Enhancement of intestinal barrier function and alleviation of mycophenolic acid toxicity by a probiotic-conditioned medium in vitro

model. We obtained an acellular probiotic conditioned medium by culturing the multistrain probiotic preparation in DMEM + FBS, either with or without MPA or MMF. The probiotic conditioned medium reduced IB permeability when added to the upper compartment of the transwell both in the presence and in the absence of these immunosuppressant drugs, as indicated by an increase in transepithelial electrical resistance. The probiotic conditioned medium also prevented cytotoxicity induced by both MPA and MMF and increased the expression of the tight junction proteins zonulin-1 and claudin-5, both of which contribute to barrier tightness. The protective effects of the probiotic medium may depend on preventing free radical damage, as we found that it reduced free oxygen radicals in cells exposed to either MPA, MMF or to the pro-oxidant compound tert-butyl hydroperoxide (tBHP). Finally, the probiotic conditioned medium reduced the activity of the ABC1B1 pump, though this did not result in changes in transwell IB crossing by MPA or MMF. In conclusion, we demonstrated that a multistrain probiotic preparation can protect the intestinal barrier from toxicity induced by MPA and MMF. The fact that this was a postbiotic effect, as it occurred in the absence of probiotic microorganisms, could be relevant for immunocompromised patients, as probiotic bacteria could potentially induce opportunistic infections in these subjects.