scholarly journals P833 Bacterial mucosa-associated microbiome in inflamed and proximal non-inflamed ileum of patients with Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S645-S646
Author(s):  
M Olaisen ◽  
A Flatberg ◽  
A van Beelen Granlund ◽  
E S Røyset ◽  
T C Martinsen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ileocecal Valve ◽  
Ileocecal Resection ◽  
Dissimilarity Index ◽  
Ileal Mucosa ◽  
Terminal Ileitis ◽  
Β Diversity ◽  
Gastrointestinal Pathology ◽  
Α Diversity

Abstract Background The microbiota most likely has an essential role in the pathogenesis of Crohn’s disease (CD). While faecal diversion after ileocecal resection (ICR) protects against CD recurrence, re-exposure triggers inflammation. After ICR, the majority of patients develop recurrence in the neoterminal ileum and the ileal microbiome is of particular interest. We have therefore assessed the mucosa-associated bacterial microbiome in the inflamed and non-inflamed ileum of patients with CD. Methods Patients with an established diagnosis of CD undergoing ileocolonoscopy and healthy controls (HC) referred for colonoscopy due to rectal bleeding or screening for disease, but without any detected gastrointestinal pathology were invited to participate. Exclusion criteria included use of antibiotic treatment for the past 2 months. Mucosal pinch biopsies were sampled 5 cm and 15 cm orally of the ileocecal valve or ileocolic anastomosis for comparisons within the same patients. The biopsies were analysed by 16S rRNA sequencing, α- and β-diversity was assessed by Shannon entropy and Bray-Curtis dissimilarity index respectively. Histologic inflammation was graded. Results Fifty-one CD patients, where of 32 with previous ICR, and 40 HC were included in the study. Of the 51 CD patients, 20 had terminal ileitis, with endoscopically inflamed mucosa at 5 cm and normal appearing mucosa at 15 cm and no history of upper GI disease involvement. Seven CD patients had ileal stenosis. CD patients (n = 51) had lower α-diversity and separated clearly from HC on β-diversity plots (Figure 1). Twenty-three bacterial taxa were differentially represented in CD patients and HC, among these Tyzzerella 4 was found to be profoundly overrepresented in CD (p = 4.1 × 10–68). When comparing the microbiome in the inflamed ileal mucosa with the proximal non-inflamed mucosa within CD patients (n = 20) neither α- or β-diversity differed (Figure 2). Furthermore, no bacterial taxa were differentially represented in the inflamed vs. proximally non-inflamed mucosa. CD patients operated with ICR had lower α-diversity (p = 0.021), but β-diversity did not differ from CD patients without ICR. CD patients with stenosis had lower abundances of Bacteroides, Sutterella and Akkermansia species. Conclusion 23 taxa were differentially expressed in CD compared with HC. The ileal mucosa-associated microbiome is similar assessed by both α- and β-diversity in the inflamed mucosa and the proximal non-inflamed mucosa within the same patients. Our results support the concept of CD specific microbiota alterations and demonstrate that neither ileal sub-location nor endoscopic inflammation itself influence the mucosa-associated microbiome.

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.

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 Early Ileocecal Resection Is an Effective Therapy in Isolated Crohn’s Disease

2021 ◽  
Vol 10 (4) ◽  
pp. 731
Author(s):  
Matthias Kelm ◽  
Friedrich Anger ◽  
Robin Eichlinger ◽  
Markus Brand ◽  
Mia Kim ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Primary Treatment ◽  
Early Surgery ◽  
Ileocecal Resection ◽  
Disease Manifestation ◽  
Terminal Ileitis ◽  
Primary Surgery ◽  
Immunosuppressive Medication

Despite the increasing incidence and prevalence of Crohn’s Disease (CD), no curative options exist and treatment remains complex. While therapy has mainly focused on medical approaches in the past, growing evidence reveals that in cases of limited inflammation, surgery can suffice as an alternative primary treatment. We retrospectively assessed the disease course and outcomes of 103 patients with terminal Ileitis who underwent primary surgery (n = 29) or received primary medical treatment followed by surgery (n = 74). Primary endpoint was the need for immunosuppressive medication after surgical treatment (ileocecal resection, ICR) during a two-years follow-up. Rates for laparoscopic ICR were enhanced in case of early surgery, but no differences were seen for postoperative complications. In case of immunosuppressive medication, patients with ICR at an early state of disease needed significantly less anti-inflammatory medication during the two-year postoperative follow-up compared to patients who were primarily treated medically. Furthermore, in a subgroup analysis for patients with localized ileocecal disease manifestation, early surgery consistently resulted in a decreased amount of medical therapy postoperatively. In conclusion primary ICR is safe and effective in patients with limited CD, and the need for immunosuppressive medication during the postoperative follow-up is low compared to patients receiving surgery at a later stage of disease.

scholarly journals P617 Mesenchymal stromal cells of bone marrow reduce the risk of postoperative recurrence of Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S513-S514
Author(s):  
O Knyazev ◽  
A V Kagramanova ◽  
A Lishchinskaya ◽  
A Parfenov
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Stromal Cells ◽  
Postoperative Recurrence ◽  
Low Risk ◽  
Average Level ◽  
Ileocecal Resection ◽  
Terminal Ileitis ◽  
Relapse Therapy

Abstract Background Crohn’s disease (CD) in the form of terminal ileitis occurs in approximately 1/3 of CD patients and is often complicated by the formation of ileum stricture or ileocecal valve. The operation of choice is resection of ileocecal Department with the formation of ileo of ascendants. Depending on the combination of risk factors, as well as on the effectiveness of previous anti-relapse therapy, patients after surgery should be stratified into groups with different risks of postoperative recurrence. The objective of the study was to evaluate the effectiveness of mesenchymal stem/stromal cells (MS/SC) as anti-relapse therapy in patients with low-risk CD after ileocecal resection. Methods Thirty-six patients with CD in the form of terminal ileitis with a stricture of the terminal ileum with signs of intestinal obstruction after the ineffectiveness of the course of conservative therapy (application of GCS) underwent resection of the ileocecal Department with the formation of ileo-ascendoanastomosis. All patients had a low risk of postoperative recurrence of Crohn’s disease. However, the first group of patients aged 19 to 58 years (Me-29) (n = 18) received MS/SC. The second group of patients aged 20 to 68 years (Me-36) (n = 18) received mesalazine 4 gr/day. The follow-up period was 60 months. The monitoring was carried out by endoscopic picture and/or CT-enterography, C-RP level, faecal calprotectin (FCP). Average baseline CRP in the first group was 29.5 ± 3.2 mg/l, in the second – to 27.75 ± 3.0 (p = 0.73), the level of the FCP in the first group 1019.4 ± 97.2 mkg/g, in the second – 998.8±127.3 mkg/g (p = 0,9). Results After 24 months in the first group of patients the average level of C-RP was 9.5 ± 1.9 mg/l, in the second group 17.8 ± 3.3 mg/l (p = 0.027). The level of the FCP in the first group 98.0 ± 12.1 mkg/g, in the second 121.7 ± 14.2 mkg/g (p = 0.27). After 24 months of follow-up, 1 (5.5%) patient from the first group (n = 18) had a relapse that required the appointment of GCS. In the second group, relapse occurred in 4 (22.2%) patients out of 18 (RR 0.25; 95% CI 0.031–2.025; p = 0.15). After 60 months in the first group of patients, the average level of C-RP was 10.76 ± 2.1 mg/l, in the second group 19.2 ± 3.5 mg/l (p = 0.039). The level of the FCP in the first group of 100.4 ± 13.7 per mkg/g, in the second 191.7 ± 24.9 mkg /g (p = 0.002). After 60 months of follow-up, 1 (5.5%) patients from the first group had a relapse. In the second group, relapse occurred in 8 (22.2%) patients out of 18 (RR 0.125; 95% CI 0.017–0.9; p = 0.008). Conclusion The use of mesenchymal stem/stromal cells (MS/SC) as anti-relapse therapy in patients with low-risk CD after ileocecal resection significantly reduces the risk of postoperative recurrence of CD.

ISOLATED TERMINAL ILEITIS AT COLONOSCOPY – DOES ULCERATION PREDICT CROHN’S DISEASE?

2020 ◽  
Author(s):  
R Patel ◽  
KM Ang ◽  
S Modelina ◽  
R Canda ◽  
S Musa ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Terminal Ileitis

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.

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.

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