Effects of feeding chenodeoxycholic acid on metabolism of cholesterol and bile acids in germ-free rats

The aim of this investigation was to study the influence of chenodeoxycholic acid administration on cholesterol and bile acid synthesis in germ-free rats. Seven rats were fed a basal diet and 2 groups of 4 rats received the same diet supplemented with 0.4 and 1% chenodeoxycholic acid, respectively. After 6 weeks, feces were collected in one 3- and one 4-day pool for analysis of cholesterol and bile acids. When the sampling period was finished, the rats were killed and the liver microsomal fractions isolated. The activities of HMG CoA reductase and cholesterol 7α-hydroxylase were determined, the 7α-hydroxylase by a mass fragmentographic method. The 2 dominating bile acids in the untreated rats were cholic acid and β-muricholic acid. During treatment with chenodeoxycholic acid, 60–70% of this bile acid was converted into α- and β-muricholic acid, indicating a high activity of the 6β-hydroxylase. The excretion of cholic acid was almost completely inhibited and the 7α-hydroxylase activity was decreased ca 75% in the rats fed 1% chenodeoxycholic acid. The activity of the hepatic HMG CoA reductase was unchanged. The fecal excretion of cholesterol increased 2–3 times. An accumulation of cholesterol was seen in the rats treated with 1% chenodeoxycholic acid, which was probably a result of the decreased catabolism of cholesterol to bile acids.     

The cholesterol-lowering effect of guar gum in rats is not accompanied by an interruption of bile acid cycling

A viscous hydrocolloid (guar gum, GG; 2.5% of the diet) or a steroid sequestrant (cholestyramine; 0.5% of the diet) was included in semipurified diets containing 0.2% cholesterol to compare the cholesterol-lowering effects of each agent in rats. In the present model, GG significantly lowered plasma cholesterol (−25%), especially in the density <1.040 kg/L fraction, whereas cholestyramine was less potent. Bile acid fecal excretion significantly increased only in rats fed cholestyramine, similar to the cecal bile acid pool; the biliary bile acid secretion was accelerated by GG, but not their fecal excretion, whereas GG effectively enhanced neutral sterol excretion. As a result, the total steroid balance (+13 μmol/d in the control) was shifted toward negative values in rats fed the GG or cholestyramine diets (−27 or −50 μmol/d, respectively). Both agents induced liver 3-hydroxy-3-methylglutaryl-CoA reductase, but cholestyramine was more potent than GG in this respect. The present data suggest that, at a relative low dose in the diet, GG may be more effective than cholestyramine in lowering plasma cholesterol by impairing cholesterol absorption and by accelerating the small intestine/liver cycling of bile acids, which is interestingly, accompanied by reduction of bile acid concentration in the large intestine.     

Effects of triton WR 1339 and orotic acid on lipid metabolism in rats

In order to investigate the effect of hepatic cholesterol flux on biliary bile acids, Triton WR 1339 and orotic acid were administered to rats, and the biliary cholesterol, phospholipids and bile acids were analyzed together with serum lipoproteins and hepatic lipids. Triton, which raised serum very low density lipoprotein and lipid levels and decreased serum high density lipoprotein liver lipid levels, increase the biliary cholic acid group/chenodeoxycholic acid group ratio (CA/CDCA) in the bile without affecting the total amount of bile acids and the other biliary lipids. Orotic acid, which decreased serum lipid and lipoprotein concentrations and increased liver lipid levels, increased the biliary excretion of cholesterol and phospholipids, but produced no significant change in the total amount of bile acids and in the CA/CDCA ratio in bile.     

The effects of polyoxyethylated cholesterol on fecal bile acids and nitrogen and on cholesterol balance in rats

Polyoxyethalated cholesterol (POEC) is a water soluble derivative of cholesterol which decreases cholesterol absorption in rats without affecting body weight, fatty acid excretion, or intestinal histology. In the present study rat feces were analyzed for cholic, deoxycholic, chenodeoxycholic, muricholic and lithocholic acid following 3 months of feeding a standard or a 2% enriched cholesterol diet with or without 1.5% POEC. In rats maintained on the cholesterol free diet, POEC increased total bile acids (mg/day) by 50% from 14±3 to 21±3 (mean ±SEM) but only the increase in chenodeoxycholic acid was significant (P<0.05). The corresponding POEC effect in the 2% cholesterol diet was 31% (70±8 to 93±3, P<0.01). Fecal nitrogen and serum cholesterol did not vary among groups. Comparing these data with neutral steroid excretion previously determined showed that POEC in the cholesterolfree diet increased the negative cholesterol balance more than three-fold (34±7vs 118±13 P<0.01). In rats fed 2% cholesterol, POEC caused a negative cholesterol balance of 222±8 compared to the control of 27±52 (P<0.01). The data indicate that POEC exerts complex effects in the intestinal tract which increase both bile acid and cholesterol excretion.     

Effect of glucose administration on cholesterol and bile acid metabolism in rats

Glucose administered to fasted rats caused a marked stimulation in hepatic cholesterogenesis and cholesterol 7 alpha-hydroxylation, and an increase in biliary excretion of cholesterol and total bile acids. The excretion of cholic acid was not incluenced during the first few hr after glucose administration, but was significantly increased after 5 hr. Chenodeoxycholic acid showed a similar change, but the increase was only ca. one tenth of that of cholic acid. The excretion of deoxycholic acid was markedly increased by 1 hr, but gradually decreased thereafter. Pretreatment with neomycin abolished the increase in deoxycholic acid by fasting and glucose administration. Other bile acid components showed no significant change. It thus was presumed that cholesterol endogenously synthesized in the liver was metabolized mainly to cholic acid. In contrast, exogenous cholesterol was metabolized mainly to chenodeoxycholic acid. During the period of the acute enhancement of cholic acid formation from the endogenous cholesterol, biliary excretion of deoxycholic acid was increased. This probably occurred through the depression of 7 alpha-rehydroxylation of deoxycholic acid, or through the enhancement of microbial formation of deoxycholic acid in the lumen, and through the increase of intestinal absorption.     

Cholesterol synthesis and degradation in normal rats fed a cholesterol-free diet with excess cystine

Feeding a diet with excess cystine to rats resulted in hypercholesterolemia. To understand the mechanism of the hypercholesterolemia’ cholesterol synthesis and degradation’ bile acid content of bile’ and fecal steroids were determined. The in vivo incorporation of tritiated water into hepatic cholesterol’ and activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase in rats fed a high-cystine diet were significantly higher than those in rats fed a control diet. The activity of hepatic cholesterol 7α-hydroxylase was similar between two groups. Little effect of cystine supplementation was found on fecal sterol excretion although there were some changes in biliary excretion of cholic acid derivatives. These results indicate that hypercholesterolemia caused by feeding of a high-cystine diet may be due to the stimulation of hepatic cholesterol synthesis.     

Bile acid metabolism in young-old parabiotic rats

Serum cholesterol, triglyceride and phospholipid levels, liver cholesterol concentration, bile flow, biliary cholesterol, phospholipid and bile acid secretion rates, fecal sterol and bile acid levels and their bile acid compositions were examined in young-old parabiotic rats and compared with those in young and old control rats and young-young parabiotic rats. Bile acid composition was expressed in terms of the cholic acid group/chenodeoxycholic acid group (CA/CDCA) ratio. Body weight (BW) gain decreased after parabiosis especially in old rats, but the liver weight (g/100 g BW), diet-intake, feces dry weight, liver cholesterol concentration and fecal sterol level were almost the same in all the groups. The biliary bile acid secretion rate was higher and the fecal bile acid level was lower in old rats than those in young rats but both the levels became comparable with those in young rats after parabiosis of old rats with young rats. Young rats, however, showed no changes in these levels after parabiosis. The serum cholesterol level and the biliary and fecal CA/CDCA ratios in old rats were higher than those in young rats but decreased after parabiosis with young rats, although they were still higher than those in young rats. The serum cholesterol level in young rats increased after parabiosis with old rats, but not after parabiosis with young rats, and the fecal bile acid level and the CA/CDCA ratio were not changed in either case. It is concluded from these findings that the serum cholesterol level and the CA/CDCA ratio increased with age and that these increases were prevented after parabiosis with young rats, while young rats, although their serum cholesterol level was increased, showed no increase in the CA/CDCA ratio after parabiosis with old rats.     

Contrasting effects of water-soluble and water-insoluble dietary fibers on bile acid conjugation and taurine metabolism in the rat

The effect of the type of dietary fiber on the bile acid and taurine metabolism was examined in rats. Diets containing 10% of various water-soluble fibers (citrus pectin, konjak mannan, guar gum) as compared to a fiber-free diet increased biliary excretion of total bile acids. In contrast, water-insoluble dietary fibers (cellulose, corn bran, chitin; 10% in the diets) as well as cholestyramine (5% in the diet) considerably, decreased bile acid excretion. Water-soluble dietary fibermediated increases in bile acid excretion were totally attributable to increases in glycine-conjugates. Thus, these fibers greatly increased by the bile acid glycine-to-taurine ratio (G/T). Excretio of glycine conjugates decreased more than that of taurine conjugates in rats fed various water-insoluble dietary fibers. As a results, G/T in rats fed water-insoluble fibers was significantly lowered as compared to G/T in animals fed a fiber-free diet. Cholestyramine did not affect the G/T ratio of bile acids. Fecal bile acid excretion and the activities of hepatic cholesterol 7α-hydroxylase (EC 1.14.13.17) in rats fed various water-soluble dietary fibers approximately doubled as compared to the respective values for rats fed a fiber-free diet. Whereas cholestyramine greatly increased these parameters, water-insoluble fibers did not significantly affect them. Various water-soluble fibers decreased hepatic concentration and urinary excretion of taurine as well as the activity of hepatic cysteine dioxygenase (EC 1.13.11.20). In contrast, water-insoluble fibers considerably increased hepatic taurine concentrations and enzyme activities. The parameters for taurine metabolism were unaffected by cholestyramine. It was suggested that the types of dietary fiber affected hepatic taurine synthesis and thus modified bile acid glycine/taurine ratios.     

Effects of phenobarbital upon bile acid synthesis in two strains of rats

Rats of the Wistar and Sprague-Dawley strains were injected with sodium phenobarbital (100 mg/kg body wt/day) for 8 days. Fecal bile acid excretion was measured on days 6 and 8 of the experiment, and biliary bile acid composition, hepatic microsomal cholesterol, 7α-hydroxylase, and 7α-hydroxy-4-cholesten-3-one 12α-hydroxylase were determined at the end of the study. In the Wistar rat, injection of phenobarbital produced a doubling of fecal bile acid output (controls, 5.3 mg/rat/day; treated rats, 10.6 mg/rat/day) and a two-three fold increase in cholesterol 7α-hydroxylase. The fecal bile acid output of Sprague-Dawley rats increased 20% in response to phenobarbital (controls, 9.5 mg/rat/day; treated rats, 11.6 mg/rat/day). The activity of cholesterol 7α-hydroxylase remained unchanged. In both strains, phenobarbital treatment produced a decrease in the proportion of cholic acid in total biliary bile acids (controls, 85%; treated groups, 65%). This was associated with a decrease of 7α-hydroxy-4-cholesten-3-one 12α-hydroxylase activity by ca. 50%. Biliary cholesterol concentrations were reduced in phenobarbital treated rats of both strains, but liver cholesterol concentrations remained unchanged. The drug produced a 25% increase in liver wt, on the average.     

Effect of 7-methylated bile acids and bile alcohols on cholesterol metabolism in hamsters

The effect of 7-methyl substituted bile acid and bile alcohol analogues on cholesterol metabolism was studied in the hamster. Animals were fed chow plus 0.1% cholesterol supplemented with 0.1% of one of the following steroids: chenodeoxycholic acid, 7-methyl-chenodeoxy-cholic acid, 7β-methyl-24-nor-5β-cholestane-3α,7α,25-triol, cholic acid, 7-methyl-cholic acid, or 7β-methyl-24-nor-5β-cholestane-3α,7α,12α,25-tetrol. Cholesterol absorption was determined from fecal analysis after feeding of radiolabeled cholesterol and β-sitosterol. Of the six compounds studied, chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid decreased intestinal cholesterol absorption (17% and 31% decrease, respectively). Only 7-methyl-chenodeoxycholic acid decreased serum cholesterol concentration (29% decrease), but there were no analogous changes of liver and biliary cholesterol concentration and cholesterol saturation of bile. Total fecal neutral sterol excretion was increased in the groups fed chenodeoxycholic acid and 7-methyl-chenodeoxycholic acid. In addition, the production of coprostanol was increased in both groups. These data suggest that 7-methyl-chenodeoxycholic acid resembles chenodeoxycholic acid in its effect on cholesterol metabolism and may be a potential candidate for further studies of its gallstone-dissolving properties.     

Distribution of bile acids in rats

Distribution and biliary and fecal excretion of bile acids were examined in Wistar strain male rats of about 300 g body weight. The pool size of the rats on ordinary diet was 40 mg/rat, biliary secretion was 14 mg/hr, and fecal excretion was 10 mg/day. Bile acids were mainly located in the small and large intestinal contents, 87% and 10%, respectively; but a portion was found in the intestinal wall and the liver. Rats fed 2% cholesterol-supplemented diet for a week showed similar values for pool size and biliary secretion with the rats on ordinary diet, but higher values for fecal excretion and distribution ratio in the large intestinal contents. Cholic acid was a major component in the bile, small intestinal wall, small intestinal content and liver, while the bile acid composition ratios were roughly similar to each other, although a relatively large amount of α-muricholic acid was found in the intentinal wall and liver. Both the wall and content compositions of the large intestine were similar to that of the feces, in which lithocholic, deoxycholic, α- and β-muricholic acids were the main components, although the ratios of α- and β-muricholic acids in the large intestinal wall were larger than those in the intestinal contents or feces. The high concentrations of these bile acids may indicate a difference of transport velocity across the cell membrane, but the mechanism is not known.     

Effect of chitosan feeding on intestinal bile acid metabolism in rats

The effect of chitosan feeding (for 21 days) on intestinal bile acids was studied in male rats. Serum cholesterol levels in rats fed a commercial diet low in cholesterol were decreased by chitosan supplementation. Chitosan inhibited the transformation of cholesterol to coprostanol without causing a qualitative change in fecal excretion of these neutral sterols. Increased fiber consumption did not increase fecal excretion of bile acids, but caused a marked change in fecal bile acid composition. Litcholic acid increased sigificantly, deoxycholic acid increased to a leasser extent, whereas hyodeoxycholic acid and the 6β-isomer and 5-epimeric 3α-hydroxy-6-keto-cholanoic acid(s) decreased. The pH in the cecum and colon became elevated by chitosan feeding which affected the conversion of primary bile acids to secondary bile acids in the large intestine. In the cecum, chitosan feeding increased the concentration of α-,β-, and ω-muricholic acids, and lithocholic acid. However, the levels of hyodeoxycholic acid and its 6β-isomer, of monohydroxy-monoketo-cholanoic acids, and of 3α, 6ξ, 7ξ-trihydroxy-cholanoic acid decreased. The data suggest that chitosan feeding affects the metabolism of intestinal bile acids in rats.     

Resistant starch is more effective than cholestyramine as a lipid-lowering agent in the rat

Amylase-resistant starch (RS) represents a substrate for the bacterial flora of the colon, and the question arises as whether RS shares with soluble fibers common mechanisms for their lipid-lowering effects. It is uncertain whether a cholesterol-lowering effect depends basically on an enhanced rate of steroid excretion or whether colonic fermentations also play a role in this effect. In the present study, the effect of RS (25% raw potato starch), of a steroid sequestrant (0.8% cholestyramine), or both were compared on bile acid excretion and lipid metabolism in rats fed semipurified diets. RS diets led to a marked rise in cecal size and the cecal pool of short-chain fatty acids (SCFA), as well as SCFA absorption; cholestyramine did not noticeably affect cecal fermentation. Whereas cholestyramine was particularly effective at enhancing bile acid excretion, RS was more effective in lowering plasma cholesterol (−32%) and triglycerides (−29%). The activity of 3-hydroxy-3-methylglutaryl-CoA reductase was increased fivefold by cholestyramine and twofold by RS. This induction in rats fed RS diets was concomittant to a depressed fatty acid synthase activity. In rats fed the RS diet, there was a lower concentration of cholesterol in all lipoprotein fractions, especially the (d=1.040−1.080) fraction high-density lipoprotein (HDL₁), while those fed cholestyramine had only a significant reduction of HDL₁ cholesterol. In contrast to cholestyramine, RS also depressed the concentration of triglycerides in the triglyceride-rich lipoprotein fraction. There was no noticeable synergy between the effects of RS and cholestyramine when both were present in the diet. This suggests that the cholesterol-lowering effect of RS is not limited to its capacity to enhance bile acids excretion. The difference between RS and cholestyramine could relate to the capacity of fermentation end-products to counteract the upregulation of cholesterol and bile acid biosynthesis. Thus, in the absence of fermentation in the large intestine, a high rate of bile acids excretion is not always sufficient to elicit a cholesterol-lowering effect.     

Differential effects of ursodeoxycholic acid and ursocholic acid on the formation of biliary cholesterol crystals in mice

The preventive effect of 3α,7β,12α-trihydroxy-5β-cholanoic acid (ursocholic acid) and ursodeoxycholic acid on the formation of biliary cholesterol crystals was studied in mice. Cholesterol crystals developed with 80% incidence after feeding for five weeks a lithogenic diet containing 0.5% cholesterol and 0.25% sodium cholate. When 0.25% ursocholic acid or ursodeoxycholic acid was added to the lithogenic diet, the incidence as well as the grade (severity) of the gallstones were reduced. Plasma and liver cholesterol levels were decreased by ursodeoxycholic acid but not by ursocholic acid. Gallbladder cholesterol and phospholipid levels were decreased by both bile acids. The biliary bile acid level was decreased by ursocholic acid but not by ursodeoxycholic acid. After feeding ursocholic acid, its level in the bile was about 25% and the levels of cholic acid and β-muricholic acid decreased. Fecal sterol excretion was not changed by ursocholic acid, but was increased by ursodeoxycholic acid. After feeding ursocholic acid, fecal excretion of deoxycholic acid, cholic acid, and ursocholic acid increased. No differences were found between mice, with or without gallstones, in plasma and liver cholesterol levels, biliary phospholipid and bile acid levels, fecal sterol and bile acid levels, and biliary and fecal bile acid composition. The results suggest that the lower incidence of crystal formation after treatment with ursocholic acid is probably by a different mechanism than with ursodeoxycholic acid. In the mouse model, ursodeoxycholic acid exerts its effect at least partially, by decreasing cholesterol absorption. Ursocholic acid is well absorbed and excreted into bile and transformed into deoxycholic acid by the intestinal microflora in mice.     

Alteration of cholesterol metabolism by 4-0-methylascochlorin in rats

The effect of 4-0-methylascochlorin (MAC), an experimental hypocholesterolemic agent, on cholesterol metabolism was investigated in rats in two separate experiments. The administration of MAC for 2 and 6 consecutive weeks at daily doses of 100–135 mg/kg resulted in reduction in serum cholesterol levels of 16% after 2 weeks of treatment in the first experiment, and 13% after 6 weeks in the second experiment in comparison to the corresponding controls. MAC administered at a daily dose of 100 mg/kg for 2 weeks showed a significant increase in the biliary excretion of bile acids and cholesterol in bile-duct cannulated rats with or without the administration of taurocholate. In the second experiment, MAC treatment for 6 weeks produced a marked increase in the fecal output of acidic sterols during a 2 to 6-week period. MAC treatment also further enhanced hepatic cholesterol 7α-hydroxylase in the rats. Therefore, it appears that the mechanism of serum cholesterol lowering due to MAC is related to the enhancement of hepatic bile acid synthesis and the increase in biliary and fecal excretion of bile acids.     

Bile acid metabolism in analbuminemic rats

The bile acid concentrations in the serum, liver, bile, intestines, and feces of 3- and 19-mon-old male and female Nagase analbuminemic (NA) rats were compared with those in Sprague-Dawley (SD) rats. There was no significant difference in the bile acid levels between NA and SD rats. However, increased biosynthesis and pool size of cholic acid (CD) derivatives and decreased levels of chenodeoxycholic acid (CDCA) derivatives (increased CA/CDCA ratio) were detected in male NA rats as compared to SD rats. The CA/CDCA ratio in female NA rats was not different from that in their SD rats in the biliary bile flow, bile acid levels in the small and large intestines, fecal bile acid excretion, bile acid concentration in the portal and systemic circulation, and in the pool size of bile acids. The blood lipid concentrations were significantly higher in the NA rats than in the SD rats. The hepatic levels of lipids were not significantly different between the two rat strains. In conclusion, this study showed that metabolism of bile acids in NA rats is not significantly affected, and that the hypercholesterolemia observed in these strains is not related to abnormalities of bile acid metabolism.     

Biliary and fecal steroid excretion in rats fed partially hydrogenated soybean oil

Male Wistar rats were fed cholesterol-free or cholesterol-enriched diets containing partially hydrogenated soybean oil with different levels of trans-fatty acids or unhydrogenated soybean oil at the 10% level. The linoleic acid content of hydrogenated fat diets was adjusted to 3.6% of the total energy. Hydrogenated fat diets contained 29% and 41% trans-acids, mainly as t-18:1. Trans-fats exerted no untoward effects on growth parameters, but increased liver weight. Dietary hydrogenated fats influenced neither the concentration nor composition of biliary steroids, irrespective of the presence or absence of cholesterol in the diet. In rats fed a cholesterol-free diet, daily fecal output of neutral and acidic steroids was enhanced by hydrogenated fats and the magnitude of augmentation was proportional to the dietary level of trans-fatty acids. The increased fecal steroid excretion corresponded to an increase in total excreta. Hydrogenated fats also tended to enhance bile acid excretion when feeding a cholesterol-enriched diet. The results suggest that dietary trans-fatty acids, in relation to cis-polyunsaturated fatty acids, provoke demonstrable change in steroid homeodynamics.     

Evidence for distinct precursor pools for biliary cholesterol and primary bile acids in cebus and cynomolgus monkeys

The abnormal metabolism and distribution of plasma lipoproteins have been associated with atherosclerosis and gallstones. To better understand the process of cholesterol excretion, a study was designed to determine whether the contribution of lipoprotein free¹⁴C-cholesterol (as LDL or HDL) to biliary cholesterol or primary bile acids differs in two species of nonhuman primates, cebus and cynomolgus monkeys, having opposite plasma LDL/HDL ratios. Since amino acid conjugation might influence bile acid synthesis or secretion, the taurine and glycine conjugates of newly synthesized primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA), were measured in the species capable of conjugating with taurine or glycine (cynomolgus). After total bile acid pool washout, monkeys were infused with human LDL or HDL labeled with free¹⁴C-cholesterol, and the specific activities (SA) of biliary cholesterol and primary bile acid conjugates were determined. In both species, regardless of the lipoprotein infused, the SA of biliary cholesterol and CA were greater than those for total bile acids and CDCA, respectively. In cynomolgus, the SA of glycine conjugates was higher for CA than CDCA, while the SA of taurine conjugates was greater for CDCA than CA. Under these conditions, (i) infused lipoprotein free cholesterol (as either LDL or HDL) contributed more to biliary cholesterol than to bile acids and more to CA than to CDCA; (ii) glycine conjugated preferentially with CA rather than CDCA, while taurine was the preferred conjugate for CDCA. Further, whereas the two primary bile acids had similar rates of synthesis and turnover in cynomolgus, basal bile acid synthesis was much greater in cebus and the CDCA turnover appeared disproportionately large.     

Hypolipidemic effects of β-cyclodextrin in the hamster and in the genetically hypercholesterolemic rico rat

The effect of increasing amounts of a cyclic oligosaccharide, β-cyclodextrin (BCD), included in the diet on plasma cholesterol and triglycerides, was investigated in two animal models, namely in male genetically hypercholesterolemic Rico rats and in male Syrian hamsters. The distribution of bile acids in the gastrointestinal tract and in the feces of hamsters was also determined. In the Rico rats and hamsters, plasma cholesterol and triglycerides decreased linearly with increasing doses of BCD. In these two species, 20% BCD as compared to control diet lowered cholesterolemia (−35%) and triglyceridemia (−70%). In the hamster, the BCD diet caused a marked decrease in cholesterol and triglycerides in chylomicrons and very low density lipoprotein, and in high density lipoproteins cholesterol. Composition and amounts of bile acids were modified in the gastrointestinal tract of hamsters receiving 10% BCD as compared to the control group. The total bile acid content of the gallbladder of treated hamsters was fourfold higher than in the control group, and the bile contained a large amount of hydrophilic bile acids. This trend was also observed in the small intestine, in which percentages and total quantities of cholic plus deoxycholic acids (cholic pathway) were higher than those of chenodeoxycholic plus ursodeoxycholic plus lithocholic acids (chenodeoxycholic pathway). The bile acid contents of the cecum and colon of treated hamsters were 2.7-fold higher than those of control animals, but the bile acid composition was similar in the two groups of hamsters. Fecal excretion of bile acids was 3.3-fold higher in the treated group than in the control group, and the percentage of lithocholic acid was markedly increased and close to that observed in the colon. The turnover of the chenodeoxycholic pool was twice as fast in treated hamsters as in control hamsters, whereas that of cholic acid was not significantly modified. These results suggest that BCD does not alter the microbial degradation of bile acids, but rather stimulates their synthesis and increases their pool size. BCD prevents the intestinal absorption of lithocholic acid and washes this cytotoxic bile acid from the colon. The hypocholesterolemic effect of BCD appears to be due to stimulation of bile acid synthesis.     

Effects of β-lactam antibiotics on intestinal microflora and bile acid metabolism in rats

Wistar male rats were treated for six days with broad spectrum β-lactam antibiotics, latamoxef, and cefotaxime. On the seventh day, the number of fecal anaerobic microbes decreased, total fecal bile acids decreased, and bile acid pools increased. Secondary bile acids such as β-hyocholic, hyodeoxycholic, lithocholic, and deoxycholic acids decreased in the feces while the primary bile acids, cholic, β-muricholic, and chenodeoxycholic acids, became predominant. Coprostanol, a microbial metabolite of cholesterol, also disappeared from the feces during the treatment. The cecum enlarged to almost twice the size of that in control rats, whereas the liver weight was not significantly changed. After treatment was stopped, the number of fecal microbes returned to the initial counts within a week, but restoration of bile acid and cholesterol metabolism required at least three weeks.