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Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations.

ABSTRACT: Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.

SUBMITTER: Pardo-Camacho C

PROVIDER: S-EPMC9265332 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations.

Pardo-Camacho Cristina C Ganda Mall John-Peter JP Martínez Cristina C Pigrau Marc M Expósito Elba E Albert-Bayo Mercé M Melón-Ardanaz Elisa E Nieto Adoración A Rodiño-Janeiro Bruno B Fortea Marina M Guagnozzi Danila D Rodriguez-Urrutia Amanda A Torres Inés de I Santos-Briones Ignacio I Azpiroz Fernando F Lobo Beatriz B Alonso-Cotoner Carmen C Santos Javier J González-Castro Ana M AM Vicario Maria M

Cells 20220628 13

Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestin ...[more]

PMID: 35805133

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Project description:BackgroundAccumulating evidence supports the pivotal role of intestinal flora in irritable bowel syndrome (IBS). Serotonin synthesis by enterochromaffin (EC) cells is influenced by the gut microbiota and has been reported to have an interaction with IBS. The comparison between the microbiota of the caecal and colonic mucosa in IBS has rarely been studied. The aim of this study was to investigate the relationship between the gut microbiota, EC cells in caecum and descending colon, and diarrhoea-predominant IBS (IBS-D) symptoms.ResultsA total of 22 IBS-D patients and 22 healthy controls (HCs) were enrolled in our study. Hamilton anxiety (HAM-A) and Hamilton depression (HAM-D) grades increased significantly in IBS-D patients. In addition, the frequency of defecation in IBS-D patients was higher than that in HCs. Among the preponderant bacterial genera, the relative abundance of the Ruminococcus_torques_ group increased in IBS-D patients in caecum samples while Raoultella and Fusobacterium were less abundant. In the descending colon, the abundance of the Ruminococcus_torques_group and Dorea increased in IBS-D patients and Fusobacterium decreased. No difference was observed between the descending colon and caecum in regards to the mucosal-associated microbiota. The number of EC cells in the caecum of IBS-D patients was higher than in HCs and the expression of TPH1 was higher in IBS-D patients both in the caecum and in the descending colon both at the mRNA and protein level. Correlation analysis showed that the Ruminococcus_torques_group was positively associated with HAM-A, HAM-D, EC cell number, IBS-SSS, degree of abdominal pain, frequency of abdominal pain and frequency of defecation. The abundance of Dorea was positively associated with EC cell number, IBS-SSS, HAM-A, HAM-D and frequency of abdominal pain.ConclusionsEC cell numbers increased in IBS-D patients and the expression of TPH1 was higher than in HCs. The Ruminococcus torques group and Dorea furthermore seem like promising targets for future research into the treatment of IBS-D patients.

Project description:AimTo study whether selected bacterial 16S ribosomal RNA (rRNA) gene phylotypes are capable of distinguishing irritable bowel syndrome (IBS).MethodsThe faecal microbiota of twenty volunteers with IBS, subdivided into eight diarrhoea-predominant (IBS-D), eight constipation-predominant (IBS-C) and four mixed symptom-subtype (IBS-M) IBS patients, and fifteen control subjects, were analysed at three time-points with a set of fourteen quantitative real-time polymerase chain reaction assays. All assays targeted 16S rRNA gene phylotypes putatively associated with IBS, based on 16S rRNA gene library sequence analysis. The target phylotypes were affiliated with Actinobacteria, Bacteroidetes and Firmicutes. Eight of the target phylotypes had less than 95% similarity to cultured bacterial species according to their 16S rRNA gene sequence. The data analyses were made with repeated-measures ANCOVA-type modelling of the data and principle component analysis (PCA) with linear mixed-effects models applied to the principal component scores.ResultsBacterial phylotypes Clostridium cocleatum 88%, Clostridium thermosuccinogenes 85%, Coprobacillus catenaformis 91%, Ruminococcus bromii-like, Ruminococcus torques 91%, and R. torques 93% were detected from all samples analysed. A multivariate analysis of the relative quantities of all 14 bacterial 16S rRNA gene phylotypes suggested that the intestinal microbiota of the IBS-D patients differed from other sample groups. The PCA on the first principal component (PC1), explaining 30.36% of the observed variation in the IBS-D patient group, was significantly altered from all other sample groups (IBS-D vs control, P = 0.01; IBS-D vs IBS-M, P = 0.00; IBS-D vs IBS-C, P = 0.05). Significant differences were also observed in the levels of distinct phylotypes using relative values in proportion to the total amount of bacteria. A phylotype with 85% similarity to C. thermosuccinogenes was quantified in significantly different quantities among the IBS-D and control subjects (-4.08 +/- 0.90 vs -3.33 +/- 1.16, P = 0.04) and IBS-D and IBS-M subjects (-4.08 +/- 0.90 vs -3.08 +/- 1.38, P = 0.05). Furthermore, a phylotype with 94% similarity to R. torques was more prevalent in IBS-D patients' intestinal microbiota than in that of control subjects (-2.43 +/- 1.49 vs -4.02 +/- 1.63, P = 0.01). A phylotype with 93% similarity to R. torques was associated with control samples when compared with IBS-M (-2.41 +/- 0.53 vs -2.92 +/- 0.56, P = 0.00). Additionally, a R. bromii-like phylotype was associated with IBS-C patients in comparison to control subjects (-1.61 +/- 1.83 vs -3.69 +/- 2.42, P = 0.01). All of the above mentioned phylotype specific alterations were independent of the effect of time.ConclusionSignificant phylotype level alterations in the intestinal microbiotas of IBS patients were observed, further emphasizing the possible contribution of the gastrointestinal microbiota in IBS.

Project description:BACKGROUND: Increased concentrations of 5-hydroxytryptamine (5-HT) can be detected in the systemic circulation after a meal and may be involved in the physiological control of gastrointestinal motility. Abnormalities of 5-HT release after a meal might explain some of the postprandial symptoms associated with the irritable bowel syndrome (IBS). AIM: To investigate the effect of a standard meal on plasma 5-HT and urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations in patients with diarrhoea predominant IBS and in healthy volunteers. METHODS: After an overnight fast, six volunteers and five patients with IBS were given a carbohydrate-rich meal. Blood and urine samples were taken before and for four hours after the meal. Platelet-poor plasma 5-HT and urinary 5-HIAA were analysed by reversed phase high performance liquid chromatography with fluorometric detection. 5-HIAA was expressed as a ratio with urinary creatinine concentration, which was measured by spectrophotometry. RESULTS: During the four hour postprandial period, 5-HT concentrations were significantly higher in patients with IBS than in healthy volunteers at 0.5 hours (p < 0.05), 2 hours (p < 0.05) and 2.5 hours (p < 0.05). 5-HT was not detected in the plasma in the fasting state in patients or volunteers. Median peak 5-HT in patients with IBS (359 (198-796) nmol/l) was significantly greater than volunteers (83 (7-190)) (p < 0.05). "Area under the curve" for 5-HT detection was greater for patients with IBS (317 (138-771)) than for healthy volunteers (51 (4-129); p < 0.05). The duration of the 5-HT peak was significantly longer in patients with IBS (3 (1-3) hours) than in the healthy volunteers (1 (1-1) hours; p < 0.01). Postprandial urinary median 5-HIAA values in controls (5.6 (5.5-5.8) mumol/mmol creatinine) and patients with IBS (3.0 (2.5-6.8) mumol/mmol creatinine) were not significantly different from preprandial values (controls: 5.9 (5.5-6.6) mumol/mmol creatinine; patients with IBS: (6.2 (2.4-9.3) mumol/mmol creatinine). CONCLUSION: These findings indicate that there may be a difference in the way that 5-HT is released in patients with diarrhoea predominant IBS, and could suggest a possible role for 5-HT in the postprandial symptoms of these patients.

Project description:BackgroundIrritable bowel syndrome (IBS) is characterised by gastrointestinal (GI) and psychological symptoms (e.g., depression, anxiety, and somatization). Depression and anxiety, but not somatization, have already been associated with altered intestinal barrier function, increased LPS, and dysbiosis. The study aimed to investigate the possible link between somatization and intestinal barrier in IBS with diarrhoea (IBS-D) patients.MethodsForty-seven IBS-D patients were classified as having low somatization (LS = 19) or high somatization (HS = 28) according to the Symptom Checklist-90-Revised (SCL-90-R), (cut-off score = 63). The IBS Severity Scoring System (IBS-SSS) and the Gastrointestinal Symptom Rating Scale (GSRS) questionnaires were administered to evaluate GI symptoms. The intestinal barrier function was studied by the lactulose/mannitol absorption test, faecal and serum zonulin, serum intestinal fatty-acid binding protein, and diamine oxidase. Inflammation was assessed by assaying serum Interleukins (IL-6, IL-8, IL-10), and tumour necrosis factor-α. Dysbiosis was assessed by the urinary concentrations of indole and skatole and serum lipopolysaccharide (LPS). All data were analysed using a non-parametric test.ResultsThe GI symptoms profiles were significantly more severe, both as a single symptom and as clusters of IBS-SSS and GSRS, in HS than LS patients. This finding was associated with impaired small intestinal permeability and increased faecal zonulin levels. Besides, HS patients showed significantly higher IL-8 and lowered IL-10 concentrations than LS patients. Lastly, circulating LPS levels and the urinary concentrations of indole were higher in HS than LS ones, suggesting a more pronounced imbalance of the small intestine in the former patients.ConclusionsIBS is a multifactorial disorder needing complete clinical, psychological, and biochemical evaluations.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03423069 .

Dataset Information

Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations.

Publications

Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations.

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