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.
Highlights
Hyocholic acid (HCA) is a major bile acid (BA) species in the Bile acids (BAs) pool of pigs, a species known for its exceptional resistance to spontaneous development of diabetic phenotypes
The results showed that the HCA species and DCA species were significantly decreased in Healthy overweight/ obese (HO) and OD relative to Healthy lean (HL)
Pairwise Spearman correlation analysis (Supplementary Fig. 2) showed that HCA species inversely correlated with body mass index (BMI), fasting and postload glucose, insulin levels and insulin resistance shown by homeostasis model assessment of insulin resistance (HOMA-IR)
Summary
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. 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. Due to the important physiological and metabolic roles of BAs, we were motivated to assess the association of circulating HCA species with the development of metabolic disorders in humans We show both obesity and diabetes are associated with lower serum and fecal concentrations of HCA species in two clinical cohorts. Two independent prospective cohorts show that serum HCA species are strong predictors for metabolic disorders in 5 or 10 years
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