Alteration of microbiota antibody-mediated immune selection contributes to dysbiosis in IBD
Ontology highlight
ABSTRACT:
SUBMITTER: Dr. Eva Michaud
PROVIDER: S-SCDT-EMM-2021-15386P | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:The goal of this project is to find out whether human intestinal IgA1 and IgA2 secretion, transport and reactivity towards the microbiota might be involved in dysbiosis induction during Crohn’s disease and Ulcerative colitis. Mass spectrometry was used to characterize SIgA from Crohn’s disease patient and Ulcerative colitis patient, in term of O- and N-glycosylation in order to study their reverse transcytosis capacity and their role in intestinal inflammation.
2022-06-27 | PXD024060 | Pride
Project description:Human secretory immunoglobulins (SIg) A1 and SIgA2 guide mucosal responses toward tolerance or inflammation, notably through reverse-transcytosis, the apical-to-basal transport of IgA2 immune complexes via M cells of gut Peyer's patches. As such, the maintenance of a diverse gut microbiota requires broad affinity IgA and glycan-glycan interaction. Here, we asked whether IgA1 and IgA2-microbiota interactions might be involved in dysbiosis induction during inflammatory bowel diseases. Using stool HPLC-purified IgA, we show that reverse-transcytosis is abrogated in ulcerative colitis (UC) while it is extended to IgA1 in Crohn's disease (CD). 16S RNA sequencing of IgA-bound microbiota in CD and UC showed distinct IgA1- and IgA2-associated microbiota; the IgA1+ fraction of CD microbiota was notably enriched in beneficial commensals. These features were associated with increased IgA anti-glycan reactivity in CD and an opposite loss of reactivity in UC. Our results highlight previously unknown pathogenic properties of IgA in IBD that could support dysbiosis.
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Project description:The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD.Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation.We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations.Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis.
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Project description:Fungal microbiota dysbiosis in IBD_16s data
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Project description:Intestinal dysbiosis is a key feature in the pathogenesis of inflammatory bowel disease (IBD). Acyl-homoserine lactones (AHL) are bacterial quorum-sensing metabolites that may play a role in the changes in host cells-gut microbiota interaction observed during IBD. The objective of our study was to investigate the presence and expression of AHL synthases and receptor genes in the human gut ecosystem during IBD. We used an in silico approach, applied to the Inflammatory Bowel Disease Multi'omics Database comprising bacterial metagenomic and metatranscriptomic data from stools of patients with Crohn's disease (CD) (n = 50), ulcerative colitis (UC) (n = 27) and non-IBD controls (n = 26). No known putative AHL synthase gene was identified; however, several putative luxR receptors were observed. Regarding the expression of these receptor genes, the luxR gene from Bacteroides dorei was under-expressed in IBD patients (p = 0.02) compared to non-IBD patients, especially in CD patients (p = 0.02). In the dysbiosis situation, one luxR receptor gene from Bacteroides fragilis appeared to be over-expressed (p = 0.04) compared to that of non-dysbiotic patients. Targeting LuxR receptors of bacterial quorum sensing might represent a new approach to modulate the gut microbiota in IBD.
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Project description:BackgroundImmune-mediated inflammatory disease (IMID) represents a substantial health concern. It is widely recognized that IMID patients are at a higher risk for developing secondary inflammation-related conditions. While an ambiguous etiology is common to all IMIDs, in recent years, considerable knowledge has emerged regarding the plausible role of the gut microbiome in IMIDs. This study used 16S rRNA gene amplicon sequencing to compare the gut microbiota of patients with Crohn's disease (CD; N = 20), ulcerative colitis (UC; N = 19), multiple sclerosis (MS; N = 19), and rheumatoid arthritis (RA; N = 21) versus healthy controls (HC; N = 23). Biological replicates were collected from participants within a 2-month interval. This study aimed to identify common (or unique) taxonomic biomarkers of IMIDs using both differential abundance testing and a machine learning approach.ResultsSignificant microbial community differences between cohorts were observed (pseudo F = 4.56; p = 0.01). Richness and diversity were significantly different between cohorts (pFDR < 0.001) and were lowest in CD while highest in HC. Abundances of Actinomyces, Eggerthella, Clostridium III, Faecalicoccus, and Streptococcus (pFDR < 0.001) were significantly higher in all disease cohorts relative to HC, whereas significantly lower abundances were observed for Gemmiger, Lachnospira, and Sporobacter (pFDR < 0.001). Several taxa were found to be differentially abundant in IMIDs versus HC including significantly higher abundances of Intestinibacter in CD, Bifidobacterium in UC, and unclassified Erysipelotrichaceae in MS and significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA. A machine learning approach to classify disease versus HC was highest for CD (AUC = 0.93 and AUC = 0.95 for OTU and genus features, respectively) followed by MS, RA, and UC. Gemmiger and Faecalicoccus were identified as important features for classification of subjects to CD and HC. In general, features identified by differential abundance testing were consistent with machine learning feature importance.ConclusionsThis study identified several gut microbial taxa with differential abundance patterns common to IMIDs. We also found differentially abundant taxa between IMIDs. These taxa may serve as biomarkers for the detection and diagnosis of IMIDs and suggest there may be a common component to IMID etiology.
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