Table Of ContentA 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].
