Potentiating the Microbiome for the Prevention of Enteric Bacterial Infection in Livestock

SUMMARY

• Approximately 1/5 of antibiotic resistant infections in humans can be traced back to food and animals. The incidence of these infections is perpetuated by the widespread prophylactic use of antibiotics on farms. As such, there is an urgent need for alternative methods of preventing bacterial infection in livestock.
• It was previously assumed that differences in susceptibility of animals to enteric infection was caused by differences in adaptive and innate immunity. The inventors discovered that in addition to traditional immunity, the bacteria Clostridiales protect the host from exogenous pathogens through colonization resistance.
• The invention is a method of administering a consortium of Clostridia bacterium to supplement the microbiome of an animal and facilitate the prevention of enteric infections through colonization resistance. 72 different strains of Clostridiales may be chosen from for optimization of the treatment in different animals. 
• In proof-of-concept experiments using neonatal mice, a common model for immature immune systems and microbiota, the inventors showed that administration of Clostridiales protected the mice from S. Typherium (Salmonella, p<0.001 for bacterial levels in mouse feces) and C. rodentium (models an E. coli infection, p=0.0053 for mouse survival). The Clostridales bacterium were able to sufficiently colonize the microbiota of the neonatal mice.

FIGURE

Adult mice (light blue), neonatal mice (lacking Clostridiales, dark blue), or neonatal mice treated with Clostridiales consortium (red) were infected with C. rodentium to model E. coli infection. C. rodentium levels were then measured in the feces (A), (p<0.001, N=4 per treatment group) and mouse survival overtime was tracked (B), (p=0.0052, N=19 per treatment group).

ADVANTAGES

ADVANTAGES

• Circumvents antibiotic resistance
• Can be used prophylactically instead of reactively
• No disruption of existing microbiota

APPLICATIONS

• Bacterial prophylaxis in livestock
• Bacterial prophylaxis in companion animals

PUBLICATIONS

• Kim, YG; et al. Neonatal acquisition of Clostridia species protects against colonization by bacterial pathogens. Science. 2017 Apr 21; 356(6335): 315-319.

August 9, 2019

In vivo proof of concept

Patent Pending

Licensing,Co-development

Cathryn Nagler

• US:16/476,216; Counterpart in the EU