Intestinal Mechanisms of Enterohepatic Circulation Disturbance of Bile Acids in Cholelithiasis

Abstract

Background: Cholelithiasis is one of the most common diseases of the digestive system which affects all segments of the population and preserves a stable growth of incidence rates. In recent years the development of cholelithiasis is associated with impaired enterohepatic circulation (EHC) of bile acids (BA). The small intestine (SI) plays an important part in EHC of BA because 80‒90% of BA are absorbed into the blood after deconjugation by bacteria in the SI. However, in spite of a number of works dealing with the problem of EHC of BA at the intestinal level, the problem is far from being solved. Aims: To assess the association between the level of bile acids in the blood and bile of patients with cholelithiasis and disturbance of resorbing function of the small intestine as well as changes in the condition of the intestinal microbiota. Materials and methods: Non-randomized controlled trial. The study group included patients aged 18‒74 with lithogenic stage of cholelithiasis. The diagnosis was based on clinical data and the results of ultrasound examination of the gallbladder. Bile acids in the blood and bile were determined by mass spectrometry using the apparatus AmazonX (Bruker Daltonik GmbH, Bremen, Germany). Biochemical examination of bile was conducted. Absorption in the small intestine was studied by functional glucose tolerance test. Condition of the intestinal microbiota was assessed by the hydrogen breath test with lactulose using the apparatus LaktofaH2 (AMA, St. Petersburg). Stool culture was performed in selective media. Results: 115 patients aged 18 to 74 with prestone stage of cholelithiasis and 25 healthy people, comparable in age and sex, were examined. In patients with prestone stage of cholelithiasis biochemical examination of bile revealed increased cholesterol and decreased bile acids and bile acids-cholesterol ratio in B and C bile. The level of bile acids in the blood was reduced in comparison with the control group; it was associated in particular with a significant reduction in chenodeoxycholic, deoxycholic and glycodeoxycholic acids. Resorption in the small intestine was increased in patients with cholelithiasis compared with the control group (blood glucose increase within 30 minutes after the glucose load was 3.13±0.17 and 2.32±0.11 mmol/l respectively; p0.05). In the majority of patients small intestinal bacterial overgrowth (SIBO), mainly (75% of patients) associated with ileocecal insufficiency, and dysbiosis in the large intestine were established (88 and 100% of patients respectively). Conclusions: The small intestine is an important component in disturbance of enterohepatic circulation of bile acids. Significant changes in deconjugation of bile acids occur due to SIBO in the distal ileum and dysbiosis in the large intestine, thus disturbings the proportion of fractions of bile acids in the blood and bile.

The role of intestinal microflora in the development of cholelithiasis (literature review)

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