Stabilization of therapeutic microbes for inclusion in a liquid matrix for delivery to the intestines

Vitakey, Inc., Washington DC

Investigators

Abstract

Project Summary/Abstract Enteral feeding (EF) is an essential medical procedure used to supply nutrients directly to the gastrointestinal (GI) tract of patients who are unable to eat independently. EF formula is often purchased as a ready-to-use liquid that contains carbohydrates, protein, fats, and micronutrients to ensure adequate nutritional benefit for the patient. Ninety three percent of EF formulas are dosed simultaneously with antibiotics. Because of this, >60% of these patients will experience antibiotic-associated diarrhea (AAD). AAD severely decreases nutrient absorption, hydration status, and quality of life substantially for EF patients. There is currently no treatment for AAD, as each antibiotic regimen prescribed to patients differs based on initial health status, and often >30% of AAD patients further develop antibiotic-resistant Clostridium difficile infections after prolonged antibiotic administration. Probiotics offer a potential therapeutic strategy to counteract AAD, as probiotics have been demonstrated to facilitate carbohydrate digestion, restore healthy microflora, and improve intestinal barrier strength and nutrient absorption. Probiotics, however, are highly susceptible to degradation due to shelf storage and upon oral consumption which has yielded conflicting clinical results across multiple trials in the treatment of AAD. Additionally, EF patients are unable to orally ingest capsule based probiotics, which presents an opportunity to generate formulated probiotics that maintain stability and viability in EF formula and upon consumption. To date, addition of probiotics to EF feed involves breaking capsules and adding powder to EF formula, however this method prevents consistent dosing, decreases viability of probiotics via exposure to formula ingredients and gastric acid, and has the potential for pathogen contamination from hospital worker’s hands. Herein, we propose to use VitaKey’s proprietary liquid- and EF-stable probiotic encapsulation platform developed in Phase I and customize it for probiotic strains selected to maximize the potential efficacy in patients with AAD including Bacteroides fragilis, Lactobacillus acidophilus, and Lactobacillus plantarum. We aim to establish mechanistic support for stabilized probiotics by evaluating treatment in a mouse AAD model followed by further development of formulations capable of: (1) withstanding pasteurization during product manufacturing, (2) attaining long-term shelf-stability, (3) reaching clinically-relevant efficacy levels in a murine model of AAD and (4) scalable manufacturing.