Laparoscopic sleeve gastrectomy elevates sulfated bile acid levels in obese Asians

Serum concentrations of sulfated bile acids (BAs) are significantly increased in morbidly obese Asians 6 months after laparoscopic sleeve gastrectomy (LSG), which may then contribute to the recovery of metabolic health in this population, a Singapore study has shown.

“BAs are traditionally associated with lipid absorption and phase II detoxification by forming various BA conjugates,” the researchers said. “Recently, it has been discovered that BAs also regulate glucose metabolism, and the increase in BAs in patients following bariatric surgery may contribute to the postsurgery improvement in insulin resistance (IR).”

Fourteen individuals scheduled for LSG participated in this study and underwent oral glucose tolerance test, biochemistry tests, and anthropometric measurements at baseline and at 6 months after LSG. Liquid chromatography–mass spectrometry was used to profile BAs.

Participants lost weight substantially from 117.4±5.4 to 92.1±3.8 kg and showed significantly better IR at 6 months. In addition, homeostasis model assessment for IR decreased from 6.2±0.7 to 2.0±0.2 and the Matsuda index elevated from 1.9±0.3 to 3.3±0.3. [Proc Singapore Healthc 2021;30:111-116]

No significant postoperative change was observed in the levels of total BAs (5,237.1±1,219.4 vs 3,631.7±457.9; p=0.181) or nonsulfated BAs postsurgery, but sulfated BA species had substantially increased after LSG. Cholic acid, chenodeoxycholic acid, and their glycine/taurine conjugated products were likewise higher after surgery, but the increase was not statistically significant.

Similar findings were noted for deoxycholic acid, ursodeoxycholic acid, and their glycine/taurine conjugated variants, but lithocholic acid and its glycine/taurine conjugated products did not change significantly from pre-LSG levels.

“Our findings were similar to other studies and add to the evidence supporting the effectiveness of LSG in achieving weight loss and reversing metabolic impairment in a morbidly obese Asian population,” the researchers said. [Surg Endosc 2017;31:4331-4345]

“Although our study was unable to demonstrate significant changes in total and nonsulfated BAs, we found that most of the sulfated BAs increased significantly 6 months after LSG,” they added.

BA sulfation occurs in the liver through phase II conjugation by the enzyme SULT2A1. Reabsorption ability is limited via BA transporters in the gut following sulfation, and fewer sulfated BAs will enter the enterohepatic circulation, the researchers explained. As a result, BA sulfation promotes faecal excretion of BAs in humans. [Am J Physiol 1998;274:G157-G169; Gastroenterology 1975;69:67-76]

“Therefore, sulfation is an important pathway for detoxification and excretion of BAs,” they said. “In this regard, any increase in BA production after bariatric surgery may be attenuated by the excretion of BA from the plasma pool via the sulfation pathway, and this may explain the heterogenous serum BA concentration after bariatric surgery.”

Understanding the role of BA sulfation could have major implications for human health. For instance, excessive hydrophobic BAs are toxic and can disrupt the plasma and mitochondrial membranes, disturb water and salt transportation, and contribute to oncogenesis. [J Pharmacol Exp Ther 2003;306:279-286; Gastroenterology 1970;59:120-129; Eur J Nutr 2008;47:301-309]

“This could explain why sulfated BAs are usually elevated in cholestatic liver disease as a compensational mechanism to promote excretion of BAs,” the researchers noted. [Gastroenterology 1975;68:545-553]