We are grateful to Dr McDonagh for underlining the different transport modalities across the placenta of bilirubin in its conjugated versus unconjugated form. The latter, indeed, seems to be more mobile than the presence of specific carriers would predict. In this respect, we recently showed in vitro and in vivo that unconjugated bilirubin increases the permeability to small molecules across the intestine.1,2  Unconjugated bilirubin interacts with the tight junction-protein complex between adjacent enterocytes, “opening the gates” from and to the intestinal lumen. Because these protein structures regulate most biological barriers (including the placenta and the blood-brain barrier), bilirubin may have a carrier-independent, previously unreported way to promote its own transport across the main biological fences.

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