Background: Inflammatory bowel disease (IBD) is an umbrella term for ulcerative colitis and Crohn's disease. These are characterized by a chronic inflammation of the intestinal mucosa. Living with chronic illness meant that life changed significantly. Quality of life was affected for these individuals and was stressful in their lives.   Aim: The aim was to describe the experiences of living with inflammatory bowel disease.   Method: A qualitative literature review was chosen to analyze articles that were related to the aim of this study.   Results: Based on the chosen articles five themes were created; Commuting between hope and fear, symptoms of the disease and medication become everyday focus, struggling with  the new identity, desire to control the disease- do I control my illness or does it control me and social relationships are affected.   Conclusion: Inflammatory bowel disease is a distressing disease and can cause limitations in social life due to lack of knowledge by others about the disease. The affected felt a loss of control in their life due to the difficulty in managing the symptoms. They experienced a constant struggle and mixed emotions, such as anxiety, depression, stress, and denial of the disease, trying to feel like a healthy person.

An imbalance of the T cell immune response is observed in inflammatory bowel disease. Intestinal microbes have been linked to the disease and the disease process leads to severe mucosal injury and systemic translocation of bacterial products. Aminosalicylates, corticosteroids and immunomodulators reduce these aggressive activities but are associated with potentially serious adverse events. The aim of this work was to investigate the effects of administration of prebiotics and probiotics that modulate the gut microflora and modulate the immune response, in ameliorating severity of colitis. The prebiotic, high amylose maize resistant starch was used at two different concentrations. A number of Bifidobacterium and Lactobacillus strains were used as probiotics. BALB/c mice were administered the prebiotics and probiotics and intrarectally infused with 2.5 mg trinitrobenzene sulfonic acid (TNBS) in 45% ethanol, thereby generating colitis. Mucosal cytokine responses, colonic microbial profiles and disease activity indices were monitored. The 5% concentration of high amylose maize resistant starch delayed progression of TNBS colitis as evidenced by reduced weight loss, lesser tissue damage, abrogation of the expression and synthesis of IFN-?? and upregulation of IL-4 and IL-10. The 30% concentration of high amylose maize resistant starch exacerbated the inflammatory response with an increase in acetic acid, coliforms and endopores in the colonic contents. Three strains of bifidobacteria and 3 strains of lactobacilli were individually screened for their activity against TNBS colitis. Each strain had a distinctive effect on the course of colon inflammation. Lactobacillus fermentum VRI 003 was selected for further study as it provided most protection. The ratio of immunosuppressive cytokines to pro-inflammatory cytokines was restored closer to the normal T cell cytokine levels. It also reduced the incidence of translocation of enteric bacteria into the spleens. Dosing a minimum daily dose of 6x109 CFU L. fermentum VRI-003 to ulcerative colitis patients in remission and maintained on standard therapy for 6 months prevented the exacerbation of symptoms, including diarrhea and abdominal pain, and improved the patient general well being. It also suppressed production of IFN-?? and sustained IL-10 levels. Moreover, absence of endospores and lower numbers of coliforms were detected in the faeces of UC patients during L. fermentum VRI-003 treatment. In summary, 5% high amylose maize resistant starch and L. fermentum VRI 003 prevented colon inflammation by changing the nature of the T cell immune response and modifying the colonic microflora in the murine model. The clinical evidence supported these findings.

Thesis (Ph. D. in Cell and Developmental Biology)--Vanderbilt University, May 2008. / Title from title screen. Includes bibliographical references.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 4 uppsatser.

Thesis (M.Sc.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science, Medicine. Title from pdf file main screen (viewed on September 18, 2009). Includes bibliographical references.

Thesis (Ph. D.)--Georgia State University, 2007. / Title from title page. Lindsey L. Cohen, committee chair; Lisa Armistead, Erin B. McClure, Mary K. Morris, committee members. Electronic text (113 p. : ill. (some col.)) : digital, PDF file. Description based on contents viewed Oct. 11, 2007. Includes bibliographical references (p. 73-80).

D’étiologie inconnue, les maladies inflammatoires chroniques de l’intestin, telles que la maladie de Crohn ou la rectocolite hémorragique, semblent résulter d’une réaction immunitaire inappropriée vis-à-vis de la flore commensale chez des individus génétiquement prédisposés. De ce fait, la modulation du microbiote par des probiotiques, majoritairement des bactéries lactiques commensales (lactobacilles et bifidobactéries), représente une alternative thérapeutique intéressante et a déjà conduit à un certain nombre d’essais cliniques concluants. Cependant, les effets thérapeutiques des bactéries probiotiques se sont avérés spécifiques de la souche utilisée et les mécanismes d’action de ces micro-organismes restent encore méconnus. Dans cette étude, nous nous sommes intéressés au rôle du peptidoglycane et de la voie de signalisation NOD2 dans les capacités anti-inflammatoires de certains lactobacilles probiotiques. Dans un modèle murin de colite expérimentale mimant la pathologie humaine, nous avons tout d’abord montré que les capacités protectrices de la souche anti-inflammatoire Lactobacillus salivarius Ls33 nécessitent la présence du récepteur NOD2. Ce récepteur reconnaissant les produits de dégradation du peptidoglycane, nous avons préparé du peptidoglycane hautement purifié de la souche Ls33 et montré que l’administration de ce composant, par voie intrapéritonéale ou orale, protège les souris de la colite expérimentale. Nous avons également mis en évidence que l’effet protecteur du peptidoglycane de Ls33 implique la production d’IL-10, la voie immunosuppressive de l’indoleamine 2,3-dioxygénase et le développement, au sein des ganglions mésentériques, de cellules dendritiques régulatrices CD103+ et de cellules T régulatrices CD4+FoxP3+. Nous avons montré que le peptidoglycane de Ls33 favorise, in vitro, la différentiation de cellules dendritiques naïves en cellules dendritiques productrices d’IL-10, capables de protéger, après transfert adoptif, les souris de la colite de façon NOD2-dépendante. Les capacités protectrices n’ayant pas été obtenues avec le peptidoglycane de la souche non anti-inflammatoire L. acidophilus NCFM, nous avons ensuite réalisé une analyse structurale des deux peptidoglycanes. Alors que les deux souches arborent le muropeptide M-tri-Lys-D-Asn, nous avons identifié un muropeptide additionnel libéré uniquement par Ls33, le M-tri-Lys. Bien que les deux muropeptides synthétiques activent NOD2 in vitro, seule l’administration systémique du M-tri-Lys protège les souris de la colite. Cette protection est dépendante du récepteur NOD2 mais ne nécessite pas la présence de l’adaptateur principal des récepteurs de type Toll ou TLR, MyD88. En conclusion, nos résultats indiquent que le peptidoglycane et certains de ses dérivés sont des composants actifs dans la fonctionnalité des lactobacilles probiotiques et représentent une nouvelle stratégie thérapeutique pour le traitement des maladies inflammatoires chroniques de l’intestin. / N genetically susceptible individuals, an inappropriate mucosal immune responseagainst the intestinal microbiota appears to be the principal mechanism leading to thepathogenesis of (including Crohn’s disease and ulcerativecolitis). Therefore, modulation of the luminal contents with probiotics, mainly represented bycommensal lactic acid bacteria (lactobacilli and bifidobacteria), represents an attractivetherapeutic alternative and has already led to successful clinical trials. However, theprotective effect of probiotic bacteria clearly depends on the strains used and the precisemechanisms of action of these microorganisms are still unknown.In this study, we investigated the role of peptidoglycan and NOD2 signalling in the antiinflammatorycapacity of selected probiotic lactobacilli.In a mouse model of experimental colitis mimicking human pathology, we first showedthat the protective capacity of the anti-inflammatory strain Lactobacillus salivarius Ls33require NOD2 signalling. Since this receptor senses peptidoglycan degradation products, weprepared highly purified peptidoglycan from Ls33 and showed that systemic as well as oraladministration of this component was able to rescue mice from experimental colitis. We alsodemonstrated that the protective effect of Ls33 peptidoglycan involved the production of IL-10, the immunosuppressive indoleamine 2,3-dioxygenase pathway and the expansion ofregulatory CD103+ dendritic cells and CD4+FoxP3+ regulatory T cells within mesentericlymph nodes. Furthermore, we showed that the IL-10-producing dendritic cells induced byLs33 peptidoglycan in vitro were able to protect mice from colitis in a NOD2-dependentmanner after adoptive transfer.Since the observed anti-inflammatory properties were not obtained with peptidoglycanderived from the non-anti-inflammatory strain L. acidophilus NCFM, we conducted astructural analysis of the two peptidoglycans. While the two strains exhibited the M-tri-Lys-DAsnmuropeptide, we identified an additional muropeptide released exclusively by Ls33, theM-tri-Lys. Although both synthetic muropeptides activated NOD2 in vitro, only systemicadministration of M-tri-Lys protects mice from colitis. This protective effect was NOD2-dependent but did not require the presence of MyD88, the main adapter used by Toll-likereceptors.In conclusion, our results indicate that purified peptidoglycan and specific derivedmuropeptides are active components in probiotic lactobacilli functionality and represent anew therapeutic strategy for treating inflammatory bowel diseases.

Crohn’s disease (CD) and ulcerative colitis (UC) constitute the two major forms of inflammatory bowel disease (IBD), which are disorders of chronic inflammation in the gastrointestinal tract that are associated with significant morbidity and socioeconomic burden. IBD patients with long-standing intestinal inflammation are more prone to developing colorectal cancer (CRC). Until now, none of the existing IBD treatments is able to heal the mucosal ulcerations satisfactorily. The endocannabinoid system (ECS), which comprises of endogenous cannabinoid ligands, their receptors, and metabolic enzymes, has been implicated in gut homeostasis, visceral sensation, inflammation and gastrointestinal motility. Available studies in rodent models of IBD suggest that enhancing the ECS tone may reduce inflammation and improve mucosal integrity. This evidence indicates that the components of the ECS seem well positioned to exert a protective role in IBD and also to offer a great opportunity for therapeutic exploitation. Despite the role of the ECS in the gut, the presence and function of the components of the ECS is not well characterised in human IBD. The primary aim of the study was to investigate the state of the major components of the ECS in human IBD and to establish whether IBD is associated with any changes of the components of the ECS. Cannabinoid CB1 and CB2 receptors, enzymes for endocannabinoid biosynthesis PLC, “LRAT”, NAPE-PLD and DAGL, and endocannabinoid metabolic enzymes FAAH and MAGL were analysed from colonic tissue samples of CD, UC and control patients by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to determine the relative mRNA expression of the above genes. The RT-qPCR analysis showed that the mRNA expression of PLC, LRAT, and NAPE-PLD were unchanged in both CD and UC, whiles DAGL mRNA was decreased in UC but was unchanged in CD. The endocannabinoid degradation enzymes, FAAH mRNA expression was also unchanged in CD but decreased in UC, whereas the mRNA expression of MAGL was significantly decreased in both CD and UC. NAPE-PLD/FAAH and DAGL/MAGL ratios, an estimation of the balance of AEA and 2-AG levels, showed that AEA and 2-AG levels could be increased and unchanged, respectively, in IBD. The mRNA expression of CB1 was significantly decreased in CD and UC whilst CB2 mRNA expression was unchanged in both forms of IBD. The study demonstrated that the components of the ECS which were investigated were present in colonic tissues of both IBD patients and healthy individuals, but they appear to be off balance in CD and UC patients. The decreased CB1 receptors in IBD patients could be an important modifier in the disease and could also provide a possible pathoaetiological mechanism linking IBD and CRC. Although these findings look promising, more studies with larger sample size are required to characterise the components of the ECS in human IBD.

Diss. Linköping : Linköpings universitet, 2005.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.