Hyodeoxycholic acid (HDCA) suppresses intestinal epithelial cell proliferation through FXR‐PI3K/AKT pathway, accompanied by alteration of bile acids metabolism profiles induced by gut bacteria

The FASEB JournalVolume 34, Issue 5 p. 7103-7117 RESEARCH ARTICLEFree to Read Hyodeoxycholic acid (HDCA) suppresses intestinal epithelial cell proliferation through FXR-PI3K/AKT pathway, accompanied by alteration of bile acids metabolism profiles induced by gut bacteria Min Song, Min Song Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorQiang Yang, Qiang Yang Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorFenglin Zhang, Fenglin Zhang Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorLin Chen, Lin Chen Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorHan Su, Han Su Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorXiaohua Yang, Xiaohua Yang Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorHaiwen He, Haiwen He Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorFangfang Liu, Fangfang Liu Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorJisong Zheng, Jisong Zheng Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorMingfa Ling, Mingfa Ling Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorXumin Lai, Xumin Lai Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorXiaotong Zhu, Xiaotong Zhu Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorLina Wang, Lina Wang Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorPing Gao, Ping Gao Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorGang Shu, Gang Shu Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorQingyan Jiang, Corresponding Author Qingyan Jiang [email protected] Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. China Correspondence Qingyan Jiang and Songbo Wang, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, P. R. China. Email: [email protected] (Q. J) and [email protected] (S. W.)Search for more papers by this authorSongbo Wang, Corresponding Author Songbo Wang [email protected] Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. China Correspondence Qingyan Jiang and Songbo Wang, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, P. R. China. Email: [email protected] (Q. J) and [email protected] (S. W.)Search for more papers by this author Min Song, Min Song Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorQiang Yang, Qiang Yang Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorFenglin Zhang, Fenglin Zhang Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorLin Chen, Lin Chen Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorHan Su, Han Su Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorXiaohua Yang, Xiaohua Yang Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorHaiwen He, Haiwen He Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorFangfang Liu, Fangfang Liu Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorJisong Zheng, Jisong Zheng Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorMingfa Ling, Mingfa Ling Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorXumin Lai, Xumin Lai Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorXiaotong Zhu, Xiaotong Zhu Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorLina Wang, Lina Wang Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorPing Gao, Ping Gao Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorGang Shu, Gang Shu Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. ChinaSearch for more papers by this authorQingyan Jiang, Corresponding Author Qingyan Jiang [email protected] Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. China Correspondence Qingyan Jiang and Songbo Wang, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, P. R. China. Email: [email protected] (Q. J) and [email protected] (S. W.)Search for more papers by this authorSongbo Wang, Corresponding Author Songbo Wang [email protected] Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, P. R. China National Engineering Research Center for Breeding Swine Industry and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou, P. R. China Correspondence Qingyan Jiang and Songbo Wang, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, P. R. China. Email: [email protected] (Q. J) and [email protected] (S. W.)Search for more papers by this author First published: 04 April 2020 https://doi.org/10.1096/fj.201903244RCitations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Bile acids (BAs) have been implicated in regulation of intestinal epithelial signaling and function. This study aimed to investigate the effects of hyodeoxycholic acid (HDCA) on intestinal epithelial cell proliferation and explore the underlying mechanisms. IPEC-J2 cells and weaned piglets were treated with HDCA and the contributions of cellular signaling pathways, BAs metabolism profiles and gut bacteria were assessed. In vitro, HDCA suppressed IPEC-J2 proliferation via the BAs receptor FXR but not TGR5. In addition, HDCA inhibited the PI3K/AKT pathway, while knockdown of FXR or constitutive activation of AKT eliminated the inhibitory effects of HDCA, suggesting that FXR-dependent inhibition of PI3K/AKT pathway was involved in HDCA-suppressed IPEC-J2 proliferation. In vivo, dietary HDCA inhibited intestinal expression of proliferative markers and PI3K/AKT pathway in weaned piglets. Meanwhile, HDCA altered the BAs metabolism profiles, with decrease in primary BA and increase in total and secondary BAs in feces, and reduction of conjugated BAs in serum. Furthermore, HDCA increased abundance of the gut bacteria associated with BAs metabolism, and thereby induced BAs profiles alternation, which might indirectly contribute to HDCA-suppressed cell proliferation. Together, HDCA suppressed intestinal epithelial cell proliferation through FXR-PI3K/AKT signaling pathway, accompanied by alteration of BAs metabolism profiles induced by gut bacteria. CONFLICT OF INTEREST The authors declare no conflicts of interest. Citing Literature Supporting Information Filename Description fsb220489-sup-0001-TableS1.docxWord document, 18 KB Table S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume34, Issue5May 2020Pages 7103-7117 RelatedInformation