATION BETWEEN STRESS CONDITIONS AND THE DEREGULATION OF EPIGENETIC CONTROL MECHANISMS BY MEANS OF MICRORNAS AND SHOW HOW THIS IMPAIRMENT FURTHER CONTRIBUTES TO THE DEVELOPMENT OF OBESITY, CLOSING THE VICIOUS CIRCLE. FINALLY, WE DISCUSS THE LIMITATIONS OF CURRENT ANTI-INFLAMMATION AND ANTIOXIDANT THERAPY TO TREAT OBESITY. 2012 5 5586 33 ROLE OF PERSONALIZED NUTRITION IN CHRONIC-DEGENERATIVE DISEASES. HUMAN NUTRITION IS A BRANCH OF MEDICINE BASED ON FOODS BIOCHEMICAL INTERACTIONS WITH THE HUMAN BODY. THE PHENOTYPIC TRANSITION FROM HEALTH TO DISEASE STATUS CAN BE ATTRIBUTED TO CHANGES IN GENES AND/OR PROTEIN EXPRESSION. FOR THIS REASON, A NEW DISCIPLINE HAS BEEN DEVELOPED CALLED "-OMIC SCIENCE". IN THIS REVIEW, WE ANALYZED THE ROLE OF "-OMICS SCIENCES" (NUTRIGENETICS, NUTRIGENOMICS, PROTEOMICS AND METABOLOMICS) IN THE HEALTH STATUS AND AS POSSIBLE THERAPEUTIC TOOL IN CHRONIC DEGENERATIVE DISEASES. IN PARTICULAR, WE FOCUSED ON THE ROLE OF NUTRIGENETICS AND THE RELATIONSHIP BETWEEN EATING HABITS, CHANGES IN THE DNA SEQUENCE AND THE ONSET OF NUTRITION-RELATED DISEASES. MOREOVER, WE EXAMINED NUTRIGENOMICS AND THE EFFECT OF NUTRIENTS ON GENE EXPRESSION. WE PERUSED THE ROLE OF PROTEOMICS AND METABOLOMICS IN PERSONALIZED NUTRITION. IN THIS SCENARIO, WE ANALYZED ALSO HOW DYSBIOSIS OF GUT MICROBIOTA CAN INFLUENCE THE ONSET AND PROGRESSION OF CHRONIC DEGENERATIVE DISEASES. MOREOVER, NUTRIENTS INFLUENCING AND REGULATING GENE ACTIVITY, BOTH DIRECTLY AND INDIRECTLY, PAVES THE WAY FOR PERSONALIZED NUTRITION THAT PLAYS A KEY ROLE IN THE PREVENTION AND TREATMENT OF CHRONIC DEGENERATIVE DISEASES. 2019 6 6204 35 THE INFLUENCE OF EPIGENETICS AND INFLAMMATION ON CARDIOMETABOLIC RISKS. CARDIOMETABOLIC DISEASES INCLUDE METABOLIC SYNDROME, OBESITY, TYPE 2 DIABETES MELLITUS, AND HYPERTENSION. EPIGENETIC MODIFICATIONS PARTICIPATE IN CARDIOMETABOLIC DISEASES THROUGH SEVERAL PATHWAYS, INCLUDING INFLAMMATION, VASCULAR DYSFUNCTION, AND INSULIN RESISTANCE. EPIGENETIC MODIFICATIONS, WHICH ENCOMPASS ALTERATIONS TO GENE EXPRESSION WITHOUT MUTATING THE DNA SEQUENCE, HAVE GAINED MUCH ATTENTION IN RECENT YEARS, SINCE THEY HAVE BEEN CORRELATED WITH CARDIOMETABOLIC DISEASES AND MAY BE TARGETED FOR THERAPEUTIC INTERVENTIONS. EPIGENETIC MODIFICATIONS ARE GREATLY INFLUENCED BY ENVIRONMENTAL FACTORS, SUCH AS DIET, PHYSICAL ACTIVITY, CIGARETTE SMOKING, AND POLLUTION. SOME MODIFICATIONS ARE HERITABLE, INDICATING THAT THE BIOLOGICAL EXPRESSION OF EPIGENETIC ALTERATIONS MAY BE OBSERVED ACROSS GENERATIONS. MOREOVER, MANY PATIENTS WITH CARDIOMETABOLIC DISEASES PRESENT WITH CHRONIC INFLAMMATION, WHICH CAN BE INFLUENCED BY ENVIRONMENTAL AND GENETIC FACTORS. THE INFLAMMATORY ENVIRONMENT WORSENS THE PROGNOSIS OF CARDIOMETABOLIC DISEASES AND FURTHER INDUCES EPIGENETIC MODIFICATIONS, PREDISPOSING PATIENTS TO THE DEVELOPMENT OF OTHER METABOLISM-ASSOCIATED DISEASES AND COMPLICATIONS. A DEEPER UNDERSTANDING OF INFLAMMATORY PROCESSES AND EPIGENETIC MODIFICATIONS IN CARDIOMETABOLIC DISEASES IS NECESSARY TO IMPROVE OUR DIAGNOSTIC CAPABILITIES, PERSONALIZED MEDICINE APPROACHES, AND THE DEVELOPMENT OF TARGETED THERAPEUTIC INTERVENTIONS. FURTHER UNDERSTANDING MAY ALSO ASSIST IN PREDICTING DISEASE OUTCOMES, ESPECIALLY IN CHILDREN AND YOUNG ADULTS. THIS REVIEW DESCRIBES EPIGENETIC MODIFICATIONS AND INFLAMMATORY PROCESSES UNDERLYING CARDIOMETABOLIC DISEASES, AND FURTHER DISCUSSES ADVANCES IN THE RESEARCH FIELD WITH A FOCUS ON SPECIFIC POINTS FOR INTERVENTIONAL THERAPY. 2023 7 6379 28 THE ROLE OF NUTRITION ON META-INFLAMMATION: INSIGHTS AND POTENTIAL TARGETS IN COMMUNICABLE AND CHRONIC DISEASE MANAGEMENT. PURPOSE OF REVIEW: CHRONIC LOW-GRADE INFLAMMATION MAY CONTRIBUTE TO THE ONSET AND PROGRESSION OF COMMUNICABLE AND CHRONIC DISEASES. THIS REVIEW EXAMINED THE EFFECTS AND EVENTUAL MEDIATION ROLES OF DIFFERENT NUTRITIONAL FACTORS ON INFLAMMATION. RECENT FINDINGS: POTENTIAL NUTRITIONAL COMPOUNDS INFLUENCING INFLAMMATION PROCESSES INCLUDE MACRO AND MICRONUTRIENTS, BIOACTIVE MOLECULES (POLYPHENOLS), SPECIFIC FOOD COMPONENTS, AND CULINARY INGREDIENTS AS WELL AS STANDARDIZED DIETARY PATTERNS, EATING HABITS, AND CHRONONUTRITION FEATURES. THEREFORE, RESEARCH IN THIS FIELD IS STILL REQUIRED, TAKING INTO ACCOUNT CRITICAL ASPECTS OF HETEROGENEITY INCLUDING TYPE OF POPULATION, MINIMUM AND MAXIMUM INTAKES AND ADVERSE EFFECTS, COOKING METHODS, PHYSIOPATHOLOGICAL STATUS, AND TIMES OF INTERVENTION. MOREOVER, THE INTEGRATIVE ANALYSIS OF TRADITIONAL VARIABLES (AGE, SEX, METABOLIC PROFILE, CLINICAL HISTORY, BODY PHENOTYPE, HABITUAL DIETARY INTAKE, PHYSICAL ACTIVITY LEVELS, AND LIFESTYLE) TOGETHER WITH INDIVIDUALIZED ISSUES (GENETIC BACKGROUND, EPIGENETIC SIGNATURES, MICROBIOTA COMPOSITION, GENE EXPRESSION PROFILES, AND METABOLOMIC FINGERPRINTS) MAY CONTRIBUTE TO THE KNOWLEDGE AND PRESCRIPTION OF MORE PERSONALIZED TREATMENTS AIMED TO IMPROVING THE PRECISION MEDICAL MANAGEMENT OF INFLAMMATION AS WELL AS THE DESIGN OF ANTI-INFLAMMATORY DIETS IN CHRONIC AND COMMUNICABLE DISEASES. 2022 8 6258 42 THE MOLECULAR MECHANISM OF POLYPHENOLS IN THE REGULATION OF AGEING HALLMARKS. AGEING IS A COMPLEX PROCESS CHARACTERIZED MAINLY BY A DECLINE IN THE FUNCTION OF CELLS, TISSUES, AND ORGANS, RESULTING IN AN INCREASED RISK OF MORTALITY. THIS PROCESS INVOLVES SEVERAL CHANGES, DESCRIBED AS HALLMARKS OF AGEING, WHICH INCLUDE GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC CHANGES, LOSS OF PROTEOSTASIS, DYSREGULATED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL DEPLETION, AND ALTERED INTRACELLULAR COMMUNICATION. THE DETERMINING ROLE THAT ENVIRONMENTAL FACTORS SUCH AS DIET AND LIFESTYLE PLAY ON HEALTH, LIFE EXPECTANCY, AND SUSCEPTIBILITY TO DISEASES, INCLUDING CANCER AND NEURODEGENERATIVE DISEASES, IS WELLESTABLISHED. IN VIEW OF THE GROWING INTEREST IN THE BENEFICIAL EFFECTS OF PHYTOCHEMICALS IN THE PREVENTION OF CHRONIC DISEASES, SEVERAL STUDIES HAVE BEEN CONDUCTED, AND THEY STRONGLY SUGGEST THAT THE INTAKE OF DIETARY POLYPHENOLS MAY BRING NUMEROUS BENEFITS DUE TO THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES, AND THEIR INTAKE HAS BEEN ASSOCIATED WITH IMPAIRED AGEING IN HUMANS. POLYPHENOL INTAKE HAS BEEN SHOWN TO BE EFFECTIVE IN AMELIORATING SEVERAL AGE-RELATED PHENOTYPES, INCLUDING OXIDATIVE STRESS, INFLAMMATORY PROCESSES, IMPAIRED PROTEOSTASIS, AND CELLULAR SENESCENCE, AMONG OTHER FEATURES, WHICH CONTRIBUTE TO AN INCREASED RISK OF AGEING-ASSOCIATED DISEASES. THIS REVIEW AIMS TO ADDRESS, IN A GENERAL WAY, THE MAIN FINDINGS DESCRIBED IN THE LITERATURE ABOUT THE BENEFITS OF POLYPHENOLS IN EACH OF THE HALLMARKS OF AGEING, AS WELL AS THE MAIN REGULATORY MECHANISMS RESPONSIBLE FOR THE OBSERVED ANTIAGEING EFFECTS. 2023 9 1395 45 DIET AND MICROBIOME IN THE BEGINNING OF THE SEQUENCE OF GUT INFLAMMATION. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC INFLAMMATORY CONDITION OF THE GASTROINTESTINAL TRACT DUE, AT LEAST PARTIALLY, TO AN ABERRANT AND EXCESSIVE MUCOSAL IMMUNE RESPONSE TO GUT BACTERIA IN GENETICALLY-PREDISPOSED INDIVIDUALS UNDER CERTAIN ENVIRONMENTAL FACTORS. THE INCIDENCE OF IBD IS RISING IN WESTERN AND NEWLY INDUSTRIALIZED COUNTRIES, PARALLELING THE INCREASE OF WESTERNIZED DIETARY PATTERNS, THROUGH NEW ANTIGENS, EPITHELIAL FUNCTION AND PERMEABILITY, EPIGENETIC MECHANISMS (E.G., DNA METHYLATION), AND ALTERATION OF THE GUT MICROBIOME. ALTERATION IN THE COMPOSITION AND FUNCTIONALITY OF THE GUT MICROBIOME (INCLUDING BACTERIA, VIRUSES AND FUNGI) SEEMS TO BE A NUCLEAR PATHOGENIC FACTOR. THE MICROBIOME ITSELF IS DYNAMIC, AND THE CHANGES IN FOOD QUALITY, DIETARY HABITS, LIVING CONDITIONS AND HYGIENE OF THESE WESTERN SOCIETIES, COULD INTERACT IN A COMPLEX MANNER AS MODULATORS OF DYSBIOSIS, THEREBY INFLUENCING THE ACTIVATION OF IMMUNE CELLS' PROMOTING INFLAMMATION. THE MICROBIOME PRODUCES DIVERSE SMALL MOLECULES VIA SEVERAL METABOLIC WAYS, WITH THE FIBER-DERIVED SHORT-CHAIN FATTY ACIDS (I.E., BUTYRATE) AS MAIN ELEMENTS AND HAVING ANTI-INFLAMMATORY EFFECTS. THESE METABOLITES AND SOME MICRONUTRIENTS OF THE DIET (I.E., VITAMINS, FOLIC ACID, BETA CAROTENE AND TRACE ELEMENTS) ARE REGULATORS OF INNATE AND ADAPTIVE INTESTINAL IMMUNE HOMEOSTASIS. AN EXCESSIVE AND UNHEALTHY CONSUMPTION OF SUGAR, ANIMAL FAT AND A LOW-VEGETABLE AND -FIBER DIET ARE RISK FACTORS FOR IBD APPEARANCE. FURTHERMORE, METABOLISM OF NUTRIENTS IN INTESTINAL EPITHELIUM AND IN GUT MICROBIOTA IS ALTERED BY INFLAMMATION, CHANGING THE DEMAND FOR NUTRIENTS NEEDED FOR HOMEOSTASIS. THIS ROLE OF FOOD AND A REDUCED GUT MICROBIAL DIVERSITY IN CAUSING IBD MIGHT ALSO HAVE A PROPHYLACTIC OR THERAPEUTIC ROLE FOR IBD. THE RELATIONSHIP BETWEEN DIETARY INTAKE, SYMPTOMS, AND BOWEL INFLAMMATION COULD LEAD TO DIETARY AND LIFESTYLE RECOMMENDATIONS, INCLUDING DIETS WITH ABUNDANT FRUITS, VEGETABLES, OLIVE OIL AND OILY FISH, WHICH HAVE ANTI-INFLAMMATORY EFFECTS AND COULD PREVENT DYSBIOSIS AND IBD. DIETARY MODULATION AND APPROPRIATE EXCLUSION DIETS MIGHT BE A NEW COMPLEMENTARY MANAGEMENT FOR TREATMENT AT DISEASE FLARES AND IN REFRACTORY PATIENTS, EVEN REDUCING COMPLICATIONS, HOSPITALIZATIONS AND SURGERY, THROUGH MODIFYING THE LUMINAL INTESTINAL ENVIRONMENT. 2021 10 2226 39 EPIGENETIC MODIFICATIONS INDUCED BY NUTRIENTS IN EARLY LIFE PHASES: GENDER DIFFERENCES IN METABOLIC ALTERATION IN ADULTHOOD. METABOLIC CHRONIC DISEASES, ALSO NAMED NONCOMMUNICABLE DISEASES (NCDS), ARE CONSIDERED MULTIFACTORIAL PATHOLOGIES, WHICH ARE DRAMATICALLY INCREASED DURING THE LAST DECADES. NONCOMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASES, OBESITY, DIABETES MELLITUS, CANCERS, AND CHRONIC RESPIRATORY DISEASES MARKEDLY INCREASE MORBIDITY, MORTALITY, AND SOCIOECONOMIC COSTS. MOREOVER, NCDS INDUCE SEVERAL AND COMPLEX CLINICAL MANIFESTATIONS THAT LEAD TO A GRADUAL DETERIORATION OF HEALTH STATUS AND QUALITY OF LIFE OF AFFECTED INDIVIDUALS. MULTIPLE FACTORS ARE INVOLVED IN THE DEVELOPMENT AND PROGRESSION OF THESE DISEASES SUCH AS SEDENTARY BEHAVIOR, SMOKING, POLLUTION, AND UNHEALTHY DIET. INDEED, NUTRITION HAS A PIVOTAL ROLE IN MAINTAINING HEALTH, AND DIETARY IMBALANCES REPRESENT MAJOR DETERMINANTS FAVORING CHRONIC DISEASES THROUGH METABOLIC HOMEOSTASIS ALTERATIONS. IN PARTICULAR, IT APPEARS THAT SPECIFIC NUTRIENTS AND ADEQUATE NUTRITION ARE IMPORTANT IN ALL PERIODS OF LIFE, BUT THEY ARE ESSENTIAL DURING SPECIFIC TIMES IN EARLY LIFE SUCH AS PRENATAL AND POSTNATAL PHASES. INDEED, EPIDEMIOLOGIC AND EXPERIMENTAL STUDIES REPORT THE DELETERIOUS EFFECTS OF AN INCORRECT NUTRITION ON HEALTH STATUS SEVERAL DECADES LATER IN LIFE. DURING THE LAST DECADE, A GROWING INTEREST ON THE POSSIBLE ROLE OF EPIGENETIC MECHANISMS AS LINK BETWEEN NUTRITIONAL IMBALANCES AND NCDS DEVELOPMENT HAS BEEN OBSERVED. FINALLY, BECAUSE OF THE PIVOTAL ROLE OF THE HORMONES IN FAT, CARBOHYDRATE, AND PROTEIN METABOLISM REGULATION THROUGHOUT LIFE, IT IS EXPECTED THAT ANY HORMONAL MODIFICATION OF THESE PROCESSES CAN IMBALANCE METABOLISM AND FAT STORAGE. THEREFORE, A PARTICULAR INTEREST TO SEVERAL CHEMICALS ABLE TO ACT AS ENDOCRINE DISRUPTORS HAS BEEN RECENTLY DEVELOPED. IN THIS REVIEW, WE WILL PROVIDE AN OVERVIEW AND DISCUSS THE EPIGENETIC ROLE OF SOME SPECIFIC NUTRIENTS AND CHEMICALS IN THE MODULATION OF PHYSIOLOGICAL AND PATHOLOGICAL MECHANISMS. 2019 11 2584 34 EPIGENETICS OF OBESITY. OBESITY IS A METABOLIC DISEASE, WHICH IS BECOMING AN EPIDEMIC HEALTH PROBLEM: IT HAS BEEN RECENTLY DEFINED IN TERMS OF GLOBAL PANDEMIC. OVER THE YEARS, THE APPROACHES THROUGH FAMILY, TWINS AND ADOPTION STUDIES LED TO THE IDENTIFICATION OF SOME CAUSAL GENES IN MONOGENIC FORMS OF OBESITY BUT THE ORIGINS OF THE PANDEMIC OF OBESITY CANNOT BE CONSIDERED ESSENTIALLY DUE TO GENETIC FACTORS, BECAUSE HUMAN GENOME IS NOT LIKELY TO CHANGE IN JUST A FEW YEARS. EPIGENETIC STUDIES HAVE OFFERED IN RECENT YEARS VALUABLE TOOLS FOR THE UNDERSTANDING OF THE WORLDWIDE SPREAD OF THE PANDEMIC OF OBESITY. THE INVOLVEMENT OF EPIGENETIC MODIFICATIONS-DNA METHYLATION, HISTONE TAILS, AND MIRNAS MODIFICATIONS-IN THE DEVELOPMENT OF OBESITY IS MORE AND MORE EVIDENT. IN THE EPIGENETIC LITERATURE, THERE ARE EVIDENCES THAT THE ENTIRE EMBRYO-FETAL AND PERINATAL PERIOD OF DEVELOPMENT PLAYS A KEY ROLE IN THE PROGRAMMING OF ALL HUMAN ORGANS AND TISSUES. THEREFORE, THE MOLECULAR MECHANISMS INVOLVED IN THE EPIGENETIC PROGRAMMING REQUIRE A NEW AND GENERAL PATHOGENIC PARADIGM, THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE THEORY, TO EXPLAIN THE CURRENT EPIDEMIOLOGICAL TRANSITION, THAT IS, THE WORLDWIDE INCREASE OF CHRONIC, DEGENERATIVE, AND INFLAMMATORY DISEASES SUCH AS OBESITY, DIABETES, CARDIOVASCULAR DISEASES, NEURODEGENERATIVE DISEASES, AND CANCER. OBESITY AND ITS RELATED COMPLICATIONS ARE MORE AND MORE ASSOCIATED WITH ENVIRONMENTAL POLLUTANTS (OBESOGENS), GUT MICROBIOTA MODIFICATIONS AND UNBALANCED FOOD INTAKE, WHICH CAN INDUCE, THROUGH EPIGENETIC MECHANISMS, WEIGHT GAIN, AND ALTERED METABOLIC CONSEQUENCES. 2016 12 1254 27 CURRENT PROGRESS ON THE MECHANISMS OF HYPERHOMOCYSTEINEMIA-INDUCED VASCULAR INJURY AND USE OF NATURAL POLYPHENOL COMPOUNDS. CARDIOVASCULAR DISEASE IS ONE OF THE MOST COMMON DISEASES IN THE ELDERLY POPULATION, AND ITS INCIDENCE HAS RAPIDLY INCREASED WITH THE PROLONGATION OF LIFE EXPECTANCY. HYPERHOMOCYSTEINEMIA IS AN INDEPENDENT RISK FACTOR FOR VARIOUS CARDIOVASCULAR DISEASES, INCLUDING ATHEROSCLEROSIS, AND DAMAGE TO VASCULAR FUNCTION PLAYS AN INITIAL ROLE IN ITS PATHOGENESIS. THIS REVIEW PRESENTS THE LATEST KNOWLEDGE ON THE MECHANISMS OF VASCULAR INJURY CAUSED BY HYPERHOMOCYSTEINEMIA, INCLUDING OXIDATIVE STRESS, ENDOPLASMIC RETICULUM STRESS, PROTEIN N-HOMOCYSTEINIZATION, AND EPIGENETIC MODIFICATION, AND DISCUSSES THE THERAPEUTIC TARGETS OF NATURAL POLYPHENOLS. STUDIES HAVE SHOWN THAT NATURAL POLYPHENOLS IN PLANTS CAN REDUCE HOMOCYSTEINE LEVELS AND REGULATE DNA METHYLATION BY ACTING ON OXIDATIVE STRESS AND ENDOPLASMIC RETICULUM STRESS-RELATED SIGNALING PATHWAYS, THUS IMPROVING HYPERHOMOCYSTEINEMIA-INDUCED VASCULAR INJURY. NATURAL POLYPHENOLS OBTAINED VIA DAILY DIET ARE SAFER AND HAVE MORE PRACTICAL SIGNIFICANCE IN THE PREVENTION AND TREATMENT OF CHRONIC DISEASES THAN TRADITIONAL DRUGS. 2021 13 44 33 A COMPREHENSIVE REVIEW ON HIGH -FAT DIET-INDUCED DIABETES MELLITUS: AN EPIGENETIC VIEW. MODERN LIFESTYLE, GENETICS, NUTRITIONAL OVERLOAD THROUGH HIGH-FAT DIET ATTRIBUTED PREVALENCE AND DIABETES OUTCOMES WITH VARIOUS COMPLICATIONS PRIMARILY DUE TO OBESITY IN WHICH ENERGY-DENSE DIETS FREQUENTLY AFFECT METABOLIC HEALTH. ONE POSSIBLE ISSUE USUALLY ASSOCIATED WITH ELEVATED CHRONIC FAT INTAKE IS INSULIN RESISTANCE, AND HYPERGLYCEMIA CONSTITUTES AN IMPORTANT FUNCTION IN ALTERING THE CARBOHYDRATES AND LIPIDS METABOLISM. SIMILARLY, IN ASSESSING HUMAN SUSCEPTIBILITY TO WEIGHT GAIN AND OBESITY, GENETIC VARIATIONS PLAY A CENTRAL ROLE, CONTRIBUTING TO KEEN INTEREST IN IDENTIFYING THE POSSIBLE ROLE OF EPIGENETICS AS A MEDIATOR OF GENE-ENVIRONMENTAL INTERACTIONS INFLUENCING THE PRODUCTION OF TYPE 2 DIABETES MELLITUS AND ITS RELATED CONCERNS. EPIGENETIC MODIFICATIONS ASSOCIATED WITH THE ACCEPTANCE OF A SEDENTARY LIFESTYLE AND ENVIRONMENTAL STRESS FACTORS IN RESPONSE TO ENERGY INTAKE AND EXPENDITURE IMBALANCES COMPLEMENT GENETIC ALTERATIONS AND LEAD TO THE PRODUCTION AND ADVANCEMENT OF METABOLIC DISORDERS SUCH AS DIABETES AND OBESITY. METHYLATION OF DNA, HISTONE MODIFICATIONS, AND INCREASES IN THE EXPRESSION OF NON-CODING RNAS CAN RESULT IN REDUCED TRANSCRIPTIONAL ACTIVITY OF KEY BETA-CELL GENES THUS CREATING INSULIN RESISTANCE. EPIGENETICS CONTRIBUTE TO CHANGES IN THE EXPRESSION OF THE UNDERLYING INSULIN RESISTANCE AND INSUFFICIENCY GENE NETWORKS, ALONG WITH LOW-GRADE OBESITY-RELATED INFLAMMATION, INCREASED ROS GENERATION, AND DNA DAMAGE IN MULTIORGANS. THIS REVIEW FOCUSED ON EPIGENETIC MECHANISMS AND METABOLIC REGULATIONS ASSOCIATED WITH HIGH-FAT DIET (HFD)-INDUCED DIABETES MELLITUS. 2022 14 183 33 ACCELERATED VASCULAR AGING IN CHRONIC KIDNEY DISEASE: THE POTENTIAL FOR NOVEL THERAPIES. THE PATHOPHYSIOLOGY OF VASCULAR DISEASE IS LINKED TO ACCELERATED BIOLOGICAL AGING AND A COMBINATION OF GENETIC, LIFESTYLE, BIOLOGICAL, AND ENVIRONMENTAL RISK FACTORS. WITHIN THE SCENARIO OF UNCONTROLLED ARTERY WALL AGING PROCESSES, CKD (CHRONIC KIDNEY DISEASE) STANDS OUT AS A VALID MODEL FOR DETAILED STRUCTURAL, FUNCTIONAL, AND MOLECULAR STUDIES OF THIS PROCESS. THE CARDIORENAL SYNDROME RELATES TO THE DETRIMENTAL BIDIRECTIONAL INTERPLAY BETWEEN THE KIDNEY AND THE CARDIOVASCULAR SYSTEM. IN ADDITION TO ESTABLISHED RISK FACTORS, THIS GROUP OF PATIENTS IS SUBJECTED TO A PLETHORA OF OTHER EMERGING VASCULAR RISK FACTORS, SUCH AS INFLAMMATION, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, VITAMIN K DEFICIENCY, CELLULAR SENESCENCE, SOMATIC MUTATIONS, EPIGENETIC MODIFICATIONS, AND INCREASED APOPTOSIS. A BETTER UNDERSTANDING OF THE MOLECULAR MECHANISMS THROUGH WHICH THE UREMIC MILIEU TRIGGERS AND MAINTAINS EARLY VASCULAR AGING PROCESSES, HAS PROVIDED IMPORTANT NEW CLUES ON INFLAMMATORY PATHWAYS AND EMERGING RISK FACTORS ALIKE, AND TO THE ALTERED BEHAVIOR OF CELLS IN THE ARTERIAL WALL. ADVANCES IN THE UNDERSTANDING OF THE BIOLOGY OF UREMIC EARLY VASCULAR AGING OPENS AVENUES TO NOVEL PHARMACOLOGICAL AND NUTRITIONAL THERAPEUTIC INTERVENTIONS. SUCH STRATEGIES HOLD PROMISE TO IMPROVE FUTURE PREVENTION AND TREATMENT OF EARLY VASCULAR AGING NOT ONLY IN CKD BUT ALSO IN THE ELDERLY GENERAL POPULATION. 2023 15 6034 36 THE CHALLENGE BY MULTIPLE ENVIRONMENTAL AND BIOLOGICAL FACTORS INDUCE INFLAMMATION IN AGING: THEIR ROLE IN THE PROMOTION OF CHRONIC DISEASE. THE AGING PROCESS IS DRIVEN BY MULTIPLE MECHANISMS THAT LEAD TO CHANGES IN ENERGY PRODUCTION, OXIDATIVE STRESS, HOMEOSTATIC DYSREGULATION AND EVENTUALLY TO LOSS OF FUNCTIONALITY AND INCREASED DISEASE SUSCEPTIBILITY. MOST AGED INDIVIDUALS DEVELOP CHRONIC LOW-GRADE INFLAMMATION, WHICH IS AN IMPORTANT RISK FACTOR FOR MORBIDITY, PHYSICAL AND COGNITIVE IMPAIRMENT, FRAILTY, AND DEATH. AT ANY AGE, CHRONIC INFLAMMATORY DISEASES ARE MAJOR CAUSES OF MORBIMORTALITY, AFFECTING UP TO 5-8% OF THE POPULATION OF INDUSTRIALIZED COUNTRIES. SEVERAL ENVIRONMENTAL FACTORS CAN PLAY AN IMPORTANT ROLE FOR MODIFYING THE INFLAMMATORY STATE. GENETICS ACCOUNTS FOR ONLY A SMALL FRACTION OF CHRONIC-INFLAMMATORY DISEASES, WHEREAS ENVIRONMENTAL FACTORS APPEAR TO PARTICIPATE, EITHER WITH A CAUSATIVE OR A PROMOTIONAL ROLE IN 50% TO 75% OF PATIENTS. SEVERAL OF THOSE CHANGES DEPEND ON EPIGENETIC CHANGES THAT WILL FURTHER MODIFY THE INDIVIDUAL RESPONSE TO ADDITIONAL STIMULI. THE INTERACTION BETWEEN INFLAMMATION AND THE ENVIRONMENT OFFERS IMPORTANT INSIGHTS ON AGING AND HEALTH. THESE CONDITIONS, OFTEN DEPENDING ON THE INDIVIDUAL'S SEX, APPEAR TO LEAD TO DECREASED LONGEVITY AND PHYSICAL AND COGNITIVE DECLINE. IN ADDITION TO BIOLOGICAL FACTORS, THE ENVIRONMENT IS ALSO INVOLVED IN THE GENERATION OF PSYCHOLOGICAL AND SOCIAL CONTEXT LEADING TO STRESS. POOR PSYCHOLOGICAL ENVIRONMENTS AND OTHER SOURCES OF STRESS ALSO RESULT IN INCREASED INFLAMMATION. HOWEVER, THE MECHANISMS UNDERLYING THE ROLE OF ENVIRONMENTAL AND PSYCHOSOCIAL FACTORS AND NUTRITION ON THE REGULATION OF INFLAMMATION, AND HOW THE RESPONSE ELICITED FOR THOSE FACTORS INTERACT AMONG THEM, ARE POORLY UNDERSTOOD. WHEREAS CERTAIN DELETERIOUS ENVIRONMENTAL FACTORS RESULT IN THE GENERATION OF OXIDATIVE STRESS DRIVEN BY AN INCREASED PRODUCTION OF REACTIVE OXYGEN AND NITROGEN SPECIES, ENDOPLASMIC RETICULUM STRESS, AND INFLAMMATION, OTHER FACTORS, INCLUDING NUTRITION (POLYUNSATURATED FATTY ACIDS) AND BEHAVIORAL FACTORS (EXERCISE) CONFER PROTECTION AGAINST INFLAMMATION, OXIDATIVE AND ENDOPLASMIC RETICULUM STRESS, AND THUS AMELIORATE THEIR DELETERIOUS EFFECT. HERE, WE DISCUSS PROCESSES AND MECHANISMS OF INFLAMMATION ASSOCIATED WITH ENVIRONMENTAL FACTORS AND BEHAVIOR, THEIR LINKS TO SEX AND GENDER, AND THEIR OVERALL IMPACT ON AGING. 2020 16 5558 26 ROLE OF GUT MICROBIOTA IN THE AETIOLOGY OF OBESITY: PROPOSED MECHANISMS AND REVIEW OF THE LITERATURE. THE AETIOLOGY OF OBESITY HAS BEEN ATTRIBUTED TO SEVERAL FACTORS (ENVIRONMENTAL, DIETARY, LIFESTYLE, HOST, AND GENETIC FACTORS); HOWEVER NONE OF THESE FULLY EXPLAIN THE INCREASE IN THE PREVALENCE OF OBESITY WORLDWIDE. GUT MICROBIOTA LOCATED AT THE INTERFACE OF HOST AND ENVIRONMENT IN THE GUT ARE A NEW AREA OF RESEARCH BEING EXPLORED TO EXPLAIN THE EXCESS ACCUMULATION OF ENERGY IN OBESE INDIVIDUALS AND MAY BE A POTENTIAL TARGET FOR THERAPEUTIC MANIPULATION TO REDUCE HOST ENERGY STORAGE. SEVERAL MECHANISMS HAVE BEEN SUGGESTED TO EXPLAIN THE ROLE OF GUT MICROBIOTA IN THE AETIOLOGY OF OBESITY SUCH AS SHORT CHAIN FATTY ACID PRODUCTION, STIMULATION OF HORMONES, CHRONIC LOW-GRADE INFLAMMATION, LIPOPROTEIN AND BILE ACID METABOLISM, AND INCREASED ENDOCANNABINOID RECEPTOR SYSTEM TONE. HOWEVER, EVIDENCE FROM ANIMAL AND HUMAN STUDIES CLEARLY INDICATES CONTROVERSIES IN DETERMINING THE CAUSE OR EFFECT RELATIONSHIP BETWEEN THE GUT MICROBIOTA AND OBESITY. METAGENOMICS BASED STUDIES INDICATE THAT FUNCTIONALITY RATHER THAN THE COMPOSITION OF GUT MICROBIOTA MAY BE IMPORTANT. FURTHER MECHANISTIC STUDIES CONTROLLING FOR ENVIRONMENTAL AND EPIGENETIC FACTORS ARE THEREFORE REQUIRED TO HELP UNRAVEL OBESITY PATHOGENESIS. 2016 17 2157 35 EPIGENETIC MECHANISMS ELICITED BY NUTRITION IN EARLY LIFE. A GROWING NUMBER OF STUDIES FOCUSING ON THE DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASE HYPOTHESIS HAVE IDENTIFIED LINKS AMONG EARLY NUTRITION, EPIGENETIC PROCESSES AND DISEASES ALSO IN LATER LIFE. DIFFERENT EPIGENETIC MECHANISMS ARE ELICITED BY DIETARY FACTORS IN EARLY CRITICAL DEVELOPMENTAL AGES THAT ARE ABLE TO AFFECT THE SUSCEPTIBILITY TO SEVERAL DISEASES IN ADULTHOOD. THE STUDIES HERE REVIEWED SUGGEST THAT MATERNAL AND NEONATAL DIET MAY HAVE LONG-LASTING EFFECTS IN THE DEVELOPMENT OF NON-COMMUNICABLE CHRONIC ADULTHOOD DISEASES, IN PARTICULAR THE COMPONENTS OF THE SO-CALLED METABOLIC SYNDROME, SUCH AS INSULIN RESISTANCE, TYPE 2 DIABETES, OBESITY, DYSLIPIDAEMIA, HYPERTENSION, AND CVD. BOTH MATERNAL UNDER- AND OVER-NUTRITION MAY REGULATE THE EXPRESSION OF GENES INVOLVED IN LIPID AND CARBOHYDRATE METABOLISM. EARLY POSTNATAL NUTRITION MAY ALSO REPRESENT A VITAL DETERMINANT OF ADULT HEALTH BY MAKING AN IMPACT ON THE DEVELOPMENT AND FUNCTION OF GUT MICROBIOTA. AN INADEQUATE GUT MICROBIOTA COMPOSITION AND FUNCTION IN EARLY LIFE SEEMS TO ACCOUNT FOR THE DEVIANT PROGRAMMING OF LATER IMMUNITY AND OVERALL HEALTH STATUS. IN THIS REGARD PROBIOTICS, WHICH HAVE THE POTENTIAL TO RESTORE THE INTESTINAL MICROBIOTA BALANCE, MAY BE EFFECTIVE IN PREVENTING THE DEVELOPMENT OF CHRONIC IMMUNE-MEDIATED DISEASES. MORE RECENTLY, THE EPIGENETIC MECHANISMS ELICITED BY PROBIOTICS THROUGH THE PRODUCTION OF SCFA ARE HYPOTHESISED TO BE THE KEY TO UNDERSTAND HOW THEY MEDIATE THEIR NUMEROUS HEALTH-PROMOTING EFFECTS FROM THE GUT TO THE PERIPHERAL TISSUES. 2011 18 1155 28 CONSIDERING MATERNAL DIETARY MODULATORS FOR EPIGENETIC REGULATION AND PROGRAMMING OF THE FETAL EPIGENOME. FETAL LIFE IS CHARACTERIZED BY A TREMENDOUS PLASTICITY AND ABILITY TO RESPOND TO VARIOUS ENVIRONMENTAL AND LIFESTYLE FACTORS, INCLUDING MATERNAL NUTRITION. IDENTIFICATION OF THE ROLE OF DIETARY FACTORS THAT CAN MODULATE AND RESHAPE THE CELLULAR EPIGENOME DURING DEVELOPMENT, INCLUDING METHYL GROUP DONORS (E.G., FOLATE, CHOLINE) AND BIOACTIVE COMPOUNDS (E.G., POLYPHENOLS) IS OF GREAT IMPORTANCE; HOWEVER, THERE IS INSUFFICIENT KNOWLEDGE OF A PARTICULAR EFFECT OF EACH TYPE OF MODULATOR AND/OR THEIR COMBINATION ON FETAL LIFE. TO ENHANCE THE QUALITY AND SAFETY OF FOOD PRODUCTS FOR PROPER FETAL HEALTH AND DISEASE PREVENTION IN LATER LIFE, A BETTER UNDERSTANDING OF THE UNDERLYING MECHANISMS OF DIETARY EPIGENETIC MODULATORS DURING THE CRITICAL PRENATAL PERIOD IS NECESSARY. THIS REVIEW FOCUSES ON THE INFLUENCE OF MATERNAL DIETARY COMPONENTS ON DNA METHYLATION, HISTONE MODIFICATION, AND MICRORNAS, AND SUMMARIZES CURRENT KNOWLEDGE OF THE EFFECT AND IMPORTANCE OF DIETARY COMPONENTS ON EPIGENETIC MECHANISMS THAT CONTROL THE PROPER EXPRESSION OF GENETIC INFORMATION. EVIDENCE REVEALS THAT SOME COMPONENTS IN THE MATERNAL DIET CAN DIRECTLY OR INDIRECTLY AFFECT EPIGENETIC MECHANISMS. UNDERSTANDING THE UNDERLYING MECHANISMS OF HOW EARLY-LIFE NUTRITIONAL ENVIRONMENT AFFECTS THE EPIGENOME DURING DEVELOPMENT IS OF GREAT IMPORTANCE FOR THE SUCCESSFUL PREVENTION OF ADULT CHRONIC DISEASES THROUGH OPTIMAL MATERNAL NUTRITION. 2015 19 3546 41 IMMUNOMODULATORY DIET IN PEDIATRIC AGE. IN THE LAST FEW DECADES, THE IMPORTANCE OF A FUNCTIONING IMMUNE SYSTEM AND HEALTH STATUS HAS BECOME MORE EVIDENT. MULTIPLE FACTORS ARE ABLE TO INFLUENCE THE DEVELOPMENT OF CHRONIC DISEASES AND DIET IS ONE OF THE MOST IMPORTANT ENVIRONMENTAL FACTORS. EVIDENCE DEMONSTRATES THAT DIETARY PATTERNS HIGH IN FAT AND LOW IN FIBER ARE ASSOCIATED WITH THE DEVELOPMENT OF NON-COMMUNICABLE DISEASES. MOREOVER, OPTIMAL NUTRITIONAL STATUS CAN MODULATE IMMUNE MATURATION AND RESPONSE TO INFLAMMATION. DURING INFLAMMATORY CONDITIONS, NUTRITIONAL DEFICIENCIES MAY OCCUR, ESTABLISHING A VICIOUS CIRCLE, CONSEQUENTLY A BALANCED NUTRITIONAL STATUS IS ESSENTIAL TO PREVENT AND COUNTERACT INFECTIONS. DIETARY DIVERSITY CAN PREVENT ALLERGIC DISEASES AND NUTRIENTS SUCH AS DHA, ARGININE, VITAMINS AND TRACE ELEMENTS HAVE AN IMPACT ON PHYSICAL BARRIERS (SUCH AS GUT MUCOSAL BARRIER AND SKIN), ON THE IMMUNE SYSTEM RESPONSE AND ON MICROBIOME MODULATION. PROTEIN DEFICIENCIES CAN COMPROMISE INNATE AND ADAPTIVE IMMUNE FUNCTIONS; ARGININE AVAILABILITY CAN AFFECT THE IMMUNE RESPONSE IN INJURED STATES AND OTHER DISEASE PROCESSES; EPA AND DHA CAN MODULATE BOTH INNATE AND ADAPTIVE IMMUNITY; PREBIOTICS HAVE A BENEFICIAL EFFECT ON THE FUNCTIONING OF THE IMMUNE SYSTEM. ZINC, COPPER, SELENIUM AND IRON ARE INVOLVED IN THE CORRECT DEVELOPMENT AND FUNCTION OF THE IMMUNE SYSTEM. VITAMINS D, E, A, B AND C HAVE A ROLE ON IMMUNE SYSTEM THROUGH DIFFERENT MECHANISMS OF ACTION. SINCE A COMPLEX INTERPLAY EXISTS BETWEEN DIET, MICROBIOME AND EPIGENETIC FACTORS WHICH DETERMINE NUTRIENT-INDUCED CHANGES ON THE IMMUNE FUNCTION, THE EFFECT OF EACH SINGLE NUTRIENT MAY BE DIFFICULT TO STUDY. WELL-DESIGNED INTERVENTION STUDIES, INVESTIGATING THE EFFECTS OF WHOLE DIETARY PATTERN, SHOULD BE PERFORMED TO CLARIFY IMPACT OF FOODS ON THE IMMUNE FUNCTION AND DISEASE RISK. 2021 20 3547 43 IMMUNOMODULATORY ROLE OF NUTRIENTS: HOW CAN PULMONARY DYSFUNCTIONS IMPROVE? NUTRITION IS AN IMPORTANT TOOL THAT CAN BE USED TO MODULATE THE IMMUNE RESPONSE DURING INFECTIOUS DISEASES. IN ADDITION, THROUGH DIET, IMPORTANT SUBSTRATES ARE ACQUIRED FOR THE BIOSYNTHESIS OF REGULATORY MOLECULES IN THE IMMUNE RESPONSE, INFLUENCING THE PROGRESSION AND TREATMENT OF CHRONIC LUNG DISEASES, SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). IN THIS WAY, NUTRITION CAN PROMOTE LUNG HEALTH STATUS. A RANGE OF NUTRIENTS, SUCH AS VITAMINS (A, C, D, AND E), MINERALS (ZINC, SELENIUM, IRON, AND MAGNESIUM), FLAVONOIDS AND FATTY ACIDS, PLAY IMPORTANT ROLES IN REDUCING THE RISK OF PULMONARY CHRONIC DISEASES AND VIRAL INFECTIONS. THROUGH THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS, NUTRIENTS ARE ASSOCIATED WITH BETTER LUNG FUNCTION AND A LOWER RISK OF COMPLICATIONS SINCE THEY CAN DECREASE THE HARMFUL EFFECTS FROM THE IMMUNE SYSTEM DURING THE INFLAMMATORY RESPONSE. IN ADDITION, BIOACTIVE COMPOUNDS CAN EVEN CONTRIBUTE TO EPIGENETIC CHANGES, INCLUDING HISTONE DEACETYLASE (HDAC) MODIFICATIONS THAT INHIBIT THE TRANSCRIPTION OF PROINFLAMMATORY CYTOKINES, WHICH CAN CONTRIBUTE TO THE MAINTENANCE OF HOMEOSTASIS IN THE CONTEXT OF INFECTIONS AND CHRONIC INFLAMMATORY DISEASES. THESE NUTRIENTS ALSO PLAY AN IMPORTANT ROLE IN ACTIVATING IMMUNE RESPONSES AGAINST PATHOGENS, WHICH CAN HELP THE IMMUNE SYSTEM DURING INFECTIONS. HERE, WE PROVIDE AN UPDATED OVERVIEW OF THE ROLES PLAYED BY DIETARY FACTORS AND HOW THEY CAN AFFECT RESPIRATORY HEALTH. THEREFORE, WE WILL SHOW THE ANTI-INFLAMMATORY ROLE OF FLAVONOIDS, FATTY ACIDS, VITAMINS AND MICROBIOTA, IMPORTANT FOR THE CONTROL OF CHRONIC INFLAMMATORY DISEASES AND ALLERGIES, IN ADDITION TO THE ANTIVIRAL ROLE OF VITAMINS, FLAVONOIDS, AND MINERALS DURING PULMONARY VIRAL INFECTIONS, ADDRESSING THE MECHANISMS INVOLVED IN EACH FUNCTION. THESE MECHANISMS ARE INTERESTING IN THE DISCUSSION OF PERSPECTIVES ASSOCIATED WITH SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION AND ITS PULMONARY COMPLICATIONS SINCE PATIENTS WITH SEVERE DISEASE HAVE VITAMINS DEFICIENCY, ESPECIALLY VITAMIN D. IN ADDITION, RESEARCHES WITH THE USE OF FLAVONOIDS HAVE BEEN SHOWN TO DECREASE VIRAL REPLICATION IN VITRO. THIS WAY, A FULL UNDERSTANDING OF DIETARY INFLUENCES CAN IMPROVE THE LUNG HEALTH OF PATIENTS. 2021