Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intestinal fungi and antifungal secretory immunoglobulin A in Crohn's disease.

ABSTRACT: The human gastrointestinal tract harbors trillions of commensal microorganisms. Emerging evidence points to a possible link between intestinal fungal dysbiosis and antifungal mucosal immunity in inflammatory bowel disease, especially in Crohn's disease (CD). As a protective factor for the gut mucosa, secretory immunoglobulin A (SIgA) prevents bacteria from invading the intestinal epithelium and maintains a healthy microbiota community. In recent years, the roles of antifungal SIgA antibodies in mucosal immunity, including the regulation of intestinal immunity binding to hyphae-associated virulence factors, are becoming increasingly recognized. Here we review the current knowledge on intestinal fungal dysbiosis and antifungal mucosal immunity in healthy individuals and in patients with CD, discuss the factors governing antifungal SIgA responses in the intestinal mucosa in the latter group, and highlight potential antifungal vaccines targeting SIgA to prevent CD.

SUBMITTER: Sun M

PROVIDER: S-EPMC10285161 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Intestinal fungi and antifungal secretory immunoglobulin A in Crohn's disease.

Sun Meng M Ju Jingyi J Xu Hongzhen H Wang Yufang Y

Frontiers in immunology 20230608

The human gastrointestinal tract harbors trillions of commensal microorganisms. Emerging evidence points to a possible link between intestinal fungal dysbiosis and antifungal mucosal immunity in inflammatory bowel disease, especially in Crohn's disease (CD). As a protective factor for the gut mucosa, secretory immunoglobulin A (SIgA) prevents bacteria from invading the intestinal epithelium and maintains a healthy microbiota community. In recent years, the roles of antifungal SIgA antibodies in ...[more]

PMID: 37359518

Similar Datasets

Free and complexed-secretory immunoglobulin A triggers distinct intestinal epithelial cell responses.

Project description:Secretory immunoglobulin A (SIgA) antibodies play an important role in protecting the mucosal surfaces against pathogens and maintaining homeostasis with the commensal microbiota. Because a substantial portion of the gut microbiota is coated with SIgA, we hypothesized that microbiota-SIgA complexes are important for the maintenance of gut homeostasis. Here we investigated the relationship between microbiota-SIgA complexes and inflammatory epithelial cell responses. We used a multi-cellular three-dimensional (3D) organotypical model of the human intestinal mucosa composed of an intestinal epithelial cell line and primary human lymphocytes/monocytes, endothelial cells and fibroblasts. We also used human SIgA from human colostrum, and a prominent bacterial member of the first colonizers, Escherichia coli, as a surrogate commensal. We found that free and microbiota-complexed SIgA triggered different epithelial responses. While free SIgA up-regulated mucus production, expression of polymeric immunoglobulin receptor (pIgR) and secretion of interleukin-8 and tumoir necrosis factor-α, microbiota-complexed SIgA mitigated these responses. These results suggest that free and complexed SIgA have different functions as immunoregulatory agents in the gut and that an imbalance between the two may affect gut homeostasis.

| S-EPMC4991520 | biostudies-literature

Intestinal epithelial cells from Crohn's Disease patients

Project description:Inflammatory Bowel Diseases are associated with marked alterations of IECs with a subsequent loss of barrier function. To identify alterations in signaling pathways in intestinal epithelium upon inflammation, we analyzed the transcriptome of IECs from patients suffering from Crohn’s disease.

2015-12-01 | GSE72780 | GEO

Immunoglobulin A Glycosylation Differs between Crohn's Disease and Ulcerative Colitis.

Project description:Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammations of the digestive tract with increasing prevalence, yet they have unknown origins or cure. CD and UC have similar symptoms but respond differently to surgery and medication. Current diagnostic tools often involve invasive procedures, while laboratory markers for patient stratification are lacking. Large glycomic studies of immunoglobulin G and total plasma glycosylation have shown biomarker potential in IBD and could help determine disease mechanisms and therapeutic treatment choice. Hitherto, the glycosylation signatures of plasma immunoglobulin A, an important immunoglobulin secreted into the intestinal mucin, have remained undetermined in the context of IBD. Our study investigated the associations of immunoglobulin A1 and A2 glycosylation with IBD in 442 IBD cases (188 CD and 254 UC) and 120 healthy controls by reversed-phase liquid chromatography electrospray-ionization mass spectrometry of tryptic glycopeptides. Differences of IgA O- and N-glycosylation (including galactosylation, bisection, sialylation, and antennarity) between patient groups were associated with the diseases, and these findings led to the construction of a statistical model to predict the disease group of the patients without the need of invasive procedures. This study expands the current knowledge about CD and UC and could help in the development of noninvasive biomarkers and better patient care.

| S-EPMC10563165 | biostudies-literature

Assessing disease activity in pediatric Crohn's disease using ultrasound: the Pediatric Crohn's Disease Intestinal Ultrasound score.

Project description:ObjectivesCurrently, there is no consensus on how to score Crohn's disease (CD) activity assessed by intestinal-ultrasound (IUS) in children. This study aimed to design an easy-to-use IUS score for disease activity in pediatric CD.MethodsChildren undergoing ileo-colonoscopy for CD assessment underwent IUS the day before ileo-colonoscopy, assessed with simple endoscopic score for CD (SES-CD). IUS features were compared to the SES-CD on segmental level. Multiple regression analyses, separately for terminal ileum (TI) and colon, were done to assess predictors of disease activity and to develop a model.ResultsIn 74 CD patients (median 15 years, 48% female), 67 TI and 364 colon segments were assessed. Based on ROC-curves, bowel wall thickness (BWT) was categorized into low (1point: 2-3 mm (TI), 1.6-2 mm (colon)), medium (2points: 3.0-3.7 mm (TI) and 2.0-2.7 mm (colon)) and high (3points: >3.7 mm (TI) and >2.7 mm (colon)). In TI, only BWT was retained in the model (high BWT:OR 11.50, p<0.001). In colon, BWT (high BWT:OR 8.63, p<0.001) and mesenteric fat (1point. OR:3.02, p<0.001) were independent predictors. A PCD-US cut-off of 1 resulted in a sensitivity of 82% (95%CI: 65-93%) and 85% (95% CI 80-89%) and a cut-off of 3 in a specificity of 88% (72-97%) and 92% (87-96%) for TI and colon, respectively. Inter-observer agreement was moderate for TI and colon (K:0.42, K:0.49, respectively).ConclusionsThe PCD-US score is an easy-to-use and reliable score to detect or rule out CD activity on segmental level in children. External validation is needed before applying this score in clinical practice.

| S-EPMC10097488 | biostudies-literature

Therapeutic Targeting of Intestinal Fibrosis in Crohn's Disease.

Project description:Intestinal fibrosis is one of the most threatening complications of Crohn's disease. It occurs in more than a third of patients with this condition, is associated with increased morbidity and mortality, and surgery often represents the only available therapeutic option. The mechanisms underlying intestinal fibrosis are partly known. Studies conducted so far have shown a relevant pathogenetic role played by mesenchymal cells (especially myofibroblasts), cytokines (e.g., transforming growth factor-β), growth factors, microRNAs, intestinal microbiome, matrix stiffness, and mesenteric adipocytes. Further studies are still necessary to elucidate all the mechanisms involved in intestinal fibrosis, so that targeted therapies can be developed. Although several pre-clinical studies have been conducted so far, no anti-fibrotic therapy is yet available to prevent or reverse intestinal fibrosis. The aim of this review is to provide an overview of the main therapeutic targets currently identified and the most promising anti-fibrotic therapies, which may be available in the near future.

| S-EPMC8834168 | biostudies-literature

Adalimumab Therapy Improves Intestinal Dysbiosis in Crohn's Disease.

Project description:The response to treatment with biologic drugs, in patients with Crohn's disease, could be associated with changes in gut microbiota composition. The aim of our study was to analyse the modification of microbiota during adalimumab therapy in patients with Crohn's disease. We performed a prospective study in patients with Crohn's disease analysing gut microbiota before start of adalimumab therapy (T0) and after six months of therapy (T1). Among the 20 included patients, the phylum Proteobacteria fell from 15.7 ± 3.5% at T0 to 10.3 ± 3.4% at T1 (p = 0.038). Furthermore, the trend in relation to therapeutic success was analysed. Regarding bacterial phyla, Proteobacteria decreased in patients in whom therapeutic success was obtained, passing from a value of 15.8% (± 4.6%) to 6.8 ± 3.1% (p = 0.049), while in non-responder patients, percentages did not change (T0 = 15.6 ± 5.7%, T1 = 16.8 ± 7.6%, p = 0.890). Regarding the Lachnospiraceae family, in patients with normalization of C reactive protein six 6 months of adalimumab therapy, it increased from 16.6 ± 3.1% at T0 to 23.9 ± 2.6% at T1 (p = 0.049). In conclusion, in patients who respond to Adalimumab therapy by decreasing inflammation, there is a trend of intestinal eubiosis being restored.

| S-EPMC6832711 | biostudies-literature

Intestinal epithelial microvilli are abnormal in Crohn's disease

Project description:Biopsy samples (n=362) were collected from terminal ileum at baseline, 8 weeks after induction (Ustekinumab or placebo), and 44 weeks after maintenance (Ustekinumab 90 mg SC q12w, Ustekinumab 90 mg SC q8w, or placebo) therapies during endoscopy for RNA extraction and microarray analysis from patients with moderate-to-severe CD who participated in stelara CD phase 3 studies (UNITI-2 and IM-UNITI). These patients failed conventional therapies previously and largely naive to anti-TNF therpy. Ileum biopsies (n=26) collected from non-IBD subjects were also analyzed to serve as control. Enrichment of a core microvilli gene set was found to be reduced in UNITI-2 CD samples relative to controls, correlated with microvilli length and endoscopy score, and associated with response to treatment.

2019-03-20 | GSE112366 | GEO

NOD2 deficiency increases retrograde transport of secretory IgA complexes in Crohn's disease.

Project description:Intestinal microfold cells are the primary pathway for translocation of secretory IgA (SIgA)-pathogen complexes to gut-associated lymphoid tissue. Uptake of SIgA/commensals complexes is important for priming adaptive immunity in the mucosa. This study aims to explore the effect of SIgA retrograde transport of immune complexes in Crohn's disease (CD). Here we report a significant increase of SIgA transport in CD patients with NOD2-mutation compared to CD patients without NOD2 mutation and/or healthy individuals. NOD2 has an effect in the IgA transport through human and mouse M cells by downregulating Dectin-1 and Siglec-5 expression, two receptors involved in retrograde transport. These findings define a mechanism of NOD2-mediated regulation of mucosal responses to intestinal microbiota, which is involved in CD intestinal inflammation and dysbiosis.

| S-EPMC7801705 | biostudies-literature

miR-19b downregulates intestinal SOCS3 to reduce intestinal inflammation in Crohn's disease.

Project description:Although aberrant microRNA (miRNA) expression has frequently been observed in inflammatory bowel disease (IBD), its biological functions and targets remain largely unknown. Present study found that miR-19b was significantly downregulated in active Crohn's disease (CD). Using bioinformatics analysis, suppressor of cytokine signalling 3 (SOCS3), a physiological regulator of innate and adaptive immunity that controls several immuno-inflammatory diseases, was predicted to be a potential target of miR-19b. An inverse correlation between miR-19b and SOCS3 protein levels, but not mRNA, was identified in active-CD intestinal tissue samples. By overexpressing or knocking down miR-19b in Caco2 cells and HT29 cells, it was experimentally validated that miR-19b is a direct regulator of SOCS3. Using a luciferase reporter assay, it was confirmed that miR-19b directly recognizes the 3'-untranslated region (3'-UTR) of SOCS3. Furthermore, overexpression of miR-19b decreased SOCS3 expression, leading to increased production of macrophage-inflammatory protein-3α (MIP-3α) in Caco2 cells. In contrast, knockdown of miR-19b increased SOCS3 and decreased MIP-3α. Finally, intracolonically delivered miR-19b decreased the severity of colitis induced with 2,4,6-trinitrobenzene sulphonic acid (TNBS). Taken together, our findings suggest that miR-19b suppresses the inflammatory response by inhibiting SOCS3 to modulate chemokine production in intestinal epithelial cells (IECs) and thereby prevents the pathogenesis of CD.

| S-EPMC4441154 | biostudies-literature

Bacterial Characteristics of Intestinal Tissues From Patients With Crohn's Disease.

Project description:Background and aimsIt is believed that intestinal bacteria play an indispensable role in promoting intestinal inflammation. However, the characteristics of these tissue-associated bacteria remain elusive. The aim of this study is to explore the bacterial loads, compositions, and structures in the noninflamed mucosa, inflamed mucosa, and creeping fat taken from patients with Crohn's disease (CD).MethodsNoninflamed mucosa, inflamed mucosa, and creeping fat samples were obtained from 10 surgical patients suffering from CD. Total bacterial DNA was extracted in a sterile environment using aseptic techniques. The V3-V4 regions of bacterial 16S rDNA were amplified and analysed using standard microbiological methods. qPCR was used to confirm the change in abundance of specific species in additional 30 independent samples.ResultsInflamed mucosa exhibited the highest bacterial load (3.8 and 12 times more than that of non-inflamed mucosa and creeping fat) and species diversity. The relative abundance of Proteobacteria was dominant in most samples and was negatively associated with Firmicutes. Moreover, the relative abundances of Methylobacterium and Leifsonia in creeping fat significantly increased more than twice as much as other tissue types. The bacterial community structure analysis showed that the bacterial samples from the same individual clustered more closely.ConclusionThis study reveals the significant differences in bacterial load, species diversity, and composition among different intestinal tissue types of CD patients and confirms that the bacterial samples from the same individual are highly correlated. Our findings will shed light on fully revealing the characteristics of tissue-associated bacteria and their roles in CD pathogenesis.

| S-EPMC8635149 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data