scholarly journals Systemic Macrophage Depletion Inhibits Helicobacter bilis-Induced Proinflammatory Cytokine-Mediated Typhlocolitis and Impairs Bacterial Colonization Dynamics in a BALB/cRag2−/−Mouse Model of Inflammatory Bowel Disease

2012 ◽  
Vol 80 (12) ◽  
pp. 4388-4397 ◽  
Author(s):  
Sureshkumar Muthupalani ◽  
Zhongming Ge ◽  
Yan Feng ◽  
Barry Rickman ◽  
Melissa Mobley ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Quantitative Pcr ◽  
Bowel Disease ◽  
Bacterial Colonization ◽  
Inbred Mice ◽  
Saline Control ◽  
Content Type ◽  
Immunodeficient Mice ◽  
Helicobacter Bilis ◽  
Inflammatory Bowel

ABSTRACTHelicobacter bilis, an enterohepatic helicobacter, is associated with chronic hepatitis in aged immunocompetent inbred mice and inflammatory bowel disease (IBD) in immunodeficient mice. To evaluate the role of macrophages inH. bilis-induced IBD,Rag2−/−BALB/c or wild-type (WT) BALB/c mice were either sham dosed or infected withH. bilisMissouri strain under specific-pathogen-free conditions, followed by an intravenous injection of a 0.2-ml suspension of liposomes coated with either phosphate-buffered saline (control) or clodronate (a macrophage depleting drug) at 15 weeks postinfection (wpi). At 16 wpi, the ceca ofH. bilis-infectedRag2−/−mice treated with control liposomes had significantly higher histopathological lesional scores (for cumulative typhlitis index, inflammation, edema, epithelial defects, and hyperplasia) and higher counts of F4/80+macrophages and MPO+neutrophils compared toH. bilis-infectedRag2−/−mice treated with clodronate liposomes. In addition, cecal quantitative PCR analyses revealed a significant suppression in the expression of macrophage-related cytokine genes, namely,Tnfa,Il-1β,Il-10,Cxcl1, andiNos, in the clodronate-treatedH. bilis-infectedRag2−/−mice compared to theH. bilis-infectedRag2−/−control mice. Finally, cecal quantitative PCR analyses also revealed a significant reduction in bacterial colonization in the clodronate-treatedRag2−/−mice. Taken together, our results suggest that macrophages are critical inflammatory cellular mediators for promotingH. bilis-induced typhlocolitis in mice.

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 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 Antibiotics for Treatment of Clostridium difficile Infection in Hospitalized Patients with Inflammatory Bowel Disease

2014 ◽  
Vol 58 (9) ◽  
pp. 5054-5059 ◽  
Author(s):  
Henry A. Horton ◽  
Seper Dezfoli ◽  
Dror Berel ◽  
Julianna Hirsch ◽  
Andrew Ippoliti ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Clostridium Difficile ◽  
Length Of Stay ◽  
Bowel Disease ◽  
Standard Of Care ◽  
Inclusion Criteria ◽  
Content Type ◽  
Lengths Of Stay ◽  
Inflammatory Bowel

ABSTRACTPatients with inflammatory bowel disease (IBD), namely ulcerative colitis (UC) and Crohn's disease (CD), have worse outcomes withClostridium difficileinfection (CDI), including increased readmissions, colectomy, and death. Oral vancomycin is recommended for the treatment of severe CDI, while metronidazole is the standard of care for nonsevere infection. We aimed to assess treatment outcomes of CDI in IBD. We conducted a retrospective observational study of inpatients with CDI and IBD from January 2006 through December 2010. CDI severity was assessed using published criteria. Outcomes included readmission for CDI within 30 days and 12 weeks, length of stay, colectomy, and death. A total of 114 patients met inclusion criteria (UC, 62; CD, 52). Thirty-day readmissions were more common among UC than CD patients (24.2% versus 9.6%;P= 0.04). Same-admission colectomy occurred in 27.4% of UC patients and 0% of CD patients (P< 0.01). Severe CDI was more common among UC than CD patients (32.2% versus 19.4%;P= 0.12) but not statistically significant. Two patients died from CDI-associated complications (UC, 1; CD, 1). Patients with UC and nonsevere CDI had fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen compared to those treated with metronidazole (30-day readmissions, 31.0% versus 0% [P= 0.04]; length of stay, 13.62 days versus 6.38 days [P= 0.02]). Patients with UC and nonsevere CDI have fewer readmissions and shorter lengths of stay when treated with a vancomycin-containing regimen relative to those treated with metronidazole alone. Patients with ulcerative colitis and CDI should be treated with vancomycin.

scholarly journals Pyoderma Gangrenosum as the Initial Presentation of Inflammatory Bowel Disease

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S51-S51
Author(s):  
S S Karimi ◽  
G Guzman
Keyword(s):  
Inflammatory Bowel Disease ◽  
Lower Extremity ◽  
Pyoderma Gangrenosum ◽  
Crohn Disease ◽  
Lupus Erythematosus ◽  
Bowel Disease ◽  
Bacterial Colonization ◽  
Neutrophilic Dermatosis ◽  
Tissue Destruction ◽  
Inflammatory Bowel

Abstract Introduction/Objective Pyoderma gangrenosum is a neutrophilic dermatosis, commonly associated with arthritis, psoriasis, and systemic lupus erythematosus. It is also an aggressive manifestation of extra-intestinal inflammatory bowel disease affecting less than 5% of patients with ulcerative colitis and Crohn disease. We present a case of pyoderma gangrenosum as an initial and rapidly progressive manifestation of Crohn disease. Methods A 35-year-old man presented with fecal urgency, periumbilical pain, and frequent diarrhea, with stool cultures revealing no infectious etiology. Colonoscopy demonstrated active inflammatory bowel disease consistent with Crohn disease. Concurrently, patient developed an ulcer on right lower extremity not otherwise contributed to history of trauma or injury. Biopsy of right lower extremity ulcer revealed histopathologic findings consistent with pyoderma gangrenosum. Despite medical management, and prolonged use of wound care and wound vac, patient’s non-healing ulcer continued to geographically expand, resulting in ankle contracture. A right below the knee amputation was performed and amputation specimen was sent to pathology for further diagnostic evaluation. Results Gross examination revealed an extensive cutaneous ulcer measuring 22.1cm x 11.7cm x 0.3cm and involving the anterior medial aspect of the right lower extremity with medial and posterior extension down to the dorsum of the foot with broad deep tissue destruction and exposure of fascia and tendon. Microscopic examination revealed severe ulceration, suppurative necrosis, superficial and deep vasculitis confined to the ulcer bed. Surrounding soft tissue revealed chronic myopathic changes secondary to ischemia. Foci of commensal filamentous gram-positive bacterial colonization in a nidus of necrosis were also identified. The inflammatory pattern involved predominantly neutrophils with weak recruitment of other inflammatory cells, consistent with pyoderma gangrenosum. Conclusion This case highlights the debilitating extent of Crohn disease, its detrimental effects on the patient’s quality of life, and the diagnostic and treatment challenges it poses to clinicians in managing Crohn disease and its complications.

scholarly journals Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

2016 ◽  
Vol 30 (1) ◽  
pp. 191-231 ◽  
Author(s):  
Lauren E. Hudson ◽  
Sarah E. Anderson ◽  
Anita H. Corbett ◽  
Tracey J. Lamb
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Rational Design ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Inflammatory Disorder ◽  
Fecal Microbiota Transplant ◽  
Content Type ◽  
Inflammatory Bowel

SUMMARY Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases.

scholarly journals Genome-Wide Association Study Reveals Genetic Link between Diarrhea-Associated Entamoeba histolytica Infection and Inflammatory Bowel Disease

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Genevieve L. Wojcik ◽  
Chelsea Marie ◽  
Mayuresh M. Abhyankar ◽  
Nobuya Yoshida ◽  
Koji Watanabe ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Association Study ◽  
Entamoeba Histolytica ◽  
Bowel Disease ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Content Type ◽  
Amebic Dysentery ◽  
Genome Wide ◽  
Inflammatory Bowel

ABSTRACT Entamoeba histolytica is the etiologic agent of amebic dysentery, though clinical manifestation of infection is highly variable ranging from subclinical colonization to invasive disease. We hypothesize that host genetics contribute to the variable outcomes of E. histolytica infection; thus, we conducted a genome-wide association study (GWAS) in two independent birth cohorts of Bangladeshi infants monitored for susceptibility to E. histolytica disease in the first year of life. Children with at least one diarrheal episode positive for E. histolytica (cases) were compared to children with no detectable E. histolytica infection in the same time frame (controls). Meta-analyses under a fixed-effect inverse variance weighting model identified multiple variants in a region of chromosome 10 containing loci associated with symptomatic E. histolytica infection. An intergenic insertion between CREM and CCNY (rs58000832) achieved genome-wide significance (P value from meta-analysis [Pmeta] = 6.05 × 10−9), and each additional risk allele of rs58000832 conferred 2.42 increased odds of a diarrhea-associated E. histolytica infection. The most strongly associated single nucleotide polymorphism (SNP) within a gene was in an intron of CREM (rs58468612; Pmeta = 8.94 × 10−8), which has been implicated as a susceptibility locus for inflammatory bowel disease (IBD). Gene expression resources suggest associated loci are related to the lower expression of CREM. Increased CREM expression is also observed in early E. histolytica infection. Further, CREM−/− mice were more susceptible to E. histolytica amebic colitis. These genetic associations reinforce the pathological similarities observed in gut inflammation between E. histolytica infection and IBD. IMPORTANCE Diarrhea is the second leading cause of death for children globally, causing 760,000 deaths each year in children less than 5 years old. Amebic dysentery contributes significantly to this burden, especially in developing countries. The identification of host factors that control or enable enteric pathogens has the potential to transform our understanding of disease predisposition, outcomes, and treatments. Our discovery of the transcriptional regulator cAMP-responsive element modulator (CREM) as a genetic modifier of susceptibility to amebic disease has implications for understanding the pathogenesis of other diarrheal infections. Further, emerging evidence for CREM in IBD susceptibility suggests that CREM is a critical regulator of enteric inflammation and may have broad therapeutic potential as a drug target across intestinal inflammatory diseases.

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.

Helicobacter-induced inflammatory bowel disease in IL-10- and T cell-deficient mice

2001 ◽  
Vol 281 (3) ◽  
pp. G764-G778 ◽  
Author(s):  
Andrew Burich ◽  
Robert Hershberg ◽  
Kim Waggie ◽  
Weiping Zeng ◽  
Thea Brabb ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Bowel Disease ◽  
Wild Type ◽  
Immunodeficient Mice ◽  
Inflammatory Bowel ◽  
Rag 1

Inflammatory bowel disease (IBD) is thought to result from a dysregulated mucosal immune response to luminal microbial antigens, with T lymphocytes mediating the colonic pathology. Infection with Helicobacter spp has been reported to cause IBD in immunodeficient mice, some of which lack T lymphocytes. To further understand the role of T cells and microbial antigens in triggering IBD, we infected interleukin (IL)-10−/−, recombinase-activating gene (Rag)1−/−, T-cell receptor (TCR)-α−/−, TCR-β−/−, and wild-type mice with Helicobacter hepaticus or Helicobacter bilis and compared the histopathological IBD phenotype. IL-10−/−mice developed severe diffuse IBD with either H. bilis or H. hepaticus, whereas Rag1−/−, TCR-α−/−, TCR-β−/−, and wild-type mice showed different susceptibilities to Helicobacter spp infection. Proinflammatory cytokine mRNA expression was increased in the colons of Helicobacter-infected IL-10−/−and TCR-α−/−mice with IBD. These results confirm and extend the role of Helicobacter as a useful tool for investigating microbial-induced IBD and show the importance, but not strict dependence, of T cells in the development of bacterial-induced IBD.

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