scholarly journals P836 Biomarkers response to anti-TNF treatment in Crohn’s disease through the intestinal microbiota

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S648-S649
Author(s):  
L Sanchis ◽  
S Manresa ◽  
J F Martínez ◽  
M Valls ◽  
M Iborra ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Microbiota ◽  
Biological Response ◽  
Alpha Diversity ◽  
Short Chain Fatty Acids ◽  
Faecal Calprotectin ◽  
Partial Restoration ◽  
Alpha And Beta Diversity ◽  
E Coli

Abstract Background The alteration of the intestinal microbiota is a necessary requirement for the development of Crohn’s disease (CD). The anti-TNF alfa (TNF) treatment has radically changed the prognosis of the disease, modifying the therapeutic objective which is the induction and subsequent maintenance of mucosal healing. It is unknown, if this cure/improvement correlates with changes in the microbiota. The objectives of the study were: evaluate the changes in the microbiota in CD pre and after six months with TNF, determine the changes in the microbiota based on the clinical-biological response to TNF and calculate the F. prausnitzii/E. coli (F/E) ratio as an indicator of therapeutic response. Methods This was a prospective observational multicentre study that included 27 patients with CD who started treatment with TNF. 16 healthy individuals were included to establish the local healthy microbiota. The existence of disease activity was determined using the Harvey-Bradshaw index (HBI), analytical parameters such as C-reactive protein and faecal calprotectin measured at the beginning of the study, 3 and 6 months; classifying patients as responders (R) and non-responders (NR). The composition of the microbiota (the alpha and beta diversity), as well as the F/E ratio as indicators of dysbiosis, were evaluated by massive genomic sequencing, at the date of inclusion and 6 months after starting TNF through faecal samples. Results Prior to TNF, the loss of Clostridia class genera, producers of short chain fatty acids, as well as the significant increase (p <0.01) of Proteobacteria, highlighting the Escherichia/Shigella genus with respect to healthy controls. The microbiota varied according to response to the TNF: the Proteobacteria phylum affected in NR with respect to healthy and R group (p <0.005). Although, R group (13/27) significantly increase Clostridia class bacteria (such as Faecalibacterium) as well as alpha diversity with respect to NR group (p <0.01), with a tendency towards a microbiota similar to controls. There is a significant association (p <0.001) in the F/E relationship between the R group and NR group The F/E ratio was the most accurate (area under a curve of 0.87), when, we compare this value with HBI and CF as biomarkers of response to TNF. Conclusion The anti-TNF treatment allows partial restoration of the intestinal microbiota in responders with a tendency towards eubiosis, with respect to non-responders. The determination of F. prausnitzii/E. coli ratio can provide a reliable indicator of response to anti-TNF treatment in Crohn’s disease.

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

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.

scholarly journals P579 Randomised open-label controlled trial of ciprofloxacin/doxycycline/hydroxychloroquine combination compared with standard budesonide in active Crohn’s disease (APRICOT)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S487-S487
Author(s):  
J M Rhodes ◽  
S Subramanian ◽  
P Flanagan ◽  
G Horgan ◽  
K Martin ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Controlled Trial ◽  
Alternative Therapy ◽  
Open Label ◽  
Faecal Calprotectin ◽  
E Coli ◽  
Intention To Treat ◽  
Secondary Endpoints ◽  
Oral Ciprofloxacin

Abstract Background Mucosal E. coli are increased in Crohn’s disease (CD). They replicate within macrophages where they are inaccessible to penicillins and gentamicin. Hydroxychloroquine is successfully used together with doxycycline, typically for 12 months, to treat Whipple’s disease. It raises macrophage intra-vesicular pH and inhibits replication of bacteria , including E. coli that require an acid pH. Ciprofloxacin and doxycycline are also effective against E. coli replicating inside macrophages. Methods Adult patients with active CD (CDAI&gt;220 plus CRP≥5mg/l and/or faecal calprotectin &gt;250 μg/g) were randomised to receive either standard oral budesonide (Entocort CR 9mg/day for 8 weeks, 6mg/day for 2 weeks, 3mg/day for 2 weeks) or antibiotics/hydroxychloroquine (AB/HCQ) - oral ciprofloxacin 500mg bd, doxycycline 100mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by continuation of doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for a further 20 weeks. The use of anti-TNF in the previous 3 months was an exclusion. Primary endpoint parameters were remission at 10 weeks, remission maintained through to 24 weeks, and remission maintained through to 52 weeks. Secondary endpoints included remission and/or response (fall in CDAI of &gt;70) at 10 weeks and remission at 4 weeks. Patients who failed to respond by 10 weeks were invited to cross-over onto the alternative therapy. Results 59 patients were recruited across 8 sites, lower than target (100) because recruitment slowed due to widening access to biologics. Including cross-over, 39 patients received AB/HCQ and 39 received budesonide. No significant differences were seen comparing AB/HCQ with budesonide at 10, 24 or 52 weeks on either intention-to-treat or per-protocol analysis (see table). Withdrawals by 10 weeks due to adverse events were seen in 16 AB/HCQ, - including nausea (3), photosensitivity (2), Achilles pain (2) and activity of CD (4); and 7 budesonide. Although not significant when analysed per protocol, when patients on AB/HCQ who responded at 10 weeks and later remitted were included, 9/24 patients were in remission at 24 weeks and 4/23 at 52 weeks. No correlation was seen between response to AB/HCQ and ASCA/OmpC status. Conclusion The longer-term remissions seen in some patients receiving AB/HCQ are encouraging and a larger phase 3 study is justified.

scholarly journals Alterations of Gut Microbiota in Patients With Intestinal Tuberculosis That Different From Crohn’s Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Cong He ◽  
Huan Wang ◽  
Chen Yu ◽  
Chao Peng ◽  
Xu Shu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiota ◽  
Intestinal Tuberculosis ◽  
Alpha Diversity ◽  
16S Rrna Gene Sequencing ◽  
Short Chain Fatty Acids ◽  
Bacterial Invasion ◽  
Rrna Gene ◽  
Microbial Structure

Intestinal tuberculosis (ITB) and Crohn’s disease (CD) are chronic inflammatory bowel disorders that are associated with dysregulated mucosal immunity. The gut microbiota plays an important role in the regulation of host immunity and inflammatory response. Although mounting evidence has linked CD with the dysbiosis of gut microbiota, the characteristic profiles of mucosal bacteria in ITB remain unclear. The aim of this study was to assess the alterations of the gut microbiota in ITB and compare the microbial structure of ITB with CD. A total of 71 mucosal samples were collected from patients with ITB, CD, and healthy controls (HC), and then, 16S rRNA gene sequencing was performed. The overall composition of gut microbiota in ITB was strikingly different from HC, with the dominance of Proteobacteria and reduction of Firmicutes. Of note, the short-chain fatty acids (SCFAs)-producing bacteria such as Faecalibacterium, Roseburia, and Ruminococcus were decreased in ITB relative to HC, while Klebsiella and Pseudomonas were enriched. Multiple predictive functional modules were altered in ITB, including the over-representation of lipopolysaccharide biosynthesis, bacterial invasion of epithelial cells, and pathogenic Escherichia coli infection that can promote inflammation. Additionally, the microbial structure in CD was distinctly different from ITB, characterized by lower alpha diversity and increased abundance of Bacteroides, Faecalibacterium, Collinsella, and Klebsiella. These four bacterial markers distinguished ITB from CD with an area under the curve of 97.6%. This study established the compositional and functional perturbation of the gut microbiome in ITB and suggested the potential for using gut microbiota as biomarkers to differentiate ITB from CD.

scholarly journals Markers of dysbiosis in patients with ulcerative colitis and Crohn's disease

2019 ◽  
Vol 91 (4) ◽  
pp. 13-20 ◽  
Author(s):  
N A Danilova ◽  
S R Abdulkhakov ◽  
T V Grigoryeva ◽  
M I Markelova ◽  
I Yu Vasilyev ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiota ◽  
Diversity Index ◽  
Alpha Diversity ◽  
Short Chain Fatty Acids ◽  
Reference Database ◽  
Fecal Samples ◽  
Coa Transferase

The results of recent studies indicate a significant role of gut microbiota in the pathogenesis of inflammatory bowel diseases (IBD). The aim of the study was to study the taxonomic and functional composition of the gut microbiota in ulcerative colitis (UC) and Crohn's disease (CD) patients to identify key markers of dysbiosis in IBD. Materials and methods. Fecal samples obtained from 95 IBD patients (78 UC and 17 CD) as well as 96 healthy volunteers were used for whole-genome sequencing carried out on the SOLiD 5500 W platform. Taxonomic profiling was performed by aligning the reeds, not maped on hg19, on MetaPhlAn2 reference database. Reeds were mapped using the HUNAnN2 algorithm to the ChocoPhlAn database to assess the representation of microbial metabolic pathways. Short-chain fatty acids (SCFA) level were measured in fecal samples by gas-liquid chromatographic analysis. Results and discussion. Changes in IBD patients gut microbiota were characterized by an increase in the representation of Proteobacteria and Bacteroidetes phyla bacteria and decrease in the number of Firmicutes phylum bacteria and Euryarchaeota phylum archaea; a decrease in the alpha-diversity index, relative representation of butyrate-producing, hydrogen-utilizing bacteria, and Methanobrevibacter smithii; increase in the relative representation of Ruminococcus gnavus in UC and CD patients and Akkermansia muciniphila in CD patients. Reduction of Butyryl-CoA: acetate CoA transferase gene relative representation in CD patients, decrease of absolute content of SCFA total number as well as particular SCFAs and main SCFAs ratio in IBD patients may indicate inhibition of functional activity and number of anaerobic microflora and/or an change in SCFA utilization by colonocytes. Conclusion: the revealed changes can be considered as typical signs of dysbiosis in IBD patients and can be used as potential targets for IBD patients personalized treatment development.

The Order in Which Antibiotics are Administered Affects the Fitness Costs of Adherent-Invasive E. coli (AIEC) Strains

2019 ◽  
Author(s):  
Jordan B Gregg
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Agar Plate ◽  
Sequential Therapy ◽  
Negative Control ◽  
Clinical Settings ◽  
Fitness Costs ◽  
Inflammatory Gene Expression ◽  
E Coli

AIEC-LF82 is a strain of bacteria that is surmised to have a role in causing IBD and Crohn’s disease by activating pro-inflammatory gene expression in organisms. Using antibiotics via combination therapy has been a technique used in clinical settings in an attempt to treat the strains, however, the attempts have not been that effective nor efficient in terms of completely halting the growth and colonization of AIEC to treat IBD and Crohn's disease patients. Research has shown that regarding hindering or preventing the colonization bacterial colonies, sequential therapy tends to be more effective and time-efficient than combination therapy, with fewer adverse effects. To test if this is also the case with the AIEC-LF82 strain of bacteria, I first tested AIEC’s response to combination therapy using the Penicillin-Streptomycin, Kanamycin-Chloramphenicol, antimicrobial peptide (AMP), Kanamycin, SPE phase and LB agar plates, all of which were experimental plates other than the LB agar plate that acted as the negative control. I then tested AIEC-LF82’s response to sequential therapy using the LB+ Kan + Spe, LB + AMP + Spe, LB+ Kan/Cam + Spe, LB + P/S + Spe, LB + P/S + Kan and LB + P/S + AMP and one LB agar plate acting as the negative control. The only differences between sets a and b were the order in which antibiotics were administered in the six aforementioned treatment sets. Ultimately, I found that set b of sequential therapy, strong-weak antibiotic treatments, was the most effective treatment but that set a regarding sequential therapy was actually the least effective of all of the treatments. In conclusion, using strong-weak sequential antibiotic therapy treatments appears to be a potentially promising option to treat patients suffering from Crohn's disease and IBD.

scholarly journals Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn’s Disease

2020 ◽  
Author(s):  
Lina Y Alkaissi ◽  
Martin E Winberg ◽  
Stéphanie DS Heil ◽  
Staffan Haapaniemi ◽  
Pär Myrelid ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ex Vivo ◽  
Ussing Chambers ◽  
E Coli ◽  
Follicle Associated Epithelium ◽  
Vitro Model ◽  
Set Up

Abstract Background The first visible signs of Crohn’s disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human α-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P &lt; 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P &lt; 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P &lt; 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.

scholarly journals Heteropolysaccharides from S. cerevisiae show anti-adhesive properties against E. coli associated with Crohn’s disease

2021 ◽  
pp. 118415
Author(s):  
Adeline Sivignon ◽  
Shin-Yi Yu ◽  
Nathalie Ballet ◽  
Pascal Vandekerckove ◽  
Nicolas Barnich ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adhesive Properties ◽  
E Coli

scholarly journals Role of Probiotics and Their Metabolites in Inflammatory Bowel Diseases (IBDs)

2021 ◽  
Vol 12 (1) ◽  
pp. 56-66
Author(s):  
Toumi Ryma ◽  
Arezki Samer ◽  
Imene Soufli ◽  
Hayet Rafa ◽  
Chafia Touil-Boukoffa
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Symptoms ◽  
Therapeutic Potential ◽  
Short Chain Fatty Acids ◽  
Active Metabolites ◽  
Complex Disorders ◽  
Inflammatory Bowel

Inflammatory Bowel Disease (IBD) is a term used to describe a group of complex disorders of the gastrointestinal (GI) tract. IBDs include two main forms: Crohn’s Disease (CD) and Ulcerative Colitis (UC), which share similar clinical symptoms but differ in the anatomical distribution of the inflammatory lesions. The etiology of IBDs is undetermined. Several hypotheses suggest that Crohn’s Disease and Ulcerative Colitis result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. While there is no cure for IBDs, most common treatments (medication and surgery) aim to reduce inflammation and help patients to achieve remission. There is growing evidence and focus on the prophylactic and therapeutic potential of probiotics in IBDs. Probiotics are live microorganisms that regulate the mucosal immune system, the gut microbiota and the production of active metabolites such as Short-Chain Fatty Acids (SCFAs). This review will focus on the role of intestinal dysbiosis in the immunopathogenesis of IBDs and understanding the health-promoting effects of probiotics and their metabolites.

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