Hyperimmune bovine colostrum as a novel therapy to combat Clostridium difficile infection.
BACKGROUND
Clostridium difficile is a primary cause of antibiotic-associated diarrhea that typically develops when gut microbiota is altered. Conventional treatment for C. difficile infection (CDI) is additional antimicrobial administration, which further disrupts normal intestinal microbiota, often resulting in poor treatment outcomes.


METHODS
A pregnant dairy cow was repeatedly immunized with recombinant mutants of toxins A and B produced by C. difficile, and the resultant hyperimmune bovine colostrum (HBC) was evaluated for therapeutic efficacy in gnotobiotic piglets with diarrhea due to CDI. Control piglets received nonimmune colostrum. To determine the impact of HBC on gut microbiota, 1 of 2 groups of piglets transplanted with normal human gut microbiota was treated with HBC.


RESULTS
Nonimmune colostrum-treated piglets developed moderate to severe diarrhea and colitis. In contrast, HBC-treated piglets had mild or no diarrhea and mild or no colitis. Lyophilization had no detectable impact on HBC efficacy. HBC had no discernible effect on the composition of normal human gut microbiota in the porcine intestinal tract.


CONCLUSIONS
HBC provides an oral, cost-effective, and safe alternative to antibiotic therapy for CDI. By preserving intestinal microbiota, HBC may be more efficacious than antibiotics. Additional studies are warranted to establish HBC as a viable immunotherapeutic agent for human use against CDI.
Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts.
Jerlyn K
JK
Sponseller
Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts.
Jennifer A
JA
Steele
Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts.
Diane J
DJ
Schmidt
Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts Department of Animal Resources Science, Dankook University, Cheonan, Choongnam, Republic of Korea.
Hyeun Bum
HB
Kim
Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts.
Gillian
G
Beamer
Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts.
Xingmin
X
Sun
Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts.
Saul
S
Tzipori
D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000276:immunology; D002417:Cattle; D016360:Clostridioides difficile / Q000276:immunology*; D003015:Clostridium Infections / Q000276:immunology* / Q000628:therapy*; D003092:Colitis / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D003126:Colostrum / Q000276:immunology*; D003967:Diarrhea / Q000276:immunology / Q000382:microbiology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology; D007410:Intestinal Diseases / Q000276:immunology; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D013552:Swine
D000900:Anti-Bacterial Agents; D007155:Immunologic Factors
Clostridium difficile; hyperimmune bovine colostrum; immunotherapeutic; intestinal microbiota; intestinal microflora