The Patterns of Glycine and Taurine Conjugates of Bile Acids in Serum in Hepatobiliary Disease

Fasting serum concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid were measured with a high-pressure liquid chromatography-enzymatic assay in patients with hepatobiliary disease. The total glycine to taurine ratio was significantly lower in extrahepatic cholestasis (median 1.1) than in cirrhosis (median, 2.0) and controls (median, 1.7). In patients with cirrhosis the ratio was significantly correlated with the S-bilirubins, P-coagulation factors (II + VII + X), and S-total conjugated bile acids. Because of large overlaps of the ratio between the groups the glycine to taurine ratio is of hardly any diagnostic value. The ratio of cholic acid conjugates to chenodeoxycholic acid conjugates was over 1.5 in 10 of 12 cholestasis patients and below this value in all but 1 patient with cirrhosis; the separation of the groups was not improved by splitting the ratio in glycine and taurine conjugates. This study does not suggest that separate determination of glycine and taurine conjugates of bile acids in serum adds diagnostic information in hepatobiliary disease.     

Postprandial plasma concentrations of glycine and taurine conjugated bile acids in healthy subjects.

Fasting and postprandial plasma concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid were measured by a high pressure liquid chromatography-enzymatic assay in nine healthy subjects. The mean value of each bile acid concentration increased significantly (2.4-4.7 times) in the postprandial period. The total glycine taurine ratio of 2.5 in the fasting state increased significantly to a maximum value of 3.3 at one to 1 1/2 hours postprandially and then declined. This shift in glycine taurine ratio shows, that the relative increase in concentrations of glycine conjugates exceeds the relative increase in concentrations of taurine conjugates in the early postprandial period, and supports the view that there is significant absorption of glycine conjugated bile acids from the proximal small intestine.     

Diagnostic value of serum primary bile acids in detecting bile acid malabsorption.

Serum cholic and chenodeoxycholic acid conjugates were measured in fasting conditions and after meals in 14 patients with bile acid malabsorption due to ileal resection. Mean serum fasting levels of both primary bile acids did not differ from the controls. After meals, serum cholic acid peaks were lower in patients with ileal resection than in control subjects (p less than 0.001), while chenodeoxycholic acid peaks were reduced in colectomised patients (p less than 0.01). In the sera from patients with ileal resection, the glycine/glycine + taurine ratio for cholic and chenodeoxycholic acid increased (p less than 0.001) from morning to evening, and glycine/glycine + taurine ratio for chenodeoxycholic acid was significantly (p less than 0.01) different from the controls in the sera collected in the evening. The results are consistent with the concept of a better intestinal conservation of chenyl, mainly of the glycine conjugated from, than of cholylconjugates, in patients with ileal resection; this is probably because of passive absorption in the intestine. The postprandial peaks of serum cholic acid conjugates may therefore be regarded as a test of ileal dysfunction, while peaks of chenodeoxycholic acid conjugates suggest colonic impairment.     

Serum bile acid concentration after a test meal.

Total serum bile acid concentrations were studied by an enzymatic-fluorimetric method employing a highly purified 3 alpha-hydroxysteroid dehydrogenase. In 28 control subjects mean total serum bile acid concentration was 2.5 mumoles/1 (S.D. 1.4). In 6 healthy subjects a significant postprandial increase in total serum bile acids occurred with maximal values at 90 and 120 minutes after ingestion of a liquid test meal. The maximal postprandial increase for each subject was 1.5 to 3 times the fasting value. In 7 patients with various hepatobiliary diseases the maximal postprandial elevation of serum bile acids was higher than in the normals, and the duration of serum bile acid elevation was significantly prolonged. In the patients with normal fasting concentration of bile acids the postprandial elevation was also significantly greater than in the controls. A 2-hour postprandial sample seems suitable for the study of the bile acid test meal response for clinical use.     

Quantification of individual serum bile acids in patients with liver diseases using high-performance liquid chromatography

Using high-performance liquid chromatography combined with a column of immobilized 3 alpha-hydroxysteroid dehydrogenase, 15 bile acids, i.e., cholate, chenodeoxycholate, deoxycholate, lithocholate, ursodeoxycholate, and their five taurine conjugates and five glycine conjugates, were clearly separated and quantified in 38 patients with various hepatobiliary diseases and 9 normal controls. The serum levels of bile acids, both primary and total, were elevated in patients with liver disease, but did not differentiate between parenchymal disease and cholestasis. The ratio of cholate/chenodeoxycholate was significantly increased in cholestasis as compared with parenchymal liver injury. In primary biliary cirrhosis, the ratio of total glycine/taurine conjugates was decreased, with a marked increase of taurochenodeoxycholate. The bile acid pattern was distinctly different between extrahepatic cholestasis and primary biliary cirrhosis, which mainly reflects intrahepatic cholestasis. In acute hepatitis, there was a quick normalization of major taurine and glycine conjugates in the convalescent stage. Most of the major taurine and glycine conjugated bile salts were significantly elevated in cirrhosis, and the elevation of taurochenodeoxycholate was particularly marked in the decompensated state. Furthermore, the quantitative relationship between taurocholate and taurochenodeoxycholate in cirrhosis was reversed from that in acute hepatitis. These changes in absolute and relative concentrations of bile acids in various liver diseases perhaps reflect differing pathology and metabolism, and may prove diagnostic. Measurement of individual bile salts is easily and quickly done with this method, and may lend itself clinical application.     

Diagnostic effectiveness of serum bile acids in liver diseases as evaluated by multivariate statistical methods

The aims of this study were to determine the diagnostic effectiveness of fasting and postprandial serum bile acid determinations in liver diseases, and to compare results with those of conventional liver function tests. In 322 patients with biopsy-proved liver disease and 93 healthy subjects, fasting and postprandial (2 hr) serum levels of cholic, chenodeoxycholic, and lithocholic acid conjugates and conventional liver function tests were evaluated. Data were subjected to variance and discriminant and factor analyses. Fasting serum bile acids were higher in patients when compared to controls and were significantly higher in severe than in mild liver diseases. Determination of cholic plus lithocholic acid provided the highest discrimination capacity. The percent of correct allocation was 75.4% for conventional liver function tests, 70.1% for fasting serum bile acids and increased to 79.6% when liver function tests plus serum bile acids were considered. Postprandial percentages were always lower than fasting. Factor analysis identified two factors possibly related to cytolysis and protein synthesis. The serum bile acid concentrations highly correlated with both factors. We conclude that serum bile acid determinations increase the diagnostic and discriminant capacities of liver function tests and are more sensitive and discriminant when obtained in fasting than postprandially.     

Postprandial changes in serum concentrations of individual bile salts in normal subjects and patients with acute viral hepatitis

A sensitive gas-liquid chromatographic assay has been used to analyze serum concentrations of the four major bile acids in both sulfated and nonsulfated forms. Twelve control subjects have been compared with 40 patients with acute viral hepatitis whose symptoms had been present from 6 to 34 days. In all subjects blood samples were collected fasting and 2 hr after a standard meal. In addition half-hourly samples were assayed for 3 hr after the meal in 6 controls and 5 patients with acute viral hepatitis. In both the control and hepatitis groups, serum concentrations of nonsulfated bile acids, especially cholic and chenodeoxycholic acids, increased after the meal. The peak levls usually occurred between 60 and 120 min in the half-hourly studies. In contrast, sulfated bile acids fell in both groups with minimum levels 60–120 min after the meal. Serum total bilirubin, aspartate aminotransferase, and alkaline phosphatase concentrations in hepatitis patients correlated significantly with postprandialitotal bile acid concentrations but were more frequently abnormal than serum total or individual bile acids. Unconjugated bile acids were not detected in control subjects but were found in 17 of the 40 hepatitis patients. Significantly higher levels of sulfated bile acids and chenodeoxycholic acid were present in hepatitis patients compared to controls. In this group of patients with acute viral hepatitis, studied soon after presentation to hospital but in some cases, some time after the onset of their disease, measurement of serum bile salts was not helpful as an index of hepatocellular function. Postprandial variation in the time of peak concentrations of the individual bile acids resulted in the postprandial bile acid studies being no more useful than fasting assays in distinguishing patients with acute viral hepatitis from control subjects.Supported by the NH and MRC of Australia and the MRC New Zealand.     

Diurnal serum levels of primary conjugated bile acids : Assessment by specific radioimmunoassays for conjugates of cholic and chenodeoxycholic acid

The serum levels of conjugates of chenodeoxycholic acid (chenyl conjugates) and of cholic acid (cholyl conjugates) were determined by specific radioimmunoassays during a 24-hour period, which included three liquid meals and an overnight fast, in five healthy volunteers, five patients with previous cholecystectomy, five patients with documented bile acid malabsorption because of ileal resection, and four pregnant women. In healthy subjects, fasting-state levels of chenyl conjugates, when compared with those of cholyl conjugates, were higher; postprandially, levels of chenyl conjugates rose to a peak sooner (30 minutes vs 60 minutes) and to higher levels (5.2 +/- 1.3 muM vs 2.0 +/- 0.5 muM, M +/- SE). In cholecystectomised patients, the integrated areas under the curve for both bile acids were similar to those of the healthy controls, but postprandial peaks were less marked. In patients with bile acid malabsorption, postprandial rises of chenyl conjugates were lower but remained relatively constant throughout the day, whereas cholyl conjugate levels diminished progressively with each successive meal, consistant with depletion of the cholyl, but not the chenyl, pool. In three of four pregnant women, the postprandial rise of chenyl conjugates was disproportionately less compared with that of healthy controls. These results confirm the dynamic complexity of serum bile acid levels in man and indicate that the major circulating primary bile acids are chenyl conjugates. They support previous proposals that jejunal absorption of chenyl conjugates is important in the normal enterohepatic circulation of bile acids; and they suggest an abnormality in the enterohepatic circulation in pregnancy.     

Enhancement of endothelial nitric oxide production by chenodeoxycholic acids in patients with hepatobiliary diseases

The purpose of this study was to clarify whether physiological concentrations of bile acids could affect endothelial nitric oxide production. We investigated the relationships between clinical concentrations of individual bile acids observed in patients with hepatobiliary diseases and endothelial nitric oxide production induced by each bile acid. Fifteen serum bile acids were measured using high-performance liquid chromatography combined with enzymatic fluorometry in 8 patients with liver cirrhosis, obstructive jaundice, and 8 healthy subjects. The effects of individual bile acids on nitric oxide production were examined in human umbilical endothelial cells by measuring the concentration of NO2- in the cultured medium. NO release in the blood was also determined by measuring the NO2-/NO3- concentration in these patients. In patients with hepatobiliary diseases, the plasma concentrations of chenodeoxycholic acid, ursodeoxycholic acid and cholic acid (free acid, taurine and glycine conjugates) were markedly elevated. Incubation of cells with chenodeoxycholic acid and deoxycholic acid (free acid, taurine and glycine conjugates) enhanced NO2- production in a concentration-dependent manner, while cholic acid (free and its conjugates) did not. The effects of individual bile acids on nitric oxide production were additive. Patients with liver cirrhosis and obstructive jaundice had higher plasma levels of NO2-/NO3- levels than the control subjects. These results suggest that increased plasma concentrations of chenodeoxycholic acid (free, taurine and glycine conjugates) in patients with hepatobiliary diseases may induce endothelial nitric oxide production. Thus, nitric oxide production induced by bile acids may be involved in the pathogenesis of circulatory abnormalities in patients with liver diseases.     

Conjugated bile acids in serum and secretions in response to cholecystokinin/secretin stimulation in children with cystic fibrosis.

More than 80% of patients with cystic fibrosis have poor pancreatic function, and have large daily faecal bile acid losses. This has been postulated to lower luminal bile acid concentrations and adversely affect fat absorption. We studied, for the first time, quantitative individual conjugated duodenal bile acid secretion rates into the duodenum during cholecystokinin/secretin infusion in 55 cystic fibrosis patients and six controls, using a quantitative non-absorbable marker technique. We were able to show adequate duodenal total bile acid concentrations and normal secretion rates in these children. The bile acid secretion pattern in cystic fibrosis patients showed a marked increase in bile acid concentration during cholecystokinin/secretin infusion, to levels which were above the critical micellar concentration indicating that the gall bladder is a functional organ in this disease. The subsequent fall in secretion rate was similar to controls. We have documented a significantly raised glycine/taurine bile acid conjugation ration in duodenal juice from cystic fibrosis patients and suggest that the combined effects of lowered ileal pH and increased glycine conjugated proportion of bile acids may cause precipitation of bile acids leading to decreased fat absorption and large faecal bile acid losses. To further investigate bile acid secretion in children with cystic fibrosis, we modified the high performance thin layer chromatography/densitometry method to enable measurement of individual glycine and taurine conjugates in serum. In comparing cystic fibrosis patients and controls, we were able to determine a group of 18 (36%) with bile acid evidence of liver damage who also showed reduced bile acid secretion into the duodenum. We were unable to study changes in serum bile acids during cholecystokinin/secretin infusion because of the high level of bile acid contamination in Boots Secretin. Some patients showed raised fasting serum bile acid concentrations more than two years before changes in conventional liver function tests or clinically evident liver disease. We have shown fasting serum bile acids to be a sensitive measure of liver dysfunction in cystic fibrosis and postulate that raised proportions of glycine conjugated bile acids may be responsible for the high incidence of liver disease in cystic fibrosis.     

Serum bile acids in primary biliary cirrhosis

Serum bile acid classes have been studied in 15 patients with primary biliary cirrhosis in five patients with cholestasis, and in five patients who had cirrhosis without cholestatic features. Conjugated monohydroxy bile acids (12-35% serum total bile acids) were found in eight of 11 sera from patients with primary biliary cirrhosis, in sera from four patients with cholestasis but not in any of the five patients with cirrhosis. The glycine conjugates/taurine conjugates (G/T) ratio in eight of 11 patients with primary biliary cirrhosis and two of four patients with cholestasis was <1.0.Bile acid concentrations in seven patients with primary biliary cirrhosis were measured before and during cholestyramine therapy. Decreases in serum total bile acid concentrations were observed which were accompanied by small increases in the trihydroxy/dihydroxy ratio and also in the G/T ratio in six of the seven patients. No association was found between the concentration of any particular conjugated or free bile acid and the presence or absence of pruritus.     

Concentrations of glycine- and taurine-conjugated bile acids in portal and systemic venous serum in man

Concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid in portal and systemic venous serum and in bile were measured in eight subjects undergoing elective cholecystectomy. Mean concentrations in systemic serum ranged from 0.07 to 0.17 mumol/l, in portal serum from 0.49 to 2.09 mumol/l, and in bile from 2.72 to 17.2 mmol/l. The percentage content of trihydroxy-bile acid conjugates in bile (49%) and in portal serum (51%) was higher than in systemic serum (35%) (P less than 0.001). The estimated hepatic fractional uptake of glycocholic acid (mean, 83%) and of taurocholic acid (83%) was higher than the uptakes of the dihydroxy-bile acid conjugates (60-68%). The percentage contents of glycine-conjugated bile acids in systemic serum (mean, 66%), portal serum (62%), and bile (65%) were not significantly different.     

Faecal bile acid excretion in children with inflammatory bowel disease.

Faecal bile acid excretion and intestinal transit time were studied in 18 children with inflammatory bowel disease in clinical remission and with normal stools: 16 with ulcerative colitis, two with Crohn's colitis, mean age 14 years (range 10-17 years). Five healthy children, mean age 12.4 years (range 10-17 years), were studied as control subjects. Most patients were taking sulphasalazine, but none were taking steroids. Transit time was determined by carmine and did not differ between groups. Faeces were collected for 72 hours, and faecal water was prepared by centrifugation of faeces at 15,000 x g for two hours. Bile acids in total faeces and faecal water were studied using capillary gas-liquid chromatography-mass spectrometry. Faecal excretion of total bile acids, unconjugated bile acids, and glycine and taurine conjugates were significantly increased in patients as was faecal water excretion of total bile acids, particularly the taurine conjugates and cholic and chenodeoxycholic acids. Total concentrations of bile acids in faeces and faecal water were two to five times higher in patients. The children with inflammatory bowel disease in clinical remission had high excretion and concentration rates of bile acids, especially taurine conjugates, in both total faeces and faecal water, a finding of considerable interest in the pathogenesis of malignancy in these diseases.     

Bile acid glycine and taurine conjugates in serum of patients with primary biliary cirrhosis: effect of ursodeoxycholic treatment.

We have applied a specific and accurate high pressure liquid chromatographic technique to determine fasting serum glycine and taurine conjugates of individual bile acids in patients with primary biliary cirrhosis before and during ursodeoxycholic acid therapy. The study was carried out in nine patients in whom the diagnosis of primary biliary cirrhosis was established according to accepted criteria. After one year of UDCA therapy liver function tests significantly improved. Total serum bile acid concentration did not change significantly (29.2 (31.5) v 28.3 (26.4) microM). Total UDCA (1.7 (2.2) v 13.3 (14.5) microM) and glyco UDCA (0.8 (1.6) v 10.9 (11.4 microM) but not tauro UDCA levels increased significantly (p less than 0.01); UDCA (7.7 (12.6) v 40.2 (12.7)%) became the major species of the circulating bile acids. Primary bile acids (23 (28.3) v 11.2 (10.5) and their glycoconjugates fell significantly (p less than 0.01). There were no significant changes in the concentrations of conjugates of the secondary bile acids (4.5 (3.8) v 3.9 (3.0]. Our study shows that oral administration of UDCA to patients with primary biliary cirrhosis induced marked changes in the circulating pool of endogenous bile acids together with improvement in liver function test values. The data also suggest that the beneficial effect of longterm administration of UDCA in these patients might be mediated through changes in the circulating primary bile acids and UDCA rather than through changes in the circulating secondary bile acids, deoxycholate and lithocholate.     

Concentrations of Glycine- and Taurine-Conjugated Bile Acids in Portal and Systemic Venous Serum in Man

Concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid in portal and systemic venous serum and in bile were measured in eight subjects undergoing elective cholecystectomy. Mean concentrations in systemic serum ranged from 0.07 to 0.17 μmol/l, in portal serum from 0.49 to 2.09 μmol/l, and in bile from 2.72 to 17.2mmol/l. The percentage content of trihydroxy-bile acid conjugates in bile (49%) and in portal serum (51%) was higher than in systemic serum (35%) (P < 0.001). The estimated hepatic fractional uptake of glycocholic acid (mean, 83%) and of taurocholic acid (83%) was higher than the uptakes of the dihydroxy-bile acid conjugates (60–68%). The percentage contents of glycine-con-jugated bile acids in systemic serum (mean, 66%), portal serum (62%), and bile (65%) were not significantly different.     

High concentration and retained amidation of fecal bile acids in patients with active ulcerative colitis

Fecal bile acid profiles of 14 patients with ulcerative colitis in the active phase were analyzed to study the potential significance of bile acids in the pathophysiology of this disease, and the results were compared with those in 12 healthy controls. The excretion levels of total bile acids (mean +/- SD) in patients were higher than in controls, 445.1 +/- 392.1 vs 215.5 +/- 148.0 mumol/day, 3.1 +/- 1.7 vs 1.6 +/- 1.0 mumol/g wet feces (P less than 0.05), and 17.2 +/- 9.2 vs 12.4 +/- 13.3 mumol/g dry feces. Fecal profiles of individual bile acids showed higher levels of primary bile acids (52 +/- 27%) in patients compared to those (26 +/- 21%) in controls. Proportions of glycine and taurine conjugates in patients (26 +/- 24%) were higher than in controls (5 +/- 2%) (P less than 0.05), whereas proportions of unconjugates and sulfates were lower in patients than in controls. Accordingly the extent of deconjugation and dehydroxylation of bile acids was lower in patients than in controls. These trends were prominent in patients with more severe disease activity. A high concentration of bile acids in the intestine may have a significant role in the pathophysiology of ulcerative colitis at active phase.     

Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: a pilot study

BackgroundPrimary biliary cirrhosis and primary sclerosing cholangitis are two cholestatic diseases characterised by hepatic accumulation of bile acids.AimsThis study compares serum bile acid levels in patients with primary biliary cirrhosis and primary sclerosing cholangitis and from age and sex-matched non cholestatic donors.MethodsSeventeen bile acids were quantified using liquid chromatography coupled to tandem mass spectrometry. Serum samples from cholestatic patients were compared with those of non-cholestatic donors.ResultsThe concentration of total bile acids, taurine and glycine conjugates of primary bile acids was elevated in both patients with primary biliary cirrhosis and primary sclerosing cholangitis when compared to non-cholestatic donors. Samples from primary sclerosing cholangitis patients displayed reduced levels of secondary acids, when compared to non cholestatic and primary biliary cirrhosis sera. The ratio of total glycine versus total taurine conjugates was reduced in patients with primary biliary cirrhosis, but not in primary sclerosing cholangitis.ConclusionThe present study suggests that circulating bile acids are altered differentially in primary biliary cirrhosis and primary sclerosing cholangitis patients.     

Comprehensive study of the biliary bile acid composition of patients with cystic fibrosis and associated liver disease before and after UDCA administration

The biliary bile acid composition was determined for patients with cystic fibrosis and associated liver disease before and after the administration of ursodeoxycholic acid (10 to 15 mg/kg body wt/day). Bile acids were analyzed by fast atom bombardment ionization-mass spectrometry, high performance liquid chromatography and gas chromatography-mass spectrometry after individual bile acids were separated according to their mode of conjugation using the lipophilic anion exchanger, diethylaminohydroxypropyl Sephadex LH-20. More than 50 individual bile acids were identified in the bile of cystic fibrosis patients and these acids were predominantly secreted as glycine and taurine conjugates. Small proportions (less than 8% of the total) of unconjugated and sulfate conjugates were present. Of interest was the identification of two side-chain-elongated (C25) bile acids, homocholic and homochenodeoxycholic acids. After ursodeoxycholic acid was administered, duodenal bile became enriched with the conjugated species of ursodeoxycholic acid (accounting for 11.9% to 32.5% of the total biliary bile acids), but to a lesser extent than reported previously for patients with other liver diseases or gallstones who received comparable doses of ursodeoxycholic acid, and this presumably occurs because of bile acid malabsorption that is a feature of cystic fibrosis. The mean glycine/taurine ratio increased from 2.4 before ursodeoxycholic acid administration to 5 after ursodeoxycholic acid administration even though these patients also received taurine. Despite the relatively low enrichment of the bile by ursodeoxycholic acid, biochemical indices of liver function all improved in these patients after ursodeoxycholic acid administration.     

Postprandial Serum Bile Acids in Resected and Non-Resected Patients with Crohn's Disease

Fasting and postprandial serum conjugates of cholic acid (CCA) and chenodeoxy-cholic acid (CCDA) were determined by radioimmunoassay in 46 healthy individuals and 15 patients with Crohn's disease (CD), 7 bowel-resected and 8 non-resected. All patients had normal conventional liver test results, and fasting values of CCA and CCDA were within the reference ranges. Two findings appeared: the mean postprandial increases in CCA and CCDA were both lower in CD patients than in healthy individuals, and the postprandial increase in CCA was lower in the resected patients than in the non-resected, whereas the postprandial increase in CCDA was the same in the resected and the non-resected patients. These findings show that in CD patients, whether resected or not, the postprandial levels of bile acids are low. This could reflect a decreased absorptive capacity of bile acids in the small intestine. The finding that postprandial CCA, but not CCDA, was lower in resected than in non-resected patients may reflect different sites of CCA and CCDA absorption.     

Serum bile acid profile in women during pregnancy and childbed.

Oestrogens produce cholestasis by inhibition of bile acid (BA) transport as well as by inhibition of BA synthesis in the liver. The present work was done to clarify the relevance of altered serum BA profile in 28 healthy pregnant women from the 15th to the 40th weeks of pregnancy with increasing oestrogen serum concentrations in comparison to 6 to 8 weeks after delivery with normalized oestrogen status. For the first time 6 free and 10 taurine- and glycine-conjugated BAs were analysed during the normal pregnancy by HPLC with postcolumn derivatisation and fluorescence detection. The primary BAs cholic (CA) and chenodeoxycholic acid (CDCA) as well as their glycine (G-) and taurine (T-) conjugates amount to nearly 70 % of total BAs in serum and were not changed from the 15th to the 40th weeks of pregnancy, but free and G-CDCA increased significantly after delivery. Among the secondary BAs, which were produced in the intestine by bacteria due to dehydroxylation of the primary bile acids CA and CDCA, only taurine-conjugated deoxycholic acid (T-DCA) decreased significantly after delivery. The free BAs, produced by bacteria in the intestine due to deconjugation, were not changed during pregnancy but had doubled in childbed. Some BAs occurred seldom and in small amounts in the serum, but during pregnancy not more frequent than after delivery. Contrary to expectation the increasing oestrogen concentrations did neither enhance total serum bile acids nor change bile acid profile during pregnancy.