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.

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.

Prominence of ileal mucosa-associated microbiota to predict postoperative endoscopic recurrence in Crohn’s disease

Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 462-472 ◽  
Author(s):  
Harry Sokol ◽  
Loic Brot ◽  
Carmen Stefanescu ◽  
Claire Auzolle ◽  
Nicolas Barnich ◽  
...  
Keyword(s):  
Risk Factors ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Alpha Diversity ◽  
Clinical Risk Factors ◽  
Ileal Mucosa ◽  
16S Sequencing ◽  
Time Of Surgery ◽  
Clinical Risk ◽  
Endoscopic Recurrence

ObjectiveFollowing ileal resection for Crohn’s disease (CD), recurrence is very frequent. Although several clinical risk factors of recurrence have been identified, predicting relapse remains challenging. Performing an ileocolonoscopy within the first year after surgery is currently recommended to assess endoscopic recurrence and to adjust the treatment. We took advantage of a large prospective multicentric cohort to investigate the role of the ileal mucosa-associated microbiota in postoperative endoscopic recurrence.Patients and methodsIleal mucosa-associated microbiota was analysed by 16S sequencing at the time of surgery and/or of endoscopic evaluation in 201 patients (288 samples in total) prospectively recruited in France.ResultsIleal mucosa-associated microbiota exhibits profound changes following surgery in CD. Compared with non-recurrence setting, endoscopic recurrence is associated with strong changes in ileal mucosa-associated microbiota that are highly reminiscent of those observed generally in ileal CD compared with healthy subjects with a reduction in alpha diversity, an increase in several members of the Proteobacteria phylum and a decrease in several members of the Lachnospiraceae and the Ruminococcaceae families within the Firmicutes phylum. At the time of surgery, we identified several bacterial taxa associated with endoscopic recurrence and that can better predict relapse than usual clinical risk factors.ConclusionSurgery has an important impact on ileal mucosa-associated microbiota. Postoperative endoscopic recurrence is associated with changes in microbiota composition and alpha diversity. The gut microbiota has the potential to predict postoperative evolution and recurrence.

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

Postoperative Management of Crohn’s Disease: What Can We Do to Prevent Recurrence?

2016 ◽  
Vol 2 (11) ◽  
Author(s):  
Adriana Georgiana Olariu ◽  
Liliana Bordeianou
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Recurrence ◽  
Postoperative Recurrence ◽  
Postoperative Management ◽  
Chronic Inflammatory Bowel Disease ◽  
Ileocecal Resection ◽  
Endoscopic Recurrence ◽  
Relapsing Remitting ◽  
Patients Experience

<p>Crohn’s disease (CD) is a chronic inflammatory bowel disease with a relapsing, remitting course.  Approximately one in four CD patients requires surgery within five years of diagnosis. Unfortunately, surgery is rarely curative and up to 70% of CD patients experience endoscopic recurrence and 40% have clinical disease recurrence within 18 months after surgery.</p><p> </p><p>This review is aimed at providing internists and gastroenterologists a foundation for the management of patients who underwent ileocecal resection for CD. We provide an overview of the current definitions of postoperative recurrence and prognostic factors for postoperative CD recurrence. As recent studies raised concerns about the value of these factors, we examine the evidence behind the current risk stratification algorithm and pharmacologic treatment recommendations. Lastly, we discuss future directions for research.</p>

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.

T cell clonal expansions in ileal Crohn’s disease are associated with smoking behaviour and postoperative recurrence

Gut ◽  
2019 ◽  
Vol 68 (11) ◽  
pp. 1961-1970 ◽  
Author(s):  
Matthieu Allez ◽  
Claire Auzolle ◽  
Marjolaine Ngollo ◽  
Hugo Bottois ◽  
Victor Chardiny ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
High Throughput Sequencing ◽  
Area Under The Curve ◽  
Postoperative Recurrence ◽  
Ileal Mucosa ◽  
Surgical Specimen ◽  
Endoscopic Recurrence ◽  
Tcr Repertoire

T cell clonal expansions are present in the inflamed mucosa of patients with Crohn’s disease (CD) and may be implicated in postoperative recurrence after ileocolonic resection.MethodsT cell receptor (TCR) analysis was performed in 57 patients included in a prospective multicentre cohort. Endoscopic recurrence was defined by a Rutgeerts score >i0. DNA and mRNA were extracted from biopsies collected from the surgical specimen and endoscopy, and analysed by high throughput sequencing and microarray, respectively.ResultsTCR repertoire in the mucosa of patients with CD displayed diverse clonal expansions. Active smokers at time of surgery had a significantly increased proportion of clonal expansions as compared with non-smokers (25.9%vs17.9%, p=0.02). The percentage of high frequency clones in the surgical specimen was significantly higher in patients with recurrence and correlated with postoperative endoscopic recurrence (area under the curve (AUC) 0.69, 95% CI 0.54 to 0.83). All patients with clonality above 26.8% (18/57) had an endoscopic recurrence. These patients with a high clonality were more frequently smokers than patients with a low clonality (61% vs 23%, p=0.005). The persistence of a similar TCR repertoire at postoperative endoscopy was associated with smoking and disease recurrence. Patients with high clonality showed increased expression of genes associated with CD8 T cells and reduced expression of inflammation-related genes. Expanded clones were found predominantly in the CD8 T cell compartment.ConclusionClonal T cell expansions are implicated in postoperative endoscopic recurrence. CD patients with increased proportion of clonal T cell expansions in the ileal mucosa represent a subgroup associated with smoking and where pathogenesis appears as T cell driven.Trial registration numberNCT03458195.

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