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Disease ⇒ Crohn’s disease {40000108}

Record Keys


Type:
Disease
Parent:[  ]
Definition:
Crohn’s disease

Details


Initialisation date:
2019-05-15
Other Terms:
Regional Enteritis, Granulomatous Ileitis, Granulomatous Ileocolitis

Links


Meta Information


MedDra ID:
10011401
MedDra Level:
pt
ICD:[  ]
Category:
Gastroenterology, Rheumatology
Zone:[  ]
Mechanism:[  ]

Notes:


- Fucose (type of Sugar) > 1,2-propanediol > AIEC (type of E. Coli) > Propionate > Inflamation of Gut wall
- Reducing of Fucose ( type of Sugar) may ameliorate the Inflammation of Crohn’s disease.

- In Crohn’s disease, there is increased abundance for degradation of glycosaminoglycans and B-vitamin biosynthesis.
- There is a decrease in abundance of methanogenesis , antimicrobial peptide response , and phosphatidylethanolamine biosynthesis. (1)

- Prior use of antibiotics is associated with a nearly 2 times increased risk of developing IBD compared with no prior use. (2)

- Patients with Crohn’s disease has significantly higher levels of the fungus Candida tropicalis and the bacteria Escherichia coli and Serratia marcescens than their healthy relatives.
-These three organisms interacted in a strategic way to form robust, pathogenic biofilms capable of driving intestinal inflammation (4)

- Electron microscopy showed that E. coli fuse to the C. tropicalis growths. Meanwhile S. marcescens make protein strings that somehow stabilize the biofilm. (5)

- Patients with Crohn NULLs disease showed significantly higher levels of the fungus Candida tropicalis and the bacteria Escherichia coli and Serratia marcescens than their healthy relatives. Further in vitro studies showed that these three organisms interacted "in a strategic way" to form robust, pathogenic biofilms capable of driving intestinal inflammation. (6)

- Patients with Crohn’s disease showed significantly higher levels of the fungus Candida tropicalis and the bacteria Escherichia coli and Serratia marcescens than their healthy relatives. Further in vitro studies showed that these three organisms interacted "in a strategic way" to form robust, pathogenic biofilms capable of driving intestinal inflammation. (13)

Shared Reference Notes


  • [1.1
    - The microbiome in the inflamed and proximal noninflamed ileal mucosa do not differ according to alpha diversity or beta diversity.
  • [1.2
    - Adherent-invasive E. coli (AIEC) are enriched in the intestinal microbiota of patients with Crohn’s disease (CD) and promote intestinal inflammation.
  • [1.3] [#Escherichia coli] [#Fecal Microbiota Transplantation
    - Comprehensive overview of functional dysbiosis in the gut microbiome during IBD activity showed increases in facultative anaerobes, such as E. coli which correlates with inflammation status, and decreases in obligate anaerobes, such as #Faecalibacterium prausnitzii and #Roseburia hominis -The results of the present study confirmed decreases in the abundance of Firmicutes and Bacteroidetes, increases in Enterobacteriaceae, Pasteurellaceae, and Veillonellaceae and the presence of Fusobacterium in stool samples of CD patients. - #Butyrate-producing bacteria are depleted in IBD patients, and probiotic treatment with these bacteria has therapeutic potential. - A higher proportion of #Lachnospiraceae in donor stool was associated with a higher success rate of FMT, and recipients that responded to FMT exhibited increases in #Butyrate-producing #Lachnospiraceae and Ruminococcaceae. - The reduced SCFA levels in patients with IBD result from lower abundance of SCFA-producing bacteria, especially those of the phylum Firmicutes. -- #Butyrate can act as an energy source for normal colon epithelial cells, promoting their proliferation, but can also inhibit proliferation and induce apoptosis.
  • [1.4] [#Multiple Sclerosis, #Rheumatoid Arthritis
    - Significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA.
  • [1.5
    - #Debaryomyces hansenii preferentially localized to and was abundant within incompletely healed intestinal wounds of mice and inflamed mucosal tissues of CD human subjects. - D. hansenii cultures from injured mice and inflamed CD tissues impaired colonic healing when introduced into injured conventionally raised or gnotobiotic mice. - Mechanistically, D. hansenii impaired mucosal healing through the myeloid cell–specific type 1 interferon–CCL5 axis.
  • [1.6] [#Inflamatory bowel disease
    - The blood–brain barrier allows the access of #Tryptophan. - In IBD, especially in CD patients, TRP metabolism increases; consequently, the amino acid levels are reduced with respect to normal healthy individuals, and these changes correlate with the gravity of the disease. - TRP undergoes two major metabolic host pathways, the #kynurenine (KYN) and #Serotonin (5-HT) biosynthetic pathways, and one microbial pathway to produce #Indole and its derivatives.
  • [1.7] [#Ulcerative Colitis] [#High-fiber diet
    - Long-term intake of fibers from fruit > protective against the development of CD, but not of UC
  • [1.8
    - Gut species found to be significantly depleted in CD compared to control include: #Faecalibacterium prausnitzii , #Roseburia inulinivorans and #Alistipes senegalensis. - While #Clostridium nexile and #Ruminococcus gnavus were found to be enriched.
  • - Microbial #Arginine and isoprene pathways were found at a higher relative abundance level in gut microbiome of Crohn’s disease.
  • - The oral microbe #Streptococcus salivarius was found to be enriched and of concordant strains in the gut and oral microbiome of Crohn’s disease subjects. This was more likely in CD subjects with higher Crohn’s Disease Activity Index and active disease status (Diarrhoea/abdominal pain/blood-in-stool/fever and fatigue).
  • [1.9
    - #Bacteroides vulgatus is both directly associated with Th17 immunity and has a higher abundance in active CD relative to non-IBD controls. - The increase of #Bacteroides vulgatus abundance in active CD can induce more Th17 cells that in turn might worsen IBD inflammation.
  • [#Escherichia coli] - Adherent-invasive E. coli (AIEC), > prevalent in up to half the individuals with Crohn’s Disease (CD) - Among the genes related to AIEC pathogenicity, fim has the potential to generate an inflammatory reaction from the intestinal epithelial cells and macrophages, as it interacts with TLR4, inducing the production of inflammatory cytokines independently of LPS.
  • [1.11] [#Condition of chronic stress
    - Stress-exposed mice > develop ileal dysbiosis, dominated by the expansion of #Enterobacteriaceae. - Stress-induced glucocorticoids promote > apoptosis of CD45+CD90+ cells that normally produce #IL-22, a cytokine that is essential for the maintenance of ileal mucosal barrier integrity. - Blockade of glucocorticoid signaling or administration of recombinant #IL-22 > restores mucosal immunity, prevents ileal dysbiosis.
  • [1.12
  • [1.13] [#Colorectal cancer, #Inflamatory bowel disease] [#Common consumer products
    - #Triclosan (TCS), an antimicrobial agent found in thousands of consumer products > exacerbates #Colitis and #Colitis-associated colorectal tumorigenesis in animal models. - intestinal commensal microbes > microbial β-glucuronidase (GUS) enzymes > mediate metabolic activation of #Triclosan in the colon > gut toxicology.
  • [1.14] [#Colitis] [#Candida tropicalis
    - C. tropicalis > induces dysbiosis that involves changes in the presence of mucin-degrading bacteria #Akkermansia muciniphila and #Ruminococcus gnavus > leading to altered tight junction protein expression with increased intestinal permeability > followed by induction of robust Th1/Th17 responses > lead to an accelerated proinflammatory phenotype in experimental colitic mice.
  • [1.15] [#Inflamatory bowel disease, #Ulcerative Colitis] [#Western-style diet
    - Two commonly used emulsifiers, #Carboxymethylcellulose and #Polysorbate-80 > induce inflammation and metabolic changes, mediated by gut microbes.
  • [1.16] [#IG A
    - a portion of the microbiota-driven sIgA response is induced by and directed towards intestinal fungi. Analysis of the human gut mycobiota bound by sIgA revealed a preference for hyphae, a fungal morphotype associated with virulence. #Candida albicans was a potent inducer of IgA class-switch recombination among plasma cells, via an interaction dependent on intestinal phagocytes and hyphal programming. Characterization of sIgA affinity and polyreactivity showed that hyphae-associated virulence factors were bound by these antibodies and that sIgA influenced C. albicans morphotypes in the murine gut.
  • [1.17] [#Inflamatory bowel disease] [#Salmonella typhimurium
    - adherent-invasive #Escherichia coli (AIEC), and Salmonella enterica serovar Typhimurium > induce inflammation (through elevated T helper (TH) 1 and TH17 immune responses) in IBD animal model > fibrosis development. - in patients with Crohn’s disease, AIEC strains > ileal mucosa > trigger the initiation or perpetuation of the inflammatory disease.
  • [1.18] [#Candida albicans, #Candida glabrata, #Candida tropicalis
    - #Candida. A common, although not universal, finding has been an increase, statistically significant or trending, in the relative amount of #Candida in the fecal mycobiome of patients with CD from diverse geographic locations. - The named species is usually C. albicans, but C. tropicalis and C. glabrata have also been reported.
  • [1.19
  • [1.21] [#Inflamatory bowel disease] [#Bile Acids, #Primary bile acids, #Secondary bile acids
    - Reduced BA deconjugation is associated with inflammatory bowel diseases (IBD) including #Ulcerative Colitis (UC) and Crohn’s disease (CD), as well as #Irritable bowel syndrome (IBS).
  • [1.22] [#Acute anterior uveitis, #Ankylosing spondylitis, #HLA-B27-associated disease, #Psoriasis, #Psoriatic Arthritis, #Ulcerative Colitis
    - HLA-B27 transgenic rats that develop a spontaneous spondyloarthropathy-like illness do not develop disease when raised in a germ-free environment, but mono-association with #Phocaeicola vulgatus is sufficient to induce disease.
  • [1.23
    - Probiotic treatment with butyrate-producing bacteria has therapeutic potential since these bacteria are depleted in IBD patients and butyrate has beneficial effects on epithelial barrier function and overall gut health.
  • [1.24] [#Colorectal cancer] [#Bacteriophage, #Western-style diet
    - the abundance of a class of crAss-like phages, a group of related viruses that includes some of the most abundant viruses of the human gut, were higher in populations with non-westernized dietary habits - several types of crAss-like phages were present at decreased levels in people with #Rheumatoid Arthritis, #Systemic lupus erythematosus, #Ulcerative Colitis and Crohn disease, and at increased levels in people with colon cancer.
  • [1.25] [#Inflamatory bowel disease
    - The common skin resident fungus #Malassezia restricta, is also linked to the presence of an IBD-associated polymorphism in the gene for CARD9, a signaling adaptor important for anti-fungal defense. - M. restricta elicits innate inflammatory responses largely through CARD9 and is recognized by Crohn’s disease patient anti-fungal antibodies. This yeast elicits strong inflammatory cytokine production from innate cells harboring the IBD-linked polymorphism in CARD9 and exacerbates colitis via CARD9 in mouse models of disease.
  • - The aggregated relative abundance of #Klebsiella species was significantly higher in patients with Crohn’s disease and #Primary sclerosing cholangitis when compared with healthy controls. - Several genes increased in the faecal microbiomes of patients with inflammatory bowel diseases > include hemolysin-coregulated protein and enzymes involved in fructose-, galactitol-, mannose-, and long-chain fatty acid-related uptake and metabolic pathways- were enriched in most faecal samples of the patients with inflammatory disease who carried #Klebsiella species.
  • [1.26] [#Clostridium cluster IV
    - #Roseburia, #Gemmiger, #Coprococcus, #Ruminococcus 2, #Butyricicoccus, #Dorea, #Fusicatenibacter, #Anaerostipes, Clostridium IV were enriched in the healthy controls. - #Blautia, Clostridium IV, #Coprococcus, #Dorea, #Fusicatenibacter continued to significantly decrease in early and advanced CD patients, and Escherichia/Shigella and Proteus continued to significantly increase. - negative correlation between #Dorea, #Butyricicoccus, #Roseburia and gland reduce, #Roseburia and FC, #Butyricicoccus and goblet cells decreased, Parabacterodies and sex, Clostridium IV and CRP, #Dorea and ESR . - positive correlation between Escherichia/Shigella and CRP, #Ruminococcus 2 and clinical symptoms.
  • - Escherichia/Shigella, #Enterococcus and #Proteus were enriched in the advanced CD patients.
  • - #Lachnospiraceae incertae sedis and #Parabacteroides were enriched in the early CD patients.
  • [1.27
    - a reduction of a major member of Firmicutes, #Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CD. - A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. - Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis
  • [1.28
    - #Acylethanolamines were more abundant in stool from patients with CD, with an associated decrease in bacteria predicted to metabolize #Ethanolamine, further implicating #Ethanolamine-metabolizing microbes as guardians against gut inflammation and protectors of gut permeability.
  • - Patients with CD that previously underwent ileocecal valve resection showed a decline in fecal abundance of #Faecalibacterium prausnitzii and #Butyrate
  • [1.29] [#Streptococcus salivarius
    - Oral S. salivarius was found to be enriched and of concordant strains in both intestinal and oral microbiota in Crohn’s disease patients, and the species diversity of the infected intestine was considerably depleted
  • [#Antibiotic Therapy] - oral antibiotics for #Acne are a risk factor for new onset Crohn’s disease
  • [1.31
    - The microbiome risk score (MRS) model yielded a hazard ratio (HR) of 2.24 and temporal validity by capturing individuals that developed CD up to five years prior to disease onset. The five most important taxa contributing to the MRS included #Ruminococcus torques, #Blautia, #Colidextribacter, an uncultured genus-level group from Oscillospiraceace, and #Roseburia.
  • [1.32
    - Notably, taxonomic perturbations during dysbiosis mirrored those previously observed cross-sectionally in IBD6, such as the depletion of obligate anaerobes including Faecalibacterium prausnitzii and Roseburia hominis in CD and the enrichment of facultative anaerobes such as E. coli. - depletion of obligate anaerobes including Faecalibacterium prausnitzii and Roseburia hominis in CD and the enrichment of facultative anaerobes such as E. coli. - The reduction in butyrate in particular is consistent with the previously observed depletion of butyrate producers such as F. prausnitzii and R. hominis, which was also observed here.- depletion of obligate anaerobes including Faecalibacterium prausnitzii and Roseburia hominis in CD and the enrichment of facultative anaerobes such as E. coli - The reduction in butyrate in particular is consistent with the previously observed depletion of butyrate producers such as F. prausnitzii and R. hominis, which was also observed here.

References Notes


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Common References