1 4365 112 MIRNA MOLECULES-LATE BREAKING TREATMENT FOR INFLAMMATORY BOWEL DISEASES? MICRORNAS (MIRNAS) ARE A GROUP OF NON-CODING RNAS THAT PLAY A CRITICAL ROLE IN REGULATING EPIGENETIC MECHANISMS IN INFLAMMATION-RELATED DISEASES. INFLAMMATORY BOWEL DISEASES (IBDS), WHICH PRIMARILY INCLUDE ULCERATIVE COLITIS (UC) AND CROHN'S DISEASE (CD), ARE CHARACTERIZED BY CHRONIC RECURRENT INFLAMMATION OF INTESTINAL TISSUES. DUE TO THE MULTIFACTORIAL ETIOLOGY OF THESE DISEASES, THE DEVELOPMENT OF INNOVATIVE TREATMENT STRATEGIES THAT CAN EFFECTIVELY MAINTAIN REMISSION AND ALLEVIATE DISEASE SYMPTOMS IS A MAJOR CHALLENGE. IN RECENT YEARS, EVIDENCE FOR THE REGULATORY ROLE OF MIRNAS IN THE PATHOGENETIC MECHANISMS OF VARIOUS DISEASES, INCLUDING IBD, HAS BEEN ACCUMULATING. IN LIGHT OF THESE FINDINGS, MIRNAS REPRESENT POTENTIAL INNOVATIVE CANDIDATES FOR THERAPEUTIC APPLICATION IN IBD. IN THIS REVIEW, WE DISCUSS RECENT FINDINGS ON THE ROLE OF MIRNAS IN REGULATING INFLAMMATORY RESPONSES, MAINTAINING INTESTINAL BARRIER INTEGRITY, AND DEVELOPING FIBROSIS IN CLINICAL AND EXPERIMENTAL IBD. THE FOCUS IS ON THE EXISTING LITERATURE, INDICATING POTENTIAL THERAPEUTIC APPLICATION OF MIRNAS IN BOTH PRECLINICAL EXPERIMENTAL IBD MODELS AND TRANSLATIONAL DATA IN THE CONTEXT OF CLINICAL IBD. TO DATE, A LARGE AND DIVERSE DATA SET, WHICH IS GROWING RAPIDLY, SUPPORTS THE POTENTIAL USE OF MIRNA-BASED THERAPIES IN CLINICAL PRACTICE, ALTHOUGH MANY QUESTIONS REMAIN UNANSWERED. 2023 2 3541 38 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 3 2875 38 FUNCTIONAL ROLE AND THERAPEUTIC TARGETING OF MICRORNAS IN INFLAMMATORY BOWEL DISEASE. INFLAMMATORY BOWEL DISEASES (IBD) ARE CHRONIC INFLAMMATORY GASTROINTESTINAL DISEASES, PRIMARILY CONSISTING OF ULCERATIVE COLITIS AND CROHN'S DISEASE. THE COMPLEX NATURE OF THE DISEASE, AS WELL AS THE LIMITED THERAPEUTIC OPTIONS CHARACTERIZED BY LOW EFFICIENCY AND MAJOR SIDE EFFECTS, HIGHLIGHTS THE IMPORTANCE OF DEVELOPING NOVEL STRATEGIES OF THERAPEUTIC INTERVENTION IN IBD. SUSCEPTIBILITY LOCI RELATED TO IBD ARE PRESENT ONLY IN A SMALL PERCENTAGE OF IBD PATIENTS, IMPLYING THAT EPIGENETIC MODIFICATIONS COULD INFLUENCE THE PATHOGENESIS OF THE DISEASE. MICRORNAS (MIRNAS) ARE SMALL NONCODING RNAS THAT REGULATE MULTIPLE MOLECULAR PATHWAYS INVOLVED IN IBD PATHOBIOLOGY. MIRNA INHIBITORS TARGETING THE IBD-ACTIVATED MIRNAS COULD HAVE THERAPEUTIC VALUE FOR IBD PATIENTS. THIS REVIEW PROVIDES AN OVERVIEW OF THE RECENT ADVANCES IN MIRNA BIOLOGY RELATED TO IBD PATHOGENESIS AND THE PHARMACOLOGICAL DEVELOPMENT OF MIRNA-BASED THERAPEUTICS. 2018 4 2675 35 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 5 4670 30 NEW INSIGHTS INTO THE EPIGENETIC REGULATION OF INFLAMMATORY BOWEL DISEASE. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC INFLAMMATORY DISEASE OF THE COLONIC MUCOSA. ENVIRONMENTAL FACTORS, GENETICS, INTESTINAL MICROBIOTA, AND THE IMMUNE SYSTEM ARE ALL INVOLVED IN THE PATHOPHYSIOLOGY OF IBD. LATELY, ACCUMULATING EVIDENCE HAS SHOWN THAT ABNORMAL EPIGENETIC CHANGES IN DNA METHYLATION, HISTONE MARKERS, AND NON-CODING RNA EXPRESSION GREATLY CONTRIBUTE TO THE DEVELOPMENT OF THE ENTIRE DISEASE. EPIGENETICS REGULATES MANY FUNCTIONS, SUCH AS MAINTAINING THE HOMEOSTASIS OF THE INTESTINAL EPITHELIUM AND REGULATING THE IMMUNE SYSTEM OF THE IMMUNE CELLS. IN THE PRESENT STUDY, WE SYSTEMATICALLY SUMMARIZED THE LATEST ADVANCES IN EPIGENETIC MODIFICATION OF IBD AND HOW EPIGENETICS REVEALS NEW MECHANISMS OF IBD. OUR PRESENT REVIEW PROVIDED NEW INSIGHTS INTO THE PATHOPHYSIOLOGY OF IBD. MOREOVER, EXPLORING THE PATTERNS OF DNA METHYLATION AND HISTONE MODIFICATION THROUGH EPIGENETICS CAN NOT ONLY BE USED AS BIOMARKERS OF IBD BUT ALSO AS A NEW TARGET FOR THERAPEUTIC INTERVENTION IN IBD PATIENTS. 2022 6 5528 27 RNA MODIFICATION IN INFLAMMATORY BOWEL DISEASES. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC INFLAMMATORY DISORDER CHARACTERIZED BY DAMAGE TO THE INTESTINAL MUCOSA, WHICH IS CAUSED BY A COMBINATION OF FACTORS. THESE INCLUDE GENETIC AND EPIGENETIC ALTERATIONS, ENVIRONMENTAL INFLUENCE, MICROORGANISM INTERACTIONS, AND IMMUNE CONDITIONS. SOME POPULATIONS WITH IBD SHOW A CANCER-PRONE PHENOTYPE. RECENT STUDIES HAVE PROVIDED INSIGHT INTO THE INVOLVEMENT OF RNA MODIFICATIONS IN THE SPECIFIC PATHOGENESIS OF IBD THROUGH REGULATION OF RNA BIOLOGY IN EPITHELIAL AND IMMUNE CELLS. STUDIES OF SEVERAL RNA MODIFICATION-TARGETING REAGENTS HAVE SHOWN PREFERABLE OUTCOMES IN PATIENTS WITH COLITIS. HERE, WE NOTE A NEW AWARENESS OF RNA MODIFICATION IN THE TARGETING OF IBD AND RELATED DISEASES, WHICH WILL CONTRIBUTE TO EARLY DIAGNOSIS, DISEASE MONITORING, AND POSSIBLE CONTROL BY INNOVATIVE THERAPEUTIC APPROACHES. 2022 7 2601 43 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 8 3017 25 GENETICS AND EPIGENETICS OF INFLAMMATORY BOWEL DISEASE. THE RELEVANCE OF GENETIC AND EPIGENETIC ALTERATIONS IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE (IBD) IS STILL POORLY UNDERSTOOD. SO FAR, 240 RISK GENE LOCI HAVE BEEN ASSOCIATED WITH IBD. THEY ARE MAINLY INVOLVED IN REGULATING INNATE AND ADAPTIVE IMMUNITY, AS WELL AS MAINTAINING INTESTINAL EPITHELIAL BARRIER FUNCTION. HOWEVER, THE FUNCTIONAL CONSEQUENCES OF THE IDENTIFIED GENETIC POLYMORPHISMS FOR IBD PATHOGENESIS IN VIVO ARE OFTEN UNKNOWN. EVEN LESS IS KNOWN ABOUT THE ROLE FOR EPIGENETIC MODIFICATIONS IN IBD PATHOGENESIS. THOUGH A NUMBER OF EPIGENETIC EVENTS SEEM TO BE CAUSATIVELY INVOLVED IBD PATHOGENESIS, OUR KNOWLEDGE ABOUT THE FUNCTIONAL RELEVANCE OF THOSE EPIGENETIC MODIFICATIONS IS SCANTY. THIS OPENS UP A BROAD RESEARCH FIELD THAT GENERATES NOVEL INSIGHTS INTO THE PATHOPHYSIOLOGY OF INTESTINAL AND CHRONIC INFLAMMATORY DISEASE. PATTERNS OF DNA METHYLATION AND HISTONE MODIFICATIONS MIGHT SERVE NOT ONLY AS BIOMARKERS OF DISEASE ACTIVITY OR DISEASE COURSE, BUT ALSO AS NEW TARGETS IN THERAPEUTIC INTERVENTIONS IN IBD PATIENTS. 2018 9 3920 27 LINKING IMMUNITY, EPIGENETICS, AND CANCER IN INFLAMMATORY BOWEL DISEASE. MOST OF WHAT IS KNOWN ABOUT THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE (IBD) PERTAINS TO COMPLEX INTERPLAY BETWEEN HOST GENETICS, IMMUNITY, AND ENVIRONMENTAL FACTORS. EPIGENETIC MODIFICATIONS PLAY PIVOTAL ROLES IN INTESTINAL IMMUNITY AND MUCOSAL HOMEOSTASIS AS WELL AS MEDIATING GENE-ENVIRONMENT INTERACTIONS. IN THIS ARTICLE, WE PROVIDE A HISTORICAL ACCOUNT OF EPIGENETIC RESEARCH EITHER DIRECTLY RELATED OR PERTINENT TO THE PATHOGENESIS AND MANAGEMENT OF IBD. WE FURTHER COLLATE EMERGING EVIDENCE SUPPORTING ROLES FOR EPIGENETIC MECHANISMS IN RELEVANT ASPECTS OF IBD BIOLOGY, INCLUDING DEREGULATED IMMUNITY, HOST-PATHOGEN RECOGNITION AND MUCOSAL INTEGRITY. FINALLY, WE HIGHLIGHT KEY EPIGENETIC MECHANISMS THAT LINK CHRONIC INFLAMMATION TO SPECIFIC IBD COMORBIDITIES, INCLUDING COLITIS-ASSOCIATED CANCER AND DISCUSS THEIR POTENTIAL UTILITY AS NOVEL BIOMARKERS OR PHARMACOLOGIC TARGETS IN IBD THERAPY. 2014 10 1522 42 DNA METHYLATION CHANGE PROFILING OF COLORECTAL DISEASE: SCREENING TOWARDS CLINICAL USE. COLON CANCER REMAINS ONE OF THE LEADING CAUSES OF CANCER-RELATED DEATHS WORLDWIDE. TRANSFORMATION OF COLON EPITHELIAL CELLS INTO INVASIVE ADENOCARCINOMAS HAS BEEN WELL KNOWN TO BE DUE TO THE ACCUMULATION OF MULTIPLE GENETIC AND EPIGENETIC CHANGES. IN THE PAST DECADE, THE ETIOLOGY OF INFLAMMATORY BOWEL DISEASE (IBD) WHICH IS CHARACTERIZED BY CHRONIC INFLAMMATION OF THE INTESTINAL MUCOSA, WAS ONLY PARTIALLY EXPLAINED BY GENETIC STUDIES PROVIDING SUSCEPTIBILITY LOCI, BUT RECENTLY EPIGENETIC STUDIES HAVE PROVIDED CRITICAL EVIDENCES AFFECTING IBD PATHOGENESIS. OVER THE PAST DECADE, A DEEP UNDERSTANDING OF EPIGENETICS ALONG WITH TECHNOLOGICAL ADVANCES HAVE LED TO IDENTIFYING NUMEROUS GENES THAT ARE REGULATED BY PROMOTER DNA HYPERMETHYLATION IN COLORECTAL DISEASES. RECENT ADVANCES IN OUR UNDERSTANDING OF THE ROLE OF DNA METHYLATION IN COLORECTAL DISEASES COULD IMPROVE A MULTITUDE OF POWERFUL DNA METHYLATION-BASED BIOMARKERS, PARTICULARLY FOR USE AS DIAGNOSIS, PROGNOSIS, AND PREDICTION FOR THERAPEUTIC APPROACHES. THIS REVIEW FOCUSES ON THE EMERGING POTENTIAL FOR TRANSLATIONAL RESEARCH OF EPIGENETIC ALTERATIONS INTO CLINICAL UTILITY AS MOLECULAR BIOMARKERS. MOREOVER, THIS REVIEW DISCUSSES RECENT PROGRESS REGARDING THE IDENTIFICATION OF UNKNOWN HYPERMETHYLATED GENES IN COLON CANCERS AND IBD, AS WELL AS THEIR POSSIBLE ROLE IN CLINICAL PRACTICE, WHICH WILL HAVE IMPORTANT CLINICAL SIGNIFICANCE, PARTICULARLY IN THE ERA OF THE PERSONALIZED MEDICINE. 2021 11 1275 38 DAMAGE-ASSOCIATED MOLECULAR PATTERNS IN INFLAMMATORY BOWEL DISEASE: FROM BIOMARKERS TO THERAPEUTIC TARGETS. THE CHRONIC INFLAMMATORY PROCESS UNDERLYING INFLAMMATORY BOWEL DISEASE (IBD), COMPRISING CROHN'S DISEASE AND ULCERATIVE COLITIS, DERIVES FROM THE INTERPLAY OF SEVERAL COMPONENTS IN A GENETICALLY SUSCEPTIBLE HOST. THESE COMPONENTS INCLUDE ENVIRONMENTAL ELEMENTS AND GUT MICROBIOTA A DYSBIOSIS. FOR DECADES, IMMUNE ABNORMALITIES HAVE BEEN INVESTIGATED AS CRITICALLY IMPORTANT IN IBD PATHOGENESIS, AND ATTEMPTS TO DEVELOP EFFECTIVE THERAPIES HAVE PREDOMINANTLY TARGETED THE IMMUNE SYSTEM. NEVERTHELESS, IMMUNE EVENTS REPRESENT ONLY ONE OF THE CONSTITUENTS CONTRIBUTING TO IBD PATHOGENESIS WITHIN THE CONTEXT OF THE COMPLEX CELLULAR AND MOLECULAR NETWORK UNDERLYING CHRONIC INTESTINAL INFLAMMATION. THESE FACTORS NEED TO BE APPRECIATED WITHIN THE MILIEU OF NON-IMMUNE COMPONENTS. DAMAGE-ASSOCIATED MOLECULAR PATTERNS (DAMPS), WHICH ARE ESSENTIALLY ENDOGENOUS STRESS PROTEINS EXPRESSED OR RELEASED AS A RESULT OF CELL OR TISSUE DAMAGE, HAVE BEEN SHOWN TO ACT AS DIRECT PRO-INFLAMMATORY MEDIATORS. EXCESSIVE OR PERSISTENT SIGNALLING MEDIATED BY SUCH MOLECULES CAN UNDERLIE SEVERAL CHRONIC INFLAMMATORY DISORDERS, INCLUDING IBD. THE RELEASE OF ENDOGENOUS DAMPS AMPLIFIES THE INFLAMMATORY RESPONSE DRIVEN BY IMMUNE AND NON-IMMUNE CELLS AND PROMOTES EPIGENETIC REPROGRAMMING IN IBD. THE EFFECTS DETERMINE PATHOLOGIC CHANGES, WHICH MAY SUSTAIN CHRONIC INTESTINAL INFLAMMATION AND ALSO UNDERLIE SPECIFIC DISEASE PHENOTYPES. IN ADDITION TO HIGHLIGHTING THE POTENTIAL USE OF DAMPS SUCH AS CALPROTECTIN AS BIOMARKERS, RESEARCH ON DAMPS MAY REVEAL NOVEL MECHANISTIC ASSOCIATIONS IN IBD PATHOGENESIS AND IS EXPECTED TO UNCOVER PUTATIVE THERAPEUTIC TARGETS. 2018 12 2333 28 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 13 2578 39 EPIGENETICS OF INFLAMMATORY BOWEL DISEASES. INFLAMMATORY BOWEL DISEASES ARE MULTIFACTORIAL, CHRONIC, CONTINUOUS, RELAPSING, AND IMMUNE-MEDIATED DISEASES OF THE GASTROINTESTINAL TRACT. IT HAS BEEN BELIEVED THAT MECHANISMS UNDERLYING INFLAMMATORY BOWEL DISEASES INCLUDE GENETIC PREDISPOSITION, ENVIRONMENTAL FACTORS, AND ALTERED IMMUNE RESPONSE TO THE GUT MICROBIOME. THE EPIGENETIC MODULATION TAKES PLACE VIA CHROMATIN MODIFICATIONS, INCLUDING PHOSPHORYLATION, ACETYLATION, METHYLATION, SUMOYLATION, AND UBIQUITINATION. THE METHYLATION LEVELS OF COLONIC TISSUE WERE FOUND WELL CORRELATED TO BLOOD SAMPLES IN INFLAMMATORY BOWEL DISEASES. MOREOVER, THE METHYLATION LEVEL OF SPECIFIC GENES WAS DIFFERENT BETWEEN CROHN'S DISEASE AND ULCERATIVE COLITIS. IT HAS BEEN SHOWN THAT THE ENZYMES AFFECTING HISTONE MODIFICATIONS LIKE HISTONE DEACETYLASES AND HISTONE ACETYLTRANSFERASES DO NOT ACT SOLELY ON HISTONES BUT ALSO AFFECT THE ACETYLATION OF MANY PROTEINS SUCH AS P53 AND STAT3. IT HAS BEEN ALREADY SHOWN THAT A NONSELECTIVE HISTONE DEACETYLASE INHIBITOR, VORINOSTAT (SAHA), WHICH IS CURRENTLY BEING USED IN SEVERAL CANCER TREATMENTS, SHOWED ANTI-INFLAMMATORY ACTIVITIES IN MOUSE MODELS. AMONG EPIGENETIC ALTERATIONS, LONG NON-CODING RNAS AND MICRORNAS PLAY SIGNIFICANT ROLES IN T-CELL MATURATION, DIFFERENTIATION, ACTIVATION, AND SENILITY. THE LONG NON-CODING RNA AND MICRORNA EXPRESSION PROFILES CAN PERFECTLY SEPARATE INFLAMMATORY BOWEL DISEASE PATIENTS FROM HEALTHY CONTROLS AND ARE REMARKED AS BIOMARKERS OF INFLAMMATORY BOWEL DISEASES. OVERALL, MANY STUDIES HAVE SHOWN THAT EPIGENETIC INHIBITORS CAN TARGET SIGNIFICANT SIGNAL PATHWAYS IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASES, AND THE IMPACT OF EPIGENETIC INHIBITORS IS BEING STUDIED IN CLINICAL TRIALS. IN CONCLUSION, EXPLORING MORE EPIGENETIC PATHWAYS REGARDING INFLAMMATORY BOWEL DISEASE PATHOGENESIS WILL HELP US TO DISCOVER THERAPEUTIC TARGETS AND NEW DRUGS AND AGENTS TARGETING MIRNAS IN INFLAMMATORY BOWEL DISEASES. IN GENERAL, DISCOVERING EPIGENETIC TARGETS COULD IMPROVE THE DIAGNOSIS AND TREATMENT OF INFLAMMATORY BOWEL DISEASES. 2023 14 4283 39 MICRORNA BIOMARKERS IN IBD-DIFFERENTIAL DIAGNOSIS AND PREDICTION OF COLITIS-ASSOCIATED CANCER. INFLAMMATORY BOWEL DISEASE (IBD) INCLUDES CROHN'S DISEASE (CD) AND ULCERATIVE COLITIS (UC). THESE ARE CHRONIC AUTOIMMUNE DISEASES OF UNKNOWN ETIOLOGY AFFECTING THE GASTROINTESTINAL TRACT. THE IBD POPULATION INCLUDES A HETEROGENEOUS GROUP OF PATIENTS WITH VARYING DISEASE COURSES REQUIRING PERSONALIZED TREATMENT PROTOCOLS. THE COMPLEXITY OF THE DISEASE OFTEN DELAYS THE DIAGNOSIS AND THE INITIATION OF APPROPRIATE TREATMENTS. IN A SUBSET OF PATIENTS, IBD LEADS TO COLITIS-ASSOCIATED CANCER (CAC). MICRORNAS ARE SINGLE-STRANDED REGULATORY NONCODING RNAS OF 18 TO 22 NUCLEOTIDES WITH PUTATIVE ROLES IN THE PATHOGENESIS OF IBD AND COLORECTAL CANCER. THEY HAVE BEEN EXPLORED AS BIOMARKERS AND THERAPEUTIC TARGETS. BOTH TISSUE-DERIVED AND CIRCULATING MICRORNAS HAVE EMERGED AS PROMISING BIOMARKERS IN THE DIFFERENTIAL DIAGNOSIS AND IN THE PROGNOSIS OF DISEASE SEVERITY OF IBD AS WELL AS PREDICTIVE BIOMARKERS IN DRUG RESISTANCE. IN ADDITION, KNOWLEDGE OF THE CELLULAR LOCALIZATION OF DIFFERENTIALLY EXPRESSED MICRORNAS IS A PREREQUISITE FOR DECIPHERING THE BIOLOGICAL ROLE OF THESE IMPORTANT EPIGENETIC REGULATORS AND THE CELLULAR LOCALIZATION MAY EVEN CONTRIBUTE TO AN ALTERNATIVE REPERTOIRE OF BIOMARKERS. IN THIS REVIEW, WE DISCUSS FINDINGS BASED ON RT-QPCR, MICROARRAY PROFILING, NEXT GENERATION SEQUENCING AND IN SITU HYBRIDIZATION OF MICRORNA BIOMARKERS IDENTIFIED IN THE CIRCULATION AND IN TISSUE BIOPSIES. 2020 15 3016 33 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 16 2952 19 GENETIC AND EPIGENETIC ETIOLOGY OF INFLAMMATORY BOWEL DISEASE: AN UPDATE. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC DISEASE WITH PERIODS OF EXACERBATION AND REMISSION OF THE DISEASE. THE ETIOLOGY OF IBD IS NOT FULLY UNDERSTOOD. MANY STUDIES POINT TO THE PRESENCE OF GENETIC, IMMUNOLOGICAL, ENVIRONMENTAL, AND MICROBIOLOGICAL FACTORS AND THE INTERACTIONS BETWEEN THEM IN THE OCCURRENCE OF IBD. THE REVIEW LOOKS AT GENETIC FACTORS IN THE CONTEXT OF BOTH IBD PREDISPOSITION AND PHARMACOGENETICS. 2022 17 1404 28 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 18 6353 34 THE ROLE OF GENETIC AND EPIGENETIC REGULATION IN INTESTINAL FIBROSIS IN INFLAMMATORY BOWEL DISEASE: A DESCENDING PROCESS OR A PROGRAMMED CONSEQUENCE? INFLAMMATORY BOWEL DISEASES (IBDS) ARE A GROUP OF CHRONIC DISEASES CHARACTERIZED BY RECURRING PERIODS OF EXACERBATION AND REMISSION. FIBROSIS OF THE INTESTINE IS ONE OF THE MOST COMMON COMPLICATIONS OF IBD. BASED ON CURRENT ANALYSES, IT IS EVIDENT THAT GENETIC FACTORS AND MECHANISMS, AS WELL AS EPIGENETIC FACTORS, PLAY A ROLE IN THE INDUCTION AND PROGRESSION OF INTESTINAL FIBROSIS IN IBD. KEY GENETIC FACTORS AND MECHANISMS THAT APPEAR TO BE SIGNIFICANT INCLUDE NOD2, TGF-BETA, TLRS, IL23R, AND ATG16L1. DEOXYRIBONUCLEIC ACID (DNA) METHYLATION, HISTONE MODIFICATION, AND RIBONUCLEIC ACID (RNA) INTERFERENCE ARE THE PRIMARY EPIGENETIC MECHANISMS. GENETIC AND EPIGENETIC MECHANISMS, WHICH SEEM TO BE IMPORTANT IN THE PATHOPHYSIOLOGY AND PROGRESSION OF IBD, MAY POTENTIALLY BE USED IN TARGETED THERAPY IN THE FUTURE. THEREFORE, THE AIM OF THIS STUDY WAS TO GATHER AND DISCUSS SELECTED MECHANISMS AND GENETIC FACTORS, AS WELL AS EPIGENETIC FACTORS. 2023 19 4330 43 MICRORNAS: AN EPIGENETIC TOOL TO STUDY CELIAC DISEASE. THIS ARTICLE SUMMARIZES RECENT FINDINGS ON THE ROLE OF MICRORNAS (MIRNAS) IN BIOLOGICAL PROCESSES ASSOCIATED WITH THE REGULATION OF CHRONIC INFLAMMATION AND AUTOIMMUNITY. MIRNAS ARE SMALL NON-CODING RNA MOLECULES THAT HAVE BEEN RECENTLY EMERGED AS A NEW CLASS OF MODULATORS OF GENE EXPRESSION AT THE POST-TRANSCRIPTIONAL LEVEL. MIRNAS BIND TO COMPLEMENTARY SEQUENCES OF SPECIFIC TARGETS OF MESSENGERS RNA, WHICH CAN INTERFERE WITH PROTEIN SYNTHESIS. WE REVIEWED STUDIES THAT EVALUATED THE EXPRESSION PATTERNS OF MIRNAS IN DIFFERENT AUTOIMMUNE DISEASES, ESPECIALLY IN CELIAC DISEASE (CD). CD IS A CHRONIC ENTEROPATHY TRIGGERED BY GLUTEN PROTEINS, CHARACTERIZED BY ALTERED IMMUNE RESPONSES IN GENETICALLY SUSCEPTIBLE INDIVIDUALS THAT RESULTS IN DAMAGE TO THE BOWEL MUCOSA. CD HAS A HIGH PREVALENCE AND AN EFFECTIVE TREATMENT BY A SPECIFIC DIET ("GLUTEN FREE DIET"). GENETIC FACTORS CONFER SUSCEPTIBILITY BUT DO NOT EXPLAIN THE WHOLE DISEASE, SUGGESTING THAT ENVIRONMENTAL FACTORS DO PLAY A RELEVANT ROLE IN THE DEVELOPMENT OF THE CONDITION.THE EVALUATION OF THE POTENTIAL ROLE OF MIRNA IS OF PARTICULAR INTEREST IN CD GIVEN THAT THESE EPIGENETIC MECHANISMS IN THE PATHOGENESIS OF AUTOIMMUNE AND INFLAMMATORY DISEASES HAVE BEEN RECENTLY DESCRIBED. IMPROVING OUR UNDERSTANDING OF MIRNAS IN CD WILL CONTRIBUTE TO CLARIFY THE ROLE OF ALTERED EPIGENETIC REGULATION IN THE DEVELOPMENT AND COURSE OF THIS DISEASE. 2014 20 3692 36 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