Irritable bowel syndrome (IBS) is characterized by chronic abdominal pain/discomfort along with altered bowel habits, which accounts for a large proportion of gastrointestinal (GI) disorders worldwide. While psychiatric distress like depression is one of the most frequent comorbidities in IBS patients, which not only influences the quality of life, it also leads to a substantial economic burden and inefficient treatment in IBS patients. Inflammation, altered activities of the HPA axis, aberrant central neuroplasticity and neurotransmission have been highly regarded as pathogenic factors of the depression. Whereas, in recent years, dysfunctions in the gut microbial community has been increasingly discovered to provoke depression disorder. Considering that gut dysbiosis plays causal role in IBS progression, dysfunction of the gut microbiota has been speculated for contributing to the depressive symptoms in IBS (IBS-DP) patients. However, whether and how gut dysbiosis affecting IBS-DP patients remain unclear. We hypothesized that gut microbiota changes contribute to the development of IBS-DP and the change of gut microbiota-driven metabolites induces the structural and/or functional changes of the central nervous system (CNS), thus resulting in the development of IBS-DP. In this thesis, IBS patients with and without depression and animal models of IBS have been systematically studied, to investigate whether gut dysbiosis mediates depressive disorder in IBS. Firstly, we conducted a cross-sectional study involving the distribution of depressive disorder in the IBS population of Hong Kong. According to this survey, we found that there is 36.6% (135/369) of IBS patients showed symptoms of depression. The severity of depressive symptoms was positively associated with the harshness of visceral pain and bloating signatures in IBS patients. Secondly, in comparison to the non-depression of IBS (IBS-ND) group, faecal metagenomic results unveiled the disrupted gut microbiota in IBS-DP patients, mainly with the deficiency of several beneficial bacterial groups, including Akkermansia, Bifidobacterium and Eubacterium, whereas the gut microbiota profile between IBS-ND patients and healthy controls (HCs) showed no significant changes. Compared with HCs, enzyme-linked immunosorbent Assay (ELISA) results showed higher levels of serum IL-1β, IL-6, and TNF-a in IBS-DP patients, indicating a low-grade peripheral inflammation in IBS-DP patients. Moreover, the abundance of Akkermansia muciniphila (A. muciniphila), was negatively correlated with Hamilton Rating Scale for Depression (HAMD) score and Zung Self-Rating Depression Scale (SDS) score, IL-1β, TGF-β, and TNF-a in IBS-DP patients. These findings indicate that gut dysbiosis, especially deficiency in A. muciniphila, is related to the depressive symptoms and inflammation in IBS-DP patients. Thirdly, in a neonatal maternal separation (NMS) rat model, behavioural tests such as colorectal distention (CRD) test, open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) results showed visceral hypersensitivity and depression symptoms in rats. These results indicate that the model can successfully mimic the visceral hyperalgeisa and the depression-like behaviour of IBS-DP. Immunohistochemical analysis showed an altered morphology and decreased the quantity of astrocytes in the hippocampus of NMS rats when compared with that of controls. More importantly, the mRNA expressions of genes related to Astroglial glutamate transmission including glutamate transporters (GLTs), glutamate receptors, and also glutamate-related exchangers, as well as astrocyte biomarker glial fibrillary acidic protein (GFAP), which are mediated with chronic inflammation and/or stress, were decreased in NMS rats when compared with the control group. These results indicate that impaired astroglial glutamate neurotransmission in NMS rats. Furthermore, pseudo-GF rats with faecal microbiota transplantation (FMT) of NMS microbiota were also conducted, and results showed that the association of A. muciniphila deficiency, depressive-like behaviours and impaired astroglial glutamate neurotransmission were repeated in the rat recipients. These results indicate a causal relationship between NMS microbiota and depressive phenotype, involving dysfunction of the astrocyte- glutamate pathway. Fourthly, to further verify the role of A. muciniphila in NMS microbiota-induced depressive phenotype and impaired astrocytic glutamate pathway, we orally administered live and heat-killed A. muciniphila bacteria in NMS adult rats. A. muciniphila (108 CFU in 1mL PBS) was administered once-daily for four consecutive weeks. Besides, rifaximin and fluoxetine were also separately treated in NMS rats as control groups. Rifaximin is a broad-spectrum GI-specific antibiotic that is commonly used for IBS treatment, and fluoxetine, a selective serotonin re-uptake inhibitor, is one of the most frequently prescribed anti-depressants. The results showed that A. muciniphila efficiently improved depressive-like behaviours, attenuated the impaired astrocytic glutamate neurotransmission, as well as restored the normal morphology and number of astrocytes in the hippocampus of NMS rats. While rifaximin-treated rats only exhibited amelioration of visceral pain, and fluoxetine group mainly performed antidepressant effect, without any significant change in astrocytic glutamate neurotransmission impairment. These results demonstrate that A. muciniphila improves depressive symptoms in IBS phenotype and ameliorate astroglial-glutamatergic pathway dysfunction. Whether and how A. muciniphila modulates astroglial glutamate transmission, therefore leading to the improvement of depressive symptom in IBS, remains to be further investigated. Taken together, the works of this thesis, combining both clinical and animal studies reveal that gut dysbiosis, particularly deficiency of A. muciniphila, contributes to the development of IBS-DP via regulating the astroglial glutamatergic pathway. This study gives a different direction to microbial-guided therapy for the IBS-DP patients in the future

Introducción: El SII se caracteriza por la presencia de dolor abdominal, diarrea, estreñimiento, o la alternancia de ambas, la causa de esta patología tiene que ver con muchos factores: alimentación, antecedentes de enfermedades, estilo de vida, etc. En el Hospital Guillermo Almenara Irigoyen (HGAI), se desconoce la prevalencia del SII. Objetivos: Determinar la prevalencia del SII en la consulta ambulatoria del servicio de Gastroenterología del HGAI, así como también describir los subtipos de SII que se presentan. Material y Métodos: El presente estudio es de tipo descriptivo y de corte transversal. La muestra consta de 1365 pacientes, se utilizo el muestreo por conveniencia. Se confecciono una encuesta ad hoc, con dos partes: una ficha de recolección de datos (clínicos y sociodemográficos) y otra con los criterios de ROMA II para el diagnostico de SII. Los pacientes fueron encuestados en la sala de espera de los dos (02) consultorios ambulatorios del Servicio de Gastroenterología (SG) del HGAI, del 06 de Abril del 2003 al 06 de Junio del 2003. Se realizo el análisis estadístico con el programa SPSS v11, para la descripción de los resultados. Resultados: La prevalencia del SII en el SG del HGAI fue de 38.8%. De los pacientes con SII de acuerdo a los criterios de Roma II tenemos; el 44% presento SII tipo diarrea, el 32% fue tipo estreñimiento, el 19% fue tipo mixto y el 5% no se pudo determinar. De la prevalencia general de 38.8 %, el sexo femenino aportó una prevalencia del 26.5%, y el sexo masculino aporto una prevalencia del 12.2 %. La variable Sexo fue significativa, por lo que la probabilidad de que el diagnostico de SII se relaciona mas con el sexo femenino. Por lo que existiría un riesgo de 1.8 veces en el sexo femenino de tener el SII en relación al sexo masculino. El grupo etareo de 60 a 69 años es el que presenta la mayor prevalencia en el diagnostico de SII (10.2%). El grupo de edad de 50 años hacia delante presenta una prevalencia acumulada de 28.8%. Asimismo se encontraron hallazgos secundarios con las variables que tuvieron significancia estadística las cuales fueron: Sexo, Grupo etareo, Diabetes Mellitus (DM), Antecedente de Cirugía Pélvica y Antecedente personal de Cáncer gastrointestinal. Conclusión: Existe una alta prevalencia del SII (38.8%) en la población estudiada, siendo el SII de tipo Diarrea el más frecuente. El grupo de edad de 50 años hacia delante presenta una prevalencia acumulada de 28.8%. / Tesis de segunda especialidad

Recent research has highlighted the connection between dysbiosis of the gut microbiome and its role in the development of Irritable Bowel Syndrome (IBS). Over the last few years, probiotics have grown in popularity as a potential treatment option in IBS. However, most current probiotic studies are limited due to small study populations, older median age, and short study time duration. The proposed study will be a multicenter, randomized, double-blinded placebo controlled study comparing the multi-strain probiotic Bifidobacterium infantis, Bifidobacterium bifidum, Bifidobacterium breve, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Escherichia coli DSM17252 to placebo in patients diagnosed with IBS based on Rome IV criteria over a 3-months duration. The study participants will have a baseline evaluation and a final evaluation at the end of the 3-months duration. The primary outcome will be the IBS Symptom Severity Score and the secondary outcomes will the individual components of the IBS Symptom Severity Score. The results of this study will begin to fill gaps in the current knowledge of the use of probiotics in the treatment of IBS.

No description available.

Irritable Bowel Syndrome (IBS) is a gut-brain-axis disorder with a prevalence of 5.8% in Canada and 3.8% globally. Despite evidence suggesting complex interactions among neural, immune, and epithelial cells, influenced by factors such as diet, microbiota, and stress, the pathophysiology of IBS remains incompletely understood. Key knowledge gaps include the irregular nature of symptoms and the specific bacterial taxa responsible for symptom generation. Therefore, this thesis aims to perform an integrated analysis of a longitudinal study to investigate the relationship between IBS symptom dynamics, gut microbiota composition, and metabolite profiles, to determine whether temporal changes in microbiota predict or drive IBS symptoms. Clustering analysis identified distinct patterns in symptom occurrence and progression, categorizing samples into clusters that captured changes in both gut and mood symptoms, and distinguishing between symptom flares and remission. Subjects with constipation-predominant IBS exhibited consistently higher levels of symptoms while diarrhea-predominant IBS subjects showed varying symptom levels among abnormal stool weeks and normal stool weeks. Examining parallel changes in symptom scores and microbiota beta diversity over time, we found a significant correlation between the two in only 25% of IBS subjects in our cohort. This suggests a potential link between microbiota composition and symptom variability in specific subsets of patients, highlighting the heterogeneity in the microbiota-symptom relationship. Integrated microbiota-metabolite analysis revealed signatures linked to IBS subtypes, with bacteria such as Lachnoclostridium and Olsenella ,and metabolites like chenodeoxycholic acid among others identified as key nodes in network analysis. In conclusion, this study offers comprehensive insights into the episodic nature and heterogeneity of IBS, revealing dynamic symptom patterns and persistent burdens across subtypes. The findings highlight the complex relationship between microbiota composition changes and symptom variation, as well as the microbiota-metabolite axis in IBS patients. / Thesis / Doctor of Philosophy (Medical Science)

published_or_final_version / abstract / Social Work and Social Administration / Doctoral / Doctor of Philosophy

Bakgrund: IBS (Irritabel Bowel Syndrome) är en funktionell mag-tarmsjukdom, med en oklar patofysiologi och etiologi. IBS är en vanlig åkomma hos den västerländska befolkningen och karakteriseras av återkommande buksmärta/obehag, uppblåsthet, diarré och/eller förstoppning samt ökad gasbildning. Det finns idag inget botemedel för IBS, men intresset för probiotika som behandling vid IBS har på senare tid ökat. Probiotika, vilket definieras som levande mikroorganismer, som när de intas i adekvata mängder ger en hälsovinst hos värden tros ha en symptomatisk effekt vid IBS, och har därmed varit av intresse för behandling av IBS. Syfte: Syftet med denna litteraturstudie är att undersöka om probiotika har någon terapeutisk effekt och kan användas som behandling vid IBS. Metod: Fem randomiserade, dubbelblindade, placebo-kontrollerade studier granskades. De undersökte den terapeutiska effekten av varierande probiotika på IBS-patienter. Artiklarna erhölls genom sökningar i den medicinska databasen PubMed, under februari månad 2016. Resultat: Av dessa fem studier visade fyra på en signifikant symptomförbättring av framförallt buksmärta/obehag. Bäst resultat sågs i en studie som undersökte probiotikan Lactobacillus plantarum 299v. Tre av fem studier visade på en signifikant förbättring av testpersonernas livskvalité. I endast en av studierna, som undersökte effekten av Escherichia coli Nissle 1917, påvisades ingen signifikant skillnad mellan E.coli (probiotika) och placebo. Slutsats: Baserat på de fem studierna föreligger det i nuläget skäliga bevis för att en behandling med specifika probiotika kan ge symtomförbättring av buksmärta/obehag hos IBS-patienter, och förbättrar patienternas livskvalité. Vidare studier krävs för att fastställa den mest effektiva probiotikan, dosen och behandlingslängden. / Background: IBS (Irritable Bowel Syndrome) is a functional gastrointestinal disorder, with an unclear etiology and pathophysiology. IBS is a common disorder in the Western population and is characterized by recurrent abdominal pain/ discomfort, bloating, flatulence, diarrhea and/ or constipation. There is currently no cure for IBS, but the interest in probiotics as an option of treatment has recently increased. Probiotics have been defined as live microorganisms that, when administered in adequate amounts, provide a health benefit on the host, and are believed to have a symptomatic effect in IBS. Probiotics have therefore been of interest for the treatment in IBS. Purpose: The purpose of this study is to examine whether probiotics have a therapeutic effect and if it could be used as a treatment for IBS. Method: Five randomized, double-blind, placebo-controlled studies were reviewed that examined the therapeutic effect of different probiotics in the IBS-patients. Articles were obtained through searches in the medical database PubMed, during the month of February 2016. Results: Four of the five studies showed a significant improvement of symptoms especially in abdominal pain/ discomfort. The best results were seen in a study that investigated the probiotic Lactobacillus plantarum 299v. Three of the five studies showed a significant improvement in quality of life (QOL) of the subjects in the study. One of the five studies which examined the effect of Escherichia coli Nissle 1917, there was no significant difference between E.coli (probiotics) and placebo. Conclusion: There is reasonable evidence that treatment with certain probiotics might provide improvement in symptoms of abdominal pain/ discomfort, and increase patients quality of life based on the five studies. Further studies are required to determine the most effective probiotic, dose and duration of IBS-treatment.

El síndrome del intestino irritable es un trastorno común que afecta a millones de personas en todo el mundo. Dicho transtorno tiene un impacto significativo en la calidad de vida de las personas que lo padecen afectando en mayor o menor medida la esfera sociolaboral de estos individuos con el consecuente sufrimiento individual e impacto macroeconómico por aumento en las tasas de ausentismo y rendimiento laboral. Los prebióticos y probióticos son suplementos de la dieta no digerible, elementos químicos y microorganismos vivos (bacterias o levaduras de la flora comensal intestinal) que al consumirlos en volúmenes óptimos (tratamiento simbiótico), resultan beneficiosos para la salud humana. La mucosa intestinal es sin duda la mayor superficie del organismo humano expuesta al medio externo, ademas de contener una alta densidad de células inmunitarias. La alteración de la homeostasis entre los microorganismos beneficiosos y potencialmente nocivos de la microflora intestinal se expresa en un incremento del riesgo a padecer infecciones y enfermedades inmunoinflamatorias y, en este sentido, los pre y probióticos ayudan a mantener esta armonía. / Irritable intestine syndrome is a common condition that affects millions of persons all over the world. It has a significant impact in the quality of life of affected persons, influencing their social and working environments and leading to individual suffering and a macroeconomic impact because of increased absenteeism and poor working performance. Prebiotics and probiotics are supplements of nondigestible diet, made up of some chemicals and live microorganisms (bacteria or yeasts from the intestinal commensal flora), which, when ingested in optimal amounts (symbiotic therapy), are beneficial for human health. With no doubt, the intestinal mucosa is the greatest surface in the human body exposed to external stimuli, and it also contains a high proportion of immune cells. Any alteration in homeostasis between beneficial and potentially harmful microorganisms in the intestinal microflora is expressed as an increased risk for the occurrence of infectious and immune and inflammatory diseases; therefore, prebiotics and probiotics may help to maintain a harmonic environment in the intestine. / Revisión por pares

Syftet med denna systematiska litteraturstudie var att belysa hur sjuksköterskans omvårdnad kan stödja egenvårdsförmågan hos patienter med IBS. Den viktigaste omvårdnadsåtgärden var att tidigt i samband med diagnostiseringen av IBS, ge information och kunskap om sjukdomen, dess prognos samt behandling, vilket visades förbättra upplevd livskvalitet samt ge symtom-lindring. IBS skolor startade av sjuksköterskor förbättrade patienternas hälsobeteende samt minskade symtomen. Genom introduktion av guidebok innehållande råd om kost, motion, stresshantering samt symtomkontroll upplevde patienterna en minskning av symtom, vilket även ledde till en minskning av antalet besök inom sjukvården. När sjuksköterskan använde olika frågeformulär i kontakten med patienter med IBS kunde patienternas problem identifieras och strategier för egenvården planeras samt individuella handlingsplaner skapas. Sjuksköterskans kunskap och förståelse om patientens egen sjukdomsupplevelse samt copingstrategi ledde till att patienten tog en mer aktiv roll i sjukdomshantering. Patienters behandling borde inriktas på livsstilsförändringar, som till exempel psykosocial arbetsmiljö, kost, fysisk aktivitet, samt stresshantering. Genom att patienten förde dagbok över kostintag och sedan gjorde jämförelser med ökade eller minskade symtom kunde faktorer identifieras i matvanor samt kostintag som inverkade på symtomen. Dorotea Orems omvårdnadsmodell har legat till grund för denna studie där tron på människans egna resurser framhålls.

Bakgrund: Irritable Bowel Syndrome (IBS) och Funktionell Dyspepsi (FD) är två syndrom som många personer lider av och som det inte finns någon botande behandling för. Då syndromen bara går att symptomlindra tar många av personerna som lider av dessa till egenvårdsmetoder som ofta är kostrelaterade. Att stötta och vägleda patienter i sin egenvård är en uppgift som sjuksköterskor i allmänhet har, och i synnerhet för dessa patienter eftersom ingen botande behandling finns. Syfte: Syftet med föreliggande litteraturstudie var att beskriva kostrelaterade egenvårdsmetoder för patienter med Irritable Bowel Syndrome och/eller Funktionell Dyspepsi där upplevda och/eller observerade effekter beskrivits. Syftet var även att beskriva de valda studiernas datainsamlingsmetoder. Metod: En litteraturstudie med beskrivande design. Datainsamlingen har skett från databaserna PubMed och CINAHL. Huvudresultat: Tretton studier har inkluderats. Utifrån dessa har det framkommit att patienter som lider av IBS och/eller FD kan ta till en mängd olika kostrelaterade egenvårdsmetoder. Effekter av dessa har visat sig förebygga och/eller lindra fysiska symptom från mag-tarmkanalen samt i och med detta ge förbättrad livskvalitet. De datainsamlingsmetoder som beskrivits har visat sig variera mellan frågeformulär och skattningsskalor, dagböcker, kroppsliga markörer samt gruppintervjuer. Slutsats: Patienter med IBS och/eller FD kan använda sig av ett flertal olika kostrelaterade egenvårdsmetoder i syfte att förebygga och/eller lindra sina symptom från mag-tarmkanalen. En mängd olika datainsamlingsmetoder kan användas för att identifiera olika kostrelaterade egenvårdsmetoder och dess påverkan på symptom från IBS och/eller FD. / Background: Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD) are two syndromes that many people suffers from and that has no curing treatment. Since the syndromes only has a symptomatic treatment many people that suffers from it uses self-care methodes that often includes diet. Support and guidance in patiens self-care are a main task for nurses in general and especially for these patients since no curing treatment is available. Aim: The aim of the present study was to describe dietary self-care practices for patients with Irritable Bowel Syndrome and/or Functional Dyspepsia where the perceived and/or observed effects was described. The aim was also to describe the selected studies data collection methods. Method: A literature review with descriptive design. Data has been collected from the databases PubMed and CINAHL. Main Results: Thirteen studies were included. From these, it has been found that patients suffering from IBS and/or FD may use a variety of dietary self-care methods. Effects of these have been shown to prevent and/or alleviate physical symptoms from the gastrointestinal tract and therefore provide better quality of life. The data collection methods described have been found to vary between questionnaires and rating scales, diaries, physical markers and group interviews. Conclusion: Patients with IBS and/or FD can make use of many diet related self-care methods to prevent and/or relieve their symptoms from the gastrointestinal tract. Many different data collection methods can be used to identify diet related self-care practices and its effect on the symptoms of IBS and/or FD.