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 Adherent-Invasive E. coli: Update on the Lifestyle of a Troublemaker in Crohn’s Disease

2020 ◽  
Vol 21 (10) ◽  
pp. 3734 ◽  
Author(s):  
Mélissa Chervy ◽  
Nicolas Barnich ◽  
Jérémy Denizot
Keyword(s):  
Escherichia Coli ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Genetic Factors ◽  
Intestinal Epithelial Cells ◽  
Intestinal Lumen ◽  
Intestinal Epithelial ◽  
E Coli ◽  
The Subject ◽  
The Impact

Besides genetic polymorphisms and environmental factors, the intestinal microbiota is an important factor in the etiology of Crohn’s disease (CD). Among microbiota alterations, a particular pathotype of Escherichia coli involved in the pathogenesis of CD abnormally colonizes the intestinal mucosa of patients: the adherent-invasive Escherichia coli (AIEC) pathobiont bacteria, which have the abilities to adhere to and to invade intestinal epithelial cells (IECs), as well as to survive and replicate within macrophages. AIEC have been the subject of many studies in recent years to unveil some genes linked to AIEC virulence and to understand the impact of AIEC infection on the gut and consequently their involvement in CD. In this review, we describe the lifestyle of AIEC bacteria within the intestine, from the interaction with intestinal epithelial and immune cells with an emphasis on environmental and genetic factors favoring their implantation, to their lifestyle in the intestinal lumen. Finally, we discuss AIEC-targeting strategies such as the use of FimH antagonists, bacteriophages, or antibiotics, which could constitute therapeutic options to prevent and limit AIEC colonization in CD patients.

scholarly journals P646 Utilisation of indocyanine green fluorescence imaging for Crohn’s disease following intestinal resection

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S534-S534
Author(s):  
Y Duan ◽  
Y Li
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Indocyanine Green ◽  
Fluorescence Imaging ◽  
Intestinal Resection ◽  
Perioperative Outcomes ◽  
Green Fluorescence ◽  
Indocyanine Green Fluorescence ◽  
Indocyanine Green Fluorescence Imaging ◽  
The Impact

Abstract Background Growing evidences have shown that there are important advantages related to the utilisation of indocyanine green fluorescence imaging (ICG-FI) to reduce the risk of postoperative anastomotic leakage (AL) in colorectal surgery. However, the impact of ICG-FI on postoperative AL of Crohn’s disease (CD) following intestinal resection has not been investigated. Methods This is a retrospective study of consecutive CD patients who were treated with intestinal resection and anastomosis at a single institution between January 2017 and August 2019. The cohort was divided into 2 groups, those with ICG-FI compared with those without ICG-FI for intestinal resection. ICG was administered intravenously with a bolus of 5 mg, and the intestinal perfusion was evaluated by a SPY Elite system. Their baseline characteristics and perioperative outcomes were further analysed. Results No adverse reactions were recorded. Of the 88 CD patients who underwent intestinal resection, 36 patients underwent ICG-FI during intestinal resection, while 52 CD patients who underwent routine intestinal resection were from a prospectively maintained database. The 2 groups were similar in terms of patient demographics, immunosuppressive medication use, and the procedural factors. In patients with ICG-FI, poor perfusion of the bowel judged by ICG-FI led to additional intestinal resection in 25% (9/36). ICG-FI reduces the AL rate from 13.5% (7 leaks) of non-ICF-FI group to 8.3% (3 leaks) in ICG-FI group (p = 0.456). Forty-four (50%) patients had previous intestinal resection. Overall, 10 anastomotic leaks were identified (11.4% leak rate). There were 2 leaks (4.5%) detected in patients with no previous intestinal resection, compared with 8 leaks (18.2%) identified in patients with a history of previous intestinal resection (p = 0.044). The number of previous resections correlated with increasing risk for AL (correlation coefficient = 0.998). In univariate analysis, steroid use, CRP level and preoperative weight loss >10% in 6 months were independently associated with AL. Conclusion ICG-FI is applicable to intestinal resection for CD and may play a role in perfusion-related AL. A large prospective randomised trial should be warranted.

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.

scholarly journals The Impact of NOD2 Genetic Variants on the Gut Mycobiota in Crohn’s Disease Patients in Remission and in Individuals Without Gastrointestinal Inflammation

2020 ◽  
Author(s):  
Andrew Nelson ◽  
Christopher J Stewart ◽  
Nicholas A Kennedy ◽  
John K Lodge ◽  
Mark Tremelling ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Relative Abundance ◽  
Mucosal Inflammation ◽  
Rrna Gene ◽  
Wild Type ◽  
Candida Spp ◽  
Principal Coordinates Analysis ◽  
Principal Coordinates ◽  
The Impact

Abstract Background and Aims Historical and emerging data implicate fungi in Crohn’s disease [CD] pathogenesis. However, a causal link between mycobiota, dysregulated immunity, and any impact of NOD2 variants remains elusive. This study aims to evaluate associations between NOD2 variants and faecal mycobiota in CD patients and non-CD subjects. Methods Faecal samples were obtained from 34 CD patients [18 NOD2 mutant, 16 NOD2 wild-type] identified from the UK IBD Genetics Consortium. To avoid confounding influence of mucosal inflammation, CD patients were in clinical remission and had a faecal calprotectin <250 μg/g; 47 non-CD subjects were included as comparator groups, including 22 matched household [four NOD2 mutant] and 25 non-household subjects with known NOD2 genotype [14 NOD2 mutant] identified by the NIHR BioResource Cambridge. Faecal mycobiota composition was determined using internal transcribed spacer 1 [ITS1] sequencing and was compared with 16S rRNA gene sequences and volatile organic compounds. Results CD was associated with higher numbers of fungal observed taxonomic units [OTUs] [p = 0.033]. Principal coordinates analysis using Jaccard index [p = 0.018] and weighted Bray-Curtis dissimilarities [p = 0.01] showed Candida spp. clustered closer to CD patients whereas Cryptococcus spp. clustered closer to non-CD. In CD, we found higher relative abundance of Ascomycota [p = 0.001] and lower relative abundance Basidiomycota [p = 0.019] phyla. An inverse relationship was found between bacterial and fungal Shannon diversity in NOD2 wild-type which was independent of CD [r = -0.349; p = 0.029]. Conclusions This study confirms compositional changes in the gut mycobiota in CD and provides evidence that fungi may play a role in CD pathogenesis. No NOD2 genotype-specific differences were observed in the faecal mycobiota.

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 Temporal dynamics of the fecal microbiota in veal calves in a 6-month field trial

2020 ◽  
Author(s):  
Méril Massot ◽  
Marisa Haenni ◽  
Thu Thuy Nguyen ◽  
Jean-Yves Madec ◽  
France Mentré ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Temporal Dynamics ◽  
Diversity Index ◽  
Milk Powder ◽  
Rrna Gene ◽  
Mixed Effect ◽  
E Coli ◽  
Veal Calves ◽  
Α Diversity ◽  
The Impact

Abstract Background Little is known about maturation of calves’ gut microbiome in veal farms, in which animals are confined under intensive-farming conditions and the administration of collective antibiotic treatment in feed is common. We conducted a field study on 45 calves starting seven days after their arrival in three veal farms. We collected monthly fecal samples over six months and performed 16S rRNA gene sequencing and quantitative PCR of Escherichia coli to follow the dynamics of their microbiota, including that of their commensal E. coli populations. We used mixed-effect models to characterize the dynamics of α-diversity indices and numbers of E. coli, and searched for an effect of collective antibiotic treatments on the estimated parameters. On two farms, we also searched for associations between recommended daily doses of milk powder and bacterial abundance. Results There was high heterogeneity between calves’ microbiota upon their arrival at the farms, followed by an increase in similarity, starting at the first month. From the second month, 16 genera were detected at each sampling in all calves, representing 67.5% (± 9.9) of their microbiota. Shannon diversity index showed a two-phase increase, an inflection occurring at the end of the first month. Calves receiving antibiotics had a lower intercept estimate for Shannon index (-0.17 CI95%[0.27; -0.06], p = 0.003) and a smaller number of E. coli/ gram of feces during the treatment and in the 15 days following it (-0.37 log10 (E. coli/g) CI95%[-0.66; -0.08], p = 0.01) than unexposed calves. There were moderate to strong positive associations between the dose of milk powder and the relative abundances of the genera Megasphaera, Enterococcus, Dialister and Mitsuokella, and the number of E. coli (rs ≥ 0.40; Bonferroni corrected p < 0.05).Conclusions This observational study shows early convergence of the developing microbiota between veal calves and associations between the dose of milk powder and members of their microbiota. It suggests that administration of collective antibiotic treatment results in a reduction of diversity and size of the E. coli population and highlights the need for additional work to fully understand the impact of antibiotic treatment in the veal industry.

scholarly journals Temporal dynamics of the fecal microbiota in veal calves in a 6-month field trial

2020 ◽  
Author(s):  
Méril Massot ◽  
Marisa Haenni ◽  
Thu Thuy Nguyen ◽  
Jean-Yves Madec ◽  
France Mentré ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Temporal Dynamics ◽  
Milk Powder ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Mixed Effect ◽  
E Coli ◽  
Intensive Farming ◽  
Α Diversity ◽  
The Impact

Abstract Background Little is known about gut maturation of calves in veal farms, in which animals are confined under intensive-farming conditions and the administration of collective antibiotic treatment in feed is common. We conducted a field study on 45 calves starting seven days after their arrival in three veal farms. We collected monthly fecal samples over six months and performed 16S rRNA gene sequencing and quantitative PCR of Escherichia coli to follow the dynamics of their fecal microbiota, including that of their commensal E. coli populations. We used mixed-effect models to characterize the dynamics of α-diversity indices and numbers of E. coli. We searched for an effect of collective antibiotic treatments on the estimated parameters of these models. On two farms, we searched for associations between recommended daily doses of milk powder and bacterial abundance. Results Time had a significant effect on microbiota composition. There was high heterogeneity between calves upon their arrival at the farms, followed by an increase in similarity, starting at the end of the first month. From the second month, 16 genera were detected at each sampling in all calves until the end of fattening, and represented a large fraction of their microbiota. Shannon index showed a two-phase increase, the pivotal shift occurring at the end of the first month. Calves receiving antibiotics had a less diverse microbiota and a smaller number of E. coli during the treatment and in the 15 days following it than unexposed calves, although these effects were limited in intensity. There were moderate to strong positive associations between the dose of milk powder and the relative abundances of four genera and the number of E. coli.Conclusions This observational study shows early homogenization of the developing microbiota of calves reared under intensive-farming conditions and positive associations between the dose of milk powder and four genera of their microbiota. It suggests that administration of collective antibiotic treatment results in a limited reduction of diversity and size of the E. coli population and highlights the need for additional work to fully understand the impact of antibiotic treatment in the context of the veal industry.

scholarly journals Efficacy of early intervention on the bowel damage and intestinal surgery of Crohn’s disease, based on the Lémann index

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Mingming Zhu ◽  
Qi Feng ◽  
Xitao Xu ◽  
Yuqi Qiao ◽  
Zhe Cui ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Early Intervention ◽  
Crohn's Disease ◽  
Bowel Resection ◽  
Intestinal Resection ◽  
Intestinal Surgery ◽  
History Of ◽  
Disease Behavior ◽  
The Impact

Abstract Background Clinicians aim to prevent progression of Crohn’s disease (CD); however, many patients require surgical resection because of cumulative bowel damage. The aim of this study was to evaluate the impact of early intervention on bowel damage in patients with CD using the Lémann Index and to identify bowel resection predictors. Methods We analyzed consecutive patients with CD retrospectively. The Lémann Index was determined at the point of inclusion and at follow-up termination. The Paris definition was used to subdivide patients into early and late CD groups. Results We included 154 patients, comprising 70 with early CD and 84 with late CD. After follow-up for 17.0 months, more patients experienced a decrease in the Lémann Index (61.4% vs. 42.9%), and fewer patients showed an increase in the Lémann Index (20% vs. 35.7%) in the early compared with the late CD group. Infliximab and other therapies reversed bowel damage to a greater extent in early CD patients than in late CD patients. Twenty-two patients underwent intestinal surgery, involving 5 patients in the early CD group and 17 patients in the late CD group. Three independent predictors of bowel resection were identified: baseline Lémann index ≥ 8.99, disease behavior B1, and history of intestinal surgery. Conclusions Early intervention within 18 months after CD diagnosis could reverse bowel damage and decrease short-term intestinal resection. Patients with CD with a history of intestinal surgery, and/or a Lémann index > 8.99 should be treated aggressively and monitored carefully to prevent progressive bowel damage.

scholarly journals Alterations of gut microbiota composition in post-finasteride patients: a pilot study

2020 ◽  
Author(s):  
F. Borgo ◽  
A. D. Macandog ◽  
S. Diviccaro ◽  
E. Falvo ◽  
S. Giatti ◽  
...  
Keyword(s):  
Sexual Dysfunction ◽  
Gut Microbiota ◽  
16S Rrna Gene Sequencing ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Sample Collection ◽  
Persistent Symptoms ◽  
Α Diversity ◽  
Gut Microbiota Composition

Abstract Purpose Post-finasteride syndrome (PFS) has been reported in a subset of patients treated with finasteride (an inhibitor of the enzyme 5alpha-reductase) for androgenetic alopecia. These patients showed, despite the suspension of the treatment, a variety of persistent symptoms, like sexual dysfunction and cognitive and psychological disorders, including depression. A growing body of literature highlights the relevance of the gut microbiota-brain axis in human health and disease. For instance, alterations in gut microbiota composition have been reported in patients with major depressive disorder. Therefore, we have here analyzed the gut microbiota composition in PFS patients in comparison with a healthy cohort. Methods Fecal microbiota of 23 PFS patients was analyzed by 16S rRNA gene sequencing and compared with that reported in ten healthy male subjects. Results Sexual dysfunction, psychological and cognitive complaints, muscular problems, and physical alterations symptoms were reported in more than half of the PFS patients at the moment of sample collection. The quality sequence check revealed a low library depth for two fecal samples. Therefore, the gut microbiota analyses were conducted on 21 patients. The α-diversity was significantly lower in PFS group, showing a reduction of richness and diversity of gut microbiota structure. Moreover, when visualizing β-diversity, a clustering effect was found in the gut microbiota of a subset of PFS subjects, which was also characterized by a reduction in Faecalibacterium spp. and Ruminococcaceae UCG-005, while Alloprevotella and Odoribacter spp were increased compared to healthy control. Conclusion Gut microbiota population is altered in PFS patients, suggesting that it might represent a diagnostic marker and a possible therapeutic target for this syndrome.

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