ArticlePloS one2018
Enteric infection coupled with chronic Notch pathway inhibition alters colonic mucus composition leading to dysbiosis, barrier disruption and colitis.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- DCLK1 isoform (DCLK1-S) as a critical player in promoting inflammation, tissue remodeling, and EMT in mouse models of colitis.PLoS pathogens · 2025Article
- The Role of Notch Signaling and Gut Microbiota in Autoinflammatory Diseases: Mechanisms and Future Views.Biomedicines · 2025Review
- Identification of potential diagnostic markers and molecular mechanisms of asthma and ulcerative colitis based on bioinformatics and machine learning.Frontiers in molecular biosciences · 2025Article
- Vitamin D/vitamin D receptor protects intestinal barrier against colitis by positively regulating Notch pathway.Frontiers in pharmacology · 2024Article
- B4galnt2-mediated host glycosylation influences the susceptibility toFrontiers in microbiology · 2022Article
- Overview of Three Proliferation Pathways (Wnt, Notch, and Hippo) in Intestine and Immune System and Their Role in Inflammatory Bowel Diseases (IBDs).Frontiers in medicine · 2022Review
- Candidate genes of SARS-CoV-2 gender susceptibility.Scientific reports · 2021Article
- DCLK1 isoforms and aberrant Notch signaling in the regulation of human and murine colitis.Cell death discovery · 2021Article
- Doublecortin-Like Kinase 1 (DCLK1) Is a Novel NOTCH Pathway Signaling Regulator in Head and Neck Squamous Cell Carcinoma.Frontiers in oncology · 2021Article
- Notch inhibitors induce diarrhea, hypercrinia and secretory cell metaplasia in the human colon.EXCLI journal · 2021Article
- The Gut-Brain Axis in Autism Spectrum Disorder: A Focus on the Metalloproteases ADAM10 and ADAM17.International journal of molecular sciences · 2020Review
- LncRNA SNHG1 promotes EMT process in gastric cancer cells through regulation of the miR-15b/DCLK1/Notch1 axis.BMC gastroenterology · 2020Article
- Review
- Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer.Gastroenterology · 2020Review
- E-cadherin Beyond Structure: A Signaling Hub in Colon Homeostasis and Disease.International journal of molecular sciences · 2019Review
- Spinal cord injury-induced neurogenic bowel: A role for host-microbiome interactions in bowel pain and dysfunction.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Intestinal mucus layer disruption and gut microflora modification in conjunction with tight junction (TJ) changes can increase colonic permeability that allows bacterial dissemination and intestinal and systemic disease. We showed previously that Citrobacter rodentium (CR)-induced colonic crypt hyperplasia and/or colitis is regulated by a functional cross-talk between the Notch and Wnt/β-catenin pathways. In the current study, mucus analysis in the colons of CR-infected (108 CFUs) and Notch blocker Dibenzazepine (DBZ, i.p.; 10μmol/Kg b.w.)-treated mice revealed significant alterations in the composition of trace O-glycans and complex type and hybrid N-glycans, compared to CR-infected mice alone that preceded/accompanied alterations in 16S rDNA microbial community structure and elevated EUB338 staining. While mucin-degrading bacterium, Akkermansia muciniphila (A. muciniphila) along with Enterobacteriaceae belonging to Proteobacteria phyla increased in the feces, antimicrobial peptides Angiogenin-4, Intelectin-1 and Intelectin-2, and ISC marker Dclk1, exhibited dramatic decreases in the colons of CR-infected/DBZ-treated mice. Also evident was a loss of TJ and adherens junction protein immuno-staining within the colonic crypts that negatively impacted paracellular barrier. These changes coincided with the loss of Notch signaling and exacerbation of mucosal injury. In response to a cocktail of antibiotics (Metronidazole/ciprofloxacin) for 10 days, there was increased survival that coincided with: i) decreased levels of Proteobacteria, ii) elevated Dclk1 levels in the crypt and, iii) reduced paracellular permeability. Thus, enteric infections that interfere with Notch activity may promote mucosal dysbiosis that is preceded by changes in mucus composition. Controlled use of antibiotics seems to alleviate gut dysbiosis but may be insufficient to promote colonic crypt regeneration.
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Registered trials
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