1 6254 121 THE MICROBIOME AND IRRITABLE BOWEL SYNDROME - A REVIEW ON THE PATHOPHYSIOLOGY, CURRENT RESEARCH AND FUTURE THERAPY. IRRITABLE BOWEL SYNDROME (IBS) IS A FUNCTIONAL DISORDER WHICH AFFECTS A LARGE PROPORTION OF THE POPULATION GLOBALLY. THE PRECISE ETIOLOGY OF IBS IS STILL UNKNOWN, ALTHOUGH CONSENSUS UNDERSTANDING PROPOSES IBS TO BE OF MULTIFACTORIAL ORIGIN WITH YET UNDEFINED SUBTYPES. GENETIC AND EPIGENETIC FACTORS, STRESS-RELATED NERVOUS AND ENDOCRINE SYSTEMS, IMMUNE DYSREGULATION AND THE BRAIN-GUT AXIS SEEM TO BE CONTRIBUTING FACTORS THAT PREDISPOSE INDIVIDUALS TO IBS. IN ADDITION TO FOOD HYPERSENSITIVITY, TOXINS AND ADVERSE LIFE EVENTS, CHRONIC INFECTIONS AND DYSBIOTIC GUT MICROBIOTA HAVE BEEN SUGGESTED TO TRIGGER IBS SYMPTOMS IN TANDEM WITH THE PREDISPOSING FACTORS. THIS REVIEW WILL SUMMARIZE THE PATHOPHYSIOLOGY OF IBS AND THE ROLE OF GUT MICROBIOTA IN RELATION TO IBS. CURRENT METHODOLOGIES FOR MICROBIOME STUDIES IN IBS SUCH AS GENOME SEQUENCING, METAGENOMICS, CULTUROMICS AND ANIMAL MODELS WILL BE DISCUSSED. THE MYRIAD OF THERAPY OPTIONS SUCH AS IMMUNOGLOBULINS (IMMUNE-BASED THERAPY), PROBIOTICS AND PREBIOTICS, DIETARY MODIFICATIONS INCLUDING FODMAP RESTRICTION DIET AND GLUTEN-FREE DIET, AS WELL AS FECAL TRANSPLANTATION WILL BE REVIEWED. FINALLY THIS REVIEW WILL HIGHLIGHT FUTURE DIRECTIONS IN IBS THERAPY RESEARCH, INCLUDING IDENTIFICATION OF NEW MOLECULAR TARGETS, APPLICATION OF 3-D GUT MODEL, GUT-ON-A-CHIP AND PERSONALIZED THERAPY. 2019 2 105 44 A REVIEW OF MICROBIOTA AND IRRITABLE BOWEL SYNDROME: FUTURE IN THERAPIES. IRRITABLE BOWEL SYNDROME (IBS), ONE OF THE MOST FREQUENT DIGESTIVE DISORDERS, IS CHARACTERIZED BY CHRONIC AND RECURRENT ABDOMINAL PAIN AND ALTERED BOWEL HABIT. THE ORIGIN SEEMS TO BE MULTIFACTORIAL AND IS STILL NOT WELL DEFINED FOR THE DIFFERENT SUBTYPES. GENETIC, EPIGENETIC AND SEX-RELATED MODIFICATIONS OF THE FUNCTIONING OF THE NERVOUS AND IMMUNE-ENDOCRINE SUPERSYSTEMS AND REGULATION OF BRAIN-GUT PHYSIOLOGY AND BILE ACID PRODUCTION AND ABSORPTION ARE CERTAINLY INVOLVED. ACQUIRED PREDISPOSITION MAY ACT IN CONJUNCTION WITH INFECTIOUS, TOXIC, DIETARY AND LIFE EVENT-RELATED FACTORS TO ENHANCE EPITHELIAL PERMEABILITY AND ELICIT MUCOSAL MICROINFLAMMATION, IMMUNE ACTIVATION AND DYSBIOSIS. NOTABLY, STRONG EVIDENCE SUPPORTS THE ROLE OF BACTERIAL, VIRAL AND PARASITIC INFECTIONS IN TRIGGERING IBS, AND TARGETING MICROBIOTA SEEMS PROMISING IN VIEW OF THE POSITIVE RESPONSE TO MICROBIOTA-RELATED THERAPIES IN SOME PATIENTS. HOWEVER, THE LACK OF HIGHLY PREDICTIVE DIAGNOSTIC BIOMARKERS AND THE COMPLEXITY AND HETEROGENEITY OF IBS PATIENTS MAKE MANAGEMENT DIFFICULT AND UNSATISFACTORY IN MANY CASES, REDUCING PATIENT HEALTH-RELATED QUALITY OF LIFE AND INCREASING THE SANITARY BURDEN. THIS ARTICLE REVIEWS SPECIFIC ALTERATIONS AND INTERVENTIONS TARGETING THE GUT MICROBIOTA IN IBS, INCLUDING PREBIOTICS, PROBIOTICS, SYNBIOTICS, NON-ABSORBABLE ANTIBIOTICS, DIETS, FECAL TRANSPLANTATION AND OTHER POTENTIAL FUTURE APPROACHES USEFUL FOR THE DIAGNOSIS, PREVENTION AND TREATMENT OF IBS. 2018 3 4673 46 NEW INSIGHTS INTO THE PATHOGENESIS AND TREATMENT OF IRRITABLE BOWEL SYNDROME. IRRITABLE BOWEL SYNDROME (IBS) IS ONE OF THE MOST COMMON FUNCTIONAL GASTROINTESTINAL DISORDERS (FGID), CHARACTERIZED BY ABDOMINAL PAIN AND A CHANGE IN STOOL FORM THAT CANNOT BE EXPLAINED BY STRUCTURAL ABNORMALITIES. ITS PREVALENCE RANGES FROM 9 TO 23% OF THE WORLDWIDE POPULATION. THE PATHOPHYSIOLOGY OF IBS IS DIVERSE AND NOT WELL UNDERSTOOD. BIOPSYCHOSOCIAL CONCEPT ASSUMES THAT THE DISEASE IS A PRODUCT OF PSYCHOSOCIAL FACTORS AND ALTERED AT MULTIPLE LEVELS OF GUT PHYSIOLOGY INTERACTIONS. SOME AETIOLOGICAL FACTORS HAVE BEEN IDENTIFIED, YET. ONE OF THE MOST IMPORTANT IS THE DISRUPTION OF BRAIN-GUT MUTUAL COMMUNICATION THAT LEADS TO VISCERAL HYPERSENSITIVITY. ALSO GENETIC AND EPIGENETIC FACTORS ARE INVOLVED. CHRONIC STRESS MAY PREDISPOSE TO IBS AS WELL AS EXACERBATE ITS SYMPTOMS. BOTH QUANTITATIVE AND QUALITATIVE DISORDERS OF THE GUT MICROBIOTA ARE OBSERVED. THERE IS ALSO A RELATIONSHIP BETWEEN THE IBS SYMPTOMS AND THE INTAKE OF A SPECIFIC TYPE OF FOOD PRODUCTS. IN THE DIARRHOEA TYPE OF IBS THE ROLE OF PREVIOUS GASTROINTESTINAL INFECTION IS DEMONSTRATED. RECENT STUDIES HAVE SUGGESTED THAT VISCERAL HYPERSENSITIVITY IN PATIENTS WITH IBS MAY BE SECONDARY TO THE ACTIVATION OF THE IMMUNE CELLS AND LOW-GRADE INFLAMMATION. CLINICAL SYMPTOMS OF IBS INCLUDE ABDOMINAL PAIN AND CHANGE IN BOWEL HABITS AS WELL AS SOMATIC AND PSYCHIATRIC COMORBIDITIES. IBS IS DIAGNOSED ON THE BASIS OF ROME DIAGNOSTIC CRITERIA. RECENTLY, THEIR NEWEST VERSION (ROME IV) HAS BEEN PRESENTED. THE AIM OF THIS REVIEW IS TO SUMMARIZE THE PAST DECADE PROGRESS IN IBS DIAGNOSIS, MAIN PATHOPHYSIOLOGICAL ASPECTS AND THERAPEUTIC MANAGEMENT STRATEGY. 2017 4 4518 25 MULTI-OMICS FOR BIOMARKER APPROACHES IN THE DIAGNOSTIC EVALUATION AND MANAGEMENT OF ABDOMINAL PAIN AND IRRITABLE BOWEL SYNDROME: WHAT LIES AHEAD. RELIABLE BIOMARKERS FOR COMMON DISORDERS OF GUT-BRAIN INTERACTION CHARACTERIZED BY ABDOMINAL PAIN, INCLUDING IRRITABLE BOWEL SYNDROME (IBS), ARE CRITICALLY NEEDED TO ENHANCE CARE AND DEVELOP INDIVIDUALIZED THERAPIES. THE DYNAMIC AND HETEROGENEOUS NATURE OF THE PATHOPHYSIOLOGICAL MECHANISMS THAT UNDERLIE VISCERAL HYPERSENSITIVITY HAVE CHALLENGED SUCCESSFUL BIOMARKER DEVELOPMENT. CONSEQUENTLY, EFFECTIVE THERAPIES FOR PAIN IN IBS ARE LACKING. HOWEVER, RECENT ADVANCES IN MODERN OMICS TECHNOLOGIES OFFER NEW OPPORTUNITIES TO ACQUIRE DEEP BIOLOGICAL INSIGHTS INTO MECHANISMS OF PAIN AND NOCICEPTION. NEWER METHODS FOR LARGE-SCALE DATA INTEGRATION OF COMPLEMENTARY OMICS APPROACHES HAVE FURTHER EXPANDED OUR ABILITY TO BUILD A HOLISTIC UNDERSTANDING OF COMPLEX BIOLOGICAL NETWORKS AND THEIR CO-CONTRIBUTIONS TO ABDOMINAL PAIN. HERE, WE REVIEW THE MECHANISMS OF VISCERAL HYPERSENSITIVITY, FOCUSING ON IBS. WE DISCUSS CANDIDATE BIOMARKERS FOR PAIN IN IBS IDENTIFIED THROUGH SINGLE OMICS STUDIES AND SUMMARIZE EMERGING MULTI-OMICS APPROACHES FOR DEVELOPING NOVEL BIOMARKERS THAT MAY TRANSFORM CLINICAL CARE FOR PATIENTS WITH IBS AND ABDOMINAL PAIN. 2023 5 2167 44 EPIGENETIC MECHANISMS IN IRRITABLE BOWEL SYNDROME. IRRITABLE BOWEL SYNDROME (IBS) IS A BRAIN-GUT AXIS DISORDER CHARACTERIZED BY ABDOMINAL PAIN AND ALTERED BOWEL HABITS. IBS IS A MULTIFACTORIAL, STRESS-SENSITIVE DISORDER WITH EVIDENCE FOR FAMILIAL CLUSTERING ATTRIBUTED TO GENETIC OR SHARED ENVIRONMENTAL FACTORS. HOWEVER, THERE ARE WEAK GENETIC ASSOCIATIONS REPORTED WITH IBS AND A LACK OF EVIDENCE TO SUGGEST THAT MAJOR GENETIC FACTOR(S) CONTRIBUTE TO IBS PATHOPHYSIOLOGY. STUDIES ON ANIMAL MODELS OF STRESS, INCLUDING EARLY LIFE STRESS, SUGGEST A ROLE FOR ENVIRONMENTAL FACTORS, SPECIFICALLY, STRESS ASSOCIATED WITH DYSREGULATION OF CORTICOTROPIN RELEASING FACTOR AND HYPOTHALAMUS-PITUITARY-ADRENAL (HPA) AXIS PATHWAYS IN THE PATHOPHYSIOLOGY OF IBS. RECENT EVIDENCE SUGGESTS THAT EPIGENETIC MECHANISMS, WHICH CONSTITUTE MOLECULAR CHANGES NOT DRIVEN BY A CHANGE IN GENE SEQUENCE, CAN MEDIATE ENVIRONMENTAL EFFECTS ON CENTRAL AND PERIPHERAL FUNCTION. EPIGENETIC ALTERATIONS INCLUDING DNA METHYLATION CHANGES, HISTONE MODIFICATIONS, AND DIFFERENTIAL EXPRESSION OF NON-CODING RNAS (MICRORNA [MIRNA] AND LONG NON-CODING RNA) HAVE BEEN ASSOCIATED WITH SEVERAL DISEASES. THE OBJECTIVE OF THIS REVIEW IS TO ELUCIDATE THE MOLECULAR FACTORS IN THE PATHOPHYSIOLOGY OF IBS WITH AN EMPHASIS ON EPIGENETIC MECHANISMS. EMERGING EVIDENCE FOR EPIGENETIC CHANGES IN IBS INCLUDES CHANGES IN DNA METHYLATION IN ANIMAL MODELS OF IBS AND PATIENTS WITH IBS, AND VARIOUS MIRNAS THAT HAVE BEEN ASSOCIATED WITH IBS AND ENDOPHENOTYPES, SUCH AS INCREASED VISCERAL SENSITIVITY AND INTESTINAL PERMEABILITY. DNA METHYLATION, IN PARTICULAR, IS AN EMERGING FIELD IN THE REALM OF COMPLEX DISEASES AND A PROMISING MECHANISM WHICH CAN PROVIDE IMPORTANT INSIGHTS INTO IBS PATHOGENESIS AND IDENTIFY POTENTIAL TARGETS FOR TREATMENT. 2020 6 4428 32 MOLECULAR BASIS OF THE IRRITABLE BOWEL SYNDROME. IRRITABLE BOWEL SYNDROME (IBS) IS A FUNCTIONAL DISORDER CHARACTERIZED BY ABDOMINAL PAIN, DISCOMFORT AND BLOATING. THE PATHOPHYSIOLOGY OF IBS IS POORLY UNDERSTOOD, BUT THE PRESENCE OF PSYCHOSOCIAL BASIS IS NOW KNOWN. THERE IS AN INCREASING NUMBER OF PUBLICATIONS SUPPORTING THE ROLE OF GENETICS IN IBS. MOST OF THE VARIATIONS ARE FOUND IN GENES ASSOCIATED WITH THE BRAIN-GUT AXIS, REVEALING THE STRONG CORRELATION OF BRAIN-GUT AXIS AND IBS. MIRNAS, WHICH PLAY CRITICAL ROLES IN PHYSIOLOGICAL PROCESSES, ARE NOT WELL STUDIED IN IBS. HOWEVER, SO FAR THERE IS FOUND AN INVOLVEMENT OF ALTERATIONS IN MIRNA EXPRESSION OR SEQUENCE, IN IBS SYMPTOMS. IBS PHENOTYPE IS AFFECTED BY EPIGENETIC ALTERATION AND ENVIRONMENT. CHANGES IN DNA AND HISTONE METHYLATION ARE OBSERVED IN PATIENTS WHO SUFFERED CHILDHOOD TRAUMA OR ABUSE, RESULTING IN ALTERED GENE EXPRESSION, SUCH AS THE GLUCOCORTICOID RECEPTOR GENE. FINALLY, DIET IS ANOTHER FACTOR ASSOCIATED WITH IBS, WHICH MAY CONTRIBUTE TO SYMPTOM ONSET. CERTAIN FOODS MAY AFFECT ON BACTERIAL METABOLISM AND EPIGENETIC MODIFICATIONS, PREDISPOSING TO IBS. 2014 7 5835 36 STRESS-INDUCED VISCERAL PAIN: TOWARD ANIMAL MODELS OF IRRITABLE-BOWEL SYNDROME AND ASSOCIATED COMORBIDITIES. VISCERAL PAIN IS A GLOBAL TERM USED TO DESCRIBE PAIN ORIGINATING FROM THE INTERNAL ORGANS, WHICH IS DISTINCT FROM SOMATIC PAIN. IT IS A HALLMARK OF FUNCTIONAL GASTROINTESTINAL DISORDERS SUCH AS IRRITABLE-BOWEL SYNDROME (IBS). CURRENTLY, THE TREATMENT STRATEGIES TARGETING VISCERAL PAIN ARE UNSATISFACTORY, WITH DEVELOPMENT OF NOVEL THERAPEUTICS HINDERED BY A LACK OF DETAILED KNOWLEDGE OF THE UNDERLYING MECHANISMS. STRESS HAS LONG BEEN IMPLICATED IN THE PATHOPHYSIOLOGY OF VISCERAL PAIN IN BOTH PRECLINICAL AND CLINICAL STUDIES. HERE, WE DISCUSS THE COMPLEX ETIOLOGY OF VISCERAL PAIN REVIEWING OUR CURRENT UNDERSTANDING IN THE CONTEXT OF THE ROLE OF STRESS, GENDER, GUT MICROBIOTA ALTERATIONS, AND IMMUNE FUNCTIONING. FURTHERMORE, WE REVIEW THE ROLE OF GLUTAMATE, GABA, AND EPIGENETIC MECHANISMS AS POSSIBLE THERAPEUTIC STRATEGIES FOR THE TREATMENT OF VISCERAL PAIN FOR WHICH THERE IS AN UNMET MEDICAL NEED. MOREOVER, WE DISCUSS THE MOST WIDELY DESCRIBED RODENT MODELS USED TO MODEL VISCERAL PAIN IN THE PRECLINICAL SETTING. THE THEORY BEHIND, AND APPLICATION OF, ANIMAL MODELS IS KEY FOR BOTH THE UNDERSTANDING OF UNDERLYING MECHANISMS AND DESIGN OF FUTURE THERAPEUTIC INTERVENTIONS. TAKEN TOGETHER, IT IS APPARENT THAT STRESS-INDUCED VISCERAL PAIN AND ITS PSYCHIATRIC COMORBIDITIES, AS TYPIFIED BY IBS, HAS A MULTIFACETED ETIOLOGY. MOREOVER, TREATMENT STRATEGIES STILL LAG FAR BEHIND WHEN COMPARED TO OTHER PAIN MODALITIES. THE DEVELOPMENT OF NOVEL, EFFECTIVE, AND SPECIFIC THERAPEUTICS FOR THE TREATMENT OF VISCERAL PAIN HAS NEVER BEEN MORE PERTINENT. 2015 8 3692 34 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 9 4274 48 MICROBIOTA IN INFLAMMATORY BOWEL DISEASE PATHOGENESIS AND THERAPY: IS IT ALL ABOUT DIET? INFLAMMATORY BOWEL DISEASE (IBD), INCLUDING ULCERATIVE COLITIS, CROHN'S DISEASE, AND UNCLASSIFIED IBD, CONTINUES TO CAUSE SIGNIFICANT MORBIDITY. WHILE ITS INCIDENCE IS INCREASING, NO CLEAR ETIOLOGY AND NO CURE HAVE YET BEEN DISCOVERED. RECENT FINDINGS SUGGEST THAT IBD MAY HAVE A MULTIFACTORIAL ETIOLOGY, WHERE COMPLEX INTERACTIONS BETWEEN GENETICS, EPIGENETICS, ENVIRONMENTAL FACTORS (INCLUDING DIET BUT ALSO INFECTIONS, ANTIBIOTICS, AND SANITATION), AND HOST IMMUNE SYSTEM LEAD TO ABNORMAL IMMUNE RESPONSES AND CHRONIC INFLAMMATION. OVER THE PAST YEARS, THE ROLE OF ALTERED GUT MICROBIOTA (IN BOTH COMPOSITION AND FUNCTION) IN IBD PATHOGENESIS HAS EMERGED AS AN OUTSTANDING AREA OF INTEREST. ACCORDING TO NEW FINDINGS, GUT DYSBIOSIS MAY APPEAR AS A KEY ELEMENT IN INITIATION OF INFLAMMATION IN IBD AND ITS COMPLICATIONS. MOREOVER, COMPLEX METAGENOMIC STUDIES PROVIDE POSSIBILITIES TO DISTINGUISH BETWEEN IBD TYPES AND APPRECIATE SEVERITY AND PROGNOSIS OF THE DISEASE, AS WELL AS RESPONSE TO THERAPY. THIS REVIEW PROVIDES AN UPDATED KNOWLEDGE OF RECENT FINDINGS LINKING ALTERED BACTERIAL COMPOSITION AND FUNCTIONS, VIRUSES, AND FUNGI TO IBD PATHOGENESIS. IT ALSO HIGHLIGHTS THE COMPLEX GENETIC, EPIGENETIC, IMMUNE, AND MICROBIAL INTERACTIONS IN RELATION TO ENVIRONMENTAL FACTORS (INCLUDING DIET). WE OVERVIEW THE ACTUAL OPTIONS TO MANIPULATE THE ALTERED MICROBIOTA, SUCH AS MODIFIED DIET, PROBIOTICS, PREBIOTICS, SYNBIOTICS, ANTIBIOTICS, AND FECAL TRANSPLANTATION. FUTURE POSSIBLE THERAPIES ARE ALSO INCLUDED. TARGETING ALTERED MICROBIOTA COULD BE THE NEXT THERAPEUTIC PERSONALIZED APPROACH, BUT MORE RESEARCH AND WELL-DESIGNED COMPARATIVE PROSPECTIVE STUDIES ARE REQUIRED TO FORMULATE ADEQUATE DIRECTIONS FOR PREVENTION AND THERAPY. 2015 10 6392 29 THE ROLE OF THE GUT MICROBIOTA IN SCHIZOPHRENIA: CURRENT AND FUTURE PERSPECTIVES. OBJECTIVES: SCHIZOPHRENIA IS A POORLY UNDERSTOOD CHRONIC DISEASE. ITS PATHOPHYSIOLOGY IS COMPLEX, DYNAMIC, AND LINKED TO EPIGENETIC MECHANISMS AND MICROBIOTA INVOLVEMENT. NOWADAYS, CORRELATING SCHIZOPHRENIA WITH THE ENVIRONMENT MAKES SENSE OWING TO ITS MULTIDIMENSIONAL IMPLICATIONS: TEMPORAL AND SPATIAL VARIABILITY. MICROBIOTA INVOLVEMENT AND EPIGENETIC MECHANISMS ARE FACTORS THAT ARE CURRENTLY BEING CONSIDERED TO BETTER UNDERSTAND ANOTHER DIMENSION OF SCHIZOPHRENIA. METHODS: THIS REVIEW SUMMARISES AND DISCUSSES CURRENTLY AVAILABLE INFORMATION, FOCUSSING ON THE MICROBIOTA, EPIGENETIC MECHANISMS, TECHNOLOGICAL APPROACHES AIMED AT PERFORMING EXHAUSTIVE ANALYSES OF THE MICROBIOTA, AND PSYCHOTHERAPIES, TO ESTABLISH FUTURE PERSPECTIVES. RESULTS: THE CONNECTION BETWEEN THE MICROBIOTA, EPIGENETIC MECHANISMS AND TECHNOLOGICAL DEVELOPMENTS ALLOWS FOR FORMULATING NEW APPROACHES OBJECTIVELY ORIENTED TOWARDS THE DEVELOPMENT OF ALTERNATIVE PSYCHOTHERAPIES THAT MAY HELP TREAT SCHIZOPHRENIA. CONCLUSIONS: IN THIS REVIEW, THE GUT MICROBIOTA AND EPIGENETIC MECHANISMS WERE CONSIDERED AS KEY REGULATORS, REVEALING A POTENTIAL NEW AETIOLOGY OF SCHIZOPHRENIA. LIKEWISE, CONTINUOUS TECHNOLOGICAL ADVANCES (E.G. CULTUROMICS), AIMED AT THE MICROBIOTA-GUT-BRAIN AXIS GENERATE NEW EVIDENCE ON THIS CONCEPT. 2018 11 1410 31 DIETARY INTERVENTIONS FOR AUTISM SPECTRUM DISORDER: AN UPDATED SYSTEMATIC REVIEW OF HUMAN STUDIES. AUTISM IS A COMPLEX SPECTRUM OF DISORDERS WITH GENETIC, EPIGENETIC, AUTOIMMUNE, OXIDATIVE STRESS, AND ENVIRONMENTAL ETIOLOGIES. TREATMENT OF ASD USING DIETARY APPROACH IS A PROMISING STRATEGY, ESPECIALLY OWING TO ITS SAFETY AND AVAILABILITY. OUR STUDY CRITICALLY ANALYSED THE ROLES AND EFFICACY OF ANTIOXIDANTS, PROBIOTICS, PREBIOTICS, CAMEL MILK AND VITAMIN D. THIS SYSTEMATIC REVIEW PROVIDES AN UPDATED SYNOPSIS OF HUMAN STUDIES THAT INVESTIGATED THERAPEUTIC BENEFITS OF THESE DIETARY INTERVENTIONS IN AUTISM. A TOTAL OF 943 PAPERS WERE IDENTIFIED OUT OF WHICH 21 ARTICLES WERE INCLUDED IN THE SYSTEMATIC REVIEW. THE SELECTED STUDIES INVESTIGATED THE IMPACT OF 5 DIFFERENT DIETARY SUPPLEMENTATIONS IN ASD SYMPTOM AND BEHAVIOURS. THESE AGENTS INCLUDE; ANTIOXIDANTS/POLYPHENOLIC COMPOUNDS, PROBIOTICS, PREBIOTICS, CAMEL MILK AND VITAMIN D. FROM THE RESULTS OF THE PRESENT REVIEW, ANTIOXIDANTS/POLYPHENOLIC COMPOUNDS DECREASED THE LEVELS OF INFLAMMATORY CYTOKINES AND IMPROVED BEHAVIOURAL SYMPTOMS. PROBIOTICS IMPROVED BEHAVIOURAL AND GI SYMPTOMS AS WELL AS RESTORED GUT MICROBIOTA EQUILIBRIUM. PREBIOTICS DECREASED LEVELS OF INFLAMMATORY CYTOKINES, IMPROVED BEHAVIOURAL AND GI SYMPTOMS AND IMPROVED GUT MICROBIOTA. VITAMIN D IMPROVED BEHAVIOURAL SYMPTOMS AND OFFERED PROTECTIVE EFFECTS AGAINST NEUROTOXICITY. CAMEL MILK REDUCED INFLAMMATORY RESPONSES AND OXIDATIVE STRESS. GIVEN THE CHRONIC NATURE AS WELL AS EARLY ONSET OF ASD, DIETARY SUPPLEMENTS BECOME USEFUL TO COMPLEMENT NUTRITIONAL DEFICIENCIES IN CHILDREN WITH ASD. KEY BENEFITS OF THESE AGENTS STEM FROM THEIR ABILITY TO TARGET MULTIPLE PHYSIOLOGICAL AREAS VIA THE GUT BRAIN-AXIS AND ARE DEVOID OF POTENTIAL HARMFUL OR AGGRAVATING EFFECTS ON ASD PATIENTS. THE EVIDENCE COLLATED IN THIS REVIEW PROPOSE THAT DIETARY INTERVENTION MAY PROVIDE A NEW PLATFORM FOR THE MANAGEMENT OF AUTISM. 2022 12 6252 34 THE MICROBIOME AND CANCER: IMPLICATIONS FOR ONCOLOGY NURSING SCIENCE. BACKGROUND: APPROXIMATELY 1.6 MILLION AMERICANS WERE DIAGNOSED WITH CANCER IN 2014. TO COMBAT THEIR DISEASE, MANY INDIVIDUALS RECEIVED EITHER CURATIVE OR PALLIATIVE TREATMENTS THAT PRODUCED UNDESIRED SYMPTOMS. THESE SYMPTOMS, WHICH OFTEN CAUSE SIGNIFICANT DISTRESS FOR INDIVIDUALS COPING WITH CANCER, MAY SHARE BIOLOGIC UNDERPINNINGS SUCH AS EPIGENETIC CHANGES AND IMMUNE DYSREGULATION. ALTERATIONS IN THE NORMAL FLORA OF THE GUT MAY ALSO INFLUENCE CANCER SYMPTOMS. OBJECTIVE: THE AIM OF THIS REVIEW IS TO DESCRIBE THE EMERGING ROLE FOR THE GUT MICROBIOME IN CANCER RESEARCH, ESPECIALLY THE POTENTIAL RELATIONSHIP BETWEEN THE GUT MICROBIOME AND CANCER SYMPTOMS. METHODS: EXTANT LITERATURE WAS REVIEWED AND SYNTHESIZED. RESULTS: THE MAJORITY OF STUDIES LINKING THE GUT MICROBIOTA AND CANCER ARE ANIMAL MODELS AND FOCUS ON THE RELATIONSHIP BETWEEN DYSBIOSIS AND COLORECTAL CANCER. EMERGING EVIDENCE SUPPORTS THAT THE "GUT-BRAIN" CONNECTION IS A PLAUSIBLE MECHANISM FOR "PSYCHONEUROLOGICAL" CANCER SYMPTOMS SUCH AS DEPRESSION, PAIN, AND FATIGUE. CONCLUSIONS: THERE IS COMPELLING EVIDENCE THAT THE GUT MICROBIOTA AFFECTS CANCER VIA SEVERAL MECHANISMS, INCLUDING MICROBIAL DIVERSITY AND NUMBER, METABOLISM, AND/OR IMMUNE INITIATION. HOWEVER, MORE RESEARCH IS NECESSARY TO ELUCIDATE THESE MECHANISMS, PARTICULARLY AMONG A VARIETY OF CANCERS AND CANCER-RELATED SYMPTOMS. IMPLICATIONS FOR PRACTICE: A BETTER UNDERSTANDING OF THE ROLE OF THE GUT MICROBIOTA IN CANCER SYMPTOMS MAY LEAD TO THE DEVELOPMENT OF TARGETED INDIVIDUALIZED INTERVENTIONS AFFECTING THE GUT MICROBIOTA THAT PREVENT OR AMELIORATE DYSBIOSIS, THEREBY REDUCING SYMPTOMS. THESE INTERVENTIONS MAY EMPHASIZE SELF-CARE MANAGEMENT STRATEGIES ESSENTIAL FOR WELLNESS, SUCH AS DIET, NUTRITION, AND STRESS REDUCTION. 2016 13 3016 35 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 14 3906 36 LESSONS LEARNED--RESOLVING THE ENIGMA OF GENETIC FACTORS IN IBS. IBS IS THE MOST PREVALENT FUNCTIONAL GASTROINTESTINAL DISORDER AND PHENOTYPICALLY CHARACTERIZED BY CHRONIC ABDOMINAL DISCOMFORT, PAIN AND ALTERED DEFECATION PATTERNS. THE PATHOPHYSIOLOGY OF IBS IS MULTIFACTORIAL, ALBEIT WITH A SUBSTANTIAL GENETIC COMPONENT. TO DATE, STUDIES USING VARIOUS METHODOLOGIES, RANGING FROM FAMILY AND TWIN STUDIES TO CANDIDATE GENE APPROACHES AND GENOME-WIDE ASSOCIATION STUDIES, HAVE IDENTIFIED SEVERAL GENETIC VARIANTS IN THE CONTEXT OF IBS. YET, DESPITE ENLARGED SAMPLE SIZES, INCREASED STATISTICAL POWER AND META-ANALYSES IN THE PAST 7 YEARS, POSITIVE ASSOCIATIONS ARE STILL SCARCE AND/OR HAVE NOT BEEN REPRODUCED. IN ADDITION, EPIGENETIC AND PHARMACOGENETIC APPROACHES REMAIN IN THEIR INFANCY. A MAJOR HURDLE IS THE LACK OF LARGE HOMOGENIZED CASE-CONTROL COHORTS RECRUITED ACCORDING TO STANDARDIZED AND HARMONIZED CRITERIA. THE COST ACTION BM1106 GENIEUR (GENES IN IRRITABLE BOWEL SYNDROME RESEARCH NETWORK EUROPE) HAS BEEN ESTABLISHED TO ADDRESS THESE OBSTACLES. IN THIS REVIEW, THE (EPI)GENETIC WORKING GROUP OF GENIEUR REPORTS ON THE CURRENT STATE-OF-THE-ART IN THE FIELD, HIGHLIGHTS FUNDAMENTAL FLAWS AND PITFALLS IN CURRENT IBS (EPI)GENETIC RESEARCH AND PROVIDES A VISION ON HOW TO ADDRESS AND IMPROVE (EPI)GENETIC APPROACHES IN THIS COMPLEX DISORDER IN THE FUTURE. 2016 15 566 35 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 16 3283 34 HIDDEN ROLE OF GUT MICROBIOME DYSBIOSIS IN SCHIZOPHRENIA: ANTIPSYCHOTICS OR PSYCHOBIOTICS AS THERAPEUTICS? SCHIZOPHRENIA IS A CHRONIC, HETEROGENEOUS NEURODEVELOPMENTAL DISORDER THAT HAS COMPLEX SYMPTOMS AND UNCERTAIN ETIOLOGY. MOUNTING EVIDENCE INDICATES THE INVOLVEMENT OF GENETICS AND EPIGENETIC DISTURBANCES, ALTERATION IN GUT MICROBIOME, IMMUNE SYSTEM ABNORMALITIES, AND ENVIRONMENTAL INFLUENCE IN THE DISEASE, BUT A SINGLE ROOT CAUSE AND MECHANISM INVOLVED HAS YET TO BE CONCLUSIVELY DETERMINED. CONSEQUENTLY, THE IDENTIFICATION OF DIAGNOSTIC MARKERS AND THE DEVELOPMENT OF PSYCHOTIC DRUGS FOR THE TREATMENT OF SCHIZOPHRENIA FACES A HIGH FAILURE RATE. THIS ARTICLE SURVEYS THE ETIOLOGY OF SCHIZOPHRENIA WITH A PARTICULAR FOCUS ON GUT MICROBIOTA REGULATION AND THE MICROBIAL SIGNALING SYSTEM THAT CORRELATES WITH THE BRAIN THROUGH THE VAGUS NERVE, ENTERIC NERVOUS SYSTEM, IMMUNE SYSTEM, AND PRODUCTION OF POSTBIOTICS. GUT MICROBIALLY PRODUCED MOLECULES MAY LAY THE GROUNDWORK FOR FURTHER INVESTIGATIONS INTO THE ROLE OF GUT MICROBIOTA DYSBIOSIS AND THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA. CURRENT TREATMENT OF SCHIZOPHRENIA IS LIMITED TO PSYCHOTHERAPY AND ANTIPSYCHOTIC DRUGS THAT HAVE SIGNIFICANT SIDE EFFECTS. THEREFORE, ALTERNATIVE THERAPEUTIC OPTIONS MERIT EXPLORATION. THE USE OF PSYCHOBIOTICS ALONE OR IN COMBINATION WITH ANTIPSYCHOTICS MAY PROMOTE THE DEVELOPMENT OF NOVEL THERAPEUTIC STRATEGIES. IN VIEW OF THE INDIVIDUAL GUT MICROBIOME STRUCTURE AND PERSONALIZED RESPONSE TO ANTIPSYCHOTIC DRUGS, A TAILORED AND TARGETED MANIPULATION OF GUT MICROBIAL DIVERSITY NATURALLY BY NOVEL PREBIOTICS (NON-DIGESTIBLE FIBER) MAY BE A SUCCESSFUL ALTERNATIVE THERAPEUTIC FOR THE TREATMENT OF SCHIZOPHRENIA PATIENTS. 2021 17 1404 33 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 5869 43 SUSCEPTIBILITY TO STRESS-INDUCED VISCERAL SENSITIVITY: A BAD LEGACY FOR NEXT GENERATIONS. DESPITE HIGH PREVALENCE, THE PRECISE IRRITABLE BOWEL SYNDROME (IBS) PATHOPHYSIOLOGY REMAINS POORLY UNDERSTOOD LIKELY DUE TO THE HETEROGENEITY OF IBS POPULATIONS AND THE MULTIFACTORIAL ETIOLOGY OF THIS DISORDER. AMONG RISK FACTORS, GENETIC PREDISPOSITION AND EARLY LIFE TRAUMA HAVE BEEN REPORTED. IN THIS CONTEXT, THE DEBATE ON GENETIC OR ENVIRONMENTAL INFLUENCES IN THE IBS PATHOGENESIS IS STILL OPEN. THE STUDY BY VAN DER WIJNGAARD ET AL., REPORTING FOR THE FIRST TIME THAT SUSCEPTIBILITY TO STRESS-INDUCED VISCERAL HYPERSENSITIVITY IN MATERNALLY SEPARATED RATS CAN BE TRANSFERRED TO THE NEXT GENERATION WITHOUT ANY FURTHER EXPOSURE OF F2 INDIVIDUALS TO MATERNAL SEPARATION, SUPPORTS THE IMPORTANCE OF ENVIRONMENTAL INFLUENCE IN THE IBS PHENOTYPE. EPIGENETIC MECHANISMS SUCH AS HYPERMETHYLATION IN THE PROMOTER REGION OF THE GLUCOCORTICOID RECEPTOR GENE MEDIATING THE LONG-TERM AND TRANSGENERATIONAL BEHAVIORAL EFFECTS OF MATERNAL CARE ON THE DEVELOPMENT HAVE BEEN SHOWN IN SOME BUT NOT IN ALL STUDIES. VAN DER WIJNGAARD ET AL. INCRIMINATED MATERNAL CARE IN THE TRANSMITTED SUSCEPTIBILITY TO STRESS-INDUCED VISCERAL HYPERSENSITIVITY, BUT NOT CHANGES IN GLUCOCORTICOID RECEPTOR PROTEIN EXPRESSION IN THE BRAIN. THIS FINDING OPENS A BROAD FIELD OF FUTURE DIRECTIONS AIMED AT EVALUATING THE MECHANISMS INVOLVED IN THE TRANSMISSION ACROSS GENERATIONS OF THE DIGESTIVE FEATURES OF IBS, INCLUDING, FOR EXAMPLE, ON THE ROLE OF GUT MICROBIOTA CHANGES IN VERTICAL TRANSMISSION OR EPIGENETIC MODIFICATIONS OF INTESTINAL MAST CELLS AND THE JUNCTIONAL REGION OF INTESTINAL EPITHELIAL CELLS IN VERTICAL TRANSFER. 2013 19 6391 29 THE ROLE OF THE GUT MICROBIOME AND MICROBIAL METABOLISM IN MEDIATING OPIOID-INDUCED CHANGES IN THE EPIGENOME. THE CURRENT OPIOID PANDEMIC IS A MAJOR PUBLIC HEALTH CRISIS IN THE UNITED STATES, AFFECTING MILLIONS OF PEOPLE AND IMPOSING SIGNIFICANT HEALTH AND SOCIOECONOMIC BURDENS. PRECLINICAL AND CLINICAL RESEARCH OVER THE PAST FEW DECADES HAS DELINEATED CERTAIN MOLECULAR MECHANISMS AND IDENTIFIED VARIOUS GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS RESPONSIBLE FOR THE PATHOPHYSIOLOGY AND COMORBIDITIES ASSOCIATED WITH OPIOID USE. OPIOID USE-INDUCED EPIGENETIC MODIFICATIONS HAVE BEEN IDENTIFIED AS ONE OF THE IMPORTANT FACTORS THAT MEDIATE GENETIC CHANGES IN BRAIN REGIONS THAT CONTROL REWARD AND DRUG-SEEKING BEHAVIOR AND ARE ALSO IMPLICATED IN THE DEVELOPMENT OF TOLERANCE. RECENTLY, IT HAS BEEN SHOWN THAT OPIOID USE RESULTS IN MICROBIAL DYSBIOSIS, LEADING TO GUT BARRIER DISRUPTION, WHICH DRIVES SYSTEMIC INFLAMMATION, IMPACTING THE PERCEPTION OF PAIN, THE DEVELOPMENT OF ANALGESIC TOLERANCE, AND BEHAVIORAL OUTCOMES. IN THIS REVIEW, WE HIGHLIGHT THE POTENTIAL ROLE OF MICROBIOTA AND MICROBIAL METABOLITES IN MEDIATING THE EPIGENETIC MODIFICATIONS INDUCED BY OPIOID USE. 2023 20 5558 32 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