Departments of Physiology/Biophysics, School of Medicine, University of California, Irvine, California, United States.
Department of Medical Research, Tibor Rubin VA Medical Center, Long Beach, California, United States.
Am J Physiol Cell Physiol. 2024 Nov 1;327(5):C1163-C1177. doi: 10.1152/ajpcell.00570.2024. Epub 2024 Sep 9.
This study examined the effect of exposure of small and large intestinal epithelial cells to the bacterial lipopolysaccharide (LPS) on uptake of free form of vitamin B1, i.e., thiamin. The intestinal tract encounters two sources of thiamin: diet and the gut microbiota. Absorption of thiamin in both the small and large intestine occurs via a carrier-mediated process that involves thiamin transporters 1 and 2 (THTR-1 and -2). Complementary in vitro (human duodenal epithelial HuTu-80 cells and human colonic epithelial NCM460 cells), in vivo (mice), and ex vivo (human primary differentiated enteroid and colonoid monolayers) models were used. The results showed that exposure to LPS causes a significant inhibition in carrier-mediated [H]-thiamin uptake by small and large intestinal epithelia, with no change in the levels of expression of THTR-1 and -2 mRNAs and their total cellular proteins. However, a significant decrease in the fractions of the THTR-1 and -2 proteins that are expressed at the cell membranes of these epithelial cells was observed. These effects of LPS appeared to involve a protein kinase A (PKA) signaling pathway as activating this pathway caused a reversal in the inhibition of thiamin uptake and level of expression of its transporters at the cell membrane. These findings demonstrate that exposure of gut epithelia to LPS (a situation that occurs under different pathological conditions) leads to inhibition in thiamin uptake due to a decrease in level of expression of its transporters at the cell membrane that is likely mediated via a PKA signaling pathway. This study shows that the exposure of gut epithelial cells to bacterial LPS negatively impact the uptake process of the free form of vitamin B1 (i.e., thiamin). This appears to be mediated via suppression in the level of thiamin transporters 1 and 2 (THTR-1 and -2) expression at the cell membrane and involves a protein kinase A (PKA) signaling pathway.
本研究考察了小肠和大肠上皮细胞暴露于细菌脂多糖（LPS）对游离形式维生素 B1（即硫胺素）摄取的影响。肠道接触两种来源的硫胺素：饮食和肠道微生物群。小肠和大肠对硫胺素的吸收都是通过涉及硫胺素转运蛋白 1 和 2（THTR-1 和 -2）的载体介导过程进行的。使用了体外（人十二指肠上皮 HuTu-80 细胞和人结肠上皮 NCM460 细胞）、体内（小鼠）和离体（人原代分化肠类器官和结肠类器官单层）模型进行互补研究。结果表明，LPS 暴露导致小肠和大肠上皮的载体介导[H]-硫胺素摄取显著抑制，THTR-1 和 -2 mRNA 及其总细胞蛋白水平无变化。然而，观察到这些上皮细胞细胞膜上表达的 THTR-1 和 -2 蛋白的分数显著减少。LPS 的这些作用似乎涉及蛋白激酶 A（PKA）信号通路，因为激活该通路导致硫胺素摄取的抑制和其转运蛋白在细胞膜上的表达水平逆转。这些发现表明，肠道上皮暴露于 LPS（在不同病理条件下发生的情况）会导致硫胺素摄取抑制，这是由于细胞膜上其转运蛋白表达水平降低所致，这可能通过 PKA 信号通路介导。本研究表明，肠道上皮细胞暴露于细菌 LPS 会对游离形式维生素 B1（即硫胺素）的摄取过程产生负面影响。这似乎是通过抑制细胞膜上的硫胺素转运蛋白 1 和 2（THTR-1 和 -2）表达来介导的，涉及蛋白激酶 A（PKA）信号通路。
