Dataset Information

Gut commensal bacteria and regional Wnt gene expression in the proximal versus distal colon.

ABSTRACT: Regional expression of Wingless/Int (Wnt) genes plays a central role in regulating intestinal development and homeostasis. However, our knowledge of such regional Wnt proteins in the colon remains limited. To understand further the effect of Wnt signaling components in controlling intestinal epithelial homeostasis, we investigated whether the physiological heterogeneity of the proximal and distal colon can be explained by differential Wnt signaling. With the use of a Wnt signaling-specific PCR array, expression of 84 Wnt-mediated signal transduction genes was analyzed, and a differential signature of Wnt-related genes in the proximal versus distal murine colon was identified. Several Wnt agonists (Wnt5a, Wnt8b, and Wnt11), the Wnt receptor frizzled family receptor 3, and the Wnt inhibitory factor 1 were differentially expressed along the colon length. These Wnt signatures were associated with differential epithelial cell proliferation and migration in the proximal versus distal colon. Furthermore, reduced Wnt/?-catenin activity and decreased Wnt5a and Wnt11 expression were observed in mice lacking commensal bacteria, an effect that was reversed by conventionalization of germ-free mice. Interestingly, myeloid differentiation primary response gene 88 knockout mice showed decreased Wnt5a levels, indicating a role for Toll-like receptor signaling in regulating Wnt5a expression. Our results suggest that the morphological and physiological heterogeneity within the colon is in part facilitated by the differential expression of Wnt signaling components and influenced by colonization with bacteria.

SUBMITTER: Neumann PA

PROVIDER: S-EPMC3936305 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Gut commensal bacteria and regional Wnt gene expression in the proximal versus distal colon.

Neumann Philipp-Alexander PA Koch Stefan S Hilgarth Roland S RS Perez-Chanona Ernesto E Denning Patricia P Jobin Christian C Nusrat Asma A

The American journal of pathology 20140111 3

Regional expression of Wingless/Int (Wnt) genes plays a central role in regulating intestinal development and homeostasis. However, our knowledge of such regional Wnt proteins in the colon remains limited. To understand further the effect of Wnt signaling components in controlling intestinal epithelial homeostasis, we investigated whether the physiological heterogeneity of the proximal and distal colon can be explained by differential Wnt signaling. With the use of a Wnt signaling-specific PCR a ...[more]

PMID: 24418259

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Project description:Aim: Microbial colonization of the intestine in newborns is a critical event that regulates host physiology with lifelong consequences. However, there is a need to identify microbial molecules and mechanisms that play a role in this process. We aimed to elucidate the effects of flagellin, an important immunomodulatory component involved in bacterial motility, on intestinal epithelial functions. Methods: Germfree mice were colonized with synthetic bacterial communities, including a flagellated mouse gut isolate of Escherichia coli or a ΔfliC mutant thereof that lacks flagella. The offspring of these mice were studied at 7 days of age by single-cell RNA sequencing of epithelial cells isolated from the small intestine. Results: Enterococcus faecalis was the most dominant species in the small intestine of newborn mice. Blautia pseudococcoides was detected at low relative abundances. Colonization by either E. coli strain reduced the relative abundance of E. faecalis to 10% on average, and E. coli became the dominant member, with no substantial differences between mice colonized with the wildtype or mutant strain. The distribution of cell types within the small intestinal epithelium was skewed toward specialized cells (goblet, enteroendocrine, stem cells) at the expense of enterocytes in mice colonized with flagellated bacteria. These mice were characterized by higher expression of genes involved in cell-cell interactions (Npl, Epcam) and responses to infection (Ctsl) in enterocytes and enhanced translation (ribosomal proteins) in stem cells. In contrast, genes involved in lipid homeostasis (transport and metabolism; Apoc 2/4, Dgat2, Fabp 1/2, Mttp) in all cell types and inflammatory and androgen-related pathways in specialized cell types were less expressed in epithelial cells exposed to wildtype E. coli. Conclusion: These findings suggest that early life exposure to flagellated commensal bacteria influences cellular processes underlying tissue metabolism and remodeling in the small intestine.

Dataset Information

Gut commensal bacteria and regional Wnt gene expression in the proximal versus distal colon.

Publications

Gut commensal bacteria and regional Wnt gene expression in the proximal versus distal colon.

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