The detrimental effect of enteropathogenic Escherichia coli infection on butyrate uptake by colonocytes could be mitigated by the probiotic Lactobacillus acidophilus. Caco-2 colon cell lines had increased butyrate uptake and apical expression of the monocarboxylate transporter 1 (MCT1) after treatment with L. acidophilus and L. acidophilus-conditioned culture medium.

“Butyrate is a key short chain fatty acid produced in the colon. It serves as a primary fuel for colonocytes, maintains epithelial integrity, ameliorates mucosal inflammation, and stimulates electrolyte (NaCl) absorption,” explains corresponding author Alip Borthakur. “Therefore, impaired absorption of butyrate could result in intestinal inflammatory diseases. MCT1 plays a major role in colonic luminal butyrate absorption. Indeed, impaired butyrate absorption due to downregulation of MCT1 has been shown in experimental models of IBD and also in patients with ulcerative colitis.”

Short-term (3 h) treatment of over-confluent Caco-2 cells—a point at which they develop apical–basal polarity—with L. acidophilus resulted in a substantial increase in butyrate uptake through MCT1. The effect was abrogated by heat-killed bacteria, but L. acidophilus-conditioned culture medium retained this effect on butyrate uptake.

In response to L. acidophilus treatment, apical membrane expression of MCT1 was upregulated, in part as a consequence of decreased endocytic internalization.

To investigate whether L. acidophilus could prevent E. coli-mediated decrease in butyrate uptake, Caco-2 cells were pre-treated with probiotic-conditioned medium. After a 30 min infection with E. coli, cells exposed to L. acidophilus-conditioned medium had higher levels of butyrate uptake than untreated control cells. In addition, treated cells had higher MCT1 expression levels at the apical membrane. Experiments revealed that this was also due to the effect of L. acidophilus soluble factors on endocytosis.

Credit: NPG

“Our next phase of studies will focus on the mechanisms governing membrane targeting of MCT1 under basal conditions or in response to pathogen infection or probiotics,” says Borthakur. “We have also initiated studies on mechanisms of regulation of short chain fatty acid absorption in vivo.” The authors also intend to fully characterize the soluble factors released into probiotic-conditioned culture medium that are associated with these beneficial effects.