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

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.

Grant Number: 2R44GM146506-02
NIH Institute/Center: NIH
Principal Investigator: Aaron Anselmo