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Liver cirrhosis and intestinal degradation of cholesterol
372
EFFECT OF LACTULOSE ADMINISTRATION ON BILE ACID METABOLISM AND BILIARY LIPID SECRETION IN MAN. M.Ronchi, P.Simoni, G.Mazzella, V.ViI= lanova, F.Bazz oli, A.Roda, L.Barbara, E.Roda. Clinica Medica e Gastroenterologia, Universit& di Bologna, Italia.
Lactulose is an unabsorbed disaccharide known to reduce intestinal transit time and to indu ce colonic acidification. Intestinal transit time, in turn, is a major determinant of entero hepatic cycling frequency and colonic pH influences bacterial biotransformation and solubi= lity of bile acids. We aimed to evaluate the effect of lactulose administration (18 g/day for a four week period) on bile acid metabolism and biliary lipid secretion by an intestinal pe~ fusion technique (Grundy) in 6normal subjects (2 males, 4 females; age range:28-67). Lactul~ se administration induced a significant decrease of biliary cholesterol output (before: 185Z37, after 153Z32 umol/l; P'O.03; while bile acid output (slight decrease) and phospholi= pJd output (slight increase) were not significantly affected. Cholesterol to phospholipid ratio decreased (P
373
LIVER CIRRHOSIS AND INTESTINAL DEGRADATIONOF CHOLESTEROL. L. Roncucci, M. Ponz de Leon, C. Sacchetti, N. Carulli. I s t i t u t o di Clinica Medica l , Universit~ di Modena, Modena, I t a l y .
A reduction of the intestinal synthesis of secondary b i l e acids, expecially deoxycholic, has been noted in l i v e r cirrhosis, whereas l i t t l e is known about intestinal metabolism of cholesterol. Purpose of the present study was to investigate whether cirrhosis associates to changes of the intestinal degradation of neutral steroids. PATIENTSAND METHODS. Subjects investigated included 39 controls and I I c i r r h o t i c patients. All the subjects were kept on a diet containing a fixed amount of cholesterol. Feces were collected for at least 3 consecutive days. On each stool specimen total and individual neutral steroids (cholesterol and i t s main intestinal metabolites, coprostanol and coprostanone) were evaluated using TLC and gas-cromatography. Cirrhotics had the study repeated after treatment with lactulose (25-50 mg/day for 15 days), in order to investigate the effect of lowering intestinal pH and changing bacterial flora. RESULTS. Although mean daily fecal output of total neutral steroids in cirrhosis (214 + 62 mg) was about half (p 0.05) that of controls (415 ~ 45 mg), mean cholesterol output did not d i f f e r in the two groups (48 ~ I I mg of cirrhotics vs 47.7 + 7 mg of controls). Indeed, cholesterol metabolites output was lower in cirrhosis, so that the % of conversion of cholesterol to coprostanol and coprostanone in cirrhosis (63 ~ I0%) resulted s i g n i f i c a n t l y (p O.Ol) lower than that of controls (87 C 2%). Lactulose administration did not produce s i g n i f i c a n t changes. CONCLUSIONS. Cirrhotics show a reduced i n t e s t i nal degradation of both acidic and neutral steroids, probably due to quantitative and/or qualitative alterations of intestinal bacterial flora. Since changes of fecal acidic and neutral steroids are so frequent in patients with colorectal cancer, cirrhosis may be considered a suitable model for the study of the relationship between intestinal sterol metabolism and colon cancer.
$192
EFFECT OF LACTULOSE ADMINISTRATION ON BILE ACID METABOLISM AND BILIARY LIPID SECRETION IN MAN. M.Ronchi, P.Simoni, G.Mazzella, V.ViI= lanova, F.Bazz oli, A.Roda, L.Barbara, E.Roda. Clinica Medica e Gastroenterologia, Universit& di Bologna, Italia.
Lactulose is an unabsorbed disaccharide known to reduce intestinal transit time and to indu ce colonic acidification. Intestinal transit time, in turn, is a major determinant of entero hepatic cycling frequency and colonic pH influences bacterial biotransformation and solubi= lity of bile acids. We aimed to evaluate the effect of lactulose administration (18 g/day for a four week period) on bile acid metabolism and biliary lipid secretion by an intestinal pe~ fusion technique (Grundy) in 6normal subjects (2 males, 4 females; age range:28-67). Lactul~ se administration induced a significant decrease of biliary cholesterol output (before: 185Z37, after 153Z32 umol/l; P'O.03; while bile acid output (slight decrease) and phospholi= pJd output (slight increase) were not significantly affected. Cholesterol to phospholipid ratio decreased (P
373
LIVER CIRRHOSIS AND INTESTINAL DEGRADATIONOF CHOLESTEROL. L. Roncucci, M. Ponz de Leon, C. Sacchetti, N. Carulli. I s t i t u t o di Clinica Medica l , Universit~ di Modena, Modena, I t a l y .
A reduction of the intestinal synthesis of secondary b i l e acids, expecially deoxycholic, has been noted in l i v e r cirrhosis, whereas l i t t l e is known about intestinal metabolism of cholesterol. Purpose of the present study was to investigate whether cirrhosis associates to changes of the intestinal degradation of neutral steroids. PATIENTSAND METHODS. Subjects investigated included 39 controls and I I c i r r h o t i c patients. All the subjects were kept on a diet containing a fixed amount of cholesterol. Feces were collected for at least 3 consecutive days. On each stool specimen total and individual neutral steroids (cholesterol and i t s main intestinal metabolites, coprostanol and coprostanone) were evaluated using TLC and gas-cromatography. Cirrhotics had the study repeated after treatment with lactulose (25-50 mg/day for 15 days), in order to investigate the effect of lowering intestinal pH and changing bacterial flora. RESULTS. Although mean daily fecal output of total neutral steroids in cirrhosis (214 + 62 mg) was about half (p 0.05) that of controls (415 ~ 45 mg), mean cholesterol output did not d i f f e r in the two groups (48 ~ I I mg of cirrhotics vs 47.7 + 7 mg of controls). Indeed, cholesterol metabolites output was lower in cirrhosis, so that the % of conversion of cholesterol to coprostanol and coprostanone in cirrhosis (63 ~ I0%) resulted s i g n i f i c a n t l y (p O.Ol) lower than that of controls (87 C 2%). Lactulose administration did not produce s i g n i f i c a n t changes. CONCLUSIONS. Cirrhotics show a reduced i n t e s t i nal degradation of both acidic and neutral steroids, probably due to quantitative and/or qualitative alterations of intestinal bacterial flora. Since changes of fecal acidic and neutral steroids are so frequent in patients with colorectal cancer, cirrhosis may be considered a suitable model for the study of the relationship between intestinal sterol metabolism and colon cancer.
$192