Increased Proliferation of the Ileal Epithelium as a Remote Effect of Ulcerative Colitis

Sedghi, Shirin; Barreau, Frédérick; Morilla, Ian; Montcuquet, Nicolas; Cazals–Hatem, Dominique; Pédruzzi, Eric; Rannou, Emilie; Hugot, Jean‐Pierre; Ogier–Denis, Éric; Daniel, Fanny

doi:10.1097/mib.0000000000000871

Cited by 11 publications

(7 citation statements)

References 20 publications

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“…Ulcerative colitis (UC) is a common refractory and life-long disease (Sedghi, 2016;Murakami et al, 2018). The common presenting symptoms include gastroenteritis, fever, diarrhea, rectal bleeding, mucus in stools, sense of urgency for bowel movements, and abdominal pain (Xu et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat

et al. 2019

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Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease with a high incidence rate and a difficult treatment regimen. Recently, significant advances in the treatment of intestinal diseases, particularly UC, have been made with the use of the drugs baicalin and baicalein, separately or in combination. However, the therapeutic efficacy and mechanism of action of baicalin, baicalein, and their combination therapy, in the treatment of UC has not been fully elucidated.Materials and Methods: we constructed a UC rat model that encompassed a variety of complex factors, including a high-sugar and high-fat diet, a high temperature and humidity environment (HTHE), excess drinking, and infection of Escherichia coli. Model rats were then treated with baicalin, baicalein, or a combination of the two. Results:The results showed significant differences in the therapeutic effects of baicalin, baicalein, and the combination therapy, in the treatment of UC, as well as differences in the inhibition of inflammation via the nuclear factor-κB and MAPK pathways. The rat model of UC was established as described above. Then, the rats were treated for 7 days with baicalin (100 mg kg -1 ), baicalein (100 mg kg -1 ), or both (100 mg kg -1 , baicalin: baicalein = 4:1/1:1). Clinical symptoms and signs, body temperature, organ indices, histopathology, blood biochemistry, and metabolites were examined to compare treatment effects and indicators of UC. Baicalin, YSR (Young Scutellaria baicalensis ratio of baicalin and baicalein), baicalein, and WSR (Withered Scutellaria baicalensis ratio of baicalin and baicalein) had significantly different effects in terms of clinical symptoms and signs, body temperature, organ indices, serum inflammatory cytokine levels, blood biochemistry, and histopathology changes in the main organs; YSR exhibited the best treatment effects. LC-MS/MS was used to detect the conversion of baicalin, baicalein, or both, into the six types of metabolites: baicalin, wogonoside, oroxin A, baicalein, wogonin, and oroxylin A. The levels of the six metabolites under the different treatment Frontiers in Pharmacology | www.frontiersin.org Baicalin, Baicalein and Their Combinations on UC Liang et al.conditions were significantly different in the large intestine, small intestine, and lungs, but not in the blood. The levels of the six metabolites were significantly different in the large intestine, small intestine, and lung, but not in the serum.Conclusion: All these results indicate that baicalin and baicalein should be used more accurately in specific diseases, especially baicalin or high content of baicalin in Scutellaria baicalensis (Tiaoqin) should be preferred in treatment of UC.

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Section: Introductionmentioning

confidence: 99%

The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat

et al. 2019

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“…These graphs were constructed based on high-throughput proteome screenings of the two samples of IBD patients, i.e., discovery and validation cohorts. Then to make this methodology more biological meaningful, we can test our predictions by means of experiments that study how specific interventions influence the reprogramming of IBD status, either via high-throughput sequencing surveys of validation populations (18) or by immunofluorescence specific to given antibodies (19). The comparison between theory and experiment will provide insight into the functional constraints of immune system in the recognition of bio-drivers varying when facing an intestinal chronic inflammatory threat.…”

Section: Discussionmentioning

confidence: 99%

Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status

Morilla

Léger

Marah

et al. 2019

Preprint

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The conditions who denotes the presence of an immune disease are often represented by interaction graphs. These informative, but complex structures are susceptible to being perturbed at different levels. The mode in which that perturbation occurs is still of utmost importance in areas such as reprogramming therapeutics. In this sense, the overall graph architecture is well characterise by module identification. Topological overlap-related measures make possible the localisation of highly specific module regulators that can perturb other nodes, potentially causing the entire system to change behaviour or collapse. We provide a geometric framework explaining such situations in the context of inflammatory bowel diseases (IBD). IBD are important chronic disorders of the gastrointestinal tract which incidence is dramatically increasing worldwide. Our approach models different IBD status as Riemannian manifolds defined by the graph Laplacian of two high throughput proteome screenings. Identifies module regulators as singularities within the manifolds (the so-called singular manifolds). And reinterprets the characteristic IBD nonlinear dynamics as compensatory responses to perturbations on those singularities. Thus, we could control the evolution of the disease status by reconfiguring particular setups of immune system to an innocuous target state. inflammatory bowel disease | wgcna | singular manifolds | revertible immune dynamic | compensatory perturbationsCorrespondence: morilla@math.univ-paris13.fr

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“…Small bowel dysfunction has, however, been reported in UC [ 3 ]. For example, histological alterations including structural alterations of villi and inflammatory cell infiltration [ 1 , 4 , 5 , 6 , 7 ], and increased intestinal permeability, have been detected in the small bowel of patients with UC [ 8 , 9 ]. There is also experimental evidence of small bowel dysfunction from animal models of colitis.…”

Section: Introductionmentioning

confidence: 99%

“…There is also experimental evidence of small bowel dysfunction from animal models of colitis. During experimental colitis, alterations in small bowel permeability and brush border enzymatic activity are observed [ 7 , 10 , 11 ]. Moreover, in IL10-deficient mice which spontaneously develop colitis, colitis is mitigated by reducing small intestinal permeability upon treatment with the zonulin peptide inhibitor AT-1001 [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis

Lee

Vancamelbeke

Verstockt

et al. 2020

Cells

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Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopathogenesis remains unknown, small bowel dysfunctions like histological and permeability alterations have been described in ulcerative colitis. We evaluated the molecular gene signature in the non-inflamed terminal ileum of 36 ulcerative colitis patients (7 active, with Mayo endoscopic subscore ≥2, and 29 inactive) as compared to 15 non-inflammatory bowel disease controls. Differential gene expression analysis with DESeq2 showed distinct expression patterns depending on disease activity and maximal disease extent. We found 84 dysregulated genes in patients with active extensive colitis and 20 in inactive extensive colitis, compared to controls. There was an overlap of 5 genes: REG1B, REG1A, MUC4, GRAMD2, and CASP10. In patients with left-sided colitis, ileal gene expression levels were similar to controls. Based on gene co-expression analysis, ileal changes in active ulcerative colitis patients were related to immune functions. The ileal changes in the inactive ulcerative colitis subjects converged into the maintenance of the intestinal barrier through increased mitochondrial function and dampened immune functions. In conclusion, we identified molecular changes in the non-inflamed ileum of ulcerative colitis that are dependent on colonic inflammation.

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Increased Proliferation of the Ileal Epithelium as a Remote Effect of Ulcerative Colitis

Abstract: These data show that despite the absence of inflammation in the small intestine, alterations in the ileal mucosa homeostasis are present in UC.

Cited by 11 publications

References 20 publications

The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat

The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat

Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status

Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis

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