New study shows bariatric surgery alters bile acid metabolism, leading to improved weight loss

Recent research published in The Lancet has shed new light on the mechanisms behind the effectiveness of bariatric surgery for obesity treatment, revealing significant changes in bile acid metabolism that may contribute to sustained weight loss and enhanced glucose metabolism.

Bariatric surgery is well-established as an effective intervention for long-term weight loss and metabolic improvements in obese individuals. However, the precise biological mechanisms driving these benefits have remained elusive. Previous research has suggested that changes in bile acid metabolism might play a role, but comprehensive human studies have been lacking.

In this study, researchers analysed the postprandial responses of bile acids, C4, and FGF19 in plasma, as well as the excretion of bile acids in feces, both before and after bariatric surgery. The study cohort consisted of 38 patients with obesity, some of whom also had type 2 diabetes, from the BARIA cohort.

The study observed that total fasting plasma bile acid levels increased post-surgery, while fecal excretion of bile acids decreased, indicating enhanced reabsorption. Correspondingly, increased postprandial levels of FGF19 and suppression of the bile acid synthesis marker C4 were noted, suggesting heightened activation of the FXR receptor in the gut. Additionally, a subset of bile acids exhibited altered postprandial responses following surgery.

One significant finding was the increase in fasting plasma levels of 6α-hydroxylated bile acids, known TGR5 agonists linked to improved glucose metabolism. Among these, HDCA showed a correlation with diabetes remission in an independent cohort.

These findings provide novel insights into bile acid kinetics, indicating that bariatric surgery alters bile acid profiles in a manner that activates the FXR and TGR5 receptors. This activation may contribute to the surgery’s effectiveness in promoting weight loss, enhancing glucose metabolism, and achieving diabetes remission.

The study highlights the potential of targeting bile acid pathways as a therapeutic strategy for obesity and related metabolic disorders, underscoring the complex interplay between bariatric surgery and metabolic health.