P676 The small intestinal microbiome in Crohn’s disease is characterised by increased luminal diversity and stable mucosa-associated communities

Abstract Background Crohn’s disease (CD) may affect the entire gut but the composition and optimal sampling of the small intestinal microbiome are understudied. We assessed the variation in small intestinal luminal and mucosal microbiota in CD compared to healthy volunteers (HV) and functional dyspepsia (FD) patients. Methods Duodenal biopsies were collected with the Brisbane aseptic biopsy device1 followed by sterile brushing of the lumen/mucus layer. Aseptic ileal biopsies and brushes were also collected in CD patients with synchronous lower endoscopy. Acid- (proton pump inhibitors, PPIs) or immune-suppression (IS) and macro- (erosions/ulcers) and/or microscopic inflammation (CD) were recorded. Contamination was minimised during sample and data processing2 with further analysis at genus level. Microbiota covariates were studied using distance-based redundancy analysis (dbRDA, genus-level Aitchison distance) and PERMANOVA. Alpha-diversity (α) was compared between sampling types (biopsy/brush), disease groups, PPIs (off/on), IS (yes/no) or location (CD). Genera abundance profiles were compared transversally (sampling type) and regionally (CD) with correction for multiple testing (FDR<.1). Results A total of 99 participants (21 CD, 48 FD and 30 HV) with similar demographics were included. Only sampling type and subject were associated with duodenal community variation (table). Transversal variation was also evident from the more significant clustering for sampling type vs. groups (fig 1). Within CD, sampling type (8.5%) and location (17.8%, both p=.005) but not treatment or inflammation were associated with community variation. Duodenal α-diversity of brushes was lower vs. biopsies (p<2*10–9) and higher in CD vs. controls (fig 2). Compared to untreated subjects, α-diversity was lower with PPI in brushes (fig 3) and higher with IS in biopsies (CD) (fig 4). The 42 differentially abundant genera between sampling types of the duodenum were largely shared between groups vs. only 3 different genera for the ileum (CD). In CD, regional differences were found for 24 genera in brushes vs. only 6 in biopsies, with inflammation driving minor changes in brush and not biopsy samples of the duodenum only. Conclusion Small intestinal microbiota variation is significant, especially between duodenal luminal and mucosal communities. Luminal α-diversity was highest in CD but lower than that of the mucosa with an effect of treatment. Despite regional variation, mucosal genera profiles were more conserved and less affected by inflammation in CD. References 1. Shanahan et al., AP&T 2016 2. Davis et al., Microbiome 2018

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Differences in the intestinal microbiome of healthy children and patients with newly diagnosed Crohn’s disease

Scientific Reports ◽

10.1038/s41598-019-55290-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 11

Author(s):

Kinga Kowalska-Duplaga ◽

Tomasz Gosiewski ◽

Przemysław Kapusta ◽

Agnieszka Sroka-Oleksiak ◽

Andrzej Wędrychowicz ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Early Stage ◽

Alpha Diversity ◽

Intestinal Microbiome ◽

Healthy Children ◽

Newly Diagnosed ◽

Bifidobacterium Adolescentis ◽

Bowel Diseases ◽

Treatment Naïve

AbstractThe aetiology of inflammatory bowel diseases (IBD) seems to be strongly connected to changes in the enteral microbiome. The dysbiosis pattern seen in Crohn’s disease (CD) differs among published studies depending on patients’ age, disease phenotype and microbiome research methods. The aims was to investigate microbiome in treatment-naive paediatric patients to get an insight into its structure at the early stage of the disease in comparison to healthy. Stool samples were obtained from controls and newly diagnosed patients prior to any intervention. Microbiota was analysed by 16SrRNAnext-generation-sequencing (NGS). Differences in the within-sample phylotype richness and evenness (alpha diversity) were detected between controls and patients. Statistically significant dissimilarities between samples were present for all used metrics. We also found a significant increase in the abundance of OTUs of the Enterococcus genus and reduction in, among others, Bifidobacterium (B. adolescentis), Roseburia (R.faecis), Faecalibacterium (F. prausnitzii), Gemmiger (G. formicilis), Ruminococcus (R. bromii) and Veillonellaceae (Dialister). Moreover, differences in alpha and beta diversities in respect to calprotectin and PCDAI were observed: patients with calprotectin <100 µg/g and with PCDAI below 10 points vs those with calprotectin >100 µg/g and mild (10–27.7 points), moderate (27.5–40 points) or severe (>40 points) CD disease activity had higher richness and diversity of gut microbiota. The results of our study highlight reduced diversity and dysbiosis at the earliest stage of the disease. Microbial imbalance and low abundance of butyrate-producing bacteria, including Bifidobacterium adolescentis, may suggest benefits of microbial modification therapy.

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Evaluation of changes in intestinal microbiota in Crohn’s disease patients after anti-TNF alpha treatment

Scientific Reports ◽

10.1038/s41598-021-88823-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Laura Sanchis-Artero ◽

Juan Francisco Martínez-Blanch ◽

Sergio Manresa-Vera ◽

Ernesto Cortés-Castell ◽

Marina Valls-Gandia ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Microbiota ◽

Area Under The Curve ◽

Alpha Diversity ◽

Amplicon Sequencing ◽

Fecal Microbiota ◽

Multicenter Observational Study ◽

Partial Restoration ◽

Before And After

AbstractIntestinal dysbiosis is key in the onset and development of Crohn’s disease (CD). We evaluated the microbiota changes in CD patients before and after a six-month anti-TNF treatment, comparing these changes with the microbiota of healthy subjects. This prospective multicenter observational study involved 27 CD patients initiating anti-TNF treatment and 16 healthy individuals. Inflammatory activity was determined at baseline, 3 and 6 months, classifying patients into responders and non-responders. Fecal microbiota was analyzed by massive genomic sequencing thought 16S rRNA amplicon sequencing before and after six months of anti-TNF treatment. The CD cohort showed a decrease in genera of the class Clostridia, short-chain fatty acid producers, and an increase in the phylum Proteobacteria (p < 0.01) versus the healthy cohort. After anti-TNF treatment, the phylum Proteobacteria also increased in non-responders versus responders (13/27) (p < 0.005), with the class Clostridia increasing. In addition, alpha diversity increased in responders versus non-responders (p < 0.01), tending towards eubiosis. An association was found (p < 0.001) in the F.prausnitzii/E.coli ratio between responders and non-responders. The F/E ratio was the most accurate biomarker of anti-TNF response (area under the curve 0.87). Thus, anti-TNF treatment allows partial restoration of intestinal microbiota in responders and the F.prausnitzii/E.coli ratio can provide a reliable indicator of response to anti-TNF in CD.

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Sa1823 Vitamin D Receptor Affects Small Intestinal Paneth Cell Phenotype in Crohn's Disease Patients Independent of ATG16L1 Modulation

Gastroenterology ◽

10.1016/s0016-5085(16)31312-9 ◽

2016 ◽

Vol 150 (4) ◽

pp. S373

Author(s):

Ta-Chiang Liu ◽

Kelli L. VanDussen ◽

Thaddeus Stappenbeck

Keyword(s):

Vitamin D ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Vitamin D Receptor ◽

Paneth Cell ◽

Cell Phenotype ◽

Small Intestinal

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Small-Intestinal Bacterial Overgrowth is Associated With Concurrent Intestinal Inflammation But Not With Systemic Inflammation in Crohn’s Disease Patients

Journal of Clinical Gastroenterology ◽

10.1097/mcg.0000000000000803 ◽

2018 ◽

Vol 52 (6) ◽

pp. 530-536 ◽

Cited By ~ 11

Author(s):

José E.R. Ricci ◽

Liliana A. Chebli ◽

Tarsila C.d.R. Ribeiro ◽

Antonio C.S. Castro ◽

Pedro D. Gaburri ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Systemic Inflammation ◽

Intestinal Inflammation ◽

Bacterial Overgrowth ◽

Small Intestinal Bacterial Overgrowth ◽

Intestinal Bacterial Overgrowth ◽

Small Intestinal

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State-of-the-Art Lecture: Distinct antibacterial-defensin deficiencies in small intestinal and colonic Crohn’s disease

Immunoregulation in Inflammatory Bowel Diseases — Current Understanding and Innovation - Falk Symposium ◽

10.1007/978-1-4020-5889-9_15 ◽

2007 ◽

pp. 128-136

Author(s):

J. Wehkamp ◽

E. -F. Stange

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

State Of The Art ◽

Small Intestinal

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Fecal microbiota Profiling in Irritable Bowel Syndrome and Inflammatory Bowel Disease Patients with Irritable Bowel Syndrome-Type Symptoms

10.21203/rs.3.rs-152044/v1 ◽

2021 ◽

Author(s):

Xiufang Cui ◽

Haiyang Wang ◽

Ziping Ye ◽

Yi Li ◽

Xinyun Qiu ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Irritable Bowel Syndrome ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Microbiota ◽

Bowel Disease ◽

Sectional Study ◽

Genus Level ◽

Inflammatory Bowel ◽

Irritable Bowel

Abstract BACKGROUND: The intestinal microbiota is thought to be involved in the occurrence of Inflammatory Bowel Disease in remission (IBDR) with Irritable Bowel Syndrome (IBS)-type symptoms, but the specific distinct profile of these bacteria remains unclear. Therefore, the purpose of this research is to investigate this issue by conducting a cross-sectional study.METHODS: IBS patients were diagnosed according to Rome Ⅳ criteria, IBD diagnosed according to the criteria of European Crohn & Colitis Organization (ECCO), IBDR patients with IBS-type symptoms were defined according to related IBS-type symptoms meeting the Rome IV criteria in IBDR patients, and were included Crohn’s disease in remission (CDR) and ulcerative colitis in remission (UCR) based on Crohn’s Disease Activity Index (DAI) and Mayo Scoring System respectively. Healthy controls come from the physical examination center and exclude people with underlying diseases. All enrolled subjects were divided into six groups, as followed: Health Control, IBS, CDR with IBS-type symptoms (CDR-IBS+), CDR without IBS-type symptoms (CDR-IBS-), UCR-IBS+ and UCR-IBS-. We collected fresh fecal samples from all subjects and applied 16S rRNA sequencing analysis to detect the structure and diversity of the microbiota among different groups. RESULTS: A total of 97 subjects were included in this study, of which 18 were health controls, 34 IBS patients, 25 CDR and 20 UCR. The richness of intestinal microbiota in CDR-IBS-was significantly lower than that in the control and IBS groups based on the analysis of observed species and Chao index (P<0.05). The observed species index in CDR-IBS+ was significantly higher than CDR-IBS- group (median index: 254.8 vs 203, P=0.036). No difference was found in Alpha diversity between UCR-IBS+ and UCR-IBS-. At phylum level, there was no significant difference between UC or CD with IBS-type symptoms and those without related symptoms. At genus level, the number of Faecalibacterium in CDR-IBS+ increased significantly while Fusobacterium decreased compared with CDR-IBS-(mean relative abundance of Faecalibacterium: 20.35% vs 5.18%, P<0.05; Fusobacterium: 1.51% vs 5.2%, P<0.05). However, compared with UCR-IBS - group, the number of Faecalibacterium in UCR-IBS+ group decreased, while the number of Streptococcus increased, but there was no statistical difference in the genus structure. Regardless of the phylum or genus level, the abundance and composition of the microbiota of IBS patients were not distinct from those of healthy people.CONCLUSIONS: CD patients in remission with IBS-type symptoms may be related to the increase of Faecalibacterium and decrease of Fusobacterium. UC patients in remission with IBS-type symptoms cannot be explained by changes in the abundance and structure of intestinal microbiota from our across-sectional study.

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