1 3585 155 IMPACT OF THE EXPOSOME ON THE EPIGENOME IN INFLAMMATORY BOWEL DISEASE PATIENTS AND ANIMAL MODELS. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC INFLAMMATORY DISORDERS OF THE GASTROINTESTINAL TRACT THAT ENCOMPASS TWO MAIN PHENOTYPES, NAMELY CROHN'S DISEASE AND ULCERATIVE COLITIS. THESE CONDITIONS OCCUR IN GENETICALLY PREDISPOSED INDIVIDUALS IN RESPONSE TO ENVIRONMENTAL FACTORS. EPIGENETICS, ACTING BY DNA METHYLATION, POST-TRANSLATIONAL HISTONES MODIFICATIONS OR BY NON-CODING RNAS, COULD EXPLAIN HOW THE EXPOSOME (OR ALL ENVIRONMENTAL INFLUENCES OVER THE LIFE COURSE, FROM CONCEPTION TO DEATH) COULD INFLUENCE THE GENE EXPRESSION TO CONTRIBUTE TO INTESTINAL INFLAMMATION. WE PERFORMED A SCOPING SEARCH USING MEDLINE TO IDENTIFY ALL THE ELEMENTS OF THE EXPOSOME THAT MAY PLAY A ROLE IN INTESTINAL INFLAMMATION THROUGH EPIGENETIC MODIFICATIONS, AS WELL AS THE UNDERLYING MECHANISMS. THE ENVIRONMENTAL FACTORS EPIGENETICALLY INFLUENCING THE OCCURRENCE OF INTESTINAL INFLAMMATION ARE THE MATERNAL LIFESTYLE (MAINLY DIET, THE OCCURRENCE OF INFECTION DURING PREGNANCY AND SMOKING); BREASTFEEDING; MICROBIOTA; DIET (INCLUDING A LOW-FIBER DIET, HIGH-FAT DIET AND DEFICIENCY IN MICRONUTRIENTS); SMOKING HABITS, VITAMIN D AND DRUGS (E.G., IBD TREATMENTS, ANTIBIOTICS AND PROBIOTICS). INFLUENCED BY BOTH MICROBIOTA AND DIET, SHORT-CHAIN FATTY ACIDS ARE GUT MICROBIOTA-DERIVED METABOLITES RESULTING FROM THE ANAEROBIC FERMENTATION OF NON-DIGESTIBLE DIETARY FIBERS, PLAYING AN EPIGENETICALLY MEDIATED ROLE IN THE INTEGRITY OF THE EPITHELIAL BARRIER AND IN THE DEFENSE AGAINST INVADING MICROORGANISMS. ALTHOUGH THE IMPACT OF SOME ENVIRONMENTAL FACTORS HAS BEEN IDENTIFIED, THE EXPOSOME-INDUCED EPIMUTATIONS IN IBD REMAIN A LARGELY UNDEREXPLORED FIELD. HOW THESE ENVIRONMENTAL EXPOSURES INDUCE EPIGENETIC MODIFICATIONS (IN TERMS OF DURATION, FREQUENCY AND THE TIMING AT WHICH THEY OCCUR) AND HOW OTHER ENVIRONMENTAL FACTORS ASSOCIATED WITH IBD MODULATE EPIGENETICS DESERVE TO BE FURTHER INVESTIGATED. 2022 2 1404 43 DIETARY COMPOSITION AND EFFECTS IN INFLAMMATORY BOWEL DISEASE. DRAMATIC CHANGES IN THE ENVIRONMENT AND HUMAN LIFESTYLE HAVE BEEN ASSOCIATED WITH THE RISE OF VARIOUS CHRONIC COMPLEX DISEASES, SUCH AS INFLAMMATORY BOWEL DISEASE (IBD). A DYSBIOTIC GUT MICROBIOTA HAS BEEN PROPOSED AS A CRUCIAL PATHOGENIC ELEMENT, CONTRIBUTING TO IMMUNE IMBALANCES AND FOSTERING A PROINFLAMMATORY MILIEU, WHICH MAY BE ASSOCIATED WITH DISEASE RELAPSES OR EVEN THE INITIATION OF IBD. IN ADDITION TO REPRESENTING IMPORTANT REGULATORS OF THE MUCOSAL IMMUNITY AND THE COMPOSITION OF THE GUT MICROBIOTA, FOOD COMPONENTS HAVE BEEN SHOWN TO BE POTENTIAL ENVIRONMENTAL TRIGGERS OF EPIGENETIC MODIFICATIONS. IN THE CONTEXT OF CHRONIC INTESTINAL INFLAMMATION, DIETARY HABITS AND SPECIFIC FOOD COMPONENTS HAVE BEEN IMPLICATED AS IMPORTANT MODULATORS OF EPIGENETIC MECHANISMS, INCLUDING DNA METHYLATION, WHICH MAY PREDISPOSE A PERSON TO THE INCREASED RISK OF THE INITIATION AND EVOLUTION OF IBD. THIS REVIEW PROVIDES NOVEL INSIGHTS ABOUT HOW DIETARY FACTORS MAY INTERACT WITH THE INTESTINAL MUCOSA AND MODULATE IMMUNE HOMEOSTASIS BY SHAPING THE INTESTINAL ECOSYSTEM, AS WELL AS THE POTENTIAL INFLUENCE OF DIET IN THE ETIOPATHOGENESIS AND MANAGEMENT OF IBD. 2019 3 566 46 BASES FOR THE ADEQUATE DEVELOPMENT OF NUTRITIONAL RECOMMENDATIONS FOR PATIENTS WITH INFLAMMATORY BOWEL DISEASE. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC AND RELAPSING INFLAMMATORY CONDITION OF THE GASTROINTESTINAL TRACT; IT IS A HETEROGENEOUS AND MULTIFACTORIAL DISORDER RESULTING FROM A COMPLEX INTERPLAY BETWEEN GENETIC VARIATION, INTESTINAL MICROBIOTA, THE HOST IMMUNE SYSTEM AND ENVIRONMENTAL FACTORS SUCH AS DIET, DRUGS, BREASTFEEDING AND SMOKING. THE INTERACTIONS BETWEEN DIETARY NUTRIENTS AND INTESTINAL IMMUNITY ARE COMPLEX. THERE IS A COMPELLING ARGUMENT FOR ENVIRONMENTAL FACTORS SUCH AS DIET PLAYING A ROLE IN THE CAUSE AND COURSE OF IBD, GIVEN THAT THREE IMPORTANT FACTORS IN THE PATHOGENESIS OF IBD CAN BE MODULATED AND CONTROLLED BY DIET: INTESTINAL MICROBIOTA, THE IMMUNE SYSTEM AND EPITHELIAL BARRIER FUNCTION. THE AIM OF THIS REVIEW IS TO SUMMARIZE THE EPIDEMIOLOGICAL FINDINGS REGARDING DIET AND TO FOCUS ON THE EFFECTS THAT NUTRIENTS EXERT ON THE INTESTINAL MUCOSA-MICROBIOTA-PERMEABILITY INTERACTION. THE NATURE OF THESE INTERACTIONS IN IBD IS INFLUENCED BY ALTERATIONS IN THE NUTRITIONAL METABOLISM OF THE GUT MICROBIOTA AND HOST CELLS THAT CAN INFLUENCE THE OUTCOME OF NUTRITIONAL INTERVENTION. A BETTER UNDERSTANDING OF DIET-HOST-MICROBIOTA INTERACTIONS IS ESSENTIAL FOR UNRAVELLING THE COMPLEX MOLECULAR BASIS OF EPIGENETIC, GENETIC AND ENVIRONMENTAL INTERACTIONS UNDERLYING IBD PATHOGENESIS AS WELL AS FOR OFFERING NEW THERAPEUTIC APPROACHES FOR THE TREATMENT OF IBD. 2019 4 4273 38 MICROBIOTA AND EPIGENETICS: HEALTH IMPACT. EPIGENETIC CHANGES ASSOCIATED WITH DISEASE DEVELOPMENT AND PROGRESSIONS ARE OF INCREASING IMPORTANCE BECAUSE OF THEIR POTENTIAL DIAGNOSTIC AND THERAPEUTIC APPLICATIONS. SEVERAL EPIGENETIC CHANGES ASSOCIATED WITH CHRONIC METABOLIC DISORDERS HAVE BEEN STUDIED IN VARIOUS DISEASES. EPIGENETIC CHANGES ARE MOSTLY MODULATED BY ENVIRONMENTAL FACTORS, INCLUDING THE HUMAN MICROBIOTA LIVING IN DIFFERENT PARTS OF OUR BODIES. THE MICROBIAL STRUCTURAL COMPONENTS AND THE MICROBIALLY DERIVED METABOLITES DIRECTLY INTERACT WITH HOST CELLS, THEREBY MAINTAINING HOMEOSTASIS. MICROBIOME DYSBIOSIS, ON THE OTHER HAND, IS KNOWN TO PRODUCE ELEVATED LEVELS OF DISEASE-LINKED METABOLITES, WHICH MAY DIRECTLY AFFECT A HOST METABOLIC PATHWAY OR INDUCE EPIGENETIC CHANGES THAT CAN LEAD TO DISEASE DEVELOPMENT. DESPITE THEIR IMPORTANT ROLE IN HOST PHYSIOLOGY AND SIGNAL TRANSDUCTION, THERE HAS BEEN LITTLE RESEARCH INTO THE MECHANICS AND PATHWAYS ASSOCIATED WITH EPIGENETIC MODIFICATIONS. THIS CHAPTER FOCUSES ON THE RELATIONSHIP BETWEEN MICROBES AND THEIR EPIGENETIC EFFECTS IN DISEASED PATHOLOGY, AS WELL AS ON THE REGULATION AND METABOLISM OF THE DIETARY OPTIONS AVAILABLE TO THE MICROBES. FURTHERMORE, THIS CHAPTER ALSO PROVIDES A PROSPECTIVE LINK BETWEEN THESE TWO IMPORTANT PHENOMENA, TERMED "MICROBIOME AND EPIGENETICS." 2023 5 3172 48 GUT MICROBIOTA AND RISK OF DEVELOPING CELIAC DISEASE. GUT MICROBIOTA SHAPES THE DEVELOPMENT OF THE MUCOSAL IMMUNE SYSTEM AND MAY PROVIDE PROTECTION AGAINST IMMUNE-MEDIATED DISEASES. CELIAC DISEASE (CD) IS A CHRONIC INFLAMMATORY CONDITION TRIGGERED BY DIETARY GLUTEN PROTEINS, RECENTLY ASSOCIATED WITH GUT MICROBIOTA ALTERATIONS IN CROSS-SECTIONAL STUDIES COMPARING PATIENTS AND CONTROLS. WHETHER OR NOT THESE DIFFERENCES ARE CAUSALLY RELATED TO THE DISEASE HAS YET TO BE ELUCIDATED, BUT EVALUATION OF SPECIFIC BACTERIA ISOLATED FROM CD PATIENTS IN EXPERIMENTAL MODELS SUGGESTS THAT THEY CAN PROMOTE AN ADVERSE RESPONSE TO DIETARY GLUTEN, WHEREAS OTHER COMMENSAL BACTERIA CAN BE PROTECTIVE. GENETIC AND ENVIRONMENTAL FACTORS ASSOCIATED WITH INCREASED CD RISK HAVE ALSO BEEN LINKED TO SHIFTS IN THE GUT MICROBIOTA COMPOSITION IN INFANTS EARLY IN LIFE. EPIGENETIC MECHANISMS ALSO SEEM TO PLAY AN IMPORTANT ROLE IN MODULATING GUT MICROBIOTA COMPOSITION AND FUNCTION AND, THEORETICALLY, COULD ALSO INFLUENCE CD RISK. HERE, WE REVIEW THE CURRENT KNOWLEDGE ON HOW HOST GENETICS, ENVIRONMENTAL FACTORS, AND EPIGENETIC MODIFICATIONS COULD MODULATE GUT MICROBIOTA FUNCTIONALITY AND HOW THIS MAY INFLUENCE CD RISK. GREATER UNDERSTANDING OF THE ROLE OF THIS TRIAD IN CD ONSET AND PATHOGENESIS WILL BE VALUABLE IN DESIGNING PROOF-OF CONCEPT INTERVENTIONS IN THE GUT ECOSYSTEM, WITH A VIEW TO IMPROVING CD MANAGEMENT. 2016 6 1395 58 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 7 5558 34 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 8 3546 47 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 9 2855 53 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 10 3541 44 IMMUNOEPIGENETIC REGULATION OF INFLAMMATORY BOWEL DISEASE: CURRENT INSIGHTS INTO NOVEL EPIGENETIC MODULATIONS OF THE SYSTEMIC IMMUNE RESPONSE. THE IMMUNE SYSTEM AND ENVIRONMENTAL FACTORS ARE INVOLVED IN VARIOUS DISEASES, SUCH AS INFLAMMATORY BOWEL DISEASE (IBD), THROUGH THEIR EFFECT ON GENETICS, WHICH MODULATES IMMUNE CELLS. IBD ENCOMPASSES TWO MAIN PHENOTYPES, CROHN'S DISEASE, AND ULCERATIVE COLITIS, WHICH ARE MANIFESTED AS CHRONIC AND SYSTEMIC RELAPSE-REMITTING GASTROINTESTINAL TRACT DISORDERS WITH RISING GLOBAL INCIDENCE AND PREVALENCE. THE PATHOPHYSIOLOGY OF IBD IS COMPLEX AND NOT FULLY UNDERSTOOD. EPIGENETIC RESEARCH HAS RESULTED IN VALUABLE INFORMATION FOR UNRAVELING THE ETIOLOGY OF THIS IMMUNE-MEDIATED DISEASE. THUS, THE MAIN OBJECTIVE OF THE PRESENT REVIEW IS TO SUMMARIZE THE CURRENT FINDINGS ON THE ROLE OF EPIGENETIC MECHANISMS IN IBD TO SHED LIGHT ON THEIR POTENTIAL CLINICAL RELEVANCE. THIS REVIEW FOCUSES ON THE LATEST EVIDENCE REGARDING PERIPHERAL BLOOD MONONUCLEAR CELLS AND EPIGENETIC CHANGES IN HISTONE MODIFICATION, DNA METHYLATION, AND TELOMERE SHORTENING IN IBD. THE VARIOUS IDENTIFIED EPIGENETIC DNA PROFILES WITH CLINICAL VALUE IN IBD COULD BE USED AS BIOMARKERS FOR MORE ACCURATELY PREDICTING DISEASE DEVELOPMENT, TREATMENT RESPONSE, AND THERAPY-RELATED ADVERSE EVENTS. ULTIMATELY, THE INFORMATION PRESENTED HERE COULD BE OF POTENTIAL RELEVANCE FOR FUTURE CLINICAL PRACTICE IN DEVELOPING MORE EFFICIENT AND PRECISE MEDICINE TO IMPROVE THE QUALITY OF LIFE FOR PATIENTS WITH IBD. 2023 11 6251 38 THE MICROBIOLOGICAL MEMORY, AN EPIGENETIC REGULATOR GOVERNING THE BALANCE BETWEEN GOOD HEALTH AND METABOLIC DISORDERS. IF THE TRANSMISSION OF BIOLOGICAL INFORMATION FROM ONE GENERATION TO THE NEXT IS BASED ON DNA, MOST HERITABLE PHENOTYPIC TRAITS SUCH AS CHRONIC METABOLIC DISEASES, ARE NOT LINKED TO GENETIC VARIATION IN DNA SEQUENCES. NON-GENETIC HERITABILITY MIGHT HAVE SEVERAL CAUSES INCLUDING EPIGENETIC, PARENTAL EFFECT, ADAPTIVE SOCIAL LEARNING, AND INFLUENCE OF THE ECOLOGICAL ENVIRONMENT. DISTINGUISHING AMONG THESE CAUSES IS CRUCIAL TO RESOLVE MAJOR PHENOTYPIC ENIGMAS. STRONG EVIDENCE INDICATES THAT CHANGES IN DNA EXPRESSION THROUGH VARIOUS EPIGENETIC MECHANISMS CAN BE LINKED TO PARENT-OFFSPRING RESEMBLANCE IN TERMS OF SENSITIVITY TO METABOLIC DISEASES. AMONG NON-GENETIC HERITABLE TRAITS, EARLY NUTRITION COULD ACCOUNT FOR A LONG TERM DEVIANT PROGRAMMING OF GENES EXPRESSION RESPONSIBLE FOR METABOLIC DISEASES IN ADULTHOOD. NUTRITION COULD SHAPE AN INADEQUATE GUT MICROBIOTA (DYSBIOSIS), TRIGGERING EPIGENETIC DEREGULATION OF TRANSCRIPTION WHICH CAN BE OBSERVED IN CHRONIC METABOLIC DISEASES. WE REVIEW HEREIN THE EVIDENCE THAT DYSBIOSIS MIGHT BE A MAJOR CAUSE OF HERITABLE EPIGENETIC PATTERNS FOUND TO BE ASSOCIATED WITH METABOLIC DISEASES. BY TAKING INTO ACCOUNT THE RECENT ADVANCES ON THE GUT MICROBIOME, WE HAVE AGGREGATED TOGETHER DIFFERENT OBSERVATIONS SUPPORTING THE HYPOTHESIS THAT THE GUT MICROBIOTA COULD PROMOTE THE MOLECULAR CROSSTALK BETWEEN BACTERIA AND SURROUNDING HOST CELLS WHICH CONTROLS THE PATHOLOGICAL EPIGENETIC SIGNATURE. WE INTRODUCE FOR THE FIRST TIME THE CONCEPT OF "MICROBIOLOGICAL MEMORY" AS THE MAIN REGULATOR OF THE EPIGENETIC SIGNATURES, THEREBY INDICATING THAT DIFFERENT CAUSES OF NON-GENETIC HERITABILITY CAN INTERACT IN COMPLEX PATHWAYS TO PRODUCE INHERITANCE. 2018 12 3692 38 INFLAMMATORY BOWEL DISEASES: THE ROLE OF GUT MICROBIOTA. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC MULTIFACTORIAL DISEASES CHARACTERIZED BY PARTIALLY UNCLEAR PATHOGENIC MECHANISMS INCLUDING CHANGES IN INTESTINAL MICROBIOTA. DESPITE THE MICROBIOTA, ALTERATION IS WELL ESTABLISHED IN IBD PATIENTS, AS REPORTED BY 16RNA SEQUENCING ANALYSIS, AN IMPORTANT GOAL IS TO DEFINE IF IT IS JUST A CONSEQUENCE OF THE DISEASE PROGRESSION OR A TRIGGER FACTOR OF THE DISEASE ITSELF. TO DATE, GUT MICROBIOTA COMPOSITION AND GUT MICROBIOTA-RELATED METABOLITES SEEM TO AFFECT THE HOST HEALTHY STATE BOTH BY MODULATING METABOLIC PATHWAYS OR ACTING ON THE EXPRESSION OF DIFFERENT GENES THROUGH EPIGENETIC EFFECTS. BECAUSE OF THIS, IT HAS BEEN SUGGESTED THAT INTESTINAL MICROBIOTA MIGHT REPRESENT A PROMISING THERAPEUTIC TARGET FOR IBD PATIENTS. THE AIM OF THIS REVIEW IS TO SUMMARIZE BOTH THE MOST RECENT ACQUISITIONS IN THE FIELD OF GUT MICROBIOTA AND ITS INVOLVEMENT IN INTESTINAL INFLAMMATION TOGETHER WITH THE AVAILABLE STRATEGIES FOR THE MODULATION OF MICROBIOTA, SUCH AS PREBIOTICS AND/OR PROBIOTICS ADMINISTRATION OR FECAL MICROBIOTA TRANSPLANTATION. 2020 13 2617 51 EPIGENOME TARGETING BY PROBIOTIC METABOLITES. BACKGROUND: THE INTESTINAL MICROBIOTA PLAYS AN IMPORTANT ROLE IN IMMUNE DEVELOPMENT AND HOMEOSTASIS. A DISTURBED MICROBIOTA DURING EARLY INFANCY IS ASSOCIATED WITH AN INCREASED RISK OF DEVELOPING INFLAMMATORY AND ALLERGIC DISEASES LATER IN LIFE. THE MECHANISMS UNDERLYING THESE EFFECTS ARE POORLY UNDERSTOOD BUT ARE LIKELY TO INVOLVE ALTERATIONS IN MICROBIAL PRODUCTION OF FERMENTATION-DERIVED METABOLITES, WHICH HAVE POTENT IMMUNE MODULATING PROPERTIES AND ARE REQUIRED FOR MAINTENANCE OF HEALTHY MUCOSAL IMMUNE RESPONSES. PROBIOTICS ARE BENEFICIAL BACTERIA THAT HAVE THE CAPACITY TO ALTER THE COMPOSITION OF BACTERIAL SPECIES IN THE INTESTINE THAT CAN IN TURN INFLUENCE THE PRODUCTION OF FERMENTATION-DERIVED METABOLITES. PRINCIPAL AMONG THESE METABOLITES ARE THE SHORT-CHAIN FATTY ACIDS BUTYRATE AND ACETATE THAT HAVE POTENT ANTI-INFLAMMATORY ACTIVITIES IMPORTANT IN REGULATING IMMUNE FUNCTION AT THE INTESTINAL MUCOSAL SURFACE. THEREFORE STRATEGIES AIMED AT RESTORING THE MICROBIOTA PROFILE MAY BE EFFECTIVE IN THE PREVENTION OR TREATMENT OF ALLERGIC AND INFLAMMATORY DISEASES. PRESENTATION OF THE HYPOTHESIS: PROBIOTIC BACTERIA HAVE DIVERSE EFFECTS INCLUDING ALTERING MICROBIOTA COMPOSITION, REGULATING EPITHELIAL CELL BARRIER FUNCTION AND MODULATING OF IMMUNE RESPONSES. THE PRECISE MOLECULAR MECHANISMS MEDIATING THESE PROBIOTIC EFFECTS ARE NOT WELL UNDERSTOOD. SHORT-CHAIN FATTY ACIDS SUCH AS BUTYRATE ARE A CLASS OF HISTONE DEACETYLASE INHIBITORS IMPORTANT IN THE EPIGENETIC CONTROL OF HOST CELL RESPONSES. IT IS HYPOTHESIZED THAT THE BIOLOGICAL FUNCTION OF PROBIOTICS MAY BE A RESULT OF EPIGENETIC MODIFICATIONS THAT MAY EXPLAIN THE WIDE RANGE OF EFFECTS OBSERVED. STUDIES DELINEATING THE EFFECTS OF PROBIOTICS ON SHORT-CHAIN FATTY ACID PRODUCTION AND THE EPIGENETIC ACTIONS OF SHORT-CHAIN FATTY ACIDS WILL ASSIST IN UNDERSTANDING THE ASSOCIATION BETWEEN MICROBIOTA AND ALLERGIC OR AUTOIMMUNE DISORDERS. TESTING THE HYPOTHESIS: WE PROPOSE THAT TREATMENT WITH SPECIFIC PROBIOTIC BACTERIA UNDER IN VIVO CONDITIONS WOULD OFFER THE IDEAL CONDITIONS TO EXAMINE THE MICROBIOLOGICAL, IMMUNOLOGICAL AND EPIGENETIC MECHANISMS OF ACTION. ADVANCES IN EPIGENETIC TECHNOLOGY NOW ALLOW INVESTIGATORS TO BETTER UNDERSTAND THE COMPLEX BIOLOGICAL PROPERTIES OF PROBIOTICS AND THEIR METABOLITES. IMPLICATIONS OF THE HYPOTHESIS: DETERMINING THE PRECISE MECHANISMS OF PROBIOTIC ACTION WILL LEAD TO MORE SPECIFIC AND EFFICACIOUS THERAPEUTIC STRATEGIES IN THE PREVENTION OR TREATMENT OF CHRONIC INFLAMMATORY CONDITIONS. 2010 14 6034 44 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 15 2601 49 EPIGENETICS, DNA ORGANIZATION, AND INFLAMMATORY BOWEL DISEASE. INFLAMMATORY BOWEL DISEASES (IBDS) ARE CHRONIC INFLAMMATORY DISORDERS AFFECTING THE GASTROINTESTINAL TRACT. THE INCIDENCE OF IBD IS INCREASING, WITH MORE CASES OCCURRING IN DEVELOPED COUNTRIES. MULTIPLE FACTORS SUCH AS GENETICS, ENVIRONMENTAL CHANGES, GUT MICROBIOTA, AND IMMUNE ABNORMALITIES HAVE BEEN ASSOCIATED WITH DEVELOPMENT OF IBD. IN RECENT YEARS, IT HAS BECOME INCREASINGLY APPARENT THAT EPIGENETIC MODIFICATIONS OF CHROMATIN AND THE MANNER IN WHICH CHROMATIN IS ORGANIZED IN THE NUCLEUS ARE ADDITIONALLY IMPORTANT ELEMENTS THAT CAN INFLUENCE RESPONSES INDUCED BY THE FACTORS DESCRIBED ABOVE, AND MAY THEREFORE CONTRIBUTE TO THE ONSET AND PATHOGENESIS OF IBD. EPIGENETICS AND CHROMATIN ORGANIZATION REGULATE DIVERSE FUNCTIONS THAT INCLUDE MAINTENANCE OF HOMEOSTASIS IN THE INTESTINAL EPITHELIUM, THE DEVELOPMENT AND DIFFERENTIATION OF IMMUNE CELLS, AND MODULATION OF RESPONSES GENERATED BY THE IMMUNE SYSTEM TO DEFEND AGAINST POTENTIAL PATHOGENS. FURTHERMORE, CHANGES IN EPIGENETIC CHROMATIN MARKS AND IN CHROMATIN ORGANIZATION HAVE NOW BEEN LINKED TO DIFFERENTIAL GENE EXPRESSION IN IBD PATIENT CELLS. ALTHOUGH DIRECT EVIDENCE FOR A ROLE OF HISTONE MODIFICATIONS IN IBD IS CURRENTLY VERY LIMITED, IN THIS REVIEW, WE SUMMARIZE THE LINKS BETWEEN VARIOUS EPIGENETIC MODIFICATIONS, THE PROTEINS THAT CATALYZE OR RECOGNIZE THESE MODIFICATIONS, AND THE DEVELOPMENT OR PROGRESSION OF IBD IN HUMAN AND EXPERIMENTAL IBD. WE ALSO DISCUSS HOW EPIGENETICS INFLUENCE THE ORGANIZATION OF DNA CONTACTS TO REGULATE GENE EXPRESSION AND THE IMPLICATIONS THIS MAY HAVE FOR DIAGNOSING AND TREATING IBD. 2019 16 5069 28 PHYSICAL ACTIVITY IN THE PREVENTION OF HUMAN DISEASES: ROLE OF EPIGENETIC MODIFICATIONS. EPIGENETIC MODIFICATION REFERS TO HERITABLE CHANGES IN GENE FUNCTION THAT CANNOT BE EXPLAINED BY ALTERATIONS IN THE DNA SEQUENCE. THE CURRENT LITERATURE CLEARLY DEMONSTRATES THAT THE EPIGENETIC RESPONSE IS HIGHLY DYNAMIC AND INFLUENCED BY DIFFERENT BIOLOGICAL AND ENVIRONMENTAL FACTORS SUCH AS AGING, NUTRIENT AVAILABILITY AND PHYSICAL EXERCISE. AS SUCH, IT IS WELL ACCEPTED THAT PHYSICAL ACTIVITY AND EXERCISE CAN MODULATE GENE EXPRESSION THROUGH EPIGENETIC ALTERNATIONS ALTHOUGH THE TYPE AND DURATION OF EXERCISE ELICITING SPECIFIC EPIGENETIC EFFECTS THAT CAN RESULT IN HEALTH BENEFITS AND PREVENT CHRONIC DISEASES REMAINS TO BE DETERMINED. THIS REVIEW HIGHLIGHTS THE MOST SIGNIFICANT FINDINGS FROM EPIGENETIC STUDIES INVOLVING PHYSICAL ACTIVITY/EXERCISE INTERVENTIONS KNOWN TO BENEFIT CHRONIC DISEASES SUCH AS METABOLIC SYNDROME, DIABETES, CANCER, CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES. 2017 17 2157 38 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 2675 37 ETIOPATHOGENESIS OF INFLAMMATORY BOWEL DISEASE: TODAY AND TOMORROW. PURPOSE OF REVIEW: CROHN'S DISEASE AND ULCERATIVE COLITIS, THE TWO MAJOR FORMS OF INFLAMMATORY BOWEL DISEASE (IBD), REPRESENT CHRONIC DISEASES OF UNKNOWN CAUSE, AND THEY ARE REGARDED AS PROTOTYPICAL COMPLEX DISEASES. DESPITE ALL THE RECENT ADVANCES, A COMPLETE APPRECIATION OF THE PATHOGENESIS OF IBD IS STILL LIMITED. IN THIS REVIEW, WE PRESENT RECENT INFORMATION CONTRIBUTING TO A BETTER UNDERSTANDING OF MECHANISMS UNDERLYING IBD. RECENT FINDINGS: HERE, WE ATTEMPT TO HIGHLIGHT NOVEL ENVIRONMENTAL TRIGGERS, DATA ON THE GUT MICROBIOTA, ITS INTERACTION WITH THE HOST, AND THE POTENTIAL INFLUENCE OF DIET AND FOOD COMPONENTS. WE DISCUSS RECENT FINDINGS ON DEFECTIVE SIGNALING PATHWAYS AND THE POTENTIAL EFFECTS ON THE IMMUNE RESPONSE, AND WE PRESENT NEW DATA ON EPIGENETIC CHANGES, INFLAMMASOME, AND DAMAGE-ASSOCIATED MOLECULAR PATTERNS ASSOCIATED WITH IBD. SUMMARY: THE CONTINUING IDENTIFICATION OF SEVERAL EPIGENETIC, TRANSCRIPTOMIC, PROTEOMIC, AND METABOLOMIC ALTERATIONS IN PATIENTS WITH IBD REFLECTS THE COMPLEX NATURE OF THE DISEASE AND SUGGESTS THE NEED FOR INNOVATIVE APPROACHES SUCH AS SYSTEMS BIOLOGY FOR IDENTIFYING NOVEL RELEVANT TARGETS IN IBD. 2017 19 2930 36 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 20 3681 45 INFLAMMATION, DNA METHYLATION AND COLITIS-ASSOCIATED CANCER. INFLAMMATION CAN RESULT FROM A RANGE OF SOURCES INCLUDING MICROBIAL INFECTIONS, EXPOSURE TO ALLERGENS AND TOXIC CHEMICALS, AUTOIMMUNE DISEASE AND OBESITY. A WELL-BALANCED IMMUNE RESPONSE CAN BE ANTI-TUMORIGENIC; HOWEVER, A SUSTAINED OR CHRONIC INFLAMMATORY RESPONSE IS GENERALLY HARMFUL AS THE IMMUNE RESPONSE BECOMES DISTORTED. A CAUSAL LINK BETWEEN CHRONIC INFLAMMATION AND CANCER IS NOW WELL ACCEPTED AND MANY CHRONICALLY INFLAMED ORGANS OF THE GASTROINTESTINAL TRACT SHOW THIS ASSOCIATION. FOR EXAMPLE, PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD), INCLUDING BOTH ULCERATIVE COLITIS AND CROHN'S DISEASE, HAVE A 2- TO 3-FOLD GREATER LIFETIME RISK OF DEVELOPING COLORECTAL CANCER COMPARED WITH THE GENERAL POPULATION. THE DEVELOPMENT OF COLITIS-ASSOCIATED CANCER (CAC) IS THOUGHT TO BE MULTIFACETED AND IS PROBABLY DUE TO A COMBINATION OF GENETIC FACTORS, EPIGENETIC FACTORS AND THE DURATION, EXTENT AND SEVERITY OF DISEASE. RECENTLY, EPIGENETIC ALTERATIONS, IN PARTICULAR ALTERATIONS IN DNA METHYLATION, HAVE BEEN OBSERVED DURING INFLAMMATION AND INFLAMMATION-ASSOCIATED CARCINOGENESIS. THE MEDIATORS OF THIS, THE SIGNIFICANCE OF THESE CHANGES IN DNA METHYLATION AND THE EFFECT THIS HAS ON GENE EXPRESSION AND THE MALIGNANT TRANSFORMATION OF THE EPITHELIAL CELLS DURING IBD AND CAC ARE DISCUSSED IN THIS REVIEW. THE RECENT ADVANCES IN TECHNOLOGIES TO STUDY GENOME-WIDE DNA METHYLATION AND THE THERAPEUTIC POTENTIAL OF UNDERSTANDING THESE MOLECULAR MECHANISMS ARE ALSO HIGHLIGHTED. 2012