Developmental maturation of the colonic uptake process of the microbiota-generated thiamin pyrophosphate.

The water-soluble vitamin B1 is essential for normal human health and physiology. In its main biologically active form, i.e., thiamin pyrophosphate (TPP), the vitamin plays many critical roles in cell metabolism; thus, its deficiency leads to a variety of adverse effects. Humans/mammals obtain vitamin B1 from two exogenous sources: diet and gut microbiota. Considerable amount of the microbiota-generated vitamin B1 exists in the form of TPP, and colonocytes can efficiently absorb this TPP via a high-affinity and specific carrier-mediated mechanism that involves the recently cloned colonic TPP transporter (cTPPT; product of SLC44A4 gene). There is nothing currently known about colonic uptake of TPP during early stages of life, and whether the process undergoes developmental regulation. We addressed this issue using the mouse as animal model. Our results showed that colonic uptake of TPP undergoes developmental up-regulation as the animal moves from the suckling period to weanling and adulthood. This up-regulation in uptake was found to be associated with a parallel induction in level of expression of the cTPPT protein, mRNA and heterologous nuclear RNA (hnRNA), suggesting possible involvement of transcriptional mechanism(s). We also found a parallel up-regulation in level of expression of the two nuclear factors that drive activity of the SLC44A4 promoter (i. e., CREB-1 and Elf-3) with maturation. These results demonstrate, for the first time, that colonic TPP uptake process and cTPPT expression are developmentally up-regulated, and that this up-regulation is likely driven via transcriptional mechanism(s).