Role of bile acids in mediating gut microbiome effects on human metabolism

Introduction:

Bile acids (BAs) play an important role in the absorption of lipids and fat-soluble vitamins in the intestine. Primary BAs are secreted by the gall bladder and transformed to secondary BAs by the microbiome. BAs have impact on lipid- and glucose metabolism as they bind to the farnesoid X receptor (FXR), which results in the secretion of fibroblast growth factor 19 (FGF19) – a hormone involved in nutritional metabolism, e.g. via promoting glycogen synthesis.

Probands and

Methods:

One cross-sectional cohort (comprising 434 probands, separated into four groups: underweight, normalweight, overweight (BMI> 30) without and with T2D) and three intervention studies (comprising 10 healthy probands, 17 overweight probands and 23 overweight probands who underwent bariatric surgery, respectively) were investigated regarding their BA status and concentrations of the metabolic parameter FGF19.

Results:

Within the cohort (n = 434), FGF19 levels were lower in probands with adipositas with and without T2D in comparison to normal- or underweight probands. For the same cohort, secondary BAs were positively associated with adipositas, T2D and Lactobacillus. In the intervention studies with overweight probands, a general increase in BAs could be observed, while no effect on FGF19 was detectable after weight loss or weight maintainance phase.

Conclusion:

Lower levels of FGF19 in adipose probands might result in impaired feed-back inhibition of BA synthesis, leading to elevated BA levels. Furthermore, systemic effects of decreased FGF19 can lead to BA diarrhea, lower glycogen synthesis rates and promotion of gluconeogenesis.