SURVIVAL OF ANTI-CLOSTRIDIUM DIFFICILE BOVINE IMMUNOGLOBULIN CONCENTRATE IN THE HUMAN GASTROINTESTINAL-TRACT

To be therapeutically active, oral hyperimmune bovine immunoglobulin c oncentrate (BIG) must survive its passage through the intestinal tract . This led us to study the gastrointestinal stability of orally admini stered BIC directed against Clostridium difficile toxins (BIC-C. diffi cile). BIC-C. difficile was stable at neutral pH in vitro but was degr aded at low pH, particularly in the presence of pepsin. Healthy volunt eers (n = 6) took BIC-C. difficile (45 or 8 g) as a single oral dose. Total bovine immunoglobulin G (IgG) and specific anti-C. difficile IgG were measured in the stool. BIC was given under the following conditi ons: in the fasting state, in the fed state, with antacid, during omep razole therapy, or in enteric capsules (released at pH > 6). The mean fecal bovine IgG content of 3-day stool collections was similar in the fasting (536 mg; 3.8% of the ingested dose of BIC), fed (221 mg; 1.6% ), and antacid (381 mg; 2.7%) groups. Omeprazole therapy was associate d with increased fecal bovine IgG levels (1253 mg; 8.8%), but this dif ference did not reach statistical significance (P = 0.07). Administrat ion of 8 g of BIC-C. difficile in enteric capsules resulted in substan tially higher fecal bovine IgG levels (1,124 mg; 32.7% of the oral dos e) than those obtained after administration of nonencapsulated BIC (22 mg; 0.6%; P = 0.001). An inverse relationship was noted between intes tinal transit time and fecal bovine IgG content (R = 0.83; P = 0.04 [d ata from omeprazoIe group]). Filtrates of stool samples collected afte r oral administration of BIC-C. difficile neutralized the cytotoxicity of C. difficile toxins A and B, whereas control stool filtrates did n ot. Bovine colostral IgG undergoes partial degradation in the intestin al tract. Exposure to acidic gastric secretions and prolonged colonic transit may both contribute to IgG degradation. Nonetheless, humans ta king BIC-C. difficile orally have neutralizing antitoxin activity in t heir stool.