7 alpha-dehydroxylating bacteria enhance deoxycholic acid input and cholesterol saturation of bile in patients with gallstones

Background & Aims: Excessive deoxycholic acid (DCA) in the bile acid pool with cholesterol supersaturation of bile is prevalent in patients with cholesterol gallstones (CGs), This study examined whether this is caused by enhanced conversion of cholic acid (CA) to DCA by intestinal bacteria, Methods: Ten patients with CGs with DCA excess (DCA/CA pool ratio, >1.5) and 10 patients with low DCA (ratio, (1.0) were compared for CA and DCA kinetics, ileal absorption of 75-Se-hometaurocholic acid (75-SeHCAT), and CA-7 alpha-dehydroxylation activity of the fecal microflora; the effects of ampicillin treatment on DCA excess were studied in 7 patients, Results: Patients with DCA excess and low DCA differed (P < 0.01) in the pool size of CA (mean, 5.8 vs. 34) and DCA (28 vs. 11 mu mol/kg) and DCA input (8.8 vs, 3.5 mu mol . kg(-1). day(-1)), Whereas 75-SeHCAT excretion was similar, CA-7 alpha-dehydroxylation activity and levels of fecal 7 alpha-dehydroxylating bacteria were 3-fold and 1000-fold higher (P < 0.01) in patients with DCA excess, respectively. Ampicillin treatment decreased (P < 0.02) CA-7 alpha-dehydroxylation activity and DCA pool size, expanded the CA pool to normal size, and lowered cholesterol saturation of bile. Conclusions: Increased CA-7 alpha-dehydroxylation activity of the intestinal microflora may be an important factor for CG formation or growth in these patients.