Involvement of Bile Acids in Regulation of Water Channel Expression in Colon Epithelial Cells

Bile acids (BAs) affect water transport in the colon, as evident in Bile acid malabsorption (BAM). In BAM patients, an increased production of BAs or a decrease in the capacity for BA reabsorption in the ileum cause BAs to overflow into the colon, where they lead to diarrhoea through mechanisms that are yet to be determined. Although there is evidence for expression of specific water channels (AQPs) in the colon, results from different studies have been contradictory. A connection between BAs and AQPs has not been described. We wanted to confirm the expression of AQPs in the colonic epithelium and we wanted to investigate, whether changes in expression of AQPs occur during BAM syndromes. Here we profiled mRNA and protein levels of AQPs in the colons of humans and rodents. As a model for BAM, we fed sodium cholate to rats for 3 days to examine the long‐term effects of naturally occurring BAs on the expression of AQPs in colonic epithelial cells. In colon biopsies from humans, AQP1, −3, −4, −7, −8 and −9 were detected at the mRNA level by reverse transcription polymerase chain reaction (PCR), with AQP1, −3, −4 and −8 confirmed at the protein level by immunohistochemistry (IHC). In colonic epithelial cells isolated from rats, AQP1, −3, −4, −7 and −8 were detected at the mRNA level by PCR, with AQP1, −3 and −8 expression confirmed at the protein level by IHC. In mouse AQP1, −4 and −8 mRNA and protein were detected by PCR and IHC. Feeding rats sodium cholate for 3 days increased the expression of AQP3, −7 and −8 at the mRNA level, which was seen by real‐time PCR, compared to a control group fed standard rat chow. In conclusion, BAs affect the expression of AQPs in the rodent large intestine. Our data suggest that AQPs may play a role in BAM syndromes. Support or Funding Information The study was supported by The Danish Council for Independent Research, MEMBRANES, Gangstedfonden and Grosserer L.F. Foghts Fond.