New paper demonstrating the microbiota impact on cell proliferation via microRNA expression changes in intestinal epithelial stem cells

Intestinal flora are known to impact the immune system and metabolism, with chronic exposures to certain flora linked to conditions such as inflammatory bowel disease and fibrosis. Breeches of the epithelial barrier and systemic infection can lead to more acute problems such as sepsis.

A recent paper by Peck et al published in J. Biol. Sci. on Jan 4 2017 (doi: 10.1074/jbc.M116.770099) has revealed that a changed microbiota can impact the proliferation of jejunal epithelial stem cells, via specific miRNAs. Specifically, the paper suggested that miR-375 may control cell proliferation in the Sox9low stem cell enriched population, and that miR-375 down regulation by the microbiota may increase cell production.

The presence of intestinal flora supressed miR-375-3p expression in the stem cells, which had previously been predicted to target members of the Wnt/β-catenin signalling pathway.

Reduced miR-375-3p expression in organoids caused increased cell proliferation.

The authors compared microRNA expression patterns in FACS sorted (based on Sox9 expression) jejunal cell populations isolated from germ free mice, freshly infected mice (germ free mice administered an oral faecal slurry, a common treatment for some forms of colitis, particularly C.Difficile induced colitis) and conventionally housed mice.

There were fewer cycling stem cells in the germ free mice. Mice receiving the faecal slurry had increased levels of epithelial cell proliferation markers and a 4x increase in lgr5 mRNA expression 2 weeks later.

The quiescent stem cell population was not affected, nor were gene expression markers of Paneth and Goblet cells. However, since the stem cells generate all the differentiated epithelial cell types, a sustained effect may well impact differentiated cell numbers. The current study did not specifically isolate and then compare expression profiles from the differentiated cells.

These data provide an intriguing insight into the therapeutic use of both bacterial flora and microRNA manipulation as a means of controlling epithelial cell proliferation, either hyperproliferative pathologies or as part of a mucosal regenerative (wound healing) response.

Epistem has a range of experimental tools which may be used to assess intestinal epithelial cell proliferation/differentiation and miRNA expression, including cell culture and in vivo models. If you would like to discuss these options for your research project, then do get in touch with our team.

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