scholarly journals Intestinal Bacteria Composition and Translocation of Bacteria in Inflammatory Bowel Disease

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0170034 ◽  
Author(s):  
Spyros Vrakas ◽  
Konstantinos C. Mountzouris ◽  
George Michalopoulos ◽  
George Karamanolis ◽  
George Papatheodoridis ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Bacteria ◽  
Inflammatory Bowel ◽  
Translocation Of Bacteria

scholarly journals Bacteroides ovatus as the Predominant Commensal Intestinal Microbe Causing a Systemic Antibody Response in Inflammatory Bowel Disease

2002 ◽  
Vol 9 (1) ◽  
pp. 54-59 ◽  
Author(s):  
Shin Saitoh ◽  
Satoshi Noda ◽  
Yuji Aiba ◽  
Atsushi Takagi ◽  
Mitsuo Sakamoto ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Antibody Response ◽  
Bowel Disease ◽  
Bacterial Species ◽  
Serum Antibody ◽  
Intestinal Bacteria ◽  
Intestinal Microbes ◽  
Inflammatory Bowel ◽  
Bacteroides Ovatus

ABSTRACT To clarify what bacterial species of commensal intestinal microbes are recognized as the antigens that induce a serum antibody response in patients with inflammatory bowel disease (IBD), 72 subjects consisting of 12 Crohn’s disease patients, 30 ulcerative colitis patients, and 30 healthy volunteers were examined for their titers of serum antibody to these intestinal bacteria. In IBD patients, as a result, significant elevations of both the immunoglobulin G (IgG) and IgA titers to Bacteroides ovatus were found. Immunoblotting showed that a definite 19.5-kDa band of B. ovatus was bound to the serum antibody raised in IBD patients. It was thus concluded that B. ovatus causes serum antibody responses in IBD patients, and a 19.5-kDa molecule of this bacterium appears to be the responsible antigen, although the role of this event in pathogenesis remains unclear.

Intestinal Microbiota: From Inflammatory Bowel Disease to Bone Marrow Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-50-SCI-50
Author(s):  
Ernst Holler ◽  
Peter Oefner ◽  
Karin Landfried ◽  
Josef Koestler ◽  
Elisabeth Huber ◽  
...  
Keyword(s):  
Risk Factors ◽  
Inflammatory Bowel Disease ◽  
16S Rrna ◽  
Antimicrobial Peptides ◽  
Intestinal Microbiota ◽  
Bowel Disease ◽  
Genetic Risk ◽  
Intestinal Bacteria ◽  
Intestinal Gvhd ◽  
Inflammatory Bowel

Abstract Abstract SCI-50 A dysregulated interaction of the intestinal microbiome with the patient's innate and adaptive immune response seems to contribute to both inflammatory bowel disease (IBD) and intestinal graft-versus-host disease (GVHD). In IBD, polymorphisms within genes involved in antibacterial defense have been identified as genetic risk factors, such as in NOD2, a gene coding for an intracytoplasmatic receptor for muramyldipeptide, a bacterial cell wall compound, or in ATG16L1, a gene involved in autophagy of bacteria. Disruption of these genes results in dysfunction of Paneth cells, which are the major producers of antimicrobial peptides such as defensins. They thereby protect epithelial stem cells from invasion and destruction by intestinal bacteria and contribute to homeostasis of the intestinal microbiota. Based on van Bekkum's finding of the absence of intestinal GVHD in germ-free mice and the central role of TNF-α release in intestinal GVHD, our group focused on the microbiome/host interactions in GVHD. In prospective studies on genetic risk factors of GVHD, single-nucleotide polymorphisms (SNPs) of NOD2 and also ATG16L1 turned out to be predictive for severe intestinal GVHD and IBD. In addition, however, pulmonary complications revealed an altered production of antibacterial peptides in the presence of NOD2 SNPs. We therefore speculated that human intestinal GVHD similar to IBD might be associated with disruption of the bacterial diversity. We applied metabolomic analyses of metabolites processed in the presence of intestinal bacteria as well as 16s rRNA sequencing to serial urine and stool samples from patients receiving allogeneic stem cell transplantation. Urinary indoxylsulfate (IS) levels dropped during the period of decontamination and use of antibiotics during the neutropenic period but recovered to pretransplant levels in patients with uneventful courses. In contrast, patients developing intestinal GVHD had significantly lower IS levels, suggesting suppression of bacterial diversity in intestinal GVHD. Analysis of 16s rRNA confirmed a major shift from an almost normal distribution pretransplant toward a loss of Firmicutes and an increase in enterococci in the neutropenic period. Although this shift may be partially explained by antibiotic decontamination or treatment during this period that was given to all patients, those patients with subsequent development of intestinal GVHD showed a significantly stronger shift toward enterococci in this period (p=0.002). Whereas patients without intestinal GVHD returned to pretransplant diversity thereafter, predominance of enteroccal flora persisted in patients with intestinal GVHD. These data indicate early microbiome changes in patients with intestinal GVHD. We are currently addressing potential Paneth cell damage and loss of antimicrobial peptides as an underlying mechanism. In summary, our data confirm the relevance of the close interaction of microbiome and host defense in GVHD patients, similar to what has been described in IBD, and raise new options for immune system modulation by restoration of intestinal tolerance. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Assessment of Causal Direction Between Gut Microbiota and Inflammatory Bowel Disease: A Mendelian Randomization Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zi-Jia Zhang ◽  
Hong-Lei Qu ◽  
Na Zhao ◽  
Jing Wang ◽  
Xiu-Yan Wang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Pathogenic Bacteria ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Intestinal Bacteria ◽  
Social Program ◽  
Significance Level ◽  
Inflammatory Bowel

BackgroundRecent studies have shown that the gut microbiota is closely related to the pathogenesis of Inflammatory Bowel Disease (IBD), but the causal nature is largely unknown. The purpose of this study was to assess the causal relationship between intestinal bacteria and IBD and to identify specific pathogenic bacterial taxa via the Mendelian randomization (MR) analysis.Materials and MethodsMR analysis was performed on genome-wide association study (GWAS) summary statistics of gut microbiota and IBD. Specifically, the TwinsUK microbiota GWAS (N = 1,126 twin pairs) was used as exposure. The UK inflammatory bowel disease (UKIBD) and the Understanding Social Program (USP) study GWAS (N = 48,328) was used as discovery outcome, and the British IBD study (N = 35,289) was used as replication outcome. SNPs associated with bacteria abundance at the suggestive significance level (α = 1.0 × 10–5) were used as instrumental variables. Bacteria were grouped into families and genera.ResultsIn the discovery sample, a total of 30 features were available for analysis, including 15 families and 15 genera. Three features were nominally significant, including one family (Verrucomicrobiaceae, 2 IVs, beta = −0.04, p = 0.05) and two genera (Akkermansia, 2 IVs, beta = 0.04, p = 0.05; Dorea, 2 IVs, beta = −0.07, p = 0.04). All of them were successfully replicated in the replication sample (Verrucomicrobiaceae and Akkermansia Preplication = 0.02, Dorea Preplication = 0.01) with consistent effect direction.ConclusionWe identified specific pathogenic bacteria features that were causally associated with the risk of IBD, thus offering new insights into the prevention and diagnosis of IBD.

scholarly journals Deleterious Genetic Variation Across the NOD Signaling Pathway Is Associated With Reduced NFKB Signaling Transcription and Upregulation of Alternative Inflammatory Transcripts in Pediatric Inflammatory Bowel Disease

2022 ◽  
Author(s):  
James J Ashton ◽  
Konstantinos Boukas ◽  
Imogen S Stafford ◽  
Guo Cheng ◽  
Rachel Haggarty ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Signaling Pathway ◽  
Bowel Disease ◽  
Intestinal Bacteria ◽  
Genomic Variation ◽  
Gene Score ◽  
Diagnostic Endoscopy ◽  
Pediatric Inflammatory Bowel Disease ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Background Inflammatory bowel disease may arise with inadequate immune response to intestinal bacteria. NOD2 is an established gene in Crohn’s disease pathogenesis, with deleterious variation associated with reduced NFKB signaling. We hypothesized that deleterious variation across the NOD2 signaling pathway impacts on transcription. Methods Treatment-naïve pediatric inflammatory bowel disease patients had ileal biopsies for targeted autoimmune RNA-sequencing and blood for whole exome sequencing collected at diagnostic endoscopy. Utilizing GenePy, a per-individual, per-gene score, genes within the NOD signaling pathway were assigned a quantitative score representing total variant burden. Where multiple genes formed complexes, GenePy scores were summed to create a “complex” score. Normalized transcript expression of 95 genes within this pathway was retrieved. Regression analysis was performed to determine the impact of genomic variation on gene transcription. Results Thirty-nine patients were included. Limited clustering of patients based on NOD signaling transcripts was related to underlying genomic variation. Patients harboring deleterious variation in NOD2 had reduced NOD2 (β = -0.702, P = 4.3 × 10-5) and increased NFKBIA (β = 0.486, P = .001), reflecting reduced NFKB signal activation. Deleterious variation in the NOD2-RIPK2 complex was associated with increased NLRP3 (β = 0.8, P = 3.1475 × 10-8) and TXN (β = -0.417, P = 8.4 × 10-5) transcription, components of the NLRP3 inflammasome. Deleterious variation in the TAK1-TAB complex resulted in reduced MAPK14 transcription (β = -0.677, P = 1.7 × 10-5), a key signal transduction protein in the NOD2 signaling cascade and increased IFNA1 (β = 0.479, P = .001), indicating reduced transcription of NFKB activators and alternative interferon transcription in these patients. Conclusions Data integration identified perturbation of NOD2 signaling transcription correlated with genomic variation. A hypoimmune NFKB signaling transcription response was observed. Alternative inflammatory pathways were activated and may represent therapeutic targets in specific patients.

scholarly journals Adrenomedullin: A Novel Therapeutic for the Treatment of Inflammatory Bowel Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1068
Author(s):  
Shinya Ashizuka ◽  
Toshihiro Kita ◽  
Haruhiko Inatsu ◽  
Kazuo Kitamura
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Intestinal Bacteria ◽  
Organ Protection ◽  
Inflammatory Cytokine Production ◽  
Inflammatory Bowel ◽  
Long Acting ◽  
And Function ◽  
Novel Therapeutic

Adrenomedullin (AM) is a bioactive peptide with various physiological functions, including vasodilation, angiogenesis, anti-inflammation, organ protection, and tissue repair. AM suppresses inflammatory cytokine production in the intestinal mucosa, improves vascular and lymphatic regeneration and function, mucosal epithelial repair, and immune function in the intestinal bacteria of animal models with intestinal inflammation. We have been promoting translational research to develop novel therapeutic agents for inflammatory bowel disease (IBD) using AM and have started clinical research for IBD patients since 2010. A multicenter clinical trial is currently underway in Japan for patients with refractory ulcerative colitis and Crohn’s disease. Moreover, since current AM administration is limited to continuous intravenous infusion, the development of a subcutaneous formulation using long-acting AM is underway for outpatient treatment.

Intestinal bacteria and inflammatory bowel disease

2009 ◽  
Vol 46 (1) ◽  
pp. 25-54 ◽  
Author(s):  
Sandra Macfarlane ◽  
Helen Steed ◽  
George T. Macfarlane
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Bacteria ◽  
Inflammatory Bowel

scholarly journals Evidence-based clinical practice guidelines for inflammatory bowel disease 2020

2021 ◽  
Author(s):  
Hiroshi Nakase ◽  
Motoi Uchino ◽  
Shinichiro Shinzaki ◽  
Minoru Matsuura ◽  
Katsuyoshi Matsuoka ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Intestinal Bacteria ◽  
General Term ◽  
Future Research ◽  
Evidence Based ◽  
Delphi Consensus ◽  
Number Of Patients ◽  
Inflammatory Bowel

AbstractInflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn’s disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment.

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