scholarly journals P683 Patients with newly diagnosed fistulizing perianal Crohn’s disease have a distinct microbial signature

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S602-S602
Author(s):  
I Goren ◽  
W Ian ◽  
L Reshef ◽  
T Sharar Fischler ◽  
M Pauker ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
16S Rrna Gene Sequencing ◽  
Fecal Calprotectin ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Newly Diagnosed ◽  
Linear Discriminant ◽  
Microbial Dysbiosis ◽  
Log Ratio

Abstract Background Alterations in gut bacterial microbiota are strongly associated with the pathogenesis of Crohn’s disease (CD). Up to 1/3 of patients with CD have perianal involvement (P-CD), either fistulizing (f-P-CD) or non-fistulizing (nf-P-CD). We hypothesized that alterations in fecal microbiota might drive perianal CD phenotypes. Methods Patients with newly diagnosed treatment naive CD were consecutively recruited. Patients were stratified into f-P-CD and nf-P-CD, and compared with CD without perianal involvement (non-P-CD). Bacterial 16S rRNA gene sequencing was performed. Microbial dysbiosis index (MDI), Shannon diversity score (H) and log ratio between anaerobic and aerobic bacteria (anaerobic index, AI) were calculated. Linear discriminant analysis effect size (LEfSe) was used to identify specific taxa discriminating between different patient groups. Fecal calprotectin (FC) was measured. Results We included 97 CD patients (50 males, median age 28 [IQR 22–41] years). Other than perianal involvement patients in both groups had comparable distribution of CD location and phenotype. The microbial indices MDI, H and AI as well as FC levels, did not differ between the P-CD (n=25) and non-P-CD (n=72) groups. When compared to non-P-CD, the P-CD exhibited significantly lower relative abundance in the Streptococci genera (p=0.01) and in the Ruminiclostridium_5 genera (p=0.02). Within the P-CD group, patients with f-P-CD (n=12) had significantly lower H than those with nf-P-CD (means: 2.0 vs 2.45, p=0.045), while FC levels were comparable between f-P-CD and nf-P-CD. Moreover, proportions of Coprococcus_3 and Lacnoclostridium were reduced in patients with f-P-CD vs nf-P-CD (p= 0.008, p=0.05, respectively), while Streptococcus was elevated (p=0.03). Conclusion Perianal CD is a spectrum with distinct microbial alterations in different phenotypes. Microbial alterations correspond to the severity of perianal involvement. This finding may suggest that the microbiome has a mechanistic role in complicated perianal CD.

Tu1793 – Eukaryotic Microbial Dysbiosis in Treatment-Naïve Patients with Newly Diagnosed Crohn's Disease

2019 ◽  
Vol 156 (6) ◽  
pp. S-1126
Author(s):  
Idan Goren ◽  
Lihi Godny ◽  
Leah Reshef ◽  
Keren M. Rabinowitz ◽  
Uri Gophna ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Newly Diagnosed ◽  
Microbial Dysbiosis ◽  
Treatment Naïve

scholarly journals Fecal Microbiota Signatures Are Associated with Response to Ustekinumab Therapy among Crohn’s Disease Patients

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Matthew K. Doherty ◽  
Tao Ding ◽  
Charlie Koumpouras ◽  
Shannon E. Telesco ◽  
Calixte Monast ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Therapeutic Response ◽  
Fecal Microbiota ◽  
Response To Therapy ◽  
Community Diversity ◽  
Health Concern ◽  
Rrna Gene ◽  
Necrosis Factor Alpha ◽  
Active Disease

ABSTRACTThe fecal microbiota is a rich source of biomarkers that have previously been shown to be predictive of numerous disease states. Less well studied is the effect of immunomodulatory therapy on the microbiota and its role in response to therapy. This study explored associations between the fecal microbiota and therapeutic response of Crohn’s disease (CD) patients treated with ustekinumab (UST; Stelara) in the phase 2 CERTIFI study. Using stool samples collected over the course of 22 weeks, the composition of these subjects’ fecal bacterial communities was characterized by sequencing the 16S rRNA gene. Subjects in remission could be distinguished from those with active disease 6 weeks after treatment using random forest models trained on subjects’ baseline microbiota and clinical data (area under the curve [AUC] of 0.844, specificity of 0.831, sensitivity of 0.774). The most predictive operational taxonomic units (OTUs) that were ubiquitous among subjects were affiliated withFaecalibacteriumandEscherichiaorShigella. The median baseline community diversity in subjects in remission 6 weeks after treatment was 1.7 times higher than that in treated subjects with active disease (P= 0.020). Their baseline community structures were also significantly different (P= 0.017). Two OTUs affiliated withFaecalibacterium(P= 0.003) andBacteroides(P= 0.022) were significantly more abundant at baseline in subjects who were in remission 6 weeks after treatment than those with active CD. The microbiota diversity of UST-treated clinical responders increased over the 22 weeks of the study, in contrast to nonresponsive subjects (P= 0.012). The observed baseline differences in fecal microbiota and changes due to therapeutic response support the potential for the microbiota as a response biomarker.IMPORTANCECD is a global health concern, with increasing incidence and prevalence, causing large economic and health care impacts. Finding prognostic biomarkers that give clinicians the ability to identify patients more likely to respond to CD treatment at diagnosis will reduce the time subjects receive drugs that are unlikely to be beneficial. OTUs associated with remission after treatment induction, especiallyFaecalibacterium, could be biomarkers for successful UST treatment of anti-tumor necrosis factor alpha (anti-TNF-α) refractory CD patients. More broadly, these results suggest that the fecal microbiota could be a useful noninvasive biomarker for directing or monitoring the treatment of gastrointestinal diseases.

scholarly journals The gastric microbiota in patients with Crohn’s disease; a preliminary study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jerzy Ostrowski ◽  
Maria Kulecka ◽  
Iwona Zawada ◽  
Natalia Żeber-Lubecka ◽  
Agnieszka Paziewska ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Pairwise Comparison ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Bacterial Phyla ◽  
Abundant Otus ◽  
Significant Difference ◽  
H Pylori ◽  
Gastric Microbiota

AbstractThe gastric microbiota in Crohn’s disease (CD) has not been studied. The purpose of the study was to evaluate differences of stomach microbiota between CD patients and controls. DNA was extracted from gastric mucosal and fluid samples, from 24 CD patients and 19 controls. 16S rRNA gene sequencing identified 1511 operational taxonomic units (OTUs), of which 239 passed the low abundance and low variance filters. All but one CD patients were HP negative. Fifteen bacterial phyla were identified in at least one mucosal or fluid site. Of these, Bacteroidota and Firmicutes accounted for 70% of all phyla. Proteobacteria, Actinobacteriota, and Fusobacteriota combined accounted for 27%. There was significant difference in the relative abundance of Bacteroidota, Proteobacteria, Fusobacteriota, and Campilobacterota between CD patients and controls only in gastric corpus samples. In gastric liquid, there was a significant difference only in Actinobacteriota. Pairwise comparison identified 67 differentially abundant OTUs in at least one site. Of these, 13 were present in more than one comparison, and four differentiating OTUs (Neisseriaceae, Neisseria, Absconditabacteriales, and Microbacteriaceae) were identified at all tested sites. The results reveal significant changes in gastric microbial profiles (beta diversity, phylum, and individual taxa levels) between H. pylori-negative CD patients and controls.

scholarly journals Metabonomics and the Gut Microbiome Associated With Primary Response to Anti-TNF Therapy in Crohn’s Disease

2020 ◽  
Vol 14 (8) ◽  
pp. 1090-1102 ◽  
Author(s):  
N S Ding ◽  
J A K McDonald ◽  
A Perdones-Montero ◽  
Douglas N Rees ◽  
S O Adegbola ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Bile Acid ◽  
Crohn's Disease ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
Gene Sequencing ◽  
16S Rrna Gene Sequencing ◽  
Primary Response ◽  
Rrna Gene ◽  
Rrna Gene Sequencing

Abstract Background and Aims Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn’s disease. Methods Patients with luminal Crohn’s disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces. Results Samples were collected from 76 Crohn’s disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn’s patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn’s disease. Conclusions This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn’s disease. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

The Gut Microbial Profile of Preclinical Crohn’s Disease Is Similar to That of Healthy Controls

2020 ◽  
Vol 26 (11) ◽  
pp. 1682-1690
Author(s):  
Anna Kuballa ◽  
Marco Geraci ◽  
Meredith Johnston ◽  
Dario Sorrentino
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Microbial Diversity ◽  
Alpha Diversity ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Disease Evolution ◽  
Microbial Profile ◽  
Microbial Dysbiosis ◽  
Principal Coordinates

Abstract Background and Aims It is unclear whether microbial dysbiosis plays an etiologic role in Crohn’s disease (CD) or is the result of protracted inflammation. Here, we test the hypothesis that dysbiosis predates clinical CD in asymptomatic first-degree relatives (FDRs) of CD patients: normal (FDR1), with borderline inflammation (FDR2), and with frank, very early inflammation (FDR3). Methods The gut microbial diversity was tested in ileocecal biopsies through next generation sequencing of the 16S rRNA gene in 10 healthy controls (HCs), 22 patients with active, untreated CD, and 25 FDRs (9 FDR1; 12 FDR2; 4 FDR3). The metagenomic functions of 41 microbiome-related processes were inferred by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. Results Compared with HCs, alpha diversity in CD patients was decreased, with an observed decrease in Faecalibacterium prausnitzii and increase in Bacteroides fragilis. In FDRs, microbial diversity was unchanged compared with HCs. In Operational Taxonomic Units and PICRUSt Principal coordinates and component analyses, the ellipse centroid of FDRs was diagonally opposed to that of CD patients, but close to the HC centroid. In both analyses, statistically significant differences in terms of beta diversity were found between CD and HC but not between FDR and HC. Conclusions In FDRs (including FDR3—who bear preclinical/biologic onset disease), we found that the microbial profile is remarkably similar to HC. If confirmed in larger studies, this finding suggests that clinical CD-associated dysbiosis could result from the changed microenvironment due to disease evolution over time.

scholarly journals OP30 The interplay of microbiome dysbiosis and immune system deregulation in patients with Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S028-S030
Author(s):  
N S Seyed Tabib ◽  
C Caenepeel ◽  
K Machiels ◽  
S Verstockt ◽  
B Verstockt ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Regression Model ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Serum Samples ◽  
Faecal Calprotectin ◽  
Key Factor ◽  
Inflammatory State ◽  
Inflammatory Proteins

Abstract Background The perturbation of composition, function, and structure of the gut microbiota known as dysbiosis is a key factor in inflammatory bowel disease (IBD) pathogenesis. There is a crosstalk between the microbiota and the gut immunological niche. To better understand this interaction, we characterised the degree of dysbiosis and dysregulation of the immune proteome in Crohn’s disease (CD) patients to see whether subtypes of patients could be identified. Methods We collected faecal and serum samples of 146 CD patients and 63 healthy controls (HC) (Figure 1), and studied microbiota phylogenetic (16S rRNA gene sequencing) and serum proteomic (91 inflammatory proteins OLINK). Microbial dysbiotic index (MDI), defined as the logarithm of the sum of [abundance in organisms increased in CD] over the [abundance of organisms decreased in CD] was calculated and patients were ranked from Q1 (the least dysbiotic state) to Q4 (the most dysbiotic state). For the proteomic score, 32 proteins that correlated (adj. p ≤ 0.01) with faecal calprotectin (FC) were selected. A penalised logistic regression model was trained on these proteins, to distinguish HC from super active (defined as FC ≥ 1800 μg/g). We next developed an inflammatory proteomic score (IPS) defined as the weighted sum of the serum level of inflammatory proteins, using the coefficient value of the regression model as the protein’s weight. Using the IPS score, patients were clustered from Q1 (the least inflammatory state) to Q4 (the most inflammatory state). Statistical analyses were performed in R 3.5.2. Results The MDI did not correlate with standard phenotypic subgroups based on the Montreal classification but did positively correlate with C-reactive protein (CRP) and FC level (p ≤ 0.001). The regression model identified 14 proteins [including CCL20, CXCL1, IL-7, IL-17A, FGF-19] distinguishing super active CD patients from HC with accuracy, sensitivity, and specificity of 95.6%, 92.3%, 100%, respectively. IPS positively correlated with CRP and FC level (p ≤ 0.001). Likewise, MDI and IPS-based clusters were significantly different in CRP and FC levels. Different components of the microbiome correlated with the proteome in a subset of samples. For example, fibroblast growth factor 19 (FGF-19) positively correlated with Faecalibacterium and negatively with Fusicatenibacterium. Of note, we observed a significant positive correlation between MDI and IPS (r = 0.33, p ≤ 0.001) (Figure 2). Conclusion We were able to define clusters of patients based on molecular characterisation of different players in IBD pathogenesis such as microbiota and proteome. This molecular clustering in a given patient could be considered as a novel therapeutic and personalised approach to IBD. Further validation in larger cohorts is required.

scholarly journals Differentially Abundant Bacterial Taxa Associated with Prognostic Variables of Crohn’s Disease: Results from the IMPACT Study

2020 ◽  
Vol 9 (6) ◽  
pp. 1748
Author(s):  
Soo-kyung Park ◽  
Han-Na Kim ◽  
Chang Hwan Choi ◽  
Jong Pil Im ◽  
Jae Myung Cha ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Resection ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Prognostic Variables ◽  
E Coli ◽  
Α Diversity ◽  
The Impact

Limited studies have examined the intestinal microbiota composition in relation to Crohn’s disease (CD) prognosis. We analyzed the differences in microbial communities and relevant metabolic pathways associated with prognostic variables in patients with CD. We applied 16S rRNA gene sequencing to analyze a cohort of 1110 CD and healthy control (HC) fecal samples. We categorized patients with CD into good (CD-G), intermediate (CD-I) and poor (CD-P) prognosis groups, according to the history of using biologics and intestinal resection. Microbiota α-diversity decreased more in CD-P than CD-G and CD-I. Microbiota ß-diversity in CD-P differed from that in CD-G and CD-I. Thirteen genera and 10 species showed differential abundance between CD-G and CD-P groups. Escherichia coli (p = 0.001) and species Producta (p = 0.01) and genera Lactobacillus (p = 0.003) and Coprococcus (p = 0.01) consistently showed differences between CD-G and CD-P groups after adjusting for confounding variables. Functional profiling suggested that the microbial catabolic pathways and pathways related to enterobacterial common antigen and lipopolysaccharide biosynthesis were better represented in the CD-P group than in the CD-G group, and E. coli were the top contributors to these pathways. CD prognosis is associated with altered microbiota composition and decreased diversity, and E. coli might be causally involved in CD progression, and may have adapted to live in inflammatory environments.

scholarly journals Influence of Enteral Nutrition on Gut Microbiota Composition in Patients with Crohn’s Disease: A Systematic Review

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2551 ◽  
Author(s):  
Paulina Horwat ◽  
Stanisław Kopeć ◽  
Aleksandra Garczyk ◽  
Iwona Kaliciak ◽  
Zuzanna Staręga ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Enteral Nutrition ◽  
Gut Microbiota ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Exclusive Enteral Nutrition ◽  
Faecal Samples ◽  
Hs Crp ◽  
Rrna Gene Sequencing

The aim of the study was to systematically and comprehensively evaluate whether exclusive enteral nutrition (EEN) has impact on gut microbiota in patients with Crohn’s disease (CD). The databases PUBMED (MEDLINE), SCOPUS and WEB OF SCIENCE were searched. Out of 232 studies, 9 met inclusion criteria. The combined analyzed population consists of 118 patients with CD and treated with EEN with a time of intervention of 2–12 weeks. Studies were conducted in children, with the exception of one study. All applied feeding formulas had similar energy value and composition. The microbiome analysis was based on 16S rRNA gene sequencing of faecal samples. In all studies, EEN treatment decreases inflammatory markers (i.e., hs-CRP and FCP). A change in abundance of numerous bacterial families (Clostridiaceae, Eubacteriaceae, Bacteroidaceae) was noticed, especially in Bacteroidaceae. An increase in families connected to the more severe clinical course (Fusobacteria, Prevotella, Lachnospiraceae) was observed in only 2.5% of CD patients. Our analyses suggest EEN has a beneficial influence on gut microbiome in patients with CD, which is interrelated with clinical patient’s improvement and time of disease remission.

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