title: Octreotide induced prolongation of colonic transit increases faecal anaerobic bacteria, bile acid metabolising enzymes, and serum deoxycholic acid in patients with acromegaly.
abstract: BACKGROUND
  Acromegalic patients have slow colonic transit, increased rates of deoxycholic acid formation, and an increased prevalence of cholesterol gall stones, especially during long term octreotide treatment. However, the effects of this prolonged large bowel transit time on the numbers of faecal anaerobes and the activities of the enzyme systems which biotransform conjugated cholic acid into unconjugated deoxycholic acid (cholylglycine hydrolase and 7alpha-dehydroxylase) are unknown.
  
  
  METHODS
  Therefore, in 10 non-acromegalic controls, 11 acromegalic patients not treated with octreotide, and 11 acromegalics on long term (8-48 months) octreotide (100-200 mug three times daily subcutaneously), we measured large bowel transit time and, in freshly voided faeces, the activities of the two bile acid metabolising enzymes, and related the results to the proportion of deoxycholic acid in fasting serum. Moreover, in patients with acromegaly, we measured quantitative bacteriology in faeces.
  
  
  RESULTS
  Mean large bowel transit time in acromegalics not treated with octreotide (35 (SEM 6.5) hours) was 66% longer than that in non-acromegalic controls (21 (3.1) hours; NS) and became further prolonged during octreotide treatment (48 (6.6) hours; p<0.001). These octreotide induced changes in transit were associated, in acromegalic patients, with more total (15.0 (2.5) v 6.3 (1.3)x10(9) colony forming units (cfu)/g; p<0.05) and Gram positive (6.3 (2.3) v 3.2 (1.0)x10(9) cfu/g; p<0.05) faecal anaerobes. Mean faecal cholylglycine hydrolase activity in the long term octreotide group (22.0 (6.0)x10(-2) U/mg protein) was 138% greater than that in non-acromegalic controls (12.0 (6.0)x10(-2); p<0.01). Similarly, mean 7alpha-dehydroxylase activity in octreotide treated acromegalics (11.1 (1.18)x10(-4) U/mg protein) was 78% greater than that in patients not receiving long term octreotide (6.3 (0.5)x10(-4); p<0.001). The mean proportion of deoxycholic acid in fasting serum also increased from 18.0 (2.88)% in the untreated group to 29.6 (2.3)% during long term octreotide (p<0.05). There were significant linear relationships between large bowel transit time and: (i) faecal 7alpha-dehydroxylase activity; and (ii) the proportion of deoxycholic acid in fasting serum and between 7alpha-dehydroxylase activity and the proportion of deoxycholic acid in serum.Summary/interpretation: These data suggest that increased deoxycholic acid formation seen in acromegalics during octreotide treatment is due not only to the greater numbers of faecal anaerobes but also to increased activity of the rate limiting enzyme pathway (7alpha-dehydroxylation) converting cholic acid to deoxycholic acid.
authors.affiliation: Gastroenterology Unit, Division of Medicine, GKT School of Medicine, Kings College, London, UK.
authors.forename: L A
authors.initials: LA
authors.lastname: Thomas
authors.forename: M J
authors.initials: MJ
authors.lastname: Veysey
authors.forename: G M
authors.initials: GM
authors.lastname: Murphy
authors.forename: D
authors.initials: D
authors.lastname: Russell-Jones
authors.forename: G L
authors.initials: GL
authors.lastname: French
authors.forename: J A H
authors.initials: JA
authors.lastname: Wass
authors.forename: R H
authors.initials: RH
authors.lastname: Dowling
mesh_terms: D000172:Acromegaly / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D000581:Amidohydrolases / Q000378:metabolism; D000704:Analysis of Variance; D001421:Bacteria, Anaerobic / Q000254:growth & development; D003106:Colon / Q000503:physiopathology; D015169:Colony Count, Microbial; D003840:Deoxycholic Acid / Q000096:biosynthesis / Q000097:blood*; D005215:Fasting / Q000097:blood; D005243:Feces / Q000737:chemistry / Q000382:microbiology*; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D003840:Deoxycholic Acid; D006913:Hydroxysteroid Dehydrogenases; C025376:7 alpha-hydroxysteroid dehydrogenase; D000581:Amidohydrolases; C023154:choloylglycine hydrolase; D015282:Octreotide