Detta är en kvalitativ studie med fenomenologisk ansats, som beskriver kvinnor med Irritable Bowel Syndrome (IBS) och deras upplevelser av sjukdomen. Vårt syfte med studien är att öka kunskapen och förståelsen hos sjuksköterskor och övrig vårdpersonal, genom att låta kvinnor med diagnosen IBS beskriva sina upplevelser av att leva med syndromet samt hur de blivit bemötta vid kontakter med sjukvården. Målsättningen är att det holistiska omhändertagandet av patienten skall förbättras. Studien baseras på semistrukturerade intervjuer med sju diagnostiserade kvinnor. Materialet har sedan bearbetats utifrån Philip Burnards modell för textanalys. Resultaten presenteras i följande kategorier sociala aktiviteter, sociala relationer, okunskap, bemötande och utredning, vilka kan relateras till de aktuella frågeställningarna (1) Hur upplever kvinnor med IBS att sjukdomen påverkar deras dagliga liv? Och (2) Hur upplever kvinnor med IBS att de blivit bemötta vid kontakter med sjukvården. Våra resultat ger en uppfattning av hur kvinnorna upplever att deras IBS påverkar det dagliga livet. Utmärkande för studiepopulationen är upplevelser av att sociala relationer och sociala aktiviteter förändrats till följd av sjukdomen. Gällande bemötande vid kontakter med sjukvården upplever kvinnorna att de bemötts med okunskap från sjuksköterskor och annan vårdpersonal. De upplever sig dessutom ofta åsidosatta och lågprioriterade av sjukvårdssystemet. / This is a qualitative study with a phenomenological approach, about females with Irritable Bowel Syndrome (IBS). The purpose of the study is to increase the knowledge and understanding among nurses and other caring personnel, by letting females diagnosed with IBS describe their experiences of living with the syndrome, and how they have been treated in contacts with the Swedish healthcare system. The intention of the study is that the holistic care should be improved. The study is based on seven semi-structured interviews of IBS-diagnosed females. The data has been analysed with Burnard´s method for transcripts. The results are presented in the following categories social activities, social relations, ignorance, treatment, analysis, which can be related to the actual questions of the study: (1) How do females with IBS experience that the illness affects their daily life? and (2) How do females with IBS experience the treatment in contacts with the Swedish care-system? The results have been presented in categories that can be related to the empiric questions in the study. The results of the study give us a conception of how IBS influences the daily life. Distinguishing for the study population is their experiences of changes in their social activities and relations due to their illness. About treatment in contacts with the Swedish healthcare system the females experience that they have been treated with ignorance from nurses and other health care personnel. They also experience themselves as disregarded and low prioritised by the healthcare system.

Irritable bowel syndrome (IBS) is a functional bowel disorder with 6.5% worldwide prevalence that causes gas production, abdominal distension, and abdominal pain or discomfort. This systematic review describes efficacy of the Low-Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols (FODMAP) diet (Low-FODMAP diet or LFD) to alleviate IBS symptoms using the PRISMA guidelines. Nine randomized controlled trials (RCT) and one non-RCT consecutive controlled study published between 2015 to 2019 were identified using PubMed and CENTRAL. Included studies involved adult IBS participants with symptoms of abdominal pain, constipation, and/or diarrhea. A total of 530 participants completed the interventions from the 10 studies included in the final systematic review with participants ranging from mean ages of 40.31±12.83 years. The LFD can be recommended to patients for its use with alleviating abdominal pain severity and quality of life; however, more research is needed to verify the efficacy of the LFD concerning stool frequency and consistency.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24131号 / 医博第4871号 / 新制||医||1059(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 阪上 優, 教授 佐藤 俊哉, 教授 小杉 眞司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Irritable bowel syndrome (IBS) är en av våra vanligaste funktionella tarmsjukdomar med en prevalens på ca 10% värden över. Diagnosen ställs utifrån ROME-kriterierna vilka är ett symptombaserat diagnostiskt verktyg samt uteslutande av andra allvarliga tillstånd. Vidare kan IBS delas in i undergrupper beroende på avföringens konsistens mätt utifrån The Bristol stool form scale (BSFS). Patologin bakom sjukdomen är idag inte helt klarlagd men flera faktorer och mekanismer tros spela in. Däribland finns visceral hypersensitivitet och avvikande uttryck av smärtreglerande signalsubstanser, rubbningar i den gastrointestinala mikrobiotan, genetik, ökad inflammation, defekt mucosabarriär med ökad permeabilitet, psykosociala faktorer och kost. Behandling är främst inriktad på symptomlindring och att utbilda patienten i att hantera sjukdomen genom att undvika triggande faktorer som kan förvärra symptom. Probiotika är levande icke-patogena mikroorganismer som används i behandlande syfte. Några av de mest studerade släkterna av bakterier som används vid behandling av IBS är Lactobacillus och Bifidobacterium. Detta arbete syftade till att analysera effekten av probiotika i form av en kombination med dessa två släkten som symptomlindrande behandling vid IBS. Detta gjordes genom litteratursökning på databasen PubMed där fem artiklar filtrerades fram utifrån satta kriterier. Resultatet visade att probiotika innehållande Lactobaciullus och Bifidobacteirum har potential att förändra den gastrointestinala mikrobiotan. Man kunde också se att en ökad nivå Bifidobacteriumkorrelerade med sänkt symptomgrad och lägre nivå inflammatoriska markörer. Studierna visade också på sänkt tarmpermeabilitet efter intag av probiotika. Den generella symptombilden och allvarlighetsgraden av sjukdomen förbättrades och även flera specifika symptom. Trots det kunde en entydig och signifikant förbättring av livskvalitén inte fastställas. Dosen probiotika som användes var mellan 5-10 miljarder colony forming units (CFU) i alla utom en studie. Denna undersökte en betydligt högre dos om 52 miljarder CFU men gav trots det inte bättre resultat än övriga studier. Studiepopulationen var sammantaget enhetlig i de olika studierna och speglade också den vanligaste patientgruppen. Slutsatsen var att probiotika innehållande släkterna Bifidobacterium och Lactobacillus kan förbättra allvarlighetsgraden av IBS och ge en generell och specifik symptomlindring. / Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders without any detectable biochemical or structural changes with a prevalence of about 10 % worldwide. The diagnosis is based on the ROME-criteria which is a symptom based diagnostic tool and also exclusion of other severe diseases. Further on, IBS can be divided into different subgroups based on stool texture evaluated by the Bristol stool form scale (BSFS).  The pathology behind IBS is not fully understood but several factors and mechanisms are thought to be involved. Amongst those are hypersensitivity in the gut and divergent pain transmission, disturbance in gut microbiota, genetics, increased inflammation, defective mucosal barrier function with increased permeability, psychosocial factors and diet. Treatment is mainly used to alleviate symptoms so as to help the patients to manage the disease by education and by avoiding the triggering factors that may exacerbate the symptoms.  Probiotics are living non-pathogen microorganisms, meaning they are not harmful, used to treat or favor the host. Some of the most studied genera of bacteria, both in general and used as treatment of IBS, are Lactobacillus and Bifidobacterium. These bacteria are often referred to as lactic acid bacteria due to their ability to metabolize specific carbohydrates and produce lactic acid.  This study aimed to investigate the effect of probiotics consisting of these two genera on symptom relief for patients with IBS. It was achieved by carrying out a literature review in the PubMed database. Five articles were found based on set criteria.  The results showed that probiotics based on Lactobacillus and Bifidobacterium have potential to alter the gut microbiota and that levels of Bifidobacterium corresponding to level of symptoms and inflammatory markers. Also, the intestinal permeability was lowered by probiotics administration. The overall symptoms and severity were decreased as well as several specific symptoms. Despite that, a significant increase in quality of life was not observed.  The dose used was between 5-10 billion colony forming units (CFU) in all but one study. This study used a much higher dose of 52 billion CFU and did also last a longer period of time but did not get better results than the other studies. The study population was in general similar in all studies and did also reflect the most common patient group based on prevalence.  In conclusion, probiotics consisting of Lactobacillus and Bifidobacterium can be used to improve severity of IBS and to relieve general and specific symptoms.

Introduction Ehlers-Danlos syndrome (EDS), specifically the hypermobility type (hEDS), is associated with a variety of gastrointestinal (GI) conditions. This study aims to evaluate the prevalence of and factors associated with gut dysmotility in patients with hEDS. Methods This is a retrospective study of hEDS patients conducted at the Cleveland Clinic's Center for Personalized Genetic Healthcare between January 2007 and December 2017. Demographics, GI motility testing, endoscopic, and imaging data were extracted from the patients' charts. Results A total of 218 patients with hEDS were identified. Among them, 136 (62.3%) patients had at least one GI symptom at the time of EDS diagnosis. Motility testing was performed and reported in 42 (19.2%) patients. Out of them, five (11.9%) had esophageal dysmotility, 18 (42.8%) had gastroparesis, five (11.9%) had small bowel/colon altered transit time, and four (9.5%) had global dysmotility. In univariable analysis, patients with postural orthostatic tachycardia syndrome (POTS) [odds ratio (OR): 8.88, 95% CI: 3.69-24.9, p<0.0001], fibromyalgia (OR: 4.43, 95% CI: 2.04-10.1, p=0.0002), history of irritable bowel syndrome (OR: 5.01, 95% CI: 2.31-11.2, p<0.0001), and gastroesophageal reflux disease (OR: 3.33, 95% CI: 1.55-7.44, p=0.002) were more likely to be diagnosed with GI dysmotility. On multivariable analysis, only POTS (OR: 5.74, 95% CI: 2.25-16.7, p=0.0005) was significantly associated with an increased likelihood of GI dysmotility. Conclusions This study suggests that GI symptoms are relatively common among patients with hEDS. Of the patients tested for dysmotility, 76.2% were found to have some form of dysmotility. POTS was found to be an independent predictive factor for GI dysmotility.

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Irritable Bowel Syndrome (IBS) is the most common gastrointestinal disorder which affects approximately 4% of the population worldwide, according to the Rome IV criteria. It is characterized by abdominal pain and altered bowel movements in the absence of relevant structural abnormalities. The diagnosis of IBS is based on symptom profiles as no biomarkers exist to guide diagnosis or treatment stratification. Accumulating data suggests that altered gut microbiota and chronic low-grade inflammation play important roles in genesis of IBS. However, the mechanisms are unclear. My thesis first addresses the hypothesis that changes in fecal β-defensin secretion reflect compositional changes in the intestinal microbiota. This was driven by the understanding that compositional changes in the microbiota (“dysbiosis”) may play a role in the expression of IBS, and that a marker of these will identify those patients who might benefit from microbiota-directed therapies. I used a murine model in which I disrupted the microbiota using interventions relevant to the natural history of IBS i.e., antibiotics, stress, or dietary changes. I showed that experimentally induced compositional changes in the microbiota, with the exception of stress, altered the secretion of fecal β-defensin. My study indicates that monitoring fecal β-defensin over time identifies compositional changes in microbiota. I next investigated mechanisms and treatment options for a recently recognized variant of post-infectious IBS (PI-IBS) developed following antibiotic treatment in patients recovering from Clostridioides difficile infection (CDI). I refer to this variant as post-CDI gut dysfunction. I used a humanized mouse model in which germ-free mice were colonized with fecal microbiota from patients with post-CDI gut dysfunction, or age and sex matched healthy controls. I found that mice colonized with microbiota from a patient with severe slow transit constipation post-CDI reproduced the donor phenotype. Mice developed slow colonic transit due to macrophage mediated damage to the interstitial cells of Cajal (ICC) that maintain normal motility. These changes were reversed after fecal microbiota transplantation (FMT) from healthy donor mice thus confirming that the post-CDI gut dysfunction is microbiota driven. Similar results were obtained in a patient with slow transit constipation without a history of infection. My findings prompted me to next evaluate the therapeutic potential of microbiota-directed dietary therapies. I chose psyllium, the flavonoid quercetin, and pectin based on their demonstrated ability to alter microbiota composition. Psyllium and pectin each normalized colonic transit, and this was accompanied by an alteration in macrophages morphology, restoration of the disrupted ICC network and an increase in short chain fatty acids production. My results demonstrate the importance of a dysbiotic microbiota in this post infectious- IBS (PI-IBS) variant and, identify two potentially useful dietary based therapeutic approaches to improve gut dysfunction in these and similar patients. If findings from my thesis are confirmed in humans, it could offer novel approaches for identifying those IBS patients who might benefit from microbiota-directed therapeutics. / Thesis / Candidate in Philosophy

Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are two of the most commonly diagnosed chronic digestive disorders in Western countries with increasing prevalence among Canadians. However, the etiology of IBS and IBD remain poorly understood due to a complex interplay of genetic, psychosocial and environmental factors, which hampers efforts at early detection/screening, accurate diagnosis and effective treatments notably in children. This thesis aims to reveal new biochemical insights into the pathophysiology underlying IBS and IBD when using an untargeted metabolite profiling (i.e., metabolomics) approach on urine and stool specimens based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). Chapter I reviews brief history and current challenges in diagnosis and treatment, as well as current metabolomics literature of IBS and IBD. Chapter II first develops a robust method for high throughput profiling of anionic metabolites in human urine samples when using MSI-CE-MS. For the first time, we demonstrate that incidental capillary fractures are caused by irreversible aminolysis of the outer polyimide coating due to the frequent use of volatile ammonia based buffers under alkaline conditions (pH > 9) in electrospray ionization-MS. Chapter III subsequently applies this validated method to investigate differentially excreted urinary metabolites between adult IBS patients and healthy controls, which indicated significantly accelerated rates of collagen degradation and cell turn-over in IBS patients. Chapter IV later develops a novel stool extraction protocol for characterization of the fecal metabolome together with meta-genomic data for elucidating complex host-gut microflora interactions from a cohort of pediatric IBD patients, including Crohn’s disease and ulcerative colitis. In this pilot study, a panel of discriminating metabolites in urine is shown to allow for differential diagnosis of major pediatric IBD sub-types as an alternative to colonoscopy and histopathology that are invasive, expensive and prone to ambiguous test results. Finally, Chapter V involves a longitudinal metabolomics study that aims to identify metabolic trajectories that predict treatment responses of a cohort of pediatric Crohn’s disease patients following initiation of exclusive enteral nutrition (EEN) therapy. In the end, Chapter VI highlights major outcomes of thesis and future direction of metabolomics in IBS and IBD with a specific focus on improved stool specimen collection and validation of biomarker specificity relative to other related gastrointestinal disorders. In summary, this thesis has demonstrated metabolic processes that are associated with exacerbation of symptoms or remission in subset of IBS and pediatric IBD patients. With follow up studies with larger cohort of patients, potential biomarkers identified in this thesis will contribute the development of more accurate and non-invasive decision making process for diagnosis and treatment, resulting in long-lasting remission and improved quality of life of patients suffering from chronic digestive disorders. / Thesis / Doctor of Science (PhD)

Diversos trabajos reportan aumento en el número de linfocitos intraepiteliales (LIE), mastocitos y células enterocromafines en pacientes con Sindrome de Intestino Irritable (SII). Muchos de estos hallazgos se basan en el uso de inmunohistoquímica que son de poca disponibilidad en hospitales generales. El objetivo del presente trabajo es estudiar los hallazgos histológicos en la biopsia de colon sólo con histoquimica en pacientes con SII comparándolos con un grupo sin SII. Fueron incluidos 25 pacientes: 16 (64%), con criterios diagnósticos de SII y 9 (36%), sin SII. Se encontró un mayor número de LIE en el grupo de SII (p=0,002). Un grupo de pacientes con criterios Roma III (41,9%) presentó LIE en el rango de Colitis Linfocitica por lo que fueron excluidos de este estudio. No se encontró diferencia estadísticamente significativa en el número de mastocitos, células enterocromafines y eosinofilos. / Several studies have shown increased numbers of intraepithelial lymphocytes (IEL), mast cells, enterochromaffin cells in colonic mucosa of patients with Irritable Bowel Syndrome (IBS). Many of these findings are based is based on immunohistochemistry results, which is not available in general hospitals. Our objective is to study the histological findings observed in colon biopsies from patients with IBS compared with a group without IBS, using only histochemistry. Twenty five (25) patients were included: 16 with IBS and 9 without IBS. We found increased numbers of IEL in patients with IBS (p=0,002). A group of patients with IBS (41.9%) who fulfilled histological criteria for lymphocytic colitis were excluded. There was no significant difference in mast cells, enterochromaffin cells or eosinophils.