1 6225 143 THE LINK AMONG MICROBIOTA, EPIGENETICS, AND DISEASE DEVELOPMENT. THE MICROBIOME IS A COMMUNITY OF VARIOUS MICROORGANISMS THAT INHABIT OR LIVE ON THE SKIN OF HUMANS/ANIMALS, SHARING THE BODY SPACE WITH THEIR HOSTS. IT IS A SORT OF COMPLEX ECOSYSTEM OF TRILLIONS OF COMMENSALS, SYMBIOTIC, AND PATHOGENIC MICROORGANISMS, INCLUDING TRILLIONS OF BACTERIA, ARCHAEA, PROTOZOA, FUNGI, AND VIRUSES. THE MICROBIOTA PLAYS A ROLE IN THE HEALTH AND DISEASE STATUS OF THE HOST. THEIR NUMBER, SPECIES DOMINANCE, AND VIABILITY ARE DYNAMIC. THEIR LONG-TERM DISTURBANCE IS USUALLY ACCOMPANIED BY SERIOUS DISEASES SUCH AS METABOLIC DISORDERS, CARDIOVASCULAR DISEASES, OR EVEN CANCER. WHILE EPIGENETICS IS A TERM THAT REFERS TO DIFFERENT STIMULI THAT INDUCE MODIFICATIONS IN GENE EXPRESSION PATTERNS WITHOUT STRUCTURAL CHANGES IN THE INHERITED DNA SEQUENCE, THESE CHANGES CAN BE REVERSIBLE OR EVEN PERSIST FOR SEVERAL GENERATIONS. EPIGENETICS CAN BE DESCRIBED AS CELL MEMORY THAT STORES EXPERIENCE AGAINST INTERNAL AND EXTERNAL FACTORS. RESULTS FROM MULTIPLE INSTITUTIONS HAVE CONTRIBUTED TO THE ROLE AND CLOSE INTERACTION OF BOTH MICROBIOTA AND EPIGENETICS IN DISEASE INDUCTION. UNDERSTANDING THE MECHANISMS OF BOTH PLAYERS ENABLES A BETTER UNDERSTANDING OF DISEASE INDUCTION AND DEVELOPMENT AND ALSO OPENS THE HORIZON TO REVOLUTIONARY THERAPEUTIC APPROACHES. THE PRESENT REVIEW ILLUSTRATES THE ROLES OF DIET, MICROBIOME, AND EPIGENETICS IN THE INDUCTION OF SEVERAL CHRONIC DISEASES. IN ADDITION, IT DISCUSSES THE APPLICATION OF EPIGENETIC DATA TO DEVELOP DIAGNOSTIC BIOMARKERS AND THERAPEUTICS AND EVALUATE THEIR SAFETY FOR PATIENTS. UNDERSTANDING THE INTERACTION AMONG ALL THESE ELEMENTS ENABLES THE DEVELOPMENT OF INNOVATIVE PREVENTIVE/THERAPEUTIC APPROACHES FOR DISEASE CONTROL. 2021 2 4273 45 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 3 3421 40 HUMAN MATTERS IN ASTHMA: CONSIDERING THE MICROBIOME IN PULMONARY HEALTH. MICROBIAL COMMUNITIES FORM AN IMPORTANT SYMBIOTIC ECOSYSTEM WITHIN HUMANS AND HAVE DIRECT EFFECTS ON HEALTH AND WELL-BEING. NUMEROUS EXOGENOUS FACTORS INCLUDING AIRBORNE TRIGGERS, DIET, AND DRUGS IMPACT THESE ESTABLISHED, BUT FRAGILE COMMUNITIES ACROSS THE HUMAN LIFESPAN. CROSSTALK BETWEEN THE MUCOSAL MICROBIOTA AND THE IMMUNE SYSTEM AS WELL AS THE GUT-LUNG AXIS HAVE DIRECT CORRELATIONS TO IMMUNE BIAS THAT MAY PROMOTE CHRONIC DISEASES LIKE ASTHMA. ASTHMA INITIATION AND PATHOGENESIS ARE MULTIFACETED AND COMPLEX WITH INPUT FROM GENETIC, EPIGENETIC, AND ENVIRONMENTAL COMPONENTS. IN THIS REVIEW, WE SUMMARIZE AND DISCUSS THE ROLE OF THE AIRWAY MICROBIOME IN ASTHMA, AND HOW THE ENVIRONMENT, DIET AND THERAPEUTICS IMPACT THIS LOW BIOMASS COMMUNITY OF MICROORGANISMS. WE ALSO FOCUS THIS REVIEW ON THE PEDIATRIC AND BLACK POPULATIONS AS HIGH-RISK GROUPS REQUIRING SPECIAL ATTENTION, EMPHASIZING THAT THE WHOLE PATIENT MUST BE CONSIDERED DURING TREATMENT. ALTHOUGH NEW CULTURE-INDEPENDENT TECHNIQUES HAVE BEEN DEVELOPED AND ARE MORE ACCESSIBLE TO RESEARCHERS, THE EXACT CONTRIBUTION THE AIRWAY MICROBIOME MAKES IN ASTHMA PATHOGENESIS IS NOT WELL UNDERSTOOD. UNDERSTANDING HOW THE AIRWAY MICROBIOME, AS A LIVING ENTITY IN THE RESPIRATORY TRACT, PARTICIPATES IN LUNG IMMUNITY DURING THE DEVELOPMENT AND PROGRESSION OF ASTHMA MAY LEAD TO CRITICAL NEW TREATMENTS FOR ASTHMA, INCLUDING POPULATION-TARGETED INTERVENTIONS, OR EVEN MORE EFFECTIVE ADMINISTRATION OF CURRENTLY AVAILABLE THERAPEUTICS. 2022 4 2333 42 EPIGENETIC REGULATION OF INFLAMMATION: THE METABOLOMICS CONNECTION. EPIGENETIC FACTORS ARE CONSIDERED THE REGULATOR OF COMPLEX MACHINERY BEHIND INFLAMMATORY DISORDERS AND SIGNIFICANTLY CONTRIBUTED TO THE EXPRESSION OF INFLAMMATION-ASSOCIATED GENES. EPIGENETIC MODIFICATIONS MODULATE VARIATION IN THE EXPRESSION PATTERN OF TARGET GENES WITHOUT AFFECTING THE DNA SEQUENCE. THE CURRENT KNOWLEDGE OF EPIGENETIC RESEARCH FOCUSED ON THEIR ROLE IN THE PATHOGENESIS OF VARIOUS INFLAMMATORY DISEASES THAT CAUSES MORBIDITY AND MORTALITY WORLDWIDE. INFLAMMATORY DISEASES ARE CATEGORIZED AS ACUTE AND CHRONIC BASED ON THE DISEASE SEVERITY AND ARE REGULATED BY THE EXPRESSION PATTERN OF VARIOUS GENES. HENCE, UNDERSTANDING THE ROLE OF EPIGENETIC MODIFICATIONS DURING INFLAMMATION PROGRESSION WILL CONTRIBUTE TO THE DISEASE OUTCOMES AND THERAPEUTIC APPROACHES. THIS REVIEW ALSO FOCUSES ON THE METABOLOMICS APPROACH ASSOCIATED WITH THE STUDY OF INFLAMMATORY DISORDERS. INFLAMMATORY RESPONSES AND METABOLIC REGULATION ARE HIGHLY INTEGRATED AND VARIOUS ADVANCED TECHNIQUES ARE ADOPTED TO STUDY THE METABOLIC SIGNATURE MOLECULES. HERE WE DISCUSS SEVERAL METABOLOMICS APPROACHES USED TO LINK INFLAMMATORY DISORDERS AND EPIGENETIC CHANGES. WE PROPOSED THAT DECIPHERING THE MECHANISM BEHIND THE INFLAMMATION-METABOLISM LOOP MAY HAVE IMMENSE IMPORTANCE IN BIOMARKERS RESEARCH AND MAY ACT AS A PRINCIPAL COMPONENT IN DRUG DISCOVERY AS WELL AS THERAPEUTIC APPLICATIONS. 2022 5 3404 46 HOW EPIGENETICS IMPACTS ON HUMAN DISEASES. EPIGENETICS IS A RAPIDLY GROWING FIELD OF BIOLOGY THAT STUDIES THE CHANGES IN GENE EXPRESSION THAT ARE NOT DUE TO ALTERATIONS IN THE DNA SEQUENCE BUT RATHER THE CHEMICAL MODIFICATIONS OF DNA AND ITS ASSOCIATED PROTEINS. EPIGENETIC MECHANISMS CAN PROFOUNDLY INFLUENCE GENE EXPRESSION, CELL DIFFERENTIATION, TISSUE DEVELOPMENT, AND DISEASE SUSCEPTIBILITY. UNDERSTANDING EPIGENETIC CHANGES IS ESSENTIAL TO ELUCIDATE THE MECHANISMS UNDERLYING THE INCREASINGLY RECOGNIZED ROLE OF ENVIRONMENTAL AND LIFESTYLE FACTORS IN HEALTH AND DISEASE AND THE INTERGENERATIONAL TRANSMISSION OF PHENOTYPES. RECENT STUDIES SUGGEST EPIGENETICS MAY BE CRITICAL IN VARIOUS DISEASES, FROM CARDIOVASCULAR DISEASE AND CANCER TO NEURODEVELOPMENTAL AND NEURODEGENERATIVE DISORDERS. EPIGENETIC MODIFICATIONS ARE POTENTIALLY REVERSIBLE AND COULD PROVIDE NEW THERAPEUTIC AVENUES FOR TREATING THESE DISEASES USING EPIGENETIC MODULATORS. MOREOVER, EPIGENETICS PROVIDE INSIGHT INTO DISEASE PATHOGENESIS AND BIOMARKERS FOR DISEASE DIAGNOSIS AND RISK STRATIFICATION. NEVERTHELESS, EPIGENETIC INTERVENTIONS HAVE THE POTENTIAL FOR UNINTENDED CONSEQUENCES AND MAY POTENTIALLY LEAD TO INCREASED RISKS OF UNEXPECTED OUTCOMES, SUCH AS ADVERSE DRUG REACTIONS, DEVELOPMENTAL ABNORMALITIES, AND CANCER. THEREFORE, RIGOROUS STUDIES ARE ESSENTIAL TO MINIMIZE THE RISKS ASSOCIATED WITH EPIGENETIC THERAPIES AND TO DEVELOP SAFE AND EFFECTIVE INTERVENTIONS FOR IMPROVING HUMAN HEALTH. THIS ARTICLE PROVIDES A SYNTHETIC AND HISTORICAL VIEW OF THE ORIGIN OF EPIGENETICS AND SOME OF THE MOST RELEVANT ACHIEVEMENTS. 2023 6 6101 26 THE EMERGING ROLE OF EPIGENETICS IN THE IMMUNE RESPONSE TO VACCINATION AND INFECTION: A SYSTEMATIC REVIEW. EXTENSIVE RESEARCH HAS HIGHLIGHTED THE ROLE OF INFECTION-INDUCED EPIGENETIC EVENTS IN THE DEVELOPMENT OF CANCER. MORE RECENTLY, ATTENTION HAS FOCUSED ON THE ABILITY OF NON-CARCINOGENIC INFECTIONS, AS WELL AS VACCINES, TO MODIFY THE HUMAN EPIGENOME AND MODULATE THE IMMUNE RESPONSE. THIS REVIEW EXPLORES THIS RAPIDLY EVOLVING AREA OF INVESTIGATION AND OUTLINES THE MANY AND VARIED WAYS IN WHICH VACCINATION AND NATURAL INFECTION CAN INFLUENCE THE HUMAN EPIGENOME FROM MODULATION OF THE INNATE AND ADAPTIVE IMMUNE RESPONSE, TO BIOLOGICAL AGEING AND MODIFICATION OF DISEASE RISK. THE IMPLICATIONS OF THESE EPIGENETIC CHANGES ON IMMUNE REGULATION AND THEIR POTENTIAL APPLICATION TO THE DIAGNOSIS AND TREATMENT OF CHRONIC INFECTION AND VACCINE DEVELOPMENT ARE ALSO DISCUSSED. 2020 7 6251 45 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 8 838 44 CHEMISTRY MEETS BIOLOGY IN COLITIS-ASSOCIATED CARCINOGENESIS. THE INTESTINE COMPRISES AN EXCEPTIONAL VENUE FOR A DYNAMIC AND COMPLEX INTERPLAY OF NUMEROUS CHEMICAL AND BIOLOGICAL PROCESSES. HERE, MULTIPLE CHEMICAL AND BIOLOGICAL SYSTEMS, INCLUDING THE INTESTINAL TISSUE ITSELF, ITS ASSOCIATED IMMUNE SYSTEM, THE GUT MICROBIOTA, XENOBIOTICS, AND METABOLITES MEET AND INTERACT TO FORM A SOPHISTICATED AND TIGHTLY REGULATED STATE OF TISSUE HOMOEOSTASIS. DISTURBANCE OF THIS HOMEOSTASIS CAN CAUSE INFLAMMATORY BOWEL DISEASE (IBD)-A CHRONIC DISEASE OF MULTIFACTORIAL ETIOLOGY THAT IS STRONGLY ASSOCIATED WITH INCREASED RISK FOR CANCER DEVELOPMENT. THIS REVIEW ADDRESSES RECENT DEVELOPMENTS IN RESEARCH INTO CHEMICAL AND BIOLOGICAL MECHANISMS UNDERLYING THE ETIOLOGY OF INFLAMMATION-INDUCED COLON CANCER. BEGINNING WITH A GENERAL OVERVIEW OF REACTIVE CHEMICAL SPECIES GENERATED DURING COLONIC INFLAMMATION, THE MECHANISTIC INTERPLAY BETWEEN CHEMICAL AND BIOLOGICAL MEDIATORS OF INFLAMMATION, THE ROLE OF GENETIC TOXICOLOGY, AND MICROBIAL PATHOGENESIS IN DISEASE DEVELOPMENT ARE DISCUSSED. WHEN POSSIBLE, WE SYSTEMATICALLY COMPARE EVIDENCE FROM STUDIES UTILIZING HUMAN IBD PATIENTS WITH EXPERIMENTAL INVESTIGATIONS IN MICE. THE COMPARISON REVEALS THAT MANY STRONG PATHOLOGICAL AND MECHANISTIC CORRELATES EXIST BETWEEN MOUSE MODELS OF COLITIS-ASSOCIATED CANCER, AND THE CLINICALLY RELEVANT SITUATION IN HUMANS. WE ALSO SUMMARIZE SEVERAL EMERGING ISSUES IN THE FIELD, SUCH AS THE CARCINOGENIC POTENTIAL OF NOVEL INFLAMMATION-RELATED DNA ADDUCTS AND GENOTOXIC MICROBIAL FACTORS, THE SYSTEMIC DIMENSION OF INFLAMMATION-INDUCED GENOTOXICITY, AND THE COMPLEX ROLE OF GENOME MAINTENANCE MECHANISMS DURING THESE PROCESSES. TAKEN TOGETHER, CURRENT EVIDENCE POINTS TO THE INDUCTION OF GENETIC AND EPIGENETIC ALTERATIONS BY CHEMICAL AND BIOLOGICAL INFLAMMATORY STIMULI ULTIMATELY LEADING TO CANCER FORMATION. 2013 9 6204 46 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 10 2154 47 EPIGENETIC MECHANISMS AND KIDNEY DISEASES. IN RECENT YEARS, MOLECULAR RESEARCH HAS BROUGHT TO LIGHT A SERIES OF MECHANISMS INVOLVED IN THE REGULATION OF GENE FUNCTION WITHOUT ALTERING THE DNA SEQUENCE. THESE MECHANISMS ARE DESCRIBED WITH THE TERM "EPIGENETICS" AND INCLUDE MODIFICATIONS IN THE STRUCTURE OF THE HUMAN GENOME, LEADING TO HERITABLE AND POTENTIALLY REVERSIBLE CHANGES IN GENE EXPRESSION. THERE IS NOW INCREASING EVIDENCE SUGGESTING THAT SEVERAL CHARACTERISTIC FEATURES OF CHRONIC KIDNEY DISEASE SUCH AS HYPERHOMOCYSTEINEMIA, SUBCLINICAL INFLAMMATION, INCREASED OXIDATIVE STRESS AND OTHERS MAY AFFECT THE HUMAN EPIGENOME. IN ADDITION, ANIMAL STUDIES HAVE SUGGESTED A POSSIBLE LINK BETWEEN NUTRITION AND ENVIRONMENTAL EXPOSURE DURING THE PERICONCEPTIONAL PERIOD AND EPIGENETIC CHANGES IN THE EXPRESSION OF MAJOR GENES IMPLICATED IN KIDNEY ORGANOGENESIS; THESE CHANGES RESULT IN A DIMINISHED NUMBER OF NEPHRONS IN THE DEVELOPING KIDNEY, WHICH PREDISPOSES TO AN INCREASED RISK FOR HYPERTENSION AND CHRONIC KIDNEY DISEASE IN FUTURE LIFE. THE UNDERSTANDING OF THE ROLE OF EPIGENETIC PHENOMENA IN THE PATHOGENESIS OF CHRONIC KIDNEY DISEASE OPENS NEW AVENUES FOR FUTURE THERAPEUTIC STRATEGIES, THROUGH THE DEVELOPMENT OF PHARMACEUTICAL AGENTS THAT TARGET DIRECTLY WITH THE CHANGES IN THE HUMAN EPIGENOME. SUCH EPIGENETIC DRUGS ARE ALREADY IN CLINICAL USE FOR THE TREATMENT OF CANCER AS WELL AS UNDER INVESTIGATION FOR THE USE IN OTHER DISEASES. THIS REVIEW WILL SUMMARIZE THE EXISTING DATA ON THE LINK BETWEEN EPIGENETIC MECHANISMS AND CHRONIC UREMIC MILIEU, AS WELL AS THE PROMISING RESULTS OF ONGOING RESEARCH IN THE FIELD OF EPIGENETIC DRUGS THAT COULD REPRESENT ADDITIONAL OPTIONS IN OUR THERAPEUTIC ARMAMENTARIUM FOR PATIENTS WITH CHRONIC KIDNEY DISEASE. 2011 11 6812 40 [EPIGENETICS, INTERFACE BETWEEN ENVIRONMENT AND GENES: ROLE IN COMPLEX DISEASES]. EPIGENETICS IS THE STUDY OF HERITABLE CHANGES IN GENE EXPRESSION OR CELLULAR PHENOTYPE CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE. EPIGENETICS IS ONE OF THE MAJOR MECHANISMS EXPLAINING THE "DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASES" (DOHAD). BESIDES GENETIC BACKGROUND INHERITED FROM PARENTS, WHICH CONFERS SUSCEPTIBILITY TO CERTAIN PATHOLOGIES, EPIGENETIC CHANGES CONSTITUTE THE MEMORY OF PREVIOUS EVENTS, EITHER POSITIVE OR NEGATIVE, ALONG THE LIFE CYCLE, INCLUDING AT THE IN UTERO STAGE. THE LATER EXPOSITION TO HOSTILE ENVIRONMENT MAY REVEAL SUCH SUSCEPTIBILITY, WITH THE DEVELOPMENT OF VARIOUS PATHOLOGIES, AMONG THEM NUMEROUS CHRONIC COMPLEX DISEASES. THE DEMONSTRATION OF SUCH A SEQUENCE OF EVENTS HAS BEEN SHOWN FOR METABOLIC DISEASES AS OBESITY, METABOLIC SYNDROME AND TYPE 2 DIABETES, CARDIOVASCULAR DISEASE AND CANCER. IN CONTRAST TO GENETIC PREDISPOSITION, WHICH IS IRREVERSIBLE, EPIGENETIC CHANGES ARE POTENTIALLY REVERSIBLE, THUS GIVING TARGETS NOT ONLY FOR PREVENTION, BUT POSSIBLY ALSO FOR THE TREATMENT OF CERTAIN COMPLEX DISEASES. 2012 12 3706 39 INFLUENCE OF GENETICS ON DISEASE SUSCEPTIBILITY AND PROGRESSION. FOR MANY CHRONIC DISEASES, THE INFLUENCE OF GENETICS IS COMPLEX AND PHENOTYPES DO NOT CONFORM TO SIMPLE MENDELIAN PATTERNS OF INHERITANCE. DISCUSSED HERE ARE TWO TYPES OF GENETIC INFLUENCES ON HEALTHY AGING. THE FIRST INVOLVES VARIATION IN THE GENE SEQUENCE ITSELF AND HOW THIS MAY INFLUENCE DISEASE SUSCEPTIBILITY, PROGRESSION, AND SEVERITY, INTERACTING WITH OTHER RECOGNIZED RISK FACTORS. THE SECOND INVOLVES EPIGENETIC REGULATORY MECHANISMS THAT MAY POTENTIALLY PROVIDE INSIGHT INTO HOW ENVIRONMENTAL INFLUENCES AFFECT THE EXPRESSED GENOME, THUS IMPROVING OUR UNDERSTANDING OF THE GENETIC MECHANISMS UNDERLYING MULTIFACTORIAL DISEASES. THE INTERLEUKIN-1 FAMILY OF CYTOKINES CAN BE USED TO ILLUSTRATE HOW GENETIC SEQUENCE VARIATION MAY AFFECT SUCH DISEASES. THIS CYTOKINE FAMILY PLAYS A KEY ROLE IN MEDIATING INFLAMMATION, WHICH IS NOW UNDERSTOOD TO BE A CENTRAL COMPONENT OF A GROWING NUMBER OF CHRONIC DISEASES. RECENT WORK HAS REVEALED MANY SEQUENCE VARIATIONS IN THE REGULATORY DNA OF GENES ENCODING IMPORTANT MEMBERS OF THE INTERLEUKIN-1 FAMILY, AND THESE VARIATIONS ARE ASSOCIATED WITH DIFFERENTIAL EFFECTS ON THE INFLAMMATORY RESPONSE. THE INTERACTIONS OF ENVIRONMENTAL FACTORS WITH BOTH DNA SEQUENCE VARIATIONS AND EPIGENETIC MODIFICATIONS ARE LIKELY TO DETERMINE THE PHENOTYPES OF MULTIFACTORIAL DISEASES OF AGING AS WELL AS THE PHENOTYPE OF HEALTHY AGING. 2007 13 2562 32 EPIGENETICS IN THE PRIMARY AND SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE: INFLUENCE OF EXERCISE AND NUTRITION. INCREASING EVIDENCE LINKS CHANGES IN EPIGENETIC SYSTEMS, SUCH AS DNA METHYLATION, HISTONE MODIFICATION, AND NON-CODING RNA EXPRESSION, TO THE OCCURRENCE OF CARDIOVASCULAR DISEASE (CVD). THESE EPIGENETIC MODIFICATIONS CAN CHANGE GENETIC FUNCTION UNDER INFLUENCE OF EXOGENOUS STIMULI AND CAN BE TRANSFERRED TO NEXT GENERATIONS, PROVIDING A POTENTIAL MECHANISM FOR INHERITANCE OF BEHAVIOURAL INTERVENTION EFFECTS. THE BENEFITS OF EXERCISE AND NUTRITIONAL INTERVENTIONS IN THE PRIMARY AND SECONDARY PREVENTION OF CVD ARE WELL ESTABLISHED, BUT THE MECHANISMS ARE NOT COMPLETELY UNDERSTOOD. IN THIS REVIEW, WE DESCRIBE THE ACUTE AND CHRONIC EPIGENETIC EFFECTS OF PHYSICAL ACTIVITY AND DIETARY CHANGES. WE PROPOSE EXERCISE AND NUTRITION AS POTENTIAL TRIGGERS OF EPIGENETIC SIGNALS, PROMOTING THE RESHAPING OF TRANSCRIPTIONAL PROGRAMMES WITH EFFECTS ON CVD PHENOTYPES. FINALLY, WE HIGHLIGHT RECENT DEVELOPMENTS IN EPIGENETIC THERAPEUTICS WITH IMPLICATIONS FOR PRIMARY AND SECONDARY CVD PREVENTION. 2022 14 5069 34 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 15 4392 38 MODIFIABLE RISK FACTORS IN PERIODONTAL DISEASE: EPIGENETIC REGULATION OF GENE EXPRESSION IN THE INFLAMMATORY RESPONSE. EPIGENETICS AS A MODIFIABLE RISK FACTOR IN PERIODONTAL DISEASES HAS BEEN INVESTIGATED IN LIGHT OF THE CURRENT KNOWLEDGE OF HOW CHRONIC INFECTION AND INFLAMMATION CAN AFFECT GENE-SPECIFIC EPIGENETIC REPROGRAMMING IN PERIODONTAL TISSUES. EPIGENOMIC PROGRAMMING MIGHT BE PARTICULARLY SENSITIVE TO ENVIRONMENTAL INFLUENCES, AND A COMBINATION OF PHYSIOLOGICAL STRESSORS AND ENVIRONMENTAL EXPOSURES APPEARS TO AFFECT THE EPIGENOMIC PROGRAM ACQUIRED BY A CELL DURING DIFFERENTIATION AND THROUGHOUT THE CELLULAR LINEAGE LIFESPAN. VIRAL AND BACTERIAL INFECTIONS CAN ESTABLISH SEVERAL TYPES OF EPIGENETIC MODIFICATIONS, WHICH SOMETIMES ENGAGE IN A COMPLEX EPIGENETIC CROSSTALK ALSO REFLECTING IN THE ESTABLISHMENT AND PROGRESS OF PERIODONTAL DISEASES. THE INFLAMMATORY AND METABOLIC STATES OF THE PERIODONTAL TISSUES ARE DRIVEN BY THE INFECTIOUS STIMULI, AND THE MAGNITUDE OF THE CELLULAR AND MOLECULAR SIGNATURE RESPONSE IS FURTHER DICTATED BY THE HOST GENETIC AND EPIGENETIC TRAITS ASSOCIATED WITH VARIOUS SYSTEMIC EXPOSURES, INCLUDING SMOKING, OBESITY AND DIABETES/HYPERGLYCEMIA. THIS REVIEW DISCUSSES THE ADVANCES IN EPIGENETICS, FOCUSING ON THE ROLE OF DNA METHYLATION IN THE PATHOGENESIS OF PERIODONTAL DISEASE AND THE POTENTIAL OF EPIGENETIC THERAPY. 2014 16 1871 40 EMERGING ROLE OF EPIGENETICS IN EXPLAINING RELATIONSHIP OF PERIODONTITIS AND CARDIOVASCULAR DISEASES. CARDIOVASCULAR DISEASES SUCH AS ISCHEMIC HEART DISEASES OR STROKE ARE AMONG THE LEADING CAUSE OF DEATHS GLOBALLY, AND EVIDENCE SUGGESTS THAT THESE DISEASES ARE MODULATED BY A MULTIFACTORIAL AND COMPLEX INTERPLAY OF GENETIC, ENVIRONMENTAL, AND LIFESTYLE FACTORS. GENETIC PREDISPOSITION AND CHRONIC EXPOSURE TO MODIFIABLE RISK FACTORS HAVE BEEN EXPLORED TO BE INVOLVED IN THE PATHOPHYSIOLOGY OF CVD. ENVIRONMENTAL FACTORS CONTRIBUTE TO AN INDIVIDUAL'S PROPENSITY TO DEVELOP MAJOR CARDIOVASCULAR RISK FACTORS THROUGH EPIGENETIC MODIFICATIONS OF DNA AND HISTONES VIA MIRNA REGULATION OF PROTEIN TRANSLATION THAT ARE TYPES OF EPIGENETIC MECHANISMS AND PARTICIPATE IN DISEASE DEVELOPMENT. PERIODONTAL DISEASE (PD) IS ONE OF THE MOST COMMON ORAL DISEASES IN HUMANS THAT IS CHARACTERIZED BY LOW-GRADE INFLAMMATION AND HAS BEEN SHOWN TO INCREASE THE RISK OF CVDS. RISK FACTORS INVOLVED IN PD AND CVD ARE DETERMINED BOTH GENETICALLY AND BEHAVIORALLY. PERIODONTAL DISEASES SUCH AS CHRONIC INFLAMMATION PROMOTE DNA METHYLATION. EPIGENETIC MODIFICATIONS INVOLVED IN THE INITIATION AND PROGRESSION OF ATHEROSCLEROSIS PLAY AN ESSENTIAL ROLE IN PLAQUE DEVELOPMENT AND VULNERABILITY. EPIGENETICS HAS OPENED A NEW WORLD TO UNDERSTAND AND MANAGE HUMAN DISEASES, INCLUDING CVDS AND PERIODONTAL DISEASES. GENETIC MEDICINE HAS STARTED A NEW ERA OF EPIGENETICS TO OVERCOME HUMAN DISEASES WITH VARIOUS NEW METHODOLOGY. EPIGENETIC PROFILING MAY AID IN BETTER DIAGNOSIS AND STRATIFICATION OF PATIENTS SHOWING POTENTIAL PREDISPOSED STATES FOR DISEASE. A BETTER UNDERSTANDING OF THE EXACT REGULATORY MECHANISMS OF EPIGENETIC PATHWAYS DRIVING INFLAMMATION IS SLOWLY EMERGING AND WILL AID IN DEVELOPING NOVEL TOOLS FOR THE TREATMENT OF DISEASE. 2021 17 5929 40 TARGETING EPIGENETIC MECHANISMS IN PERIODONTAL DISEASES. EPIGENETIC FACTORS ARE HERITABLE GENOME MODIFICATIONS THAT POTENTIALLY IMPACT GENE TRANSCRIPTION, CONTRIBUTING TO DISEASE STATES. EPIGENETIC MARKS PLAY AN IMPORTANT ROLE IN CHRONIC INFLAMMATORY CONDITIONS, AS OBSERVED IN PERIODONTAL DISEASES, BY ALLOWING MICROBIAL PERSISTENCE OR BY PERMITTING MICROBIAL INSULT TO PLAY A ROLE IN THE SO-CALLED 'HIT-AND-RUN' INFECTIOUS MECHANISM, LEADING TO LASTING PATHOGEN INTERFERENCE WITH THE HOST GENOME. EPIGENETICS ALSO AFFECTS THE HEALTH SCIENCES BY PROVIDING A DYNAMIC MECHANISTIC FRAMEWORK TO EXPLAIN THE WAY IN WHICH ENVIRONMENTAL AND BEHAVIORAL FACTORS INTERACT WITH THE GENOME TO ALTER DISEASE RISK. IN THIS ARTICLE WE REVIEW CURRENT KNOWLEDGE OF EPIGENOME REGULATION IN LIGHT OF THE MULTIFACTORIAL NATURE OF PERIODONTAL DISEASES. WE DISCUSS EPIGENETIC TAGGING IN IDENTIFIED GENES, AND CONSIDER THE POTENTIAL IMPLICATIONS OF EPIGENETIC CHANGES ON HOST-MICROBIOME DYNAMICS IN CHRONIC INFLAMMATORY STATES AND IN RESPONSE TO ENVIRONMENTAL STRESSORS. THE MOST RECENT ADVANCES IN GENOMIC TECHNOLOGIES HAVE PLACED US IN A POSITION TO ANALYZE INTERACTION EFFECTS (EG, BETWEEN PERIODONTAL DISEASE AND TYPE 2 DIABETES MELLITUS), WHICH CAN BE INVESTIGATED THROUGH EPIGENOME-WIDE ASSOCIATION ANALYSIS. FINALLY, BECAUSE OF THE INDIVIDUALIZED TRAITS OF EPIGENETIC BIOMARKERS, PHARMACOEPIGENOMIC PERSPECTIVES ARE ALSO CONSIDERED AS POTENTIALLY NOVEL THERAPEUTIC APPROACHES FOR IMPROVING PERIODONTAL DISEASE STATUS. 2018 18 3016 27 GENETICS AND EPIGENETICS OF IBD. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC INTERMITTENT INFLAMMATORY DISORDERS OF THE GASTROINTESTINAL TRACT OF UNKNOWN ETIOLOGY BUT A CLEAR GENETIC PREDISPOSITION. PROMPTED BY THE FIRST INVESTIGATIONS ON IBD FAMILIES AND TWINS, THE GENETIC AND EPIGENETIC STUDIES HAVE PRODUCED AN UNPRECEDENTED AMOUNT OF INFORMATION IN COMPARISON WITH OTHER IMMUNE-MEDIATED OR COMPLEX DISEASES. NEW INFLAMMATORY PATHWAYS AND POSSIBLE MECHANISMS OF ACTION HAVE BEEN DISCLOSED, POTENTIALLY LEADING TO NEW-TARGETED THERAPY. HOWEVER, THE IDENTIFICATION OF GENETIC MARKERS DUE TO THE GREAT DISEASE HETEROGENEITY AND THE OVERWHELMING CONTRIBUTION OF ENVIRONMENTAL RISK FACTORS HAS NOT MODIFIED YET THE DISEASE MANAGEMENT. THE POSSIBILITY FOR THE FUTURE OF A BETTER PREDICTION OF DISEASE COURSE, RESPONSE TO THERAPY AND THERAPY-RELATED ADVERSE EVENTS MAY ALLOW A MORE EFFICIENT AND PERSONALIZED STRATEGY. THIS REVIEW WILL FOCUS ON MORE RECENT DISCOVERIES THAT MAY POTENTIALLY BE OF RELEVANCE IN DAILY CLINICAL PRACTICE. 2020 19 6288 42 THE POTENTIAL ROLE OF EPIGENETIC MODIFICATIONS ON DIFFERENT FACETS IN THE PERIODONTAL PATHOGENESIS. PERIODONTITIS IS A CHRONIC INFLAMMATORY DISEASE THAT AFFECTS THE SUPPORTING STRUCTURES OF TEETH. IN THE LITERATURE, THE ASSOCIATION BETWEEN THE PATHOGENICITY OF BACTERIA AND ENVIRONMENTAL FACTORS IN THIS REGARD HAVE BEEN EXTENSIVELY EXAMINED. IN THE PRESENT STUDY, WE WILL SHED LIGHT ON THE POTENTIAL ROLE THAT EPIGENETIC CHANGE CAN PLAY ON DIFFERENT FACETS OF ITS PROCESS, MORE PARTICULARLY THE MODIFICATIONS CONCERNING THE GENES INVOLVED IN INFLAMMATION, DEFENSE, AND IMMUNE SYSTEMS. SINCE THE 1960S, THE ROLE OF GENETIC VARIANTS IN THE ONSET AND SEVERITY OF PERIODONTAL DISEASE HAS BEEN WIDELY DEMONSTRATED. THESE MAKE SOME PEOPLE MORE SUSCEPTIBLE TO DEVELOPING IT THAN OTHERS. IT HAS BEEN DOCUMENTED THAT THE WIDE VARIATION IN ITS FREQUENCY FOR VARIOUS RACIAL AND ETHNIC POPULATIONS IS DUE PRIMARILY TO THE COMPLEX INTERPLAY AMONG GENETIC FACTORS WITH THOSE AFFECTING THE ENVIRONMENT AND THE DEMOGRAPHY. IN MOLECULAR BIOLOGY, EPIGENETIC MODIFICATIONS ARE DEFINED AS ANY CHANGE IN THE PROMOTER FOR THE CPG ISLANDS, IN THE STRUCTURE OF THE HISTONE PROTEIN, AS WELL AS POST-TRANSLATIONAL REGULATION BY MICRORNAS (MIRNAS), BEING KNOWN TO CONTRIBUTE TO THE ALTERATION IN GENE EXPRESSION FOR COMPLEX MULTIFACTORIAL DISEASES SUCH AS PERIODONTITIS. THE KEY ROLE OF EPIGENETIC MODIFICATION IS TO UNDERSTAND THE MECHANISM INVOLVED IN THE GENE-ENVIRONMENT INTERACTION, AND THE DEVELOPMENT OF PERIODONTITIS IS NOW THE SUBJECT OF MORE AND MORE STUDIES THAT ATTEMPT TO IDENTIFY WHICH FACTORS ARE STIMULATING IT, BUT ALSO AFFECT THE REDUCED RESPONSE TO THERAPY. 2023 20 2027 39 EPIGENETIC CHANGES IN CHRONIC INFLAMMATORY DISEASES. THE NUMBER OF PEOPLE DIAGNOSED WITH CHRONIC INFLAMMATORY DISEASES HAS INCREASED NOTEWORTHY IN THE LAST 40 YEARS. SPONDYLOARTHRITIS (SPA), INFLAMMATORY BOWEL DISEASES (IBD), AND PSORIASIS ARE THE MOST FREQUENT CHRONIC INFLAMMATORY DISEASES, RESULTING FROM A COMBINATION OF GENETIC PREDISPOSITION AND ENVIRONMENTAL FACTORS. EPIGENETIC MODIFICATIONS INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS, AND SMALL AND LONG NONCODING RNAS. THEY ARE INFLUENCED BY ENVIRONMENTAL EXPOSURE, LIFE-STYLE, AND AGING AND HAVE RECENTLY BEEN SHOWN TO BE ALTERED IN MANY COMPLEX DISEASES INCLUDING INFLAMMATORY DISEASES. WHILE EPIGENETIC MODIFICATIONS HAVE BEEN WELL CHARACTERIZED IN OTHER DISEASES SUCH AS CANCER AND AUTOIMMUNE DISEASES, KNOWLEDGE ON CHANGES IN INFLAMMATORY DISEASES IS LAGGING BEHIND WITH SOME DISEASE-SPECIFIC DIFFERENCES. WHILE THE DNA METHYLATION PROFILE OF DIFFERENT CELL TYPES IN PATIENTS WITH IBD HAS BEEN RELATIVELY WELL DESCRIBED, LESS IS KNOWN ON CHANGES IMPLICATED IN PSORIASIS, AND NO SYSTEMATIC GENOME-WIDE STUDIES HAVE SO FAR BEEN PERFORMED IN SPA. IN THIS CHAPTER, WE REVIEW IN DETAIL THE REPORTED CHANGES IN PATTERNS OF DNA METHYLATION AND POSTTRANSLATIONAL HISTONE MODIFICATIONS IN CHRONIC INFLAMMATORY DISEASES HIGHLIGHTING POTENTIAL CONNECTIONS BETWEEN DISEASE-ASSOCIATED PATHOPHYSIOLOGICAL CHANGES SUCH AS THE DYSBIOSIS OF THE MICROBIOME OR GENETIC VARIATIONS ASSOCIATED WITH DISEASE SUSCEPTIBILITY AND THE EPIGENOME. WE ALSO DISCUSS IMPORTANT PARAMETERS OF MEANINGFUL EPIGENETIC STUDIES SUCH AS THE USE OF WELL DEFINED, DISEASE-RELEVANT CELL POPULATIONS, AND ELUDE ON THE POTENTIAL FUTURE OF ENGINEERING OF THE EPIGENOME IN INFLAMMATORY DISEASES. 2017