1 1400 83 DIET-REGULATING MICROBIOTA AND HOST IMMUNE SYSTEM IN LIVER DISEASE. THE GUT MICROBIOTA HAS BEEN KNOWN TO MODULATE THE IMMUNE RESPONSES IN CHRONIC LIVER DISEASES. RECENT EVIDENCE SUGGESTS THAT EFFECTS OF DIETARY FOODS ON HEALTH CARE AND HUMAN DISEASES ARE RELATED TO BOTH THE IMMUNE REACTION AND THE MICROBIOME. THE GUT-MICROBIOME AND INTESTINAL IMMUNE SYSTEM PLAY A CENTRAL ROLE IN THE CONTROL OF BACTERIAL TRANSLOCATION-INDUCED LIVER DISEASE. DYSBIOSIS, SMALL INTESTINAL BACTERIAL OVERGROWTH, TRANSLOCATION, ENDOTOXEMIA, AND THE DIRECT EFFECTS OF METABOLITES ARE THE MAIN EVENTS IN THE GUT-LIVER AXIS, AND IMMUNE RESPONSES ACT ON EVERY PATHWAYS OF CHRONIC LIVER DISEASE. MICROBIOME-DERIVED METABOLITES OR BACTERIA THEMSELVES REGULATE IMMUNE CELL FUNCTIONS SUCH AS RECOGNITION OR ACTIVATION OF RECEPTORS, THE CONTROL OF GENE EXPRESSION BY EPIGENETIC CHANGE, ACTIVATION OF IMMUNE CELLS, AND THE INTEGRATION OF CELLULAR METABOLISM. HERE, WE REVIEWED RECENT REPORTS ABOUT THE IMMUNOLOGIC ROLE OF GUT MICROBIOTAS IN LIVER DISEASE, HIGHLIGHTING THE ROLE OF DIET IN CHRONIC LIVER DISEASE. 2021 2 6253 30 THE MICROBIOME AND HEPATOCELLULAR CARCINOMA. THE HUMAN MICROBIOME IS A VAST AND COMPLEX SYSTEM ENCOMPASSING ALL OF THE MICROBES AND THEIR GENES THAT OCCUPY THE ENVIRONMENTALLY EXPOSED SURFACES OF THE HUMAN BODY. THE GUT MICROBIOTA AND ITS ASSOCIATED MICROBIOME PLAY AN INTEGRAL ROLE IN MAMMALIAN METABOLISM AND IMMUNE TOLERANCE AS WELL AS IN IMMUNOCOMPETENCE. DISRUPTIONS IN THE HUMAN GUT MICROBIOME ARE ASSOCIATED WITH A CYCLE OF HEPATOCYTE INJURY AND REGENERATION CHARACTERISTIC OF CHRONIC LIVER DISEASE. THE PERSISTENCE OF THIS INFLAMMATION HAS BEEN SHOWN TO INDUCE THE ACCUMULATION OF GENETIC AND EPIGENETIC CHANGES LEADING TO HEPATOCELLULAR CARCINOMA (HCC). THEREFORE, THE IMPORTANCE AND PROGNOSTIC INFLUENCE OF THE GUT MICROBIOME ON HEPATOCARCINOGENESIS HAS BEEN INCREASINGLY STUDIED IN RECENT YEARS. THIS REVIEW DISCUSSES THE MECHANISMS BY WHICH IMBALANCES IN THE GUT MICROBIOME DISTURB THE GUT-LIVER AXIS TO IMPACT HEPATOCARCINOGENESIS, INCLUDING DISRUPTION OF THE INTESTINAL BARRIER, CHANGES IN BILE ACID METABOLISM, AND REDUCTION IN TUMOR-SUPPRESSING MICRORNA. FURTHERMORE, THIS REVIEW SUMMARIZES RECENT ADVANCES IN POTENTIAL MICROBIOME-BASED THERAPEUTIC OPPORTUNITIES IN HCC. 2020 3 4273 31 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 4 5540 33 ROLE OF DIET AND GUT MICROBIOTA ON COLORECTAL CANCER IMMUNOMODULATION. COLORECTAL CANCER (CRC) IS ONE OF THE MOST COMMONLY DIAGNOSED CANCERS, AND IT IS CHARACTERIZED BY GENETIC AND EPIGENETIC ALTERATIONS, AS WELL AS BY INFLAMMATORY CELL INFILTRATION AMONG MALIGNANT AND STROMAL CELLS. HOWEVER, THIS DYNAMIC INFILTRATION CAN BE INFLUENCED BY THE MICROENVIRONMENT TO PROMOTE TUMOR PROLIFERATION, SURVIVAL AND METASTASIS OR CANCER INHIBITION. IN PARTICULAR, THE CANCER MICROENVIRONMENT METABOLITES CAN REGULATE THE INFLAMMATORY CELLS TO INDUCE A CHRONIC INFLAMMATORY RESPONSE THAT CAN BE A PREDISPOSING CONDITION FOR CRC RETENTION. IN ADDITION, SOME NUTRITIONAL COMPONENTS MIGHT CONTRIBUTE TO A CHRONIC INFLAMMATORY CONDITION BY REGULATING VARIOUS IMMUNE AND INFLAMMATORY PATHWAYS. BESIDES THAT, DIET STRONGLY MODULATES THE GUT MICROBIOTA COMPOSITION, WHICH HAS A KEY ROLE IN MAINTAINING GUT HOMEOSTASIS AND IS ASSOCIATED WITH THE MODULATION OF HOST INFLAMMATORY AND IMMUNE RESPONSES. THEREFORE, DIET HAS A FUNDAMENTAL ROLE IN CRC INITIATION, PROGRESSION AND PREVENTION. IN PARTICULAR, FUNCTIONAL FOODS SUCH AS PROBIOTICS, PREBIOTICS AND SYMBIOTICS CAN HAVE A POTENTIALLY POSITIVE EFFECT ON HEALTH BEYOND BASIC NUTRITION AND HAVE ANTI-INFLAMMATORY EFFECTS. IN THIS REVIEW, WE DISCUSS THE INFLUENCE OF DIET ON GUT MICROBIOTA COMPOSITION, FOCUSING ON ITS ROLE ON GUT INFLAMMATION AND IMMUNITY. FINALLY, WE DESCRIBE THE POTENTIAL BENEFITS OF USING PROBIOTICS AND PREBIOTICS TO MODULATE THE HOST INFLAMMATORY RESPONSE, AS WELL AS ITS APPLICATION IN CRC PREVENTION AND TREATMENT. 2019 5 3268 31 HEPATOCELLULAR CARCINOMA IMMUNOTHERAPY AND THE POTENTIAL INFLUENCE OF GUT MICROBIOME. DISRUPTIONS IN THE HUMAN GUT MICROBIOME HAVE BEEN ASSOCIATED WITH A CYCLE OF HEPATOCYTE INJURY AND REGENERATION CHARACTERISTIC OF CHRONIC LIVER DISEASE. EVIDENCE SUGGESTS THAT THE GUT MICROBIOTA CAN PROMOTE THE DEVELOPMENT OF HEPATOCELLULAR CARCINOMA THROUGH THE PERSISTENCE OF THIS INFLAMMATION BY INDUCING GENETIC AND EPIGENETIC CHANGES LEADING TO CANCER. AS THE GUT MICROBIOME IS KNOWN FOR ITS EFFECT ON HOST METABOLISM AND IMMUNE RESPONSE, IT COMES AS NO SURPRISE THAT THE GUT MICROBIOME MAY HAVE A ROLE IN THE RESPONSE TO THERAPEUTIC STRATEGIES SUCH AS IMMUNOTHERAPY AND CHEMOTHERAPY FOR LIVER CANCER. GUT MICROBIOTA MAY INFLUENCE THE EFFICACY OF IMMUNOTHERAPY BY REGULATING THE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS IN PATIENTS WITH HEPATOCELLULAR CARCINOMA. HERE, WE REVIEW THE MECHANISMS BY WHICH GUT MICROBIOTA INFLUENCES HEPATIC CARCINOGENESIS, THE IMMUNE CHECKPOINT INHIBITORS CURRENTLY BEING USED TO TREAT HEPATOCELLULAR CARCINOMA, AS WELL AS SUMMARIZE THE CURRENT FINDINGS TO SUPPORT THE POTENTIAL CRITICAL ROLE OF GUT MICROBIOME IN HEPATOCELLULAR CARCINOMA (HCC) IMMUNOTHERAPY. 2021 6 1404 27 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 7 2617 31 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 8 3965 24 LONG NONCODING RNAS IN THE METABOLIC CONTROL OF INFLAMMATION AND IMMUNE DISORDERS. THE METABOLIC CONTROL OF IMMUNE CELL DEVELOPMENT AND FUNCTION HAS BEEN SHOWN TO BE CRITICAL FOR THE MAINTENANCE OF IMMUNE HOMEOSTASIS AND IS ALSO INVOLVED IN THE PATHOGENESIS OF IMMUNE DISORDERS. PATHOGENIC INFECTIONS OR CANCERS MAY INDUCE METABOLIC REPROGRAMMING THROUGH DIFFERENT PATHWAYS TO MEET THE ENERGY AND METABOLITE DEMANDS FOR PATHOGEN PROPAGATION OR CANCER PROGRESSION. IN ADDITION, SOME DEREGULATED METABOLITES COULD TRIGGER OR REGULATE IMMUNE RESPONSES, THUS CAUSING CHRONIC INFLAMMATION OR IMMUNE DISORDERS, SUCH AS VIRAL INFECTION, CANCER AND OBESITY. THEREFORE, THE METHODS THROUGH WHICH METABOLISM IS REGULATED AND THE ROLE OF METABOLIC REGULATION IN INFLAMMATION AND IMMUNITY ATTRACT MUCH ATTENTION. EPIGENETIC REGULATION OF INFLAMMATION AND IMMUNITY IS AN EMERGING FIELD. LONG NONCODING RNAS (LNCRNAS) HAVE BEEN WELL DOCUMENTED TO PLAY CRUCIAL ROLES IN MANY BIOLOGICAL PROCESSES THROUGH DIVERSE MECHANISMS, INCLUDING IMMUNE REGULATION AND METABOLIC ALTERNATION. HERE, WE REVIEW THE FUNCTIONS AND MECHANISMS OF LNCRNAS IN THE METABOLIC REGULATION OF INFLAMMATORY IMMUNE DISORDERS, AIMING TO DEEPEN OUR UNDERSTANDING OF THE EPIGENETIC REGULATION OF INFLAMMATION AND IMMUNITY. 2019 9 4043 28 MACROPHAGES IN CHRONIC LIVER FAILURE: DIVERSITY, PLASTICITY AND THERAPEUTIC TARGETING. CHRONIC LIVER INJURY RESULTS IN IMMUNE-DRIVEN PROGRESSIVE FIBROSIS, WITH RISK OF CIRRHOSIS DEVELOPMENT AND IMPACT ON MORBIDITY AND MORTALITY. PERSISTENT LIVER CELL DAMAGE AND DEATH CAUSES IMMUNE CELL ACTIVATION AND INFLAMMATION. PATIENTS WITH ADVANCED CIRRHOSIS ADDITIONALLY EXPERIENCE PATHOLOGICAL BACTERIAL TRANSLOCATION, EXPOSURE TO MICROBIAL PRODUCTS AND CHRONIC ENGAGEMENT OF THE IMMUNE SYSTEM. BACTERIAL INFECTIONS HAVE A HIGH INCIDENCE IN CIRRHOSIS, WITH SPONTANEOUS BACTERIAL PERITONITIS BEING THE MOST COMMON, WHILE THE SUBSEQUENT SYSTEMIC INFLAMMATION, ORGAN FAILURE AND IMMUNE DYSREGULATION INCREASE THE MORTALITY RISK. TISSUE-RESIDENT AND RECRUITED MACROPHAGES PLAY A CENTRAL PART IN THE DEVELOPMENT OF INFLAMMATION AND FIBROSIS PROGRESSION. IN THE LIVER, ADIPOSE TISSUE, PERITONEUM AND INTESTINES, DIVERSE MACROPHAGE POPULATIONS EXHIBIT GREAT PHENOTYPIC AND FUNCTIONAL PLASTICITY DETERMINED BY THEIR ONTOGENY, EPIGENETIC PROGRAMMING AND LOCAL MICROENVIRONMENT. THESE CHANGES CAN, AT DIFFERENT TIMES, PROMOTE OR AMELIORATE DISEASE STATES AND THEREFORE REPRESENT POTENTIAL TARGETS FOR MACROPHAGE-DIRECTED THERAPIES. IN THIS REVIEW, WE DISCUSS THE EVIDENCE FOR MACROPHAGE PHENOTYPIC AND FUNCTIONAL ALTERATIONS IN TISSUE COMPARTMENTS DURING THE DEVELOPMENT AND PROGRESSION OF CHRONIC LIVER FAILURE IN DIFFERENT AETIOLOGIES AND HIGHLIGHT THE POTENTIAL OF MACROPHAGE MODULATION AS A THERAPEUTIC STRATEGY FOR LIVER DISEASE. 2021 10 3547 33 IMMUNOMODULATORY ROLE OF NUTRIENTS: HOW CAN PULMONARY DYSFUNCTIONS IMPROVE? NUTRITION IS AN IMPORTANT TOOL THAT CAN BE USED TO MODULATE THE IMMUNE RESPONSE DURING INFECTIOUS DISEASES. IN ADDITION, THROUGH DIET, IMPORTANT SUBSTRATES ARE ACQUIRED FOR THE BIOSYNTHESIS OF REGULATORY MOLECULES IN THE IMMUNE RESPONSE, INFLUENCING THE PROGRESSION AND TREATMENT OF CHRONIC LUNG DISEASES, SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). IN THIS WAY, NUTRITION CAN PROMOTE LUNG HEALTH STATUS. A RANGE OF NUTRIENTS, SUCH AS VITAMINS (A, C, D, AND E), MINERALS (ZINC, SELENIUM, IRON, AND MAGNESIUM), FLAVONOIDS AND FATTY ACIDS, PLAY IMPORTANT ROLES IN REDUCING THE RISK OF PULMONARY CHRONIC DISEASES AND VIRAL INFECTIONS. THROUGH THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS, NUTRIENTS ARE ASSOCIATED WITH BETTER LUNG FUNCTION AND A LOWER RISK OF COMPLICATIONS SINCE THEY CAN DECREASE THE HARMFUL EFFECTS FROM THE IMMUNE SYSTEM DURING THE INFLAMMATORY RESPONSE. IN ADDITION, BIOACTIVE COMPOUNDS CAN EVEN CONTRIBUTE TO EPIGENETIC CHANGES, INCLUDING HISTONE DEACETYLASE (HDAC) MODIFICATIONS THAT INHIBIT THE TRANSCRIPTION OF PROINFLAMMATORY CYTOKINES, WHICH CAN CONTRIBUTE TO THE MAINTENANCE OF HOMEOSTASIS IN THE CONTEXT OF INFECTIONS AND CHRONIC INFLAMMATORY DISEASES. THESE NUTRIENTS ALSO PLAY AN IMPORTANT ROLE IN ACTIVATING IMMUNE RESPONSES AGAINST PATHOGENS, WHICH CAN HELP THE IMMUNE SYSTEM DURING INFECTIONS. HERE, WE PROVIDE AN UPDATED OVERVIEW OF THE ROLES PLAYED BY DIETARY FACTORS AND HOW THEY CAN AFFECT RESPIRATORY HEALTH. THEREFORE, WE WILL SHOW THE ANTI-INFLAMMATORY ROLE OF FLAVONOIDS, FATTY ACIDS, VITAMINS AND MICROBIOTA, IMPORTANT FOR THE CONTROL OF CHRONIC INFLAMMATORY DISEASES AND ALLERGIES, IN ADDITION TO THE ANTIVIRAL ROLE OF VITAMINS, FLAVONOIDS, AND MINERALS DURING PULMONARY VIRAL INFECTIONS, ADDRESSING THE MECHANISMS INVOLVED IN EACH FUNCTION. THESE MECHANISMS ARE INTERESTING IN THE DISCUSSION OF PERSPECTIVES ASSOCIATED WITH SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION AND ITS PULMONARY COMPLICATIONS SINCE PATIENTS WITH SEVERE DISEASE HAVE VITAMINS DEFICIENCY, ESPECIALLY VITAMIN D. IN ADDITION, RESEARCHES WITH THE USE OF FLAVONOIDS HAVE BEEN SHOWN TO DECREASE VIRAL REPLICATION IN VITRO. THIS WAY, A FULL UNDERSTANDING OF DIETARY INFLUENCES CAN IMPROVE THE LUNG HEALTH OF PATIENTS. 2021 11 6913 22 [VARIOUS PATHWAYS LEADING TO THE PROGRESSION OF CHRONIC LIVER DISEASES]. AS THE RESULT OF VARIOUS EFFECTS (VIRUSES, METABOLIC DISEASES, NUTRITIONAL FACTORS, TOXIC AGENTS, AUTOIMMUNE PROCESSES) ABNORMAL LIVER FUNCTION, LIVER STEATOSIS AND CONNECTIVE TISSUE REMODELING MAY DEVELOP. PROGRESSION OF THIS PROCESS IS COMPLEX INCLUDING VARIOUS PATHWAYS AND A NUMBER OF FACTORS. THE AUTHORS SUMMARIZE THE FACTORS INVOLVED IN THE PROGRESSION OF CHRONIC LIVER DISEASE. THEY DESCRIBE THE ROLE OF CELLS AND THE PRODUCED INFLAMMATORY MEDIATORS AND CYTOKINES, AS WELL AS THE RELATIONSHIP BETWEEN THE DISEASE AND THE INTESTINAL FLORA. THEY EMPHASIZE THE ROLE OF OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION AND CELL DEATH IN DISEASE PROGRESSION. INSULIN RESISTANCE AND MICRO-ELEMENTS (IRON, COPPER) IN RELATION TO LIVER DAMAGE ARE ALSO DISCUSSED, AND GENETIC AND EPIGENETIC ASPECTS UNDERLYING DISEASE PROGRESSION ARE SUMMARIZED. DISCOVERY OF NOVEL TREATMENT OPTIONS, ASSESSMENT OF THE EFFECTIVENESS OF TREATMENT, AS WELL AS THE SUCCESS AND PROPER TIMING OF LIVER TRANSPLANTATION MAY DEPEND ON A BETTER UNDERSTANDING OF THE PROCESS OF DISEASE PROGRESSION. 2016 12 3692 31 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 1149 37 CONNECTING THE IMMUNE SYSTEM, SYSTEMIC CHRONIC INFLAMMATION AND THE GUT MICROBIOME: THE ROLE OF SEX. UNRESOLVED LOW GRADE SYSTEMIC INFLAMMATION REPRESENTS THE UNDERLYING PATHOLOGICAL MECHANISM DRIVING IMMUNE AND METABOLIC PATHWAYS INVOLVED IN AUTOIMMUNE DISEASES (AID). MECHANISTIC STUDIES IN ANIMAL MODELS OF AID AND OBSERVATIONAL STUDIES IN PATIENTS HAVE FOUND ALTERATIONS IN GUT MICROBIOTA COMMUNITIES AND THEIR METABOLITES, SUGGESTING A MICROBIAL CONTRIBUTION TO THE ONSET OR PROGRESSION OF AID. THE GUT MICROBIOTA AND ITS METABOLITES HAVE BEEN SHOWN TO INFLUENCE IMMUNE FUNCTIONS AND IMMUNE HOMEOSTASIS BOTH WITHIN THE GUT AND SYSTEMATICALLY. MICROBIAL DERIVED-SHORT CHAIN FATTY ACID (SCFA) AND BIO-TRANSFORMED BILE ACID (BA) HAVE BEEN SHOWN TO INFLUENCE THE IMMUNE SYSTEM ACTING AS LIGANDS SPECIFIC CELL SIGNALING RECEPTORS LIKE GPRCS, TGR5 AND FXR, OR VIA EPIGENETIC PROCESSES. SIMILARLY, INTESTINAL PERMEABILITY (LEAKY GUT) AND BACTERIAL TRANSLOCATION ARE IMPORTANT CONTRIBUTORS TO CHRONIC SYSTEMIC INFLAMMATION AND, WITHOUT REPAIR OF THE INTESTINAL BARRIER, MIGHT REPRESENT A CONTINUOUS INFLAMMATORY STIMULUS CAPABLE OF TRIGGERING AUTOIMMUNE PROCESSES. RECENT STUDIES INDICATE GENDER-SPECIFIC DIFFERENCES IN IMMUNITY, WITH THE GUT MICROBIOTA SHAPING AND BEING CONCOMITANTLY SHAPED BY THE HORMONAL MILIEU GOVERNING DIFFERENCES BETWEEN THE SEXES. A BI-DIRECTIONAL CROSS-TALK BETWEEN MICROBIOTA AND THE ENDOCRINE SYSTEM IS EMERGING WITH BACTERIA BEING ABLE TO PRODUCE HORMONES (E.G. SEROTONIN, DOPAMINE AND SOMATOSTATINE), RESPOND TO HOST HORMONES (E.G. ESTROGENS) AND REGULATE HOST HORMONES' HOMEOSTASIS (E.G BY INHIBITING GENE PROLACTIN TRANSCRIPTION OR CONVERTING GLUCOCORTICOIDS TO ANDROGENS). WE REVIEW HEREIN HOW GUT MICROBIOTA AND ITS METABOLITES REGULATE IMMUNE FUNCTION, INTESTINAL PERMEABILITY AND POSSIBLY AID PATHOLOGICAL PROCESSES. FURTHER, WE DESCRIBE THE DYSBIOSIS WITHIN THE GUT MICROBIOTA OBSERVED IN DIFFERENT AID AND SPECULATE HOW RESTORING GUT MICROBIOTA COMPOSITION AND ITS REGULATORY METABOLITES BY DIETARY INTERVENTION INCLUDING PREBIOTICS AND PROBIOTICS COULD HELP IN PREVENTING OR AMELIORATING AID. FINALLY, WE SUGGEST THAT, GIVEN CONSISTENT OBSERVATIONS OF MICROBIOTA DYSBIOSIS ASSOCIATED WITH AID AND THE ABILITY OF SCFA AND BA TO REGULATE INTESTINAL PERMEABILITY AND INFLAMMATION, FURTHER MECHANISTIC STUDIES, EXAMINING HOW DIETARY MICROBIOTA MODULATION CAN PROTECT AGAINST AID, HOLD CONSIDERABLE POTENTIAL TO TACKLE INCREASED INCIDENCE OF AID AT THE POPULATION LEVEL. 2018 14 2601 36 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 15 2577 28 EPIGENETICS OF INFLAMMATION, MATERNAL INFECTION, AND NUTRITION. STUDIES HAVE DEMONSTRATED THAT EPIGENETIC CHANGES SUCH AS DNA METHYLATION, HISTONE MODIFICATION, AND CHROMATIN REMODELING ARE LINKED TO AN INCREASED INFLAMMATORY RESPONSE AS WELL AS INCREASED RISK OF CHRONIC DISEASE DEVELOPMENT. A FEW STUDIES HAVE BEGUN TO INVESTIGATE WHETHER DIETARY NUTRIENTS PLAY A BENEFICIAL ROLE BY MODIFYING OR REVERSING EPIGENETICALLY INDUCED INFLAMMATION. RESULTS OF THESE STUDIES SHOW THAT NUTRIENTS MODIFY EPIGENETIC PATHWAYS. HOWEVER, LITTLE IS KNOWN ABOUT HOW NUTRIENTS MODULATE INFLAMMATION BY REGULATING IMMUNE CELL FUNCTION AND/OR IMMUNE CELL DIFFERENTIATION VIA EPIGENETIC PATHWAYS. THIS OVERVIEW WILL PROVIDE INFORMATION ABOUT THE CURRENT UNDERSTANDING OF THE ROLE OF NUTRIENTS IN THE EPIGENETIC CONTROL MECHANISMS OF IMMUNE FUNCTION. 2015 16 6006 29 THE ALTERATIONS IN AND THE ROLE OF THE TH17/TREG BALANCE IN METABOLIC DISEASES. CHRONIC INFLAMMATION PLAYS AN IMPORTANT ROLE IN THE DEVELOPMENT OF METABOLIC DISEASES. THESE INCLUDE OBESITY, TYPE 2 DIABETES MELLITUS, AND METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE. THE PROINFLAMMATORY ENVIRONMENT MAINTAINED BY THE INNATE IMMUNITY, INCLUDING MACROPHAGES AND RELATED CYTOKINES, CAN BE INFLUENCED BY ADAPTIVE IMMUNITY. THE FUNCTION OF T HELPER 17 (TH17) AND REGULATORY T (TREG) CELLS IN THIS PROCESS HAS ATTRACTED ATTENTION. THE TH17/TREG BALANCE IS REGULATED BY INFLAMMATORY CYTOKINES AND VARIOUS METABOLIC FACTORS, INCLUDING THOSE ASSOCIATED WITH CELLULAR ENERGY METABOLISM. THE POSSIBLE UNDERLYING MECHANISMS INCLUDE METABOLISM-RELATED SIGNALING PATHWAYS AND EPIGENETIC REGULATION. SEVERAL STUDIES CONDUCTED ON HUMAN AND ANIMAL MODELS HAVE SHOWN MARKED DIFFERENCES IN AND THE IMPORTANT ROLES OF TH17/TREG IN CHRONIC INFLAMMATION ASSOCIATED WITH OBESITY AND METABOLIC DISEASES. MOREOVER, TH17/TREG SEEMS TO BE A BRIDGE LINKING THE GUT MICROBIOTA TO HOST METABOLIC DISORDERS. IN THIS REVIEW, WE HAVE PROVIDED AN OVERVIEW OF THE ALTERATIONS IN AND THE FUNCTIONS OF THE TH17/TREG BALANCE IN METABOLIC DISEASES AND ITS ROLE IN REGULATING IMMUNE RESPONSE-RELATED GLUCOSE AND LIPID METABOLISM. 2021 17 6213 24 THE INTESTINAL EPITHELIAL CELL CYCLE: UNCOVERING ITS 'CRYPTIC' NATURE. PURPOSE OF REVIEW: TO DISCUSS THE RECENT LANDMARK FINDINGS THAT HAVE INCREASED OUR UNDERSTANDING NOT ONLY OF THE ROLE OF THE EPITHELIAL CELL CYCLE IN THE HOMEOSTASIS OF THE SMALL INTESTINE, BUT ALSO ITS RELEVANCE TO INFLAMMATION AND CANCER. RECENT FINDINGS: RECENT DATA HAVE UNVEILED NOVEL INFORMATION ON PROTEIN INTERACTIONS DIRECTLY INVOLVED IN THE CELL CYCLE AS WELL AS IN THE PATHWAYS THAT TRANSDUCE EXTERNAL ENVIRONMENTAL SIGNALS TO THE CELL CYCLE. A GROWING BODY OF THE RECENT EVIDENCE CONFIRMS THE IMPORTANCE OF FOOD AS WELL AS HORMONAL REGULATION IN THE GUT ON CELL CYCLE. INFORMATION ON THE CONTRIBUTION OF THE EPITHELIAL MICROENVIRONMENT, INCLUDING THE MICROBIOTA, HAS GROWN SUBSTANTIALLY IN THE RECENT YEARS AS WELL AS ON THE GENE-ENVIRONMENT INTERACTIONS AND THE MULTIPLE EPIGENETIC MECHANISMS INVOLVED IN REGULATING CELL-CYCLE PROTEINS AND SIGNALLING. FINALLY, FURTHER STUDIES INVESTIGATING THE DYSREGULATION OF THE CELL CYCLE DURING INFLAMMATION AND PROLIFERATION HAVE INCREASED OUR UNDERSTANDING OF THE PATHOPHYSIOLOGY OF CHRONIC INFLAMMATORY DISEASES AND CANCER. SUMMARY: THIS REVIEW HIGHLIGHTS SOME OF THE MOST RECENT ADVANCES THAT FURTHER EMPHASIZE THE IMPORTANCE OF THE CELL CYCLE IN THE SMALL INTESTINE DURING HOMEOSTASIS AS WELL AS IN INFLAMMATION AND CANCER. 2015 18 5558 27 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 19 6879 32 [RELATIONSHIP BETWEEN INTESTINAL HYPERPERMEABILITY AND OBESITY]. OBESITY IS A COMBINATION OF GENETIC, ENVIRONMENTAL FACTORS, AND SYSTEMIC INFLAMMATION OF ADIPOSE TISSUE. IN THE LAST DECADE, MORE AND MORE EVIDENCE SUGGESTS THAT INTESTINAL MICROBIOTA IS AN ENVIRONMENTAL FACTOR THAT PLAYS A CRUCIAL ROLE IN OBESITY AND ASSOCIATED METABOLIC DISORDERS. HERE, WE REVIEW THE ASSOCIATION BETWEEN INTESTINAL MICROBIOTA AND OBESITY BASED ON THE LITERATURE DATA AVAILABLE TO US. THE INTESTINAL FLORA, IN THE EQUILIBRIUM STATE OF CONVENTIONAL BACTERIA, PROTECTS THE HEALTH OF THE HOST AND HELPS THE DEVELOPMENT OF THE IMMUNE SYSTEM. THE GENOME, DIET, LIFESTYLE, AND EPIGENETIC CHANGES OF THE HOST CAN PATHOLOGICALLY ALTER THE COMPOSITION OF THE MICROBIOTA. IN DYSBIOSIS, THE DEVELOPMENT OF THE GUT-ASSOCIATED LYMPHOID TISSUE (GALT) ASSOCIATED WITH THE INTESTINAL TRACT IS IMPAIRED AND THE INTEGRITY OF THE INTESTINAL BARRIER IS IMPAIRED. DUE TO THE CONSEQUENT INTESTINAL HYPERPERMEABILITY, COMPONENTS OF PATHOGENIC PATHOGENS SUCH AS LIPOPOLYSACCHARIDES ENTER THE BLOODSTREAM. THESE COMPONENTS BIND TO RECEPTORS ON ADIPOSE TISSUE IMMUNE CELLS AS LIGANDS FOR MOLECULAR SAMPLES WITH PATHOGENIC PROPERTIES AND INDUCE ADIPOSE TISSUE DYSFUNCTION. THE SECRETION OF INFLAMMATORY CYTOKINES IN ADIPOSE TISSUE IS INCREASED. THIS INDUCES PERSISTENT LOW CHRONIC INFLAMMATION, WHICH IS RESPONSIBLE FOR THE DEVELOPMENT OF OBESITY. THE DAMAGE TO HEALTH CAUSED BY THE HYPERPERMEABILITY OF THE INTESTINAL BARRIER CAN BE REDUCED BY INTERVENTIONS, OR RESTORED EARLY IN THE PROCESS. KNOWING THE RELATIONSHIPS WILL HELP PREVENT AND TREAT OBESITY. 2022 20 2333 25 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