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

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.

Download Full-text

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

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa107 ◽

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.

Download Full-text

P229 Environmental and clinical risk factors for severe Crohn's disease

Journal of Crohn s and Colitis ◽

10.1016/s1873-9946(14)60350-0 ◽

2014 ◽

Vol 8 ◽

pp. S157-S158

Author(s):

N. Azzopardi ◽

P. Ellul ◽

S. Chetcuti ◽

G. Laferla

Keyword(s):

Risk Factors ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Risk Factors ◽

Clinical Risk

Download Full-text

Mo1763 Clinical Risk Factors for Crohn's Disease Postoperative Recurrence are Reflected in Alterations in Mucosally Adherent Microbiota at Surgical Resection

Gastroenterology ◽

10.1016/s0016-5085(12)62617-1 ◽

2012 ◽

Vol 142 (5) ◽

pp. S-679

Author(s):

Aravinth U. Murugananthan ◽

Phil Tozer ◽

David Bernardo Ordiz ◽

Ailsa Hart ◽

Stella C. Knight ◽

...

Keyword(s):

Risk Factors ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Surgical Resection ◽

Postoperative Recurrence ◽

Clinical Risk Factors ◽

Clinical Risk

Download Full-text

PMO-230 Clinical risk factors for Crohn's disease postoperative recurrence are reflected in alterations in mucosally adherent microbiota at surgical resection

Gut ◽

10.1136/gutjnl-2012-302514b.230 ◽

2012 ◽

Vol 61 (Suppl 2) ◽

pp. A168.1-A168

Author(s):

A U Murugananthan ◽

D O Bernardo ◽

P Tozer ◽

A L Hart ◽

S C Knight ◽

...

Keyword(s):

Risk Factors ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Surgical Resection ◽

Postoperative Recurrence ◽

Clinical Risk Factors ◽

Clinical Risk

Download Full-text

P463 Clinical risk factors for Crohn's disease postoperative recurrence are reflected in alterations in mucosally adherent microbiota at surgical resection

Journal of Crohn s and Colitis ◽

10.1016/s1873-9946(12)60482-6 ◽

2012 ◽

Vol 6 ◽

pp. S193

Author(s):

A. Murugananthan ◽

P. Tozer ◽

D. Bernardo ◽

A. Hart ◽

S. Knight ◽

...

Keyword(s):

Risk Factors ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Surgical Resection ◽

Postoperative Recurrence ◽

Clinical Risk Factors ◽

Clinical Risk

Download Full-text

The Influence of Microscopic Inflammation at Resection Margins on Early Postoperative Endoscopic Recurrence After Ileocaecal Resection for Crohn’s Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz153 ◽

2019 ◽

Vol 14 (3) ◽

pp. 361-368 ◽

Cited By ~ 1

Author(s):

Karolina Poredska ◽

Lumir Kunovsky ◽

Filip Marek ◽

Zdenek Kala ◽

Vladimir Prochazka ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Duration ◽

Resection Margins ◽

Endoscopic Recurrence ◽

Histological Results ◽

Resected Bowel ◽

Microscopic Inflammation

Abstract Background and Aims The pathogenesis and risk factors for early postoperative endoscopic recurrence of Crohn’s disease [CD] remain unclear. Thus, this study aimed to identify whether histological inflammation at the resection margins after an ileocaecal resection influences endoscopic recurrence. Methods We have prospectively followed up patients with CD who underwent ileocaecal resection at our hospital between January 2012 and January 2018. The specimens were histologically analysed for inflammation at both of the resection margins [ileal and colonic]. We evaluated whether histological results of the resection margins are correlated with endoscopic recurrence of CD based on colonoscopy 6 months after ileocaecal resection. Second, we assessed the influence of known risk factors and preoperative therapy on endoscopic recurrence of CD. Results A total of 107 patients were included in our study. Six months after ileocaecal resection, 23 patients [21.5%] had an endoscopic recurrence of CD. The histological signs of CD at the resection margins were associated with a higher endoscopic recurrence [56.5% versus 4.8%, p < 0.001]. Disease duration from diagnosis to surgery [p = 0.006] and the length of the resected bowel [p = 0.019] were significantly longer in patients with endoscopic recurrence. Smoking was also proved to be a risk factor for endoscopic recurrence [p = 0.028]. Conclusions Histological inflammation at the resection margins was significantly associated with a higher risk of early postoperative endoscopic recurrence after an ileocaecal resection for CD.

Download Full-text

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

Gut ◽

10.1136/gutjnl-2018-317878 ◽

2019 ◽

Vol 68 (11) ◽

pp. 1961-1970 ◽

Cited By ~ 10

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.

Download Full-text