scholarly journals Escherichia coliPathobionts Associated with Inflammatory Bowel Disease

2019 ◽  
Vol 32 (2) ◽  
Author(s):  
Hengameh Chloé Mirsepasi-Lauridsen ◽  
Bruce Andrew Vallance ◽  
Karen Angeliki Krogfelt ◽  
Andreas Munk Petersen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Cell Activation ◽  
Immune Cell ◽  
Intestinal Biopsy ◽  
Content Type ◽  
E Coli ◽  
Immune Cell Activation ◽  
Facilitative Role ◽  
Inflammatory Bowel

SUMMARYGut bacteria play a key role in initiating and maintaining the inflammatory process in the gut tissues of inflammatory bowel disease (IBD) patients, by supplying antigens or other stimulatory factors that trigger immune cell activation. Changes in the composition of the intestinal microbiota in IBD patients compared to that in healthy controls and a reduced diversity of intestinal microbial species are linked to the pathogenesis of IBD. Adherent invasiveEscherichia coli(AIEC) has been linked to Crohn’s disease (CD) patients, while diffusely adherentE. coli(DAEC) has been associated with ulcerative colitis (UC). Bacteriological analysis of intestinal biopsy specimens and fecal samples from IBD patients shows an increased number ofE. colistrains belonging to the B2 phylogenetic group, which are typically known as extraintestinal pathogenicE. coli(ExPEC). Results from studies of both cell cultures and animal models reveal pathogenic features of theseE. colipathobionts, which may link them to IBD pathogenesis. This suggests that IBD-associatedE. colistrains play a facilitative role during IBD flares. In this review, we explain IBD-associatedE. coliand its role in IBD pathogenesis.

scholarly journals Microevolution infimHGene of Mucosa-Associated Escherichia coli Strains Isolated from Pediatric Patients with Inflammatory Bowel Disease

2012 ◽  
Vol 80 (4) ◽  
pp. 1408-1417 ◽  
Author(s):  
Valerio Iebba ◽  
Maria Pia Conte ◽  
Maria Stefania Lepanto ◽  
Giovanni Di Nardo ◽  
Floriana Santangelo ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Pediatric Patients ◽  
Environmental Changes ◽  
Mucosal Inflammation ◽  
Content Type ◽  
E Coli ◽  
Inflammatory Bowel ◽  
Tract Infections

ABSTRACTSeveral studies reported increased numbers of mucosa-associatedEscherichia colistrains in patients with inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC). The majority ofE. colistrains possess type 1 fimbriae, whose tip fibrillum protein, FimH, naturally undergoes amino acid replacements, an important process in the adaptation of commensalE. colistrains to environmental changes, like those observed in IBD and urinary tract infections. In this study, we analyzed mutational patterns in thefimHgene of 52 mucosa-associatedE. colistrains isolated from IBD and non-IBD pediatric patients, in order to investigate microevolution of this genetic trait. FimH-positive strains were also phylogenetically typed and tested for their adhesive ability on Caco-2 cells. Specific FimH alleles for each grouping feature were found. Mutations G66S and V27A were related to CD, while mutations A242V, V163A, and T74I were attributed to UC. Otherwise, the G66S, N70S, and S78N mutations were specifically attributed to B2/D phylogroups. The N70S and A119V mutations were related to adhesiveE. colistrains. Phylogroup B2, adhesive, and IBDE. colistrains showed a higher site substitution rate (SSR) in thefimHgene, together with a higher number of mutations. The degree of naïve mucosal inflammation was related to specific FimH alleles. Moreover, we could suggest that the V27A mutation is pathoadaptive for the CD intestinal habitat, while we could also suggest that both the N70S and S78N mutations are related to the more virulentE. coliB2 phylogroup. In conclusion, we found some FimH variants that seem to be more involved than others in the evolution of IBD pathogenesis.

scholarly journals Targeting Immune Cell Metabolism in the Treatment of Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Vanessa Zaiatz Bittencourt ◽  
Fiona Jones ◽  
Glen Doherty ◽  
Elizabeth J Ryan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Metabolic Pathways ◽  
Cell Activation ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Critical Role ◽  
Mammalian Target Of Rapamycin ◽  
External Threats ◽  
Inflammatory Bowel

Abstract The cells of the immune system are highly dynamic, constantly sensing and adapting to changes in their surroundings. Complex metabolic pathways govern leukocytes’ ability to fine-tune their responses to external threats. Mammalian target of rapamycin complex 1 and hypoxia inducible factor are important hubs of these pathways and play a critical role coordinating cell activation and proliferation and cytokine production. For this reason, these molecules are attractive therapeutic targets in inflammatory disease. Insight into perturbations in immune cell metabolic pathways and their impact on inflammatory bowel disease (IBD) progression are starting to emerge. However, it remains to be determined whether the aberrations in immune metabolism that occur in gut resident immune cells contribute to disease pathogenesis or are reflected in the peripheral blood of patients with IBD. In this review, we explore what is known about the metabolic profile of T cells, monocytes, macrophages, dendritic cells, and natural killer cells in IBD and discuss the potential of manipulating immune cell metabolism as a novel approach to treating IBD.

scholarly journals Mucosa-Associated Faecalibacterium prausnitzii Phylotype Richness Is Reduced in Patients with Inflammatory Bowel Disease

2015 ◽  
Vol 81 (21) ◽  
pp. 7582-7592 ◽  
Author(s):  
Mireia Lopez-Siles ◽  
Margarita Martinez-Medina ◽  
Carles Abellà ◽  
David Busquets ◽  
Miriam Sabat-Mir ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
Bowel Disease ◽  
Denaturing Gradient Gel Electrophoresis ◽  
Gastrointestinal Disease ◽  
Rrna Gene ◽  
Content Type ◽  
Faecalibacterium Prausnitzii ◽  
Inflammatory Bowel

ABSTRACTFaecalibacterium prausnitziidepletion in intestinal diseases has been extensively reported, but little is known about intraspecies variability. This work aims to determine if subjects with gastrointestinal disease host mucosa-associatedF. prausnitziipopulations different from those hosted by healthy individuals. A new species-specific PCR-denaturing gradient gel electrophoresis (PCR-DGGE) method targeting the 16S rRNA gene was developed to fingerprintF. prausnitziipopulations in biopsy specimens from 31 healthy control (H) subjects and 36 Crohn's disease (CD), 23 ulcerative colitis (UC), 6 irritable bowel syndrome (IBS), and 22 colorectal cancer (CRC) patients. The richness ofF. prausnitziisubtypes was lower in inflammatory bowel disease (IBD) patients than in H subjects. The most prevalent operational taxonomic units (OTUs) consisted of four phylotypes (OTUs with a 99% 16S rRNA gene sequence similarity [OTU99]), which were shared by all groups of patients. Their distribution and the presence of some disease-specificF. prausnitziiphylotypes allowed us to differentiate the populations in IBD and CRC patients from that in H subjects. At the level of a minimum similarity of 97% (OTU97), two phylogroups accounted for 98% of the sequences. Phylogroup I was found in 87% of H subjects but in under 50% of IBD patients (P= 0.003). In contrast, phylogroup II was detected in >75% of IBD patients and in only 52% of H subjects (P= 0.005). This study reveals that even though the main members of theF. prausnitziipopulation are present in both H subjects and individuals with gut diseases, richness is reduced in the latter and an altered phylotype distribution exists between diseases. This approach may serve as a basis for addressing the suitability ofF. prausnitziiphylotypes to be quantified as a putative biomarker of disease and depicting the importance of the loss of these subtypes in disease pathogenesis.

scholarly journals Hyperactive chemotaxis contributes to anti-TNFα treatment resistance in inflammatory bowel disease

2021 ◽  
Author(s):  
Tung On Yau ◽  
Jayakumar Vadakekolathu ◽  
Gemma Ann Foulds ◽  
Guodong Du ◽  
Christos Polytarchou ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Immune Cell ◽  
Treatment Resistance ◽  
Enrichment Analysis ◽  
Cell Populations ◽  
Treated Animal ◽  
Necrosis Factor Alpha ◽  
Potential Biomarker ◽  
Inflammatory Bowel

Background & Aims Anti-tumour necrosis factor-alpha (anti-TNFα) agents have been used for inflammatory bowel disease (IBD), however, it has up to 30% non-response rate. Identifying molecular pathways and finding reliable diagnostic biomarkers for patient response to anti-TNFα treatment are clearly needed. Methods Publicly available transcriptomic data from IBD patients receiving anti-TNFα therapy was systemically collected and integrated. In silico flow cytometry approaches and MetaScape were applied to evaluate immune cell populations and to perform gene enrichment analysis, respectively. Genes identified within enrichment pathways validated in neutrophils were tracked in an anti TNFα-treated animal model (with lipopolysaccharide (LPS)-induced inflammation). The receiver operating characteristic (ROC) curve was applied to all genes to identify the best prediction biomarkers. Results A total of 449 samples were retrieved from control, baseline and after primary anti-TNFα therapy or placebo. No statistically significant differences were observed between anti-TNFα treatment responders and non-responders at baseline in immune microenvironment scores. Neutrophils, endothelial and B cell populations were higher in baseline non-responders and chemotaxis pathways may contribute to the treatment resistance. Genes related to chemotaxis pathways were significantly up-regulated in LPS-induced neutrophils but no statistically significant changes were observed in neutrophils treated with anti-TNFα. Interleukin 13 receptor subunit alpha 2 (IL13RA2) is the best predictor (ROC: 80.7%, 95% CI: 73.8% - 87.5%) with a sensitivity of 68.13% and specificity of 84.93%, and significantly higher in non-responders compared to responders (p < 0.0001). Conclusions Hyperactive chemotaxis influences responses to anti TNFα treatment and IL13RA2 is a potential biomarker to predict anti-TNFα treatment response.

scholarly journals OP33 Multi-omics analysis reveals specific bio-geographical and functional characteristics in inflammatory bowel disease intestinal mucosa

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S031-S034
Author(s):  
N Maimon ◽  
S Gerassy-Vainberg ◽  
H Bar-Yosef ◽  
A Alpert ◽  
E Starosvetsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Immune Cell ◽  
Response To Therapy ◽  
Anatomical Location ◽  
Specific Cell ◽  
Cell Composition ◽  
Dominant Feature ◽  
Inflammatory Bowel

Abstract Background Anatomical location and extent of disease are main factors that affect inflammatory bowel disease (IBD) course and prognosis. No explanation is available for segmental intestinal involvement in either Crohn’s disease (CD) or ulcerative colitis (UC), or for selective segmental response to therapy or disease complications. Therefore, studying the cellular composition of different intestinal segments may provide pathophysiological insights into these phenomena. Methods We compared location-specific cell composition and function by Cytometry Time-of-Flight (CyTOF), gene expression and single-cell (sc) RNAseq data obtained from 3 independent cohorts of healthy donors and IBD patients during remission and flare-ups. Using CyTOF data (n = 38 biopsies), we built a high-resolution screening of immune cell behaviour along the intestine. We validated the findings with gene expression data of 370 samples, and expanded screening resolution by computational methodologies. We then tested a specific pathway in scRNAseq data (n = 10 paired biopsies from 5 patients) and validated its significance by cell-specific Significance Analysis of Microarrays (csSAM). Results We found a location along the intestine to be a dominant feature determining immune and non-immune cell composition. We observed that inflammation reduced anatomic segregation beyond cell infiltration, and decreased the ability to cope with oxidative stress. An upregulated IL-6 pathway in T regulatory cells in UC patients was recognised as sigmoid-specific compared with known inflammatory IL-6 roles in macrophages, as seen in the right colon. This observation may be linked to colonic perforations associated with anti-IL-6R treatment. Suppressor of cytokine signalling 3 (SOCS3) may control IL-6 location-specific action. Conclusion Our study displays a unique and comprehensive cell map of IBD in a location-specific context, providing potential explanations to unexplained clinical phenomena. These observations may allow to tailor therapies to affected areas with improved therapeutic index and efficacy.

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