Plasma Bile Acid Profile in Patients with and without Type 2 Diabetes

A paucity of information currently exists on plasma bile acid (BA) profiles in patients with and without type 2 diabetes mellitus (T2DM). We assayed 14 plasma BA species in 224 patients with T2DM and in 102 nondiabetic individuals with metabolic syndrome. Plasma BA levels were measured with ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) technique. Multivariable linear regression analyses were undertaken to assess associations between measured plasma BA species and T2DM status after adjustment for confounding factors. The presence of T2DM was significantly associated with higher plasma concentrations of both primary BAs (adjusted-standardized β coefficient: 0.279, p = 0.005) and secondary BAs (standardized β coefficient: 0.508, p < 0.001) after adjustment for age, sex, adiposity measures, serum alanine aminotransferase and use of statins or metformin. More specifically, the presence of T2DM was significantly associated with higher levels of plasma taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid, hyodeoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid and glycodeoxycholic acid (adjusted-standardized β coefficients ranging from 0.315 to 0.600; p < 0.01 or less), as well as with lower plasma levels of cholic acid (adjusted-standardized β coefficient: −0.250, p = 0.013) and taurocholic acid (adjusted-standardized β coefficient: −0.309, p = 0.001). This study shows that there are marked differences in plasma BA profiles between patients with and without T2DM. Further research will be needed to better understand how these differences in plasma BA profiles may interplay with the pathophysiology of T2DM.

Deconjugation of Bile Acids with Immobilized Genetically EngineeredLactobacillus plantarum80(pCBH1)

Bile acids are important to normal human physiology. However, bile acids can be toxic when produced in pathologically high concentrations in hepatobileary and other diseases. This study shows that immobilized genetically engineeredLactobacillus plantarum80 (pCBH1) (LP80 (pCBH1)) can efficiently hydrolyze bile acids and establishes a basis for their use. Results show that immobilized LP80 (pCBH1) is able to effectively break down the conjugated bile acids into glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) with bile salt hydrolase (BSH) activities of 0.17 and 0.07 μmol DCA/mg CDW/h, respectively. The deconjugation product, deoxycholic acid (DCA), was diminished by LP80 (pCBH1) within 4 h of initial BSH activity. Thisin-vitrostudy suggests that immobilized genetically engineered bacterial cells have important potential for deconjugation of bile acids for lowering of high levels of bile acids for therapy.

Microencapsulated Genetically EngineeredLactobacillus plantarum80 (pCBH1) for Bile Acid Deconjugation and Its Implication in Lowering Cholesterol

Cholesterol is known to be a major risk factor for coronary heart disease (CHD). Current treatments for elevated blood cholesterol include dietary management, regular exercise, and drug therapy with fibrates, bile acid sequestrants, and statins. Such therapies, however, are often suboptimal and carry a risk for serious side effects. This study shows that microencapsulatedLactobacillus plantarum80 (pCBH1) cells can efficiently break down and remove bile acids, and establishes a basis for their use in lowering blood serum cholesterol. Results show that microencapsulated LP80 (pCBH1) is able to effectively break down the conjugated bile acids glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) with bile salt hydrolase (BSH) activities of 0.19 and 0.08μmol DCA/mg CDW/h respectively. This article also summarizes the physiological interrelationship between bile acids and cholesterol and predicts the oral doses of microencapsulatedLactobacillus plantarum80 (pCBH1) cells required for lowering cholesterol.