High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease

Abstract Background The expression profiles of the intestinal mucosa have not been comprehensively investigated in asthma. We aimed to explore this in the Correlated Expression and Disease Association Research (CEDAR) patient cohort. Methods Differential expression analysis of ileal, transverse colon, and rectal biopsies were supplemented by a comparison of transcriptomes from platelets and leukocytes subsets, including CD4+, CD8+, CD14+, CD15+, and CD19+ cells. Asthma patients (n = 15) and controls (n = 15) had similar age (p = 0.967), body mass index (p = 0.870), similar numbers of females (80%) and smoking rates (13.3%). Results Significant differential expression was found in the ileum alone, and not in any other cell/tissue types. More genes were found to be overexpressed (1,150) than under-expressed (380). The most overexpressed genes included Fc Fragment of IgG Binding Protein (FCGBP, logFC = 3.01, pFDR = 0.015), Mucin 2 (MUC2, logFC = 2.78, pFDR = 0.015), and Alpha 1B Defensin (DEFA1B, logFC = 2.73, pFDR = 0.024). Gene ontology implicated the immune system, including interleukins 4 and 13, as well as antimicrobial peptides in this overexpression. There was concordance of gene over- (STAT1, XBP1) and underexpression (NELF, RARA) in asthma and Crohn’s disease ileum when our results were compared to another dataset (p = 3.66 × 10–7). Conclusion Ileal mucosa in asthma exhibits a specific transcriptomic profile, which includes the overexpression of innate immune genes, mostly characteristic of Paneth and goblet cells, in addition to other changes that may resemble Crohn’s disease.

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Diving into inflammation: a pilot study exploring the dynamics of the immune-microbiota axis in ileal tissue layers of patients with Crohn’s disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab034 ◽

2021 ◽

Author(s):

Edda Russo ◽

Francesco Giudici ◽

Federica Ricci ◽

Stefano Scaringi ◽

Giulia Nannini ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Tissue Injury ◽

Microbiota Composition ◽

Response Distribution ◽

Ileal Mucosa ◽

The Family ◽

New Biomarkers ◽

Clinical Conditions ◽

Ileal Tissue

Abstract Background and aims Crohn’s Disease (CD) pathogenesis is still unclear. Disorders in the mucosal immunoregulation and its crosstalk with the microbiota may represent an important component in tissue injury. We aimed to characterize the molecular immune response distribution within the ileal layers and to evaluate the correlated microbiota in pathological/healthy settings comparing first surgery/relapse clinical conditions. Methods We enrolled 12 CD patients. A comprehensive analysis of ileal mucosa, submucosa and serosa broad-spectrum cytokines’ panel was performed through a multiplex approach. In addition, ileal microbiota composition was assessed through Next Generation Sequencing. Results We observed a distinct profile (of IL1-α, IL-1β, IL-4, IL-8, ICAM-1, E-Selectin, P-Selectin, IP-10, IL 6, and IL 18) across the CD vs healthy ileal layers; and a different distribution of IFN-γ, P-Selectin, IL-27 and IL-21 in first surgery vs relapse patients. In addition, the phylum Tenericutes, the family of Ruminococcaceae, and the genus Mesoplasma and Mycoplasma were significantly enriched in pathological setting. Significant microbiota differences were observed between relapse vs first surgery patients regarding the class Bacteroidia, the genus of Prevotella, Flavobacterium, Tepidimonas and Escherichia/Shigella. Finally, the abundance of the genus Mycoplasma was positively correlated with IL-18. Conclusions We describe a dissimilarity of cytokines’ distribution and microbiota composition within the CD and the adjacent healthy ileal tissue layers and between first operation and surgical relapse. Our results give a potential insight into the dynamics of the gut microbiota-immune axis in CD patients, leading to new biomarkers’ detection.

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