Diving into inflammation: a pilot study exploring the dynamics of the immune-microbiota axis in ileal tissue layers of patients with Crohn’s disease

2021 ◽  
Author(s):  
Edda Russo ◽  
Francesco Giudici ◽  
Federica Ricci ◽  
Stefano Scaringi ◽  
Giulia Nannini ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Tissue Injury ◽  
Microbiota Composition ◽  
Response Distribution ◽  
Ileal Mucosa ◽  
The Family ◽  
New Biomarkers ◽  
Clinical Conditions ◽  
Ileal Tissue

Abstract Background and aims Crohn’s Disease (CD) pathogenesis is still unclear. Disorders in the mucosal immunoregulation and its crosstalk with the microbiota may represent an important component in tissue injury. We aimed to characterize the molecular immune response distribution within the ileal layers and to evaluate the correlated microbiota in pathological/healthy settings comparing first surgery/relapse clinical conditions. Methods We enrolled 12 CD patients. A comprehensive analysis of ileal mucosa, submucosa and serosa broad-spectrum cytokines’ panel was performed through a multiplex approach. In addition, ileal microbiota composition was assessed through Next Generation Sequencing. Results We observed a distinct profile (of IL1-α, IL-1β, IL-4, IL-8, ICAM-1, E-Selectin, P-Selectin, IP-10, IL 6, and IL 18) across the CD vs healthy ileal layers; and a different distribution of IFN-γ, P-Selectin, IL-27 and IL-21 in first surgery vs relapse patients. In addition, the phylum Tenericutes, the family of Ruminococcaceae, and the genus Mesoplasma and Mycoplasma were significantly enriched in pathological setting. Significant microbiota differences were observed between relapse vs first surgery patients regarding the class Bacteroidia, the genus of Prevotella, Flavobacterium, Tepidimonas and Escherichia/Shigella. Finally, the abundance of the genus Mycoplasma was positively correlated with IL-18. Conclusions We describe a dissimilarity of cytokines’ distribution and microbiota composition within the CD and the adjacent healthy ileal tissue layers and between first operation and surgical relapse. Our results give a potential insight into the dynamics of the gut microbiota-immune axis in CD patients, leading to new biomarkers’ detection.

scholarly journals Expression profiling of ileal mucosa in asthma reveals upregulation of innate immunity and genes characteristic of Paneth and goblet cells

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Jan K. Nowak ◽  
Marzena Dworacka ◽  
Nazgul Gubaj ◽  
Arystan Dossimov ◽  
Zhumabek Dossimov ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Differential Expression ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Goblet Cells ◽  
Ileal Mucosa ◽  
Significant Differential Expression ◽  
Immune Genes ◽  
Asthma Patients

Abstract Background The expression profiles of the intestinal mucosa have not been comprehensively investigated in asthma. We aimed to explore this in the Correlated Expression and Disease Association Research (CEDAR) patient cohort. Methods Differential expression analysis of ileal, transverse colon, and rectal biopsies were supplemented by a comparison of transcriptomes from platelets and leukocytes subsets, including CD4+, CD8+, CD14+, CD15+, and CD19+ cells. Asthma patients (n = 15) and controls (n = 15) had similar age (p = 0.967), body mass index (p = 0.870), similar numbers of females (80%) and smoking rates (13.3%). Results Significant differential expression was found in the ileum alone, and not in any other cell/tissue types. More genes were found to be overexpressed (1,150) than under-expressed (380). The most overexpressed genes included Fc Fragment of IgG Binding Protein (FCGBP, logFC = 3.01, pFDR = 0.015), Mucin 2 (MUC2, logFC = 2.78, pFDR = 0.015), and Alpha 1B Defensin (DEFA1B, logFC = 2.73, pFDR = 0.024). Gene ontology implicated the immune system, including interleukins 4 and 13, as well as antimicrobial peptides in this overexpression. There was concordance of gene over- (STAT1, XBP1) and underexpression (NELF, RARA) in asthma and Crohn’s disease ileum when our results were compared to another dataset (p = 3.66 × 10–7). Conclusion Ileal mucosa in asthma exhibits a specific transcriptomic profile, which includes the overexpression of innate immune genes, mostly characteristic of Paneth and goblet cells, in addition to other changes that may resemble Crohn’s disease.

scholarly journals The role of epigenetic modifications for the pathogenesis of Crohn's disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
M. Hornschuh ◽  
E. Wirthgen ◽  
M. Wolfien ◽  
K. P. Singh ◽  
O. Wolkenhauer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
New Biomarkers ◽  
Insight Into ◽  
Specific Evaluation

AbstractEpigenetics has become a promising field for finding new biomarkers and improving diagnosis, prognosis, and drug response in inflammatory bowel disease. The number of people suffering from inflammatory bowel diseases, especially Crohn's disease, has increased remarkably. Crohn's disease is assumed to be the result of a complex interplay between genetic susceptibility, environmental factors, and altered intestinal microbiota, leading to dysregulation of the innate and adaptive immune response. While many genetic variants have been identified to be associated with Crohn's disease, less is known about the influence of epigenetics in the pathogenesis of this disease. In this review, we provide an overview of current epigenetic studies in Crohn's disease. In particular, we enable a deeper insight into applied bioanalytical and computational tools, as well as a comprehensive update toward the cell-specific evaluation of DNA methylation and histone modifications.

New biomarkers of Crohn’s disease: serum biomarkers and development of diagnostic tools

2008 ◽  
Vol 8 (3) ◽  
pp. 327-337 ◽  
Author(s):  
Marie-Alice Meuwis ◽  
Marianne Fillet ◽  
Jean-Paul Chapelle ◽  
Michel Malaise ◽  
Edouard Louis ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Serum Biomarkers ◽  
Diagnostic Tools ◽  
New Biomarkers

scholarly journals Invasive Ability of an Escherichia coliStrain Isolated from the Ileal Mucosa of a Patient with Crohn’s Disease

1999 ◽  
Vol 67 (9) ◽  
pp. 4499-4509 ◽  
Author(s):  
Jerome Boudeau ◽  
Anne-Lise Glasser ◽  
Estelle Masseret ◽  
Bernard Joly ◽  
Arlette Darfeuille-Michaud
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Host Cell ◽  
Bacterial Invasion ◽  
Intestinal Epithelial ◽  
Invasive Ability ◽  
Ileal Mucosa ◽  
Gastrointestinal Infections ◽  
E Coli ◽  
Host Cell Membranes

ABSTRACT Crohn’s disease (CD) is an inflammatory bowel disease in whichEscherichia coli strains have been suspected of being involved. We demonstrated previously that ileal lesions of CD are colonized by E. coli strains able to adhere to intestinal Caco-2 cells but devoid of the virulence genes so far described in the pathogenic E. coli strains involved in gastrointestinal infections. In the present study we compared the invasive ability of one of these strains isolated from an ileal biopsy of a patient with CD, strain LF82, with that of reference enteroinvasive (EIEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enteraggregative (EAggEC), enterohemorrhagic (EHEC), and diffusely adhering (DAEC)E. coli strains. Gentamicin protection assays showed thatE. coli LF82 was able to efficiently invade HEp-2 cells. Its invasive level was not significantly different from that of EIEC and EPEC strains (P > 0.5) but significantly higher than that of ETEC (P < 0.03), EHEC (P < 0.005), EAggEC (P < 0.004) and DAEC (P < 0.02) strains. Strain LF82 also demonstrated efficient ability to invade intestinal epithelial cultured Caco-2, Intestine-407, and HCT-8 cells. Electron microscopy examination of infected HEp-2 cells revealed the presence of numerous intracellular bacteria located in vacuoles or free in the host cell cytoplasm. In addition, the interaction of strain LF82 with epithelial cells was associated with the elongation of microvillar extensions that extruded from the host cell membranes and engulfed the bacteria. This internalization mechanism strongly resembles Salmonella- orShigella-induced macropinocytosis. The use of cytochalasin D and colchicine showed that the uptake of strain LF82 by HEp-2 cells was mediated by both an actin microfilament-dependent mechanism and microtubule involvement. In addition, strain LF82 survived for at least 24 h in HEp-2 and Intestine-407 cells and efficiently replicated intracellularly in HEp-2 cells. PCR and hybridization experiments did not reveal the presence of any of the genetic determinants encoding EIEC, EPEC, or ETEC proteins involved in bacterial invasion. Thus, these findings show that LF82, which colonized the ileal mucosa of a patient with CD, is a true invasive E. coli strain and suggest the existence of a new potentially pathogenic group of E. coli, which we propose be designated adherent-invasive E. coli.

scholarly journals DOP06 Non-invasive identification of adherent-invasive E. coli in patients with Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S044-S045 ◽  
Author(s):  
A Buisson ◽  
E Vazeille ◽  
X Hébuterne ◽  
M Fumery ◽  
B Pariente ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Unmet Need ◽  
Inhibition Test ◽  
Invasive Ability ◽  
Ileal Mucosa ◽  
Multi Centre Study ◽  
E Coli ◽  
Non Invasive ◽  
Adhesion Inhibition

Abstract Background Medications limiting the adhesion of ‘adherent and invasive E. coli’ (AIEC) represent potential strategies to treat Crohn’s disease (CD). However, the ileal AIEC identification is a time-consuming procedure, and the number of AIEC strains which colonise ileal CD mucosa remains unknown. There is an unmet need for non-invasive biomarkers to identify patients colonised by AIEC. We aimed to evaluate non-invasive biomarker of ileal AIEC colonisation in patients with CD. Methods This prospective and multi-centre study included CD patients requiring ileocoloscopy. Saliva, serum, stools and ileal biopsies were collected. Abundance and global invasive ability of ileal or faecal E. coli were performed. Isolated E. coli were characterised as AIEC or non-AIEC on I407 epithelial cells and THP1 macrophages. The ERIC-PCR profiles of ileal E. coli were performed. Ileal E. coli/CEACAM6 interaction was analysed by a yeast aggregation test and T84 assays (CEACAM6 protein expression, adhesion inhibition test with D-mannose). Quantification of serum anti-E. coli and ileal or salivary CEACAM6 was realised by ELISA. Results Overall, 102 CD patients were enrolled in this study and 25.8% of them exhibited ileal AIEC colonisation (AIEC+). The abundance and global invasive ability of ileal mucosa-associated E. coli were higher in AIEC+ CD patients compared with CD patients without AIEC (AIEC−) (p = 0.0065 and p = 0.0007, respectively). There was no difference between faecal abundance and invasive ability of E. coli between AIEC+ and AIEC− patients. The ERIC-PCR profiles of ileal E. coli showed that CD AIEC+ were for 78% of them colonised by not more than 2 clonal AIEC strains. In addition, AIEC were able to interact with CEACAM6 by binding D-mannose residues and to induce CEACAM6 expression in T84 cells (p = 0.0009 and p = 0.0185, vs. non-AIEC; respectively). This was also supported by adhesion inhibition test. Serum anti-E. coli level was higher for CD AIEC+ (vs. CD AIEC-). Ileal CEACAM6 level were positively correlated with abundance of ileal associated E. coli in AIEC+ patients (r = 0.4000; p = 0.0362) and with salivary CEACAM6 level (r = 0.4690; p &lt; 0.0001). The non-invasive biomarker ‘serum anti-E.coli/salivary CEACAM6’ index was higher for CD AIEC+ (p = 0.0174; vs. CD AIEC-). A cut-off value &lt; 1.34 × 10−6 eliminated the presence of ileal AIEC with a high negative predictive value (90% CI95% [69%–95%]). Conclusion Our study reported that identification of faecal AIEC cannot replace identification of AIEC from ileal biopsies, most of AIEC infection are mono or bi-clonal (≤ 2 strains) and that non-invasive biomarker such as ‘serum anti-E.coli/salivary CEACAM6’ index could be helpful to screen CD patients for AIEC infection.

High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease

2004 ◽  
Vol 127 (2) ◽  
pp. 412-421 ◽  
Author(s):  
Arlette Darfeuille-Michaud ◽  
Jérôme Boudeau ◽  
Philippe Bulois ◽  
Christel Neut ◽  
Anne-Lise Glasser ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ileal Mucosa ◽  
High Prevalence

Su2004 ILEAL MUCOSA-ASSOCIATED MICROBIOME SIGNATURE IN CHILDREN WITH CROHN'S DISEASE UNDERGOING ILEOCECAL RESECTION

2020 ◽  
Vol 158 (6) ◽  
pp. S-740
Author(s):  
Jessica Breton ◽  
Ceylan Tanes ◽  
Sarah Rowley ◽  
Kelly Kachelries ◽  
Kyle Bittinger ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ileocecal Resection ◽  
Ileal Mucosa

scholarly journals Bacterial Mucosa-associated Microbiome in Inflamed and Proximal Noninflamed Ileum of Patients With Crohn’s Disease

2020 ◽  
Vol 27 (1) ◽  
pp. 12-24
Author(s):  
Maya Olaisen ◽  
Arnar Flatberg ◽  
Atle van Beelen Granlund ◽  
Elin Synnøve Røyset ◽  
Tom Christian Martinsen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Beta Diversity ◽  
Ileocecal Valve ◽  
Alpha Diversity ◽  
Normal Mucosa ◽  
Ileocecal Resection ◽  
Ileal Mucosa ◽  
Terminal Ileitis ◽  
Endoscopic Recurrence

Abstract Background Microbiota is most likely essential in the pathogenesis of Crohn’s disease (CD). Fecal diversion after ileocecal resection (ICR) protects against CD recurrence, whereas infusion of fecal content triggers inflammation. After ICR, the majority of patients experience endoscopic recurrence in the neoterminal ileum, and the ileal microbiome is of particular interest. We have assessed the mucosa-associated microbiome in the inflamed and noninflamed ileum in patients with CD. Methods Mucosa-associated microbiome was assessed by 16S rRNA sequencing of biopsies sampled 5 and 15 cm orally of the ileocecal valve or ileocolic anastomosis. Results Fifty-one CD patients and forty healthy controls (HCs) were included in the study. Twenty CD patients had terminal ileitis, with endoscopic inflammation at 5 cm, normal mucosa at 15 cm, and no history of upper CD involvement. Crohn’s disease patients (n = 51) had lower alpha diversity and separated clearly from HC on beta diversity plots. Twenty-three bacterial taxa were differentially represented in CD patients vs HC; among these, Tyzzerella 4 was profoundly overrepresented in CD. The microbiome in the inflamed and proximal noninflamed ileal mucosa did not differ according to alpha diversity or beta diversity. Additionally, no bacterial taxa were differentially represented. Conclusions The microbiome is similar in the inflamed and proximal noninflamed ileal mucosa within the same patients. Our results support the concept of CD-specific microbiota alterations and demonstrate that neither ileal sublocation nor endoscopic inflammation influence the mucosa-associated microbiome.

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