Effect of Neomycin and Other Antibiotics on Serum Cholesterol Levels and on 7α-Dehydroxylation of Bile Acids by the Fecal Bacterial Flora in Man

Abstract

Fresh feces from 25 patients were homogenized and incubated with labeled cholic or chenodeoxycholic acid. After 24 hours of incubation, the percent change to the 7a-dehydroxylated form was measured. In 11 patients, the oral administration of 2g of neomycin daily significantly reduced the levels of serum cholesterol (from an average of 316 mg/100 ml plasma to 237 mg/100 ml plasma) and markedly inhibited the extent of 7a-dehydroxylation of cholic acid (from 89% to 9%); in 2 patients whose serum cholesterol levels were not lowered, the degradation of cholic acid remained unchanged (control 93%, neomycin 91%). In 5 patients the administration of kanamycin reduced serum cholesterol levels (from 280 mg/100 ml plasma to 252 mg/100 ml plasma) and also inhibited 7a-dehydroxylation of cholic acid (from 92% to 21%); in 3 additional patients this drug failed to lower serum cholesterol concentrations and had no effect on bile acid degradation (control 91%, kanamycin 92%). Similar results were obtained with chloramphenicol in 3 patients, and equivocal results were obtained with chlortetracyeline in 3 patients. The correlation coefficient between undegraded cholic acid and percent decrease in serum cholesterol concentrations (r = 0.732) was statistically significant ( P < 0.001). It is proposed that serum cholesterol levels might be controlled in part by the prevalence of bile acid-degrading bacteria within the gastrointestinal tract.

Bile Salts and Glycine as Cogerminants for Clostridium difficile Spores

“…Spores that did not germinate during passage through the upper part of the digestive system may germinate in response to deoxycholate but are then unable to grow in the toxic environment. Upon antibiotic treatment, the normal microbial flora is perturbed and the species that are capable of 7␣-dehydroxylation of primary bile salts are significantly reduced (32). This reduction would lead to an increase in the concentration of primary bile salts (cholate derivatives) and a decrease in the concentration of secondary bile salts (deoxycholate) in the cecum (32).…”

“…Upon antibiotic treatment, the normal microbial flora is perturbed and the species that are capable of 7␣-dehydroxylation of primary bile salts are significantly reduced (32). This reduction would lead to an increase in the concentration of primary bile salts (cholate derivatives) and a decrease in the concentration of secondary bile salts (deoxycholate) in the cecum (32). This decrease in secondary bile acids may provide an environment in which C. difficile can grow and colonize.…”

Effects of neomycin on absorption, synthesis, and/or flux of cholesterol in man.

“…Of these kanamycin (2) and paromomycin (3) are similar in structure to neomycin, but chlortetracycline (2), chloramphenicol (4), and para-aminosalicylic acid (2) have markedly different molecular conDr. Sedaghat's present address is: Department of Medicine, Pahlavi University, Shiraz, Iran. Received for publication 29 March 1974 and in revised form 11 July 1974.…”

Inhibiting the Initiation ofClostridium difficileSpore Germination using Analogs of Chenodeoxycholic Acid, a Bile Acid

“…C. scindens actively transports unconjugated primary bile acids into the cytoplasm, where they are 7␣-dehydroxylated, converting cholate to deoxycholate and chenodeoxycholate to lithocholate (21,40). The disruption of the colonic flora by antibiotic treatment abolishes 7␣-dehydroxylation activity (41).…”