Hyocholic acid species as novel biomarkers for metabolic disorders

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.

Decreased Abundance of Akkermansia muciniphila Leads to the Impairment of Insulin Secretion and Glucose Homeostasis in Lean Type 2 Diabetes

“…[ 73 , 74 , 75 ] A series of standard calibration solutions were diluted with desalted serum (depleted of BAs using activated charcoal) for the calibration curve. [ 76 ] The concentration of BA in an unknown sample was determined by comparing the unknown to calibration curve.…”

Dynamics of gut microbiome – mediated bile acid metabolism in progression to islet autoimmunity

“…FXR and TGR5 signaling plays a critical role in regulating the systemic lipid, glucose, and energy homeostasis (Jiang et al, 2015;Shapiro et al, 2018). Dysregulation of systemic BA metabolism has been linked to multiple diseases, including fatty liver disease, cardiovascular disease, and type 2 diabetes (Chan & Wong, 2019;Shapiro et al, 2018;Zheng et al, 2021). Thus, the gut-microbiome-BA axis is increasingly recognized as a therapeutic target for treating metabolic and immune disorders (Chan & Wong, 2019;Gu et al, 2017;Targher et al, 2021).…”

Hyocholic acid and glycemic regulation: comments on ‘Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism’

“…The first use of pig bile for treatment of ‘xiao-ke’, a condition known today as diabetes, was recorded ∼400 years ago by the Chinese medical practitioners in the Compendium of Materia Medica ( Li, 1573‒1593 ). Recently, we found HCA species as novel biomarkers for metabolic diseases ( Zheng et al, 2021b ) and also identified the role of HCA species in the prevention of diabetes as well as their mechanism of action ( Zheng et al, 2021a ). Although bile acids (BAs) are mostly associated with their aid in food digestion, they have also been shown to act as signaling molecules by binding to two particular receptors, farnesoid X receptor (FXR) and the G-protein-coupled receptor TGR5.…”