Slc10a2, also known as the apical sodium-dependent bile acid transporter (ASBT), is a key protein in the solute carrier family. It is mainly expressed in the small intestine and is crucial for the reabsorption of ileal bile acids. This function is central to the enterohepatic circulation of bile acids and cholesterol homeostasis, which is vital for fat digestion [1,3].

In Slc10a2-null mice, fecal bile acid excretion is augmented more than 10-fold. These mice show a 54% increase in aberrant crypt foci, and 70% and 59% increases in colon tumor number and size respectively, indicating that endogenous fecal bile acids promoted by Slc10a2 deficiency may play a role in colon carcinogenesis [4]. Also, a human case with a homozygous mutation of SLC10A2 presented chronic bile acid diarrhea and severe stunting, expanding the mutant spectrum of the gene [2].

In conclusion, Slc10a2 is essential for maintaining bile acid and cholesterol balance through its role in the enterohepatic circulation. The study of Slc10a2-null mouse models and human genetic mutants has provided insights into its role in diseases such as colon cancer and bile acid-related diarrhea, highlighting its potential as a therapeutic target for these conditions.

References:

1. Yang, Na, Dong, Ya-Qian, Jia, Guo-Xiang, Yang, Shen-Shen, Li, Yu-Bo. 2020. ASBT(SLC10A2): A promising target for treatment of diseases and drug discovery. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 132, 110835. doi:10.1016/j.biopha.2020.110835. https://pubmed.ncbi.nlm.nih.gov/33035828/

2. Qie, Di, Zhang, Yulin, Gong, Xue, Lu, Guoyan, Li, Yifei. 2021. SLC10A2 deficiency-induced congenital chronic bile acid diarrhea and stunting. In Molecular genetics & genomic medicine, 9, e1740. doi:10.1002/mgg3.1740. https://pubmed.ncbi.nlm.nih.gov/34192422/

3. Xiao, Ling, Pan, Guoyu. 2017. An important intestinal transporter that regulates the enterohepatic circulation of bile acids and cholesterol homeostasis: The apical sodium-dependent bile acid transporter (SLC10A2/ASBT). In Clinics and research in hepatology and gastroenterology, 41, 509-515. doi:10.1016/j.clinre.2017.02.001. https://pubmed.ncbi.nlm.nih.gov/28336180/

4. Raufman, Jean-Pierre, Dawson, Paul A, Rao, Anuradha, Polli, James E, Cheng, Kunrong. 2015. Slc10a2-null mice uncover colon cancer-promoting actions of endogenous fecal bile acids. In Carcinogenesis, 36, 1193-200. doi:10.1093/carcin/bgv107. https://pubmed.ncbi.nlm.nih.gov/26210740/