The methionine precursor DL-2-hydroxy-(4-methylthio)butanoic acid protects intestinal epithelial barrier function

Abstract

DL-2-hydroxy-(4-methylthio)butanoic acid (HMTBA) is a source of dietary methionine (Met) that is widely used in poultry nutrition. We have previously shown that HMTBA is preferentially diverted to the transsulfuration pathway, which gives antioxidant metabolites such as taurine and glutathione. Therefore, here we hypothesize that this Met source can protect epithelial barrier function in an in vitro model of intestinal inflammation of Caco-2 cells. The results show that HMTBA prevents the increase in paracellular permeability induced by H2O2 or tumour necrosis factor-α. This effect can be attributed to the increased production of taurine and reduced glutathione. Similar results were obtained for DL-Met, although the protective role of the amino acid was less pronounced than that of the hydroxy analogue. In conclusion, the diversion to the transsulfuration pathway means that this Met precursor is of greater value than previously thought, due to its capacity to improve intestinal homeostasis and the quality of poultry products destined for human consumption.

Keywords: 2-(N-morpholino)ethanesulfonic acid; 2-keto-(4-methylthio)butanoic acid; 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; BSA; Caco-2 cells; DHA; DMEM; Dulbecco’s Modified Eagle Medium; FBS; GSH; GSSG; Glutathione; H(2)O(2); HEPES; HMTBA; Hcy; KMB; LDH; MCT1; MES; MLCK; Met; Oxidative stress; PAG; PBS; PP; Paracellular permeability; RNS; ROS; TER; TJ; TNF-α; Tau; Taurine; Tight junctions; ZO; bovine serum albumin; dl-2-hydroxy-(4-methylthio)butanoic acid; dl-propargyl glycine; docosahexaenoic acid; foetal bovine serum; glutathione; glutathione disulfide; homocysteine; hydrogen peroxide; lactate dehydrogenase; methionine; monocarboxylate transporter 1; myosin light chain kinase; paracellular permeability; phosphate buffered saline; rGSH; reactive nitrogen species; reactive oxygen species; reduced glutathione; taurine; tight junctions; transepithelial electrical resistance; tumour necrosis factor-α; zona occludens.