Altered microbiota caused by disordered gut motility leads to an overactivation of intestinal immune system in APC1638T mice.

Abstract

Adenomatous polyposis coli (APC) is recognized as an antioncogene related to familial adenomatous polyposis and colorectal cancers. However, APC is a large protein with multiple binding partners, indicating APC has diverse roles besides as a tumor suppressor. We have ever studied the roles of APC by using APC^1638T/1638T (APC1638T) mice. Through those studies, we have noticed stools of APC1638T mice were smaller than those of APC^+/+ mice and hypothesized there be a disturbance in fecal formation processes in APC1638T mice. The gut motility was morphologically analyzed by immunohistochemical staining of the Auerbach's plexus. Gut microbiota was analyzed by terminal restriction fragment length polymorphism (T-RFLP). IgA concentration in stools was determined by enzyme-linked immunosorbent assay (ELISA). As results, macroscopic findings suggestive of large intestinal dysmotility and microscopic findings of disorganization and inflammation of the plexus were obtained in APC1638T mice. An alteration of microbiota composition, especially increased Bacteroidetes population was observed. Increases in IgA positive cells and dendritic cells in the ileum with high fecal IgA concentration were also confirmed, suggesting over-activation of gut immunity. Our findings will contribute to our understanding of APC's functions in the gastrointestinal motility, and lead to a development of novel therapies for gut dysmotility-related diseases.