1 1366 100 DEVELOPMENTAL ORIGINS OF CHRONIC KIDNEY DISEASE: SHOULD WE FOCUS ON EARLY LIFE? CHRONIC KIDNEY DISEASE (CKD) IS BECOMING A GLOBAL BURDEN, DESPITE RECENT ADVANCES IN MANAGEMENT. CKD CAN BEGIN IN EARLY LIFE BY SO-CALLED "DEVELOPMENTAL PROGRAMMING" OR "DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE" (DOHAD). EARLY-LIFE INSULTS CAUSE STRUCTURAL AND FUNCTIONAL CHANGES IN THE DEVELOPING KIDNEY, WHICH IS CALLED RENAL PROGRAMMING. EPIDEMIOLOGICAL AND EXPERIMENTAL EVIDENCE SUPPORTS THE PROPOSITION THAT EARLY-LIFE ADVERSE EVENTS LEAD TO RENAL PROGRAMMING AND MAKE SUBJECTS VULNERABLE TO DEVELOPING CKD AND ITS COMORBIDITIES IN LATER LIFE. IN ADDITION TO LOW NEPHRON ENDOWMENT, SEVERAL MECHANISMS HAVE BEEN PROPOSED FOR RENAL PROGRAMMING. THE DOHAD CONCEPT OPENS A NEW WINDOW TO OFFSET THE PROGRAMMING PROCESS IN EARLY LIFE TO PREVENT THE DEVELOPMENT OF ADULT KIDNEY DISEASE, NAMELY REPROGRAMMING. HERE, WE REVIEW THE KEY THEMES ON THE DEVELOPMENTAL ORIGINS OF CKD. WE HAVE PARTICULARLY FOCUSED ON THE FOLLOWING AREAS: EVIDENCE FROM HUMAN STUDIES SUPPORT FETAL PROGRAMMING OF KIDNEY DISEASE; INSIGHT FROM ANIMAL MODELS OF RENAL PROGRAMMING; HYPOTHETICAL MECHANISMS OF RENAL PROGRAMMING; ALTERATIONS OF RENAL TRANSCRIPTOME IN RESPONSE TO EARLY-LIFE INSULTS; AND THE APPLICATION OF REPROGRAMMING INTERVENTIONS TO PREVENT THE PROGRAMMING OF KIDNEY DISEASE. 2017 2 6814 36 [EVIDENCE AND MECHANISMS OF FETAL ORIGINS OF ADULT DISEASES]. THIS REVIEW FOCUSES ON THE FETAL ORIGINS OF ADULT DISEASE HYPOTHESIS PUT FORWARD BY DAVID BARKER AND HIS COLLEAGUES, RECENT ADVANCES IN EPIDEMIOLOGICAL STUDIES AND EXPERIMENTAL RESEARCH IN THIS FIELD. BARKER HYPOTHESIS STATES THAT ENVIRONMENTAL FACTORS, PARTICULARLY INTRAUTERINE NUTRITION, AS INDICATED BY BIRTH WEIGHT, OPERATE IN EARLY LIFE TO PROGRAM THE RISKS FOR ADVERSE HEALTH OUTCOMES IN ADULT LIFE. A LARGE GROWING BODY OF REPORTS DESCRIBED THE ASSOCIATION BETWEEN THE EARLY DEVELOPMENT AND ADULT DISEASES, SUCH AS DIABETES, HYPERTENSION, CORONARY HEART DISEASE, ABNORMAL LIPIDS METABOLISM, OBESITY AND CANCER, ETC. EXPERIMENTAL STUDIES SHOW THAT THE CHANGES OF SOME KEY GENES' EXPRESSION, CAUSED BY EPIGENETIC MODIFICATIONS, LEAD TO A PERMANENT ALTERATION OF CELLULAR PROLIFERATION AND DIFFERENTIATION AND FINALLY THE GENESIS IN KEY TISSUES AND ORGANS. THESE RESULTS BRING ABOUT THE IMPAIRMENT IN STRUCTURES AND FUNCTIONS AND THE INCREASED SUSCEPTIBILITY TO CHRONIC DISEASES IN ADULT LIFE. THE HYPOTHESIS PROVIDES A NEW PERSPECTIVE FOR THE PREVENTION AND THERAPY OF CHRONIC DISEASES. 2007 3 5457 26 RESEARCH AND THE PROMOTION OF CHILD HEALTH: A POSITION PAPER OF THE EUROPEAN SOCIETY FOR PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION. CHILDREN COMPRISE ONE-FIFTH OF EUROPE'S POPULATION. PROMOTING CHILD HEALTH AND DEVELOPMENT IS OF KEY IMPORTANCE FOR SOCIETY AND ITS FUTURE. THIS POSITION PAPER HIGHLIGHTS OPPORTUNITIES OF INVESTING IN GASTROINTESTINAL, LIVER, AND NUTRITIONAL RESEARCH TO PROMOTE CHILD HEALTH AND DELINEATES PRIORITIES FOR RESEARCH. INVESTING IN CHILD HEALTH PLAYS A KEY ROLE IN THE PROMOTION OF POPULATION HEALTH, WELL-BEING, AND DISEASE PREVENTION LIFELONG, WITH LARGE HEALTH ECONOMIC BENEFITS. MAJOR OPPORTUNITIES FOR IMPROVING KNOWLEDGE AND TRANSLATIONAL APPLICATION ARISE FROM RECENT SCIENTIFIC AND TECHNOLOGICAL DEVELOPMENTS, FOR EXAMPLE, THE LONG-TERM IMPACT OF EARLY ENVIRONMENTAL CUES INTERACTING WITH GENES. PERSONALISED APPROACHES TO THERAPY AND PREVENTION SHOULD BE ENHANCED. DECIPHERING THE MICROBIOME AND ITS EFFECTS ON FUNCTIONS CAN HELP IN PROMOTING LONG-TERM HEALTH. EPIGENETIC RESEARCH CAN HELP TO UNDERSTAND HOW EARLY ENVIRONMENTAL FACTORS INFLUENCE LATER GASTROINTESTINAL AND HEPATIC HEALTH AND DISEASE. A LINKED NUTRITION AND PHYSICAL ACTIVITY STRATEGY CAN PROMOTE HEALTH AND PREVENT NUTRITIONAL DEFICIENCIES, INACTIVITY, AND CHRONIC NONCOMMUNICABLE DISEASES, SUCH AS DIABETES, TO ENSURE OPTIMAL HEALTH AND COGNITION. SPECIAL ATTENTION SHOULD BE DEVOTED TO POPULATIONS WITH LOW SOCIOECONOMIC STATUS, MIGRANT BACKGROUND, AND ETHNIC MINORITIES, AND TO CRITICAL LIFE PERIODS, INCLUDING PREGNANCY, LACTATION, INFANCY, AND CHILDHOOD. IMPROVED UNDERSTANDING OF OPTIMAL NUTRITION AND ON MAINTAINING GUT AND LIVER HOMEOSTASIS THROUGHOUT CHILDHOOD WILL HELP PREVENT CHRONIC DISEASES IN LATER LIFE. 2014 4 4280 31 MICRONUTRIENTS IN EARLY LIFE AND OFFSPRING METABOLIC HEALTH PROGRAMMING: A PROMISING TARGET FOR PREVENTING NON-COMMUNICABLE DISEASES. CHRONIC NON-COMMUNICABLE DISEASES ARE THE LEADING CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE. DEVELOPING AND IMPLEMENTING EFFECTIVE PREVENTIVE STRATEGIES IS THE BEST WAY TO ENSURE THE OVERALL METABOLIC HEALTH STATUS OF THE POPULATION AND TO COUNTER THE GLOBAL BURDEN OF NON-COMMUNICABLE DISEASES. PREDISPOSITION TO OBESITY AND OTHER NON-COMMUNICABLE DISEASES IS DUE TO A COMBINATION OF GENETIC AND ENVIRONMENTAL FACTORS THROUGHOUT LIFE, BUT THE EARLY ENVIRONMENT, PARTICULARLY THE ENVIRONMENT DURING THE FETAL PERIOD AND THE EARLY YEARS OF LIFE, IS CRUCIAL IN DETERMINING METABOLIC HEALTH, HENCE THE CONCEPT OF 'FETAL PROGRAMMING'. THE ORIGINS OF THIS CAUSAL LINK BETWEEN ENVIRONMENTAL FACTORS AND DISEASE LIE IN EPIGENETIC MECHANISMS. AMONG THE ENVIRONMENTAL FACTORS, DIET PLAYS A CRUCIAL ROLE IN THIS PROCESS. SUBSTANTIAL EVIDENCE DOCUMENTED THE KEY ROLE OF MACRONUTRIENTS IN THE PROGRAMMING OF METABOLIC DISEASES EARLY IN LIFE. RECENTLY, THE EFFECT OF MATERNAL MICRONUTRIENT INTAKE ON OFFSPRING METABOLIC HEALTH IN LATER LIFE EMERGED. THE PURPOSE OF THIS NARRATIVE REVIEW IS TO BRING TO LIGHT AVAILABLE EVIDENCE IN THE LITERATURE ON THE EFFECT OF MATERNAL MICRONUTRIENT STATUS ON OFFSPRING METABOLIC HEALTH AND UNDERLYING EPIGENETIC MECHANISMS THAT DRIVE THIS LINK TO HIGHLIGHT ITS POTENTIAL ROLE IN THE PREVENTION OF NON-COMMUNICABLE DISEASES. 2023 5 4084 27 MATERNAL NUTRITION DURING PREGNANCY AND HEALTH OF THE OFFSPRING. THE ABILITY OF MOTHER TO PROVIDE NUTRIENTS AND OXYGEN FOR HER BABY IS A CRITICAL FACTOR FOR FETAL HEALTH AND ITS SURVIVAL. FAILURE IN SUPPLYING THE ADEQUATE AMOUNT OF NUTRIENTS TO MEET FETAL DEMAND CAN LEAD TO FETAL MALNUTRITION. THE FETUS RESPONDS AND ADAPTS TO UNDERNUTRITION BUT BY DOING SO IT PERMANENTLY ALTERS THE STRUCTURE AND FUNCTION OF THE BODY. MATERNAL OVERNUTRITION ALSO HAS LONG-LASTING AND DETRIMENTAL EFFECTS ON THE HEALTH OF THE OFFSPRING. THERE IS GROWING EVIDENCE THAT MATERNAL NUTRITION CAN INDUCE EPIGENETIC MODIFICATIONS OF THE FETAL GENOME. ONLY RELATIVELY RECENTLY HAS EVIDENCE FROM EPIDEMIOLOGICAL AND ANIMAL STUDIES EMERGED SUGGESTING THAT FETAL RESPONSES TO THE INTRAUTERINE ENVIRONMENT MAY UNDERLIE THE PREVALENCE OF MANY CHRONIC DISEASES OF ADULTHOOD INCLUDING TYPE 2 (NON-INSULIN-DEPENDENT) DIABETES. IT IS NOW OF CRUCIAL IMPORTANCE TO GAIN THE UNDERSTANDING OF THE MOLECULAR MECHANISMS UNDERLYING THE RELATIONSHIP BETWEEN FETAL ALTERATIONS TO THE INTRA-UTERINE ENVIRONMENT AND THEIR LONG-TERM EFFECTS ON THE HEALTH OF AN INDIVIDUAL. 2006 6 1992 31 EPIGENETIC AND DEVELOPMENTAL INFLUENCES ON THE RISK OF OBESITY, DIABETES, AND METABOLIC SYNDROME. METABOLIC SYNDROME IS A GROWING CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE. METABOLIC SYNDROME IS CHARACTERIZED BY THE PRESENCE OF A VARIETY OF METABOLIC DISTURBANCES INCLUDING OBESITY, HYPERLIPIDEMIA, HYPERTENSION, AND ELEVATED FASTING BLOOD SUGAR. ALTHOUGH THE RISK FOR METABOLIC SYNDROME HAS LARGELY BEEN ATTRIBUTED TO ADULT LIFESTYLE FACTORS SUCH AS POOR NUTRITION, LACK OF EXERCISE, AND SMOKING, THERE IS NOW STRONG EVIDENCE SUGGESTING THAT PREDISPOSITION TO THE DEVELOPMENT OF METABOLIC SYNDROME BEGINS IN UTERO. FIRST POSITED BY HALES AND BARKER IN 1992, THE "THRIFTY PHENOTYPE" HYPOTHESIS PROPOSES THAT SUSCEPTIBILITY TO ADULT CHRONIC DISEASES CAN OCCUR IN RESPONSE TO EXPOSURES IN THE PRENATAL AND PERINATAL PERIODS. THIS HYPOTHESIS HAS BEEN CONTINUALLY SUPPORTED BY EPIDEMIOLOGIC STUDIES AND STUDIES INVOLVING ANIMAL MODELS. IN THIS REVIEW, WE DESCRIBE THE STRUCTURAL, METABOLIC AND EPIGENETIC CHANGES THAT OCCUR IN RESPONSE TO ADVERSE INTRAUTERINE ENVIRONMENTS INCLUDING PRENATAL AND POSTNATAL DIET, MATERNAL OBESITY, AND PREGNANCY COMPLICATIONS. GIVEN THE INCREASING PREVALENCE OF METABOLIC SYNDROME IN BOTH THE DEVELOPED AND DEVELOPING WORLDS, A GREATER UNDERSTANDING AND APPRECIATION FOR THE ROLE OF THE INTRAUTERINE ENVIRONMENT IN ADULT CHRONIC DISEASE ETIOLOGY IS IMPERATIVE. 2015 7 617 35 BIOACTIVE FOOD COMPOUNDS, EPIGENETICS AND CHRONIC DISEASE PREVENTION: FOCUS ON EARLY-LIFE INTERVENTIONS WITH POLYPHENOLS. CONSUMPTION OF BIOACTIVE COMPOUNDS SUCH AS POLYPHENOLS, ISOTHIOCYANATES, SULFUR-CONTAINING COMPOUNDS AND TERPENOIDS, FOUND IN FRUITS AND VEGETABLES, IS ASSOCIATED WITH PREVENTION OF CHRONIC DISEASE. THESE BIOACTIVE FOOD COMPOUNDS ELICIT THEIR PROTECTIVE EFFECTS THROUGH COMPLEX MECHANISMS AT THE CELLULAR AND MOLECULAR, INCLUDING EPIGENETIC LEVELS. ACCORDING TO THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) PARADIGM, IN UTERO EXPOSURE TO STRESSORS SUCH AS MALNUTRITION THROUGH MATERNAL DIET WOULD IMPAIR FETAL DEVELOPMENT AND EPIGENETICALLY PROGRAM INCREASED RISK OF METABOLIC DISEASES AND SOME CANCERS IN ADULT LIFE. IN ADDITION, A ROLE FOR FATHERS DIET DURING PRECONCEPTION ON THEIR OFFSPRING HEALTH AND CHRONIC DISEASE SUSCEPTIBILITY HAS ALSO EMERGED. THIS HIGHLIGHTS EARLY LIFE AS A PROMISING WINDOW OF OPPORTUNITY FOR STARTING DIETARY INTERVENTIONS FOCUSING ON PREVENTING CHRONIC DISEASES. HOWEVER, KNOWLEDGE ON THE POTENTIAL BENEFICIAL IMPACT OF EARLY LIFE EXPOSURE TO BIOACTIVE FOOD COMPOUNDS IS LIMITED. AMONG THE STUDIES THAT HAVE INVESTIGATED BIOACTIVE FOOD COMPOUNDS IN THE CONTEXT OF DOHAD, MOST HAVE FOCUSED ON THE IMPACT OF DIETARY POLYPHENOLS. THUS, IN THIS REVIEW WE DISCUSS EXPERIMENTAL EVIDENCE SUPPORTING A ROLE FOR THE DIETARY POLYPHENOLS RESVERATROL, GENISTEIN, EPIGALLOCATECHIN-3-GALLATE AND ANTHOCYANINS IN CHRONIC DISEASE PREVENTION CONSIDERING A PERSPECTIVE FROM EARLY-LIFE INTERVENTIONS THROUGH MATERNAL AND PATERNAL DIETS AND FOCUSING ON EPIGENETICS AS A POTENTIAL UNDERLYING MECHANISM. 2019 8 1374 53 DEVELOPMENTAL PROGRAMMING OF ADULT DISEASE: REPROGRAMMING BY MELATONIN? ADULT-ONSET CHRONIC NON-COMMUNICABLE DISEASES (NCDS) CAN ORIGINATE FROM EARLY LIFE THROUGH SO-CALLED THE "DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE" (DOHAD) OR "DEVELOPMENTAL PROGRAMMING". THE DOHAD CONCEPT OFFERS THE "REPROGRAMMING" STRATEGY TO SHIFT THE TREATMENT FROM ADULTHOOD TO EARLY LIFE, BEFORE CLINICAL DISEASE IS APPARENT. MELATONIN, AN ENDOGENOUS INDOLEAMINE PRODUCED BY THE PINEAL GLAND, HAS PLEIOTROPIC BIOACTIVITIES THOSE ARE BENEFICIAL IN A VARIETY OF HUMAN DISEASES. EMERGING EVIDENCE SUPPORT THAT MELATONIN IS CLOSELY INTER-RELATED TO OTHER PROPOSED MECHANISMS CONTRIBUTING TO THE DEVELOPMENTAL PROGRAMMING OF A VARIETY OF CHRONIC NCDS. RECENT ANIMAL STUDIES HAVE BEGUN TO UNRAVEL THE MULTIFUNCTIONAL ROLES OF MELATONIN IN MANY EXPERIMENTAL MODELS OF DEVELOPMENTAL PROGRAMMING. EVEN THOUGH SOME PROGRESS HAS BEEN MADE IN RESEARCH ON MELATONIN AS A REPROGRAMMING STRATEGY TO PREVENT DOHAD-RELATED NCDS, FUTURE HUMAN STUDIES SHOULD AIM AT FILLING THE TRANSLATIONAL GAP BETWEEN ANIMAL MODELS AND CLINICAL TRIALS. HERE, WE REVIEW SEVERAL KEY THEMES ON THE REPROGRAMMING EFFECTS OF MELATONIN IN DOHAD RESEARCH. WE HAVE PARTICULARLY FOCUSED ON THE FOLLOWING AREAS: MECHANISMS OF DEVELOPMENTAL PROGRAMMING; THE INTERRELATIONSHIP BETWEEN MELATONIN AND MECHANISMS UNDERLYING DEVELOPMENTAL PROGRAMMING; PATHOPHYSIOLOGICAL ROLES OF MELATONIN IN PREGNANCY AND FETAL DEVELOPMENT; AND INSIGHT PROVIDED BY ANIMAL MODELS TO SUPPORT MELATONIN AS A REPROGRAMMING THERAPY. RATES OF NCDS ARE INCREASING FASTER THAN ANTICIPATED ALL OVER THE WORLD. HENCE, THERE IS AN URGENT NEED TO UNDERSTAND REPROGRAMMING MECHANISMS OF MELATONIN AND TO TRANSLATE EXPERIMENTAL RESEARCH INTO CLINICAL PRACTICE FOR HALTING A GROWING LIST OF DOHAD-RELATED NCDS. 2017 9 2226 29 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 10 6803 22 [EPIGENETIC MECHANISMS IN PHYSIOLOGIC AND PATHOLOGIC PREGNANCIES]. EPIGENETIC FACTORS ARE NOWADAYS IN THE FOCUS OF SCIENTIFIC INTEREST IN MEDICINE INCLUDING OBSTETRICS. THE ENVIRONMENT IN UTERO AND EARLY NEONATAL LIFE MAY INDUCE A PERMANENT RESPONSE IN THE FETUS AND THE NEWBORN LEADING TO ENHANCED SUSCEPTIBILITY TO LATER DISEASES. THERE IS NOW GROWING EVIDENCE THAT THE EFFECTS OF DEVELOPMENTAL PROGRAMMING MAY ALSO MANIFEST THEMSELVES IN THE NEXT GENERATIONS WITHOUT FURTHER SUBOPTIMAL EXPOSURE. THE SO-CALLED FETAL PROGRAMMING MAY ALSO HIGHLIGHT A TIGHT CONNECTION BETWEEN PATHOLOGICAL CONDITIONS IN PREGNANCY, ENVIRONMENTAL FACTORS AND THE DEVELOPMENT OF CHRONIC DISEASES IN ADULTHOOD. INVESTIGATION OF EPIGENETIC FACTORS MAY YIELD NEW POSSIBILITIES FOR THE PREVENTION OF CHRONIC DISEASES AFFECTING A SIGNIFICANT PART OF THE POPULATION. 2014 11 2496 25 EPIGENETICS AND EARLY LIFE ORIGINS OF CHRONIC NONCOMMUNICABLE DISEASES. IN LIGHT OF THE INCREASING THREATS OF CHRONIC NONCOMMUNICABLE DISEASES IN DEVELOPING COUNTRIES, THE GROWING RECOGNITION OF THE EARLY LIFE ORIGINS OF CHRONIC DISEASE, AND INNOVATIVE BREAKTHROUGHS IN BIOMEDICAL RESEARCH AND TECHNOLOGY, IT IS IMPERATIVE THAT WE HARNESS CUTTING-EDGE DATA TO IMPROVE HEALTH PROMOTION AND MAINTENANCE. IT IS WELL RECOGNIZED THAT CHRONIC DISEASES ARE COMPLEX TRAITS AFFECTED BY A WIDE RANGE OF ENVIRONMENTAL AND GENETIC FACTORS; HOWEVER, THE ROLE OF EPIGENETIC FACTORS, PARTICULARLY WITH REGARD TO EARLY LIFE ORIGINS, REMAINS LARGELY UNEXPLORED. GIVEN THE UNIQUE PROPERTIES OF THE EPIGENOME-FUNCTIONALITY DURING CRITICAL TIME WINDOWS, SUCH AS THE INTRAUTERINE PERIOD, HERITABILITY, AND REVERSIBILITY-ENHANCING OUR UNDERSTANDING OF EPIGENETIC MECHANISMS MAY OFFER NEW OPPORTUNITIES FOR THE DEVELOPMENT OF NOVEL EARLY PREDICTION AND PREVENTION PARADIGMS. THIS MAY PRESENT AN UNPARALLELED OPPORTUNITY TO OFFER MATERNAL AND CHILD HEALTH PROFESSIONALS IMPORTANT TOOLS WITH THE TRANSLATIONAL VALUE TO PREDICT, DETECT, AND PREVENT DISEASE AT AN EARLY AGE, LONG BEFORE ITS CLINICAL OCCURRENCE, AND AS SUCH, BREAK LIFELONG AND TRANSGENERATIONAL CYCLES OF DISEASE. IN DOING SO, MODERN TECHNOLOGY CAN BE LEVERAGED TO MAKE GREAT CONTRIBUTIONS TO POPULATION HEALTH, QUALITY OF LIFE, AND REDUCING THE BURDENSOME ECONOMIC COSTS OF NONCOMMUNICABLE DISEASES IN DEVELOPING COUNTRIES. 2013 12 6557 22 TRANSGENERATIONAL EPIGENETIC INHERITANCE OF DIABETES RISK AS A CONSEQUENCE OF EARLY NUTRITIONAL IMBALANCES. IN TODAY'S WORLD, THERE IS AN UNPRECEDENTED RISE IN THE PREVALENCE OF CHRONIC METABOLIC DISEASES, INCLUDING OBESITY, INSULIN RESISTANCE AND TYPE 2 DIABETES (T2D). THE PATHOGENESIS OF T2D INCLUDES BOTH GENETIC AND ENVIRONMENTAL FACTORS, SUCH AS EXCESSIVE ENERGY INTAKE AND PHYSICAL INACTIVITY. IT HAS RECENTLY BEEN SUGGESTED THAT ENVIRONMENTAL FACTORS EXPERIENCED DURING EARLY STAGES OF DEVELOPMENT, INCLUDING THE INTRAUTERINE AND NEONATAL PERIODS, MIGHT PLAY A MAJOR ROLE IN PREDISPOSING INDIVIDUALS TO T2D. FURTHERMORE, SEVERAL STUDIES HAVE SHOWN THAT SUCH EARLY ENVIRONMENTAL CONDITIONS MIGHT EVEN CONTRIBUTE TO DISEASE RISK IN FURTHER GENERATIONS. IN THIS REVIEW, WE SUMMARISE RECENT DATA DESCRIBING HOW PARENTAL NUTRITION DURING DEVELOPMENT INCREASES THE RISK OF DIABETES IN THE OFFSPRING. WE ALSO DISCUSS THE POTENTIAL MECHANISMS UNDERLYING TRANSGENERATIONAL INHERITANCE OF METABOLIC DISEASE, WITH PARTICULAR EMPHASIS ON EPIGENETIC MECHANISMS. 2016 13 1365 38 DEVELOPMENTAL ORIGIN OF CHRONIC DISEASES: TOXICOLOGICAL IMPLICATION. HUMAN EPIDEMIOLOGICAL AND EXPERIMENTAL ANIMAL STUDIES SHOW THAT SUBOPTIMAL ENVIRONMENTS IN FETAL AND NEONATAL LIFE EXERTS A PROFOUND INFLUENCE ON PHYSIOLOGICAL FUNCTION AND RISK OF DISEASE IN ADULT LIFE. THE MOLECULAR, CELLULAR, METABOLIC, ENDOCRINE AND PHYSIOLOGICAL ADAPTATIONS TO INTRAUTERINE NUTRITIONAL CONDITIONS RESULT IN PERMANENT ALTERATIONS OF CELLULAR PROLIFERATION AND DIFFERENTIATION OF TISSUES AND ORGAN SYSTEMS, WHICH IN TURN CAN MANIFEST BY PATHOLOGICAL CONSEQUENCES OR INCREASED VULNERABILITY TO CHRONIC DISEASES IN ADULTHOOD. INTRAUTERINE GROWTH RESTRICTION (IUGR) DUE TO INTRAUTERINE DEVELOPMENT DERANGEMENTS IS CONSIDERED THE IMPORTANT FACTOR IN DEVELOPMENT OF SUCH DISEASES AS ESSENTIAL HYPERTENSION, DIABETES MELLITUS, ISCHEMIC DISEASES OF THE HEART, OSTEOPOROSIS, RESPIRATORY, NEUROPSYCHIATRIC AND IMMUNE SYSTEM DISEASES.AN EARLY LIFE EXPOSURES TO DIETARY AND ENVIRONMENTAL EXPOSURES CAN HAVE A IMPORTANT EFFECT ON EPIGENETIC CODE, RESULTING IN DISEASES DEVELOPED LATER IN LIFE. THE CONCEPT OF THE "DEVELOPMENTAL PROGRAMMING" AND DEVELOPMENTAL ORIGINS OF ADULT DISEASES (DOHAD) HAS BECOME WELL ACCEPTED BECAUSE OF THE COMPELLING ANIMAL STUDIES THAT HAVE PRECISELY DEFINED THE OUTCOMES OF SPECIFIC EXPOSURES.THE ENVIRONMENTAL POLLULLUTANTS AND OTHER CHEMICAL TOXICANTS MAY INFLUENCE CRUCIAL CELLULAR FUNCTIONS DURING CRITICAL PERIODS OF FETAL DEVELOPMENT AND PERMANENTLY ALTER THE STRUCTURE OR FUNCTION OF SPECIFIC ORGAN SYSTEMS. DEVELOPMENTAL EPIGENETICS IS BELIEVED TO ESTABLISH "ADAPTIVE" PHENOTYPES TO MEET THE DEMANDS OF THE LATER-LIFE ENVIRONMENT. RESULTING PHENOTYPES THAT MATCH PREDICTED LATER-LIFE DEMANDS WILL PROMOTE HEALTH, WHILE A HIGH DEGREE OF MISMATCH WILL IMPEDE ADAPTABILITY TO LATER-LIFE CHALLENGES AND ELEVATE DISEASE RISK. THE RAPID INTRODUCTION OF SYNTHETIC CHEMICALS, ENVIRONMENTAL POLLUTANTS AND MEDICAL INTERVENTIONS, MAY RESULT IN CONFLICT WITH THE PROGRAMMED ADAPTIVE CHANGES MADE DURING EARLY DEVELOPMENT, AND EXPLAIN THE ALARMING INCREASES IN SOME DISEASES. 2008 14 4189 36 METABOLIC DISEASE PROGRAMMING: FROM MITOCHONDRIA TO EPIGENETICS, GLUCOCORTICOID SIGNALLING AND BEYOND. EMBRYONIC AND FOETAL DEVELOPMENT ARE CRITICAL PERIODS OF DEVELOPMENT IN WHICH SEVERAL ENVIRONMENTAL CUES DETERMINE HEALTH AND DISEASE IN ADULTHOOD. MATERNAL CONDITIONS AND AN UNFAVOURABLE INTRAUTERINE ENVIRONMENT IMPACT FOETAL DEVELOPMENT AND MAY PROGRAMME THE OFFSPRING FOR INCREASED PREDISPOSITION TO METABOLIC DISEASES AND OTHER CHRONIC PATHOLOGIC CONDITIONS THROUGHOUT ADULT LIFE. PREVIOUSLY, NON-COMMUNICABLE CHRONIC DISEASES WERE ONLY ASSOCIATED WITH GENETICS AND LIFESTYLE. NOW THE ORIGINS OF NON-COMMUNICABLE CHRONIC DISEASES ARE ASSOCIATED WITH EARLY-LIFE ADAPTATIONS THAT PRODUCE LONG-TERM DYSFUNCTION. EARLY-LIFE ENVIRONMENT SETS THE LONG-TERM HEALTH AND DISEASE RISK AND CAN SPAN THROUGH MULTIPLE GENERATIONS. RECENT RESEARCH IN DEVELOPMENTAL PROGRAMMING AIMS AT IDENTIFYING THE MOLECULAR MECHANISMS RESPONSIBLE FOR DEVELOPMENTAL PROGRAMMING OUTCOMES THAT IMPACT CELLULAR PHYSIOLOGY AND TRIGGER ADULTHOOD DISEASE. THE IDENTIFICATION OF NEW THERAPEUTIC TARGETS CAN IMPROVE OFFSPRING'S HEALTH MANAGEMENT AND PREVENT OR OVERCOME ADVERSE CONSEQUENCES OF FOETAL PROGRAMMING. THIS REVIEW SUMMARIZES RECENT BIOMEDICAL DISCOVERIES IN THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) HYPOTHESIS AND HIGHLIGHT POSSIBLE DEVELOPMENTAL PROGRAMMING MECHANISMS, INCLUDING PRENATAL STRUCTURAL DEFECTS, METABOLIC (MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, PROTEIN MODIFICATION), EPIGENETIC AND GLUCOCORTICOID SIGNALLING-RELATED MECHANISMS SUGGESTING MOLECULAR CLUES FOR THE CAUSES AND CONSEQUENCES OF PROGRAMMING OF INCREASED SUSCEPTIBILITY OF OFFSPRING TO METABOLIC DISEASE AFTER BIRTH. IDENTIFYING MECHANISMS INVOLVED IN DOHAD CAN CONTRIBUTE TO EARLY INTERVENTIONS IN PREGNANCY OR EARLY CHILDHOOD, TO RE-SET THE METABOLIC HOMEOSTASIS AND BREAK THE CHAIN OF SUBSEQUENT EVENTS THAT COULD LEAD TO THE DEVELOPMENT OF DISEASE. 2021 15 1771 31 EARLY-LIFE ORIGIN OF INTESTINAL INFLAMMATORY DISORDERS. A GROWING BODY OF EVIDENCE SUPPORTS THE CONCEPT OF PERINATAL PROGRAMMING THROUGH WHICH THE PERINATAL ENVIRONMENT AFFECTS THE DEVELOPMENT OF THE FETUS AND INFANT, THEREBY MODIFYING THE RISK PROFILE FOR DISEASE LATER IN LIFE. INCREASING ATTENTION IS FOCUSING ON THE ROLE OF THE EARLY ENVIRONMENT IN THE DEVELOPMENT OF CHRONIC INTESTINAL DISORDERS. EPIDEMIOLOGICAL STUDIES HAVE HIGHLIGHTED THE LINK BETWEEN PERINATAL FACTORS, SUCH AS BREASTFEEDING, CESAREAN DELIVERY, AND ANTIBIOTIC USE, AND AN INCREASED RISK FOR INFLAMMATORY BOWEL DISEASE AND/OR CELIAC DISEASE. THESE LINKS ARE CONSISTENT WITH THE CONCEPT OF PERINATAL PROGRAMMING OF INTESTINAL INFLAMMATORY DISORDERS. ANIMAL MODELS HAVE SHOWN THAT THE EARLY-LIFE ENVIRONMENT AFFECTS THE DEVELOPMENT OF THE GASTROINTESTINAL TRACT, BUT FURTHER EXPERIMENTAL STUDIES ARE NEEDED TO CONFIRM THE LONG-TERM EFFECTS OF THE PERINATAL ENVIRONMENT ON SUSCEPTIBILITY TO CHRONIC INTESTINAL DISORDERS LATER IN LIFE. CHANGES IN THE DEVELOPMENT AND COMPOSITION OF THE INTESTINAL MICROBIOTA AS WELL AS EPIGENETIC CHANGES ARE EMERGING AS KEY MECHANISMS THROUGH WHICH THE PERINATAL ENVIRONMENT DETERMINES SUSCEPTIBILITY TO INTESTINAL INFLAMMATORY DISORDERS. 2017 16 1769 30 EARLY-LIFE NUTRITIONAL PROGRAMMING OF LONGEVITY. AVAILABLE DATA FROM BOTH EXPERIMENTAL AND EPIDEMIOLOGICAL STUDIES SUGGEST THAT INADEQUATE DIET IN EARLY LIFE CAN PERMANENTLY CHANGE THE STRUCTURE AND FUNCTION OF SPECIFIC ORGANS OR HOMOEOSTATIC PATHWAYS, THEREBY 'PROGRAMMING' THE INDIVIDUAL'S HEALTH STATUS AND LONGEVITY. SUFFICIENT EVIDENCE HAS ACCUMULATED SHOWING SIGNIFICANT IMPACT OF EPIGENETIC REGULATION MECHANISMS IN NUTRITIONAL PROGRAMMING PHENOMENON. THE ESSENTIAL ROLE OF EARLY-LIFE DIET IN THE DEVELOPMENT OF AGING-RELATED CHRONIC DISEASES IS WELL ESTABLISHED AND DESCRIBED IN MANY SCIENTIFIC PUBLICATIONS. HOWEVER, THE PROGRAMMING EFFECTS ON LIFESPAN HAVE NOT BEEN EXTENSIVELY REVIEWED SYSTEMATICALLY. THE AIM OF THE REVIEW IS TO PROVIDE A SUMMARY OF RESEARCH FINDINGS AND THEORETICAL EXPLANATIONS THAT INDICATE THAT LONGEVITY CAN BE INFLUENCED BY EARLY NUTRITION. 2014 17 6858 18 [NUTRIGENOMICS, OBESITY AND PUBLIC HEALTH]. FUNCTIONAL GENOMICS WILL CHANGE KNOWLEDGE AND PRACTICE IN CLINICAL NUTRITION IN THE FORTHCOMING YEARS. THE POSSIBILITY OF PERFORMING AN INDIVIDUAL'S GENETIC PROFILE (GENETIC VARIATIONS AND EPIGENETIC MODIFICATIONS) AS WELL AS THE ABILITY OF ITS INTEGRATION IN A COMPLEX NETWORK OF METABOLIC INTERACTIONS REPRESENTS A HUGE CHALLENGE IN HUMAN NUTRITION. THE INFLUENCE OF NUTRIGENOMICS IN TERMS OF PREVENTION AND TREATMENT OF CHRONIC DISEASES, SUCH AS OBESITY, TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE IN A POPULATION LEVEL REMAINS UNDETERMINED FOR THE MOMENT. THE OPPORTUNITY OF NUTRITIONAL INTERVENTION IN CRITICAL STAGES OF DEVELOPMENT AND THE CHANCE OF CHANGING GENETIC SUSCEPTIBILITY TO DISEASES THROUGH DIET IN A PUBLIC HEALTH BASIS SHOULD LEAD THE FUTURE OF NUTRIGENOMICS BEYOND THE MERE DESIGN OF "PERSONALIZED" FUNCTIONAL FOOD OR DIETS. 2007 18 6191 31 THE IMPACT OF MILK AND ITS COMPONENTS ON EPIGENETIC PROGRAMMING OF IMMUNE FUNCTION IN EARLY LIFE AND BEYOND: IMPLICATIONS FOR ALLERGY AND ASTHMA. SPECIFIC AND ADEQUATE NUTRITION DURING PREGNANCY AND EARLY LIFE IS AN IMPORTANT FACTOR IN AVOIDING NON-COMMUNICABLE DISEASES SUCH AS OBESITY, TYPE 2 DIABETES, CARDIOVASCULAR DISEASE, CANCERS, AND CHRONIC ALLERGIC DISEASES. ALTHOUGH EPIDEMIOLOGIC AND EXPERIMENTAL STUDIES HAVE SHOWN THAT NUTRITION IS IMPORTANT AT ALL STAGES OF LIFE, IT IS ESPECIALLY IMPORTANT IN PRENATAL AND THE FIRST FEW YEARS OF LIFE. DURING THE LAST DECADE, THERE HAS BEEN A GROWING INTEREST IN THE POTENTIAL ROLE OF EPIGENETIC MECHANISMS IN THE INCREASING HEALTH PROBLEMS ASSOCIATED WITH ALLERGIC DISEASE. EPIGENETICS INVOLVES SEVERAL MECHANISMS INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND MICRORNAS WHICH CAN MODIFY THE EXPRESSION OF GENES. IN THIS STUDY, WE FOCUS ON THE EFFECTS OF MATERNAL NUTRITION DURING PREGNANCY, THE EFFECTS OF THE BIOACTIVE COMPONENTS IN HUMAN AND BOVINE MILK, AND THE ENVIRONMENTAL FACTORS THAT CAN AFFECT EARLY LIFE (I.E., FARMING, MILK PROCESSING, AND BACTERIAL EXPOSURE), AND WHICH CONTRIBUTE TO THE EPIGENETIC MECHANISMS UNDERLYING THE PERSISTENT PROGRAMMING OF IMMUNE FUNCTIONS AND ALLERGIC DISEASES. THIS KNOWLEDGE WILL HELP TO IMPROVE APPROACHES TO NUTRITION IN EARLY LIFE AND HELP PREVENT ALLERGIES IN THE FUTURE. 2020 19 6378 30 THE ROLE OF NUTRITION ON EPIGENETIC MODIFICATIONS AND THEIR IMPLICATIONS ON HEALTH. NUTRITION PLAYS A KEY ROLE IN MANY ASPECTS OF HEALTH AND DIETARY IMBALANCES ARE MAJOR DETERMINANTS OF CHRONIC DISEASES INCLUDING CARDIOVASCULAR DISEASE, OBESITY, DIABETES AND CANCER. ADEQUATE NUTRITION IS PARTICULARLY ESSENTIAL DURING CRITICAL PERIODS IN EARLY LIFE (BOTH PRE- AND POSTNATAL). IN THIS REGARD, THERE IS EXTENSIVE EPIDEMIOLOGIC AND EXPERIMENTAL DATA SHOWING THAT EARLY SUB-OPTIMAL NUTRITION CAN HAVE HEALTH CONSEQUENCES SEVERAL DECADES LATER. THE HYPOTHESIS THAT EPIGENETIC MECHANISMS MAY LINK SUCH NUTRITIONAL IMBALANCES WITH ALTERED DISEASE RISK HAS BEEN GAINING ACCEPTANCE OVER RECENT YEARS. EPIGENETICS CAN BE DEFINED AS THE STUDY OF HERITABLE CHANGES IN GENE EXPRESSION THAT DO NOT INVOLVE ALTERATIONS IN THE DNA SEQUENCE. EPIGENETIC MARKS INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS AND A VARIETY OF NON-CODING RNAS. STRIKINGLY, THEY ARE PLASTIC AND RESPOND TO ENVIRONMENTAL SIGNALS, INCLUDING DIET. HERE WE WILL REVIEW HOW DIETARY FACTORS MODULATE THE ESTABLISHMENT AND MAINTENANCE OF EPIGENETIC MARKS, THEREBY INFLUENCING GENE EXPRESSION AND, HENCE, DISEASE RISK AND HEALTH. 2012 20 1738 34 EARLY DEVELOPMENTAL CONDITIONING OF LATER HEALTH AND DISEASE: PHYSIOLOGY OR PATHOPHYSIOLOGY? EXTENSIVE EXPERIMENTAL ANIMAL STUDIES AND EPIDEMIOLOGICAL OBSERVATIONS HAVE SHOWN THAT ENVIRONMENTAL INFLUENCES DURING EARLY DEVELOPMENT AFFECT THE RISK OF LATER PATHOPHYSIOLOGICAL PROCESSES ASSOCIATED WITH CHRONIC, ESPECIALLY NONCOMMUNICABLE, DISEASE (NCD). THIS FIELD IS RECOGNIZED AS THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD). WE DISCUSS THE EXTENT TO WHICH DOHAD REPRESENTS THE RESULT OF THE PHYSIOLOGICAL PROCESSES OF DEVELOPMENTAL PLASTICITY, WHICH MAY HAVE POTENTIAL ADVERSE CONSEQUENCES IN TERMS OF NCD RISK LATER, OR WHETHER IT IS THE MANIFESTATION OF PATHOPHYSIOLOGICAL PROCESSES ACTING IN EARLY LIFE BUT ONLY BECOMING APPARENT AS DISEASE LATER. WE ARGUE THAT THE EVIDENCE SUGGESTS THE FORMER, THROUGH THE OPERATION OF CONDITIONING PROCESSES INDUCED ACROSS THE NORMAL RANGE OF DEVELOPMENTAL ENVIRONMENTS, AND WE SUMMARIZE CURRENT KNOWLEDGE OF THE PHYSIOLOGICAL PROCESSES INVOLVED. THE ADAPTIVE PATHWAY TO LATER RISK ACCORDS WITH CURRENT CONCEPTS IN EVOLUTIONARY DEVELOPMENTAL BIOLOGY, ESPECIALLY THOSE CONCERNING PARENTAL EFFECTS. OUTSIDE THE NORMAL RANGE, EFFECTS ON DEVELOPMENT CAN RESULT IN NONADAPTIVE PROCESSES, AND WE REVIEW THEIR UNDERLYING MECHANISMS AND CONSEQUENCES. NEW CONCEPTS CONCERNING THE UNDERLYING EPIGENETIC AND OTHER MECHANISMS INVOLVED IN BOTH DISRUPTIVE AND NONDISRUPTIVE PATHWAYS TO DISEASE ARE REVIEWED, INCLUDING THE EVIDENCE FOR TRANSGENERATIONAL PASSAGE OF RISK FROM BOTH MATERNAL AND PATERNAL LINES. THESE CONCEPTS HAVE WIDER IMPLICATIONS FOR UNDERSTANDING THE CAUSES AND POSSIBLE PREVENTION OF NCDS SUCH AS TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE, FOR BROADER SOCIAL POLICY AND FOR THE INCREASING ATTENTION PAID IN PUBLIC HEALTH TO THE LIFECOURSE APPROACH TO NCD PREVENTION. 2014