Hyocholic acid species as novel biomarkers for metabolic disorders PMID: 33674561

ADC Targets in Oncology

2026-04-10

Hyocholic acid species as novel biomarkers for metabolic disorders

Nat Commun. 2021 Mar 5;12(1):1487. doi: 10.1038/s41467-021-21744-w.

Xiaojiao Zheng ^# ¹ , Tianlu Chen ^# ¹ , Aihua Zhao ^# ¹ , Zhangchi Ning ^# ² ³ , Junliang Kuang ¹ , Shouli Wang ¹ , Yijun You ¹ , Yuqian Bao ⁴ , Xiaojing Ma ⁴ , Haoyong Yu ⁴ , Jian Zhou ⁴ , Miao Jiang ⁵ , Mengci Li ¹ , Jieyi Wang ¹ , Xiaohui Ma ⁶ , Shuiping Zhou ⁶ , Yitao Li ² , Kun Ge ¹ , Cynthia Rajani ⁷ , Guoxiang Xie ⁷ , Cheng Hu ⁴ , Yike Guo ² , Aiping Lu ⁸ , Weiping Jia ⁹ ¹⁰ , Wei Jia ¹¹ ¹² ¹³

Affiliations

1. Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
2. School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
3. Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
4. Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai, China.
5. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
6. Department of Pharmacology and Toxicology, Tasly Pharmaceutical Co. Ltd, Tianjin, China.
7. University of Hawaii Cancer Center, Honolulu, HI, USA.
8. School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. [email protected].
9. Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. [email protected].
10. Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai, China. [email protected].
11. Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. [email protected].
12. School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. [email protected].
13. University of Hawaii Cancer Center, Honolulu, HI, USA. [email protected].
# Contributed equally.

Abstract

Hyocholic acid (HCA) is a major bile acid (BA) species in the BA pool of pigs, a species known for its exceptional resistance to spontaneous development of diabetic phenotypes. HCA and its derivatives are also present in human blood and urine. We investigate whether human HCA profiles can predict the development of metabolic disorders. We find in the first cohort (n = 1107) that both obesity and diabetes are associated with lower serum concentrations of HCA species. A separate cohort study (n = 91) validates this finding and further reveals that individuals with pre-diabetes are associated with lower levels of HCA species in feces. Serum HCA levels increase in the patients after gastric bypass surgery (n = 38) and can predict the remission of diabetes two years after surgery. The results are replicated in two independent, prospective cohorts (n = 132 and n = 207), where serum HCA species are found to be strong predictors for metabolic disorders in 5 and 10 years, respectively. These findings underscore the association of HCA species with diabetes, and demonstrate the feasibility of using HCA profiles to assess the future risk of developing metabolic abnormalities.