| 1. |
- Sundin, Johanna, 1982-, et al.
(författare)
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Aberrant mucosal lymphocyte number and subsets in the colon of post-infectious irritable bowel syndrome patients
- 2014
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 49:9, s. 1068-1075
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Tidskriftsartikel (refereegranskat)abstract
- Background: Irritable bowel syndrome (IBS) is characterized by chronic abdominal symptoms such as pain, discomfort, and altered bowel habits. A subset of IBS patients, denoted as post-infectious IBS (PI-IBS) patients, develop symptoms after an enteric infection. Distinct abnormalities in the gut mucosa, including mucosal inflammation, have been proposed to contribute to or be the cause of PI-IBS. This study investigated lymphocyte subsets in PI-IBS patients compared to healthy controls.Materials and methods: Ten PI-IBS patients and nine healthy controls participated. All PI-IBS patients met the Rome III diagnostic criteria for IBS and reported sustained symptoms at least 1 year after an episode of acute gastroenteritis. Intraepithelial lymphocytes and lamina propria lymphocytes (LPLs), isolated from mucosal tissue samples, were stained and analyzed for a comprehensive set of cell markers using flow cytometry.Results: The number of LPLs in PI-IBS was significantly increased compared to those in healthy controls (p < 0.05). PI-IBS patients showed significantly increased proportions of CD45RO(+) CD4(+) activated/memory T cells (p < 0.05) and double-positive CD4(+) CD8(+) cells (p < 0.05), respectively, in the lamina propria. The number of CD19(+) LPLs was decreased in PI-IBS patients compared to healthy controls (p < 0.001).Conclusion: This study presents new evidence that PI-IBS is associated with a sustained aberrant mucosal immune response and support future studies of anti-inflammatory or immune-modulating treatments in these patients.
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| 2. |
- Ahluwalia, Bani, et al.
(författare)
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A Distinct Faecal Microbiota and Metabolite Profile Linked to Bowel Habits in Patients with Irritable Bowel Syndrome
- 2021
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Patients with irritable bowel syndrome (IBS) are suggested to have an altered intestinal microenvironment. We therefore aimed to determine the intestinal microenvironment profile, based on faecal microbiota and metabolites, and the potential link to symptoms in IBS patients. The faecal microbiota was evaluated by the GA-map(TM) dysbiosis test, and tandem mass spectrometry (GC-MS/MS) was used for faecal metabolomic profiling in patients with IBS and healthy subjects. Symptom severity was assessed using the IBS Severity Scoring System and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. A principal component analysis based on faecal microbiota (n = 54) and metabolites (n = 155) showed a clear separation between IBS patients (n = 40) and healthy subjects (n = 18). Metabolites were the main driver of this separation. Additionally, the intestinal microenvironment profile differed between IBS patients with constipation (n = 15) and diarrhoea (n = 11), while no clustering was detected in subgroups of patients according to symptom severity or anxiety. Furthermore, ingenuity pathway analysis predicted amino acid metabolism and several cellular and molecular functions to be altered in IBS patients. Patients with IBS have a distinct faecal microbiota and metabolite profile linked to bowel habits. Intestinal microenvironment profiling, based on faecal microbiota and metabolites, may be considered as a future non-invasive diagnostic tool, alongside providing valuable insights into the pathophysiology of IBS.
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| 3. |
- Iribarren, Cristina, 1993, et al.
(författare)
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Fecal luminal factors from patients with irritable bowel syndrome induce distinct gene expression of colonoids
- 2022
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 34:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alteration of the host-microbiota cross talk at the intestinal barrier may participate in the pathophysiology of irritable bowel syndrome (IBS). Therefore, we aimed to determine effects of fecal luminal factors from IBS patients on the colonic epithelium using colonoids. Methods: Colon-derived organoid monolayers, colonoids, generated from a healthy subject, underwent stimulation with fecal supernatants from healthy subjects and IBS patients with predominant diarrhea, phosphate-buffered saline (PBS), or lipopolysaccharide (LPS). Cytokines in cell cultures and fecal LPS were measured by ELISA and mRNA gene expression of monolayers was analyzed using Qiagen RT2 Profiler PCR Arrays. The fecal microbiota profile was determined by the GA-map (TM) dysbiosis test and the fecal metabolite profile was analyzed by untargeted liquid chromatography/mass spectrometry. Key results: Colonoid monolayers stimulated with fecal supernatants from healthy subjects (n = 7), PBS (n = 4) or LPS (n = 3) presented distinct gene expression profiles, with some overlap ((RY)-Y-2 = 0.70, Q(2) = 0.43). Addition of fecal supernatants from healthy subjects and IBS patients (n = 9) gave rise to different gene expression profiles of the colonoid monolayers ((RY)-Y-2 = 0.79, Q(2) = 0.64). Genes (n = 22) related to immune response (CD1D, TLR5) and barrier integrity (CLDN15, DSC2) contributed to the separation. Levels of proinflammatory cytokines in colonoid monolayer cultures were comparable when stimulated with fecal supernatants from either donor types. Fecal microbiota and metabolite profiles, but not LPS content, differed between the study groups. Conclusions: Fecal luminal factors from IBS patients induce a distinct colonic epithelial gene expression, potentially reflecting the disease pathophysiology. The culture of colonoids from healthy subjects with fecal supernatants from IBS patients may facilitate the exploration of IBS related intestinal micro-environmental and barrier interactions.
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| 4. |
- Maasfeh, Lujain, et al.
(författare)
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Impaired Luminal Control of Intestinal Macrophage Maturation in Patients With Ulcerative Colitis During Remission
- 2021
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Ingår i: Cellular and Molecular Gastroenterology and Hepatology. - : Elsevier BV. - 2352-345X. ; 12:4, s. 1415-1432
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Intestinal macrophages adopt a hyporesponsive phenotype through education by local signals. Lack of proper macrophage maturation in patients with ulcerative colitis (UC) in remission may initiate gut inflammation. The aim, therefore, was to determine the effects of fecal luminal factors derived from healthy donors and UC patients in remission on macrophage phenotype and function. METHODS: Fecal supernatants (FS) were extracted from fecal samples of healthy subjects and UC patients in remission. Monocytes were matured into macrophages in the presence of granulocyte-macrophage colony-stimulating factor without/with FS, stimulated with lipopolysaccharide, and macrophage phenotype and function were assessed. Fecal metabolomic profiles were analyzed by gas-chromatography/mass-spectrometry. RESULTS: Fecal luminal factors derived from healthy donors were effective in down-regulating Toll-like receptor signaling, cytokine signaling, and antigen presentation in macrophages. Fecal luminal factors derived from UC patients in remission were less potent in inducing lipopolysaccharide hyporesponsiveness and modulating expression of genes involved in macrophage cytokine and Toll-like receptor signaling pathways. Although phagocytic and bactericidal abilities of macrophages were not affected by FS treatment, healthy FS-treated macrophages showed a greater ability to suppress cluster of differentiation 4(+) T-cell activation and interferon gamma secretion compared with UC remission FS-treated counterparts. Furthermore, metabolomic analysis showed differential fecal metabolite composition for healthy donors and UC patients in remission. CONCLUSIONS: Our data indicate that UC patients in remission lack luminal signals able to condition macrophages toward a hyporesponsive and tolerogenic phenotype, which may contribute to their persistent vulnerability to relapse.
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| 5. |
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| 6. |
- Rangel, Ignacio, 1969-, et al.
(författare)
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The relationship between faecal-associated and mucosal-associated microbiota in irritable bowel syndrome patients and healthy subjects
- 2015
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 42:10, s. 1211-1221
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Tidskriftsartikel (refereegranskat)abstract
- Background: The faecal-associated microbiota is commonly seen as a surrogate of the mucosal-associated microbiota. However, previous studies indicate that they are different. Furthermore, analyses of the mucosal microbiota are commonly done after standard bowel cleansing, affecting the microbial composition.Aim: To compare the mucosal-associated microbiota, obtained from unprepared colon, with faecal-associated microbiota in healthy subjects and irritable bowel syndrome (IBS) patients.Methods: Faecal and mucosal biopsies were obtained from 33 IBS patients and 16 healthy controls. Of IBS patients, 49% belonged to the diarrhoea-predominant subgroup and 80% suffered from IBS symptoms during at least 5 years. Biopsies were collected from unprepared sigmoid colon and faecal samples a day before colonoscopy. Microbiota analyses were performed with a phylogenetic microarray and redundancy discriminant analysis.Results: The composition of the mucosal- and the faecal-associated microbiota in unprepared sigmoid colon differs significantly (P = 0.002). Clinical characteristics of IBS did not correlate with this difference. Bacteroidetes dominate the mucosal-associated microbiota. Firmicutes, Actinobacteria and Proteobacteria dominate the faecal-associated microbiota. Healthy subjects had a significantly higher (P < 0.005) abundance (1.9%) of the bacterial group uncultured Clostridiales I in the mucosal-associated microbiota than IBS patients (0.3%). Bacterial diversity was higher in faecal- compared with mucosal-associated microbiota in IBS patients (P < 0.005). No differences were found in healthy subjects.Conclusions: Differences in the mucosal-associated microbiota between healthy individuals and IBS patients are minimal (one bacterial group) compared to differences in the faecal microbiota of both groups (53 bacterial groups). Microbial aberrations characterising IBS are more pronounced in the faeces than in the mucosa.
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| 7. |
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| 8. |
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| 9. |
- Rondung, Elisabet, 1980-, et al.
(författare)
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Comparing Internet-Based Cognitive Behavioral Therapy With Standard Care for Women With Fear of Birth : Randomized Controlled Trial
- 2018
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Ingår i: JMIR Mental Health. - : JMIR PUBLICATIONS, INC. - 2368-7959. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although many pregnant women report fear related to the approaching birth, no consensus exists on how fear of birth should be handled in clinical care.Objective: This randomized controlled trial aimed to compare the efficacy of a guided internet-based self-help program based on cognitive behavioral therapy (guided ICBT) with standard care on the levels of fear of birth in a sample of pregnant women reporting fear of birth.Methods: This nonblinded, multicenter randomized controlled trial with a parallel design was conducted at three study centers (hospitals) in Sweden. Recruitment commenced at the ultrasound screening examination during gestational weeks 17-20. The therapist-guided ICBT intervention was inspired by the Unified protocol for transdiagnostic treatment of emotional disorders and consisted of 8 treatment modules and 1 module for postpartum follow-up. The aim was to help participants observe and understand their fear of birth and find new ways of coping with difficult thoughts and emotions Standard care was offered in the three different study regions. The primary outcome was self-assessed levels of fear of birth, measured using the Fear of Birth Scale.Results: We included 258 pregnant women reporting clinically significant levels of fear of birth (guided ICBT group, 127; standard care group, 131). Of the 127 women randomized to the guided ICBT group, 103 (81%) commenced treatment, 60 (47%) moved on to the second module, and only 13 (10%) finished >= 4 modules. The levels of fear of birth did not differ between the intervention groups postintervention. At 1-year postpartum follow-up, participants in the guided ICBT group exhibited significantly lower levels of fear of birth (U=3674.00, z=-1.97, P=.049, Cohen d=0.28, 95% CI -0.01 to 0.57). Using the linear mixed models analysis, an overall decrease in the levels of fear of birth over time was found (P <= .001), along with a significant interaction between time and intervention, showing a larger reduction in fear of birth in the guided ICBT group over time (F-1,(192).(538) =4.96, P=.03).Conclusions: Fear of birth decreased over time in both intervention groups; while the decrease was slightly larger in the guided ICBT group, the main effect of time alone, regardless of treatment allocation, was most evident. Poor treatment adherence to guided ICBT implies low feasibility and acceptance of this treatment.
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| 10. |
- Sundin, Johanna, 1982-, et al.
(författare)
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Altered faecal and mucosal microbial composition in post-infectious irritable bowel syndrome patients correlates with mucosal lymphocyte phenotypes and psychological distress
- 2015
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Ingår i: Alimentary Pharmacology and Therapeutics. - Hoboken, USA : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 41:4, s. 342-351
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Tidskriftsartikel (refereegranskat)abstract
- Background: A subset of irritable bowel syndrome (IBS) patients, denoted post-infectious IBS (PI-IBS), develop symptoms after an enteric infection. Bacterial dysbiosis and mucosal inflammation have been proposed to be involved in the pathophysiology of this entity.Aim: To characterise the mucosal and faecal microbiota in PI-IBS, general IBS and healthy controls, and to investigate associations between the microbiota and the mucosal immune system.Methods: Mucosal biopsies and faeces were collected from 13 PI-IBS patients, 19 general IBS patients and 16 healthy controls. Global bacterial composition was determined by generating 16S rRNA amplicons that were examined by phylogenetic microarray hybridisation, principal component and redundancy analysis. We correlated previously reported lymphocyte proportions with the microbiota.Results: Faecal microbiota composition of PI-IBS patients differed significantly from both general IBS patients and healthy controls (P < 0.02). Both mucosal (P < 0.01) and faecal (P = 0.05) microbial diversity were reduced in PI-IBS compared to healthy controls. In the intraepithelial lymphocytes the previously published proportion of CD8+ CD45RA+ was negatively correlated with mucosal microbial diversity (P < 0.005). The previously published number of lamina propria lymphocytes was negatively correlated with mucosal microbial diversity (P < 0.05). Faecal microbial diversity was significantly negatively correlated with the Hospital Anxiety and Depression scale (P < 0.05).Conclusions: We present data that distinguishes the intestinal microbiota of PI-IBS patients from that of both general IBS patients and HC. The microbial composition is significantly associated with the HADs score and alterations in lymphocyte subsets proportions.
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