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A C O M P R E H E N S I V E O V E R V I E W O F I R R I T A B L E B O W E L S Y N D R O M E A C O M P R E H E N S I V E O V E R V I E W O F I R R I T A B L E B O W E L S Y N D R O M E Clinical and Basic Science Aspects Edited by JAKUB FICHNA Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland AcademicPressisanimprintofElsevier 125LondonWall,LondonEC2Y5AS,UnitedKingdom 525BStreet,Suite1650,SanDiego,CA92101,UnitedStates 50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom ©2020ElsevierInc.Allrightsreserved. Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronicor mechanical,includingphotocopying,recording,oranyinformationstorageandretrievalsystem,without permissioninwritingfromthepublisher.Detailsonhowtoseekpermission,furtherinformationaboutthe Publisher’spermissionspoliciesandourarrangementswithorganizationssuchastheCopyrightClearance CenterandtheCopyrightLicensingAgency,canbefoundatourwebsite:www.elsevier.com/permissions. ThisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythePublisher(other thanasmaybenotedherein). Notices Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchandexperiencebroadenour understanding,changesinresearchmethods,professionalpractices,ormedicaltreatmentmaybecome necessary. Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgeinevaluatingand usinganyinformation,methods,compounds,orexperimentsdescribedherein.Inusingsuchinformationor methodstheyshouldbemindfuloftheirownsafetyandthesafetyofothers,includingpartiesforwhom theyhaveaprofessionalresponsibility. Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,assumeany liabilityforanyinjuryand/ordamagetopersonsorpropertyasamatterofproductsliability,negligence orotherwise,orfromanyuseoroperationofanymethods,products,instructions,orideascontainedinthe materialherein. LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress BritishLibraryCataloguing-in-PublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary ISBN978-0-12-821324-7 ForinformationonallAcademicPresspublications visitourwebsiteathttps://www.elsevier.com/books-and-journals Publisher:MicaHaley AcquisitionsEditor:StacyMasucci EditorialProjectManager:MonaZahir ProductionProjectManager:NiranjanBhaskaran CoverDesigner:ChristianJ.Bilbow Creditsforthecoverimage:LeonPawlik TypesetbySPiGlobal,India Contributors RaquelAbaloDepartmentofBasicHealthSciences,UniversityReyJuan Carlos(URJC);HighPerformanceResearchGroupinPhysiopathology andPharmacologyofthedigestivesystem(NeuGut),URJC,Alcorco´n; R+D+iUnitAssociatedtoMedicalChemistryInstitute(IQM,CSIC), Madrid,Spain AnaBagu€e(cid:2)sDepartmentofBasicHealthSciences,UniversityReyJuan Carlos(URJC);HighPerformanceResearchGroupinExperimental Pharmacology(PHARMAKOM),URJC,Alcorco´n;R+D+iUnit AssociatedtoMedicalChemistryInstitute(IQM,CSIC),Madrid,Spain AgataBiniendaDepartmentofBiochemistry,FacultyofMedicine, MedicalUniversityofLodz,Lodz,Poland MiłoszCabanDepartmentofBiochemistry,FacultyofMedicine,Medical UniversityofLodz,Lodz,Poland JakubFichnaDepartmentofBiochemistry,FacultyofMedicine,Medical UniversityofLodz,Lodz,Poland DamianJacenikDepartmentofCytobiochemistry,FacultyofBiologyand EnvironmentalProtection,UniversityofLodz,Lodz,Poland LauraLo´pez-Go´mezDepartmentofBasicHealthSciences,University ReyJuanCarlos(URJC);HighPerformanceResearchGroupin PhysiopathologyandPharmacologyofthedigestivesystem(NeuGut), URJC,Alcorco´n,Spain LeonPawlikDepartmentofBiochemistry,FacultyofMedicine,Medical UniversityofLodz,Lodz,Poland MaciejSalagaDepartmentofBiochemistry,FacultyofMedicine,Medical UniversityofLodz,Lodz,Poland MichałSienkiewiczDepartmentofBiochemistry,FacultyofMedicine, MedicalUniversityofLodz,Lodz,Poland AleksandraSobolewska-WłodarczykDepartmentofBiochemistry; DepartmentofGastroenterology,FacultyofMedicine,Medical UniversityofLodz,Lodz,Poland MikołajS´wierczyn´skiDepartmentofBiochemistry,FacultyofMedicine, MedicalUniversityofLodz,Lodz,Poland PatrycjaSzałwin´skaDepartmentofBiochemistry,MedicalUniversityof Lodz,Lodz,Poland xi xii Contributors AdrianSzczepaniakDepartmentofBiochemistry,FacultyofMedicine, MedicalUniversityofLodz,Lodz,Poland AgataSzymaszkiewiczDepartmentofBiochemistry,FacultyofMedicine, MedicalUniversityofLodz,Lodz,Poland AleksandraTarasiukDepartmentofBiochemistry,FacultyofMedicine, MedicalUniversityofLodz,Lodz,Poland Jose(cid:2)AntonioUrangaDepartmentofBasicHealthSciences,University ReyJuanCarlos(URJC);HighPerformanceResearchGroupin PhysiopathologyandPharmacologyofthedigestivesystem(NeuGut), URJC,Alcorco´n,Spain MarekWalugaDepartmentofGastroenterologyandHepatology,School ofMedicineinKatowice,MedicalUniversityofSilesia,Katowice, Poland JakubWłodarczykDepartmentofBiochemistry,MedicalUniversityof Lodz,Lodz,Poland MarcinWłodarczykDepartmentofGeneralandColorectalSurgery; DepartmentofBiochemistry,FacultyofMedicine,MedicalUniversity ofLodz,Lodz,Poland AnnaZielin´skaDepartmentofBiochemistry,FacultyofMedicine, MedicalUniversityofLodz,Lodz,Poland MartaZielin´skaDepartmentofBiochemistry,FacultyofMedicine, MedicalUniversityofLodz,Lodz,Poland Preface Richorpoor,youngorold…Nearly15%ofourpopulationsuf- fer from irritable bowel syndrome (IBS) and only very few are takengoodcareof.Intheeraof“westernization”ofourlifestyles and increasing environmental pollution, but also in the times wheninfectionsspreadacrosstheworld,therewillonlybemore IBScasesinthecomingyears.ProperIBSdiagnosisandefficient therapy areneeded, and they areneeded now. ThisbooksummarizescurrentknowledgeonIBSandpointsto newdirectionsinbasicandclinicalstudies.Thebookmayberead in its entity, but also by single chapters, depending if one is a scientist, a clinician, or a patient. I do hope that it will become a helpful guide for all through IBS causes, symptoms, and treatment. xiii 1 Introduction to irritable bowel syndrome: General overview and epidemiology Jakub Fichna DepartmentofBiochemistry,FacultyofMedicine,MedicalUniversityofLodz, Lodz,Poland Abstract Irritablebowelsyndrome(IBS)isafunctionalgastrointestinalconditioncharacter- izedbythedisruptionofthebowelmovementandabdominalpain.Thereisno singlefactorknowntocauseIBS,henceitsdiagnosisandtreatmentaretrouble- some.Yet,duetoincreasingincidence,IBShasbecomeaseriousglobalissue. Inthischapter,theincidenceandprevalenceofIBSarediscussed.Also,epidemi- ologyindifferentcornersoftheworldiscomparedtoelucidatewhetherthereis any association with geographical location or socioeconomical status. Finally, age and genderare briefly discussedinan attemptto drawa picture of anIBS sufferer. Keywords Irritablebowelsyndrome,Epidemiology,Incidence,Prevalence List of abbreviations IBS irritablebowelsyndrome IBS-C constipation-predominantirritablebowelsyndrome IBS-D diarrhea-predominantirritablebowelsyndrome IBS-M mixedirritablebowelsyndrome Irritablebowelsyndrome(IBS)isafunctionalgastrointestinal condition,towhichbothinternalandexternalfactorscontribute. There is no single (in)organic causative agent identified so far, hence several hypotheses were formed to what extent genetic, AComprehensiveOverviewofIrritableBowelSyndrome.https://doi.org/10.1016/B978-0-12-821324-7.00001-0 1 #2020ElsevierInc.Allrightsreserved. 2 Chapter1 Introductiontoirritablebowelsyndrome neuronal, microbial, immunological or environmental factors promote the development of IBS. Typical symptoms: abdominal pain and changes in stool frequency or consistency, leading to constipation and/or diarrhea are debilitating to an extent where IBS is a major cause for visits in general practitioners office. Together with a significant impact on patients quality of life due to physical suffering, work absenteeism and economic non- productivity, but also psychological co-morbidity (increased risk of depression and suicidal ideation), IBS constitutes a major socioeconomic issue worldwide [1–3]. Nellesen et al. [4] report that the direct annual cost of diagnosing and treating IBS in the United States alone is estimated between $1.7 and $10 billion, while Chatila et al. [5] evaluate that the indirect costs in terms ofabsenteeism, workdays lost, disabilitywill doublethat figure. As there are no diagnostic or monitoring biological markers, IBS diagnosis bases on well-established criteria (currently Rome IV)inwhichpatient’ssymptomreportingiscrucial[6].However, as the guidelines are constantly being updated, studies on inci- dence and prevalence based on Rome I, Rome II, Rome III and Manningcriterianeedalsotobetakenintoconsideration.Worth mentioning,asnoticedbyCanavanetal.[7],theManningcriteria accountforthehighestreportedprevalence[8,9]whilsttheRome iterations are associated with lower estimates of prevalence [8]. Consequently, different figures regarding IBS epidemiology are obtained, which can be additionally influenced by the fact that not in all the countries criteria regarding IBShave been defined. Moreover, factors like survey methods and the study instrument could also affect the estimates. This has been best illustrated by Endoetal.[10]:theprevalenceofIBSinIranianadultsbasedon the modified Rome IIIcriteria was established at 21.5% [11] and only9.0%(95%CI,6.0–13.0)basedontheRomeIIcriteria[12]. In terms of incidence, Canavan et al. [7] reported two US studies,ofwhichoneconductedtwopopulationcohortsurveys 1yearapart[13]andtheotherdefinedcasesasfirstdiagnosisby a physician [14]. In the former, 9% of subjects had developed symptoms over the year, an incidence rate of 67 per 1000 person-years. Asignificantlylowerestimate basedon the latter, with around two per 1000 person years was provided. In 2012, based on a systematic review and meta-analysis of 260,960 subjects from 80 studies the global pooled prevalence ofIBSwasestimatedat11.2% [12],but laterthedatawereques- tioned due to significant heterogeneity between the studies [6]. Major geographical differences have been observed: in 2012 IBS ratesintheWesterncountriesrangedfrom10%to20%[15]com- paredto1%to10%intheAsiancountries[16];thelowestreported rateswereinSoutheastAsia(7.0%)whilethehighest(21.0%)were Chapter1 Introductiontoirritablebowelsyndrome 3 in South America. However, these estimates change rapidly over time:ariseinIBSratesinAsiancountriesisobserved,andmore developed nations, such as Japan and Singapore, already report prevalencecomparable to that inthe Western countries [17]. In terms of IBS subtypes, Lovell and Ford [12] point to diarrhea-predominant IBS (IBS-D) as the most prevalent (40.0%), followed by constipation-predominant (IBS-C, 35.0%) and mixed (IBS-M, 23.0%). A small study by Kibune-Nagasako etal.[18]onBrazilianpopulationstaysinlinewiththesestatis- tics:themostfrequentIBSsubtypewasIBS-D(46%),followedby IBS-C (32%) and IBS-M (22%). However, other studies cited by these authors report opposite results: for example IBS-M was the largest bowel habit subgroup in population-based studies performed in United Kingdom and the United States [19, 20], while IBS-C was the most frequent among Iranian adults [11]. It is thus hypothesized that the increased prevalence of a given IBS subtype depends primarily—but not exclusively—on the severity of symptoms in a given subtype and on who provides the epi- demiological data. Consequently, IBS-D—which may demand a more complex investigation in a gastrointestinal outpatient clinic—will rather be reported by GI specialists; general practi- tioners may be more confident inthe management ofIBS-C. There are several demographic parameters that need to be mentioned in relation to IBS epidemiology, including sex, age, and socioeconomical status. Canavan et al. [7] report that in most populations the IBS rates in women are approximately 1.5-to3-foldhigherthanthoseseeninmen[21–23]andinterna- tionally, the overall prevalence of IBS in women is 67% higher than in men (odds ratio 1.67 [95% CI 1.53–1.82]). These data may also be presented as outnumbering males by females by the ratio of 2:1 in the Western countries, and by 3:2 in United States [24]. On the other hand, in South Asia, South America, and Africa, the rates of IBS in men are almost equal to those of women, and in some cases even higher [12]. Forexample, Pim- parkaretal.reportareversedfemalestomalesIBSratioinIndia comparedtotheWesterncountries,i.e.1:3,withtheprevalence ofIBSingeneralpopulationofIndiaat15%[25].Thismayresult fromdisparitiesintheaccesstohealthcare,butalsosex-related motivation to seek consulting. IBSisreportedinallagegroups,withnodifferenceinthefre- quency of subtypes by age [7, 26]. However, the disease is more prevalent among adolescents and declines with age [12]. Inline, Canavanetal.pointtothefactthat50%ofpatientswithIBSreport havingfirstsymptomsbeforetheageof35years,andthatpreva- lenceis25%lowerinthoseagedover50yearsthaninthosewho areyounger [7, 12,27].

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