Defining a Novel Therapeutic Application of Lactoferrin for Intestinal Inflammation
Abstract
Acute intestinal infections can be inciting events for the development of chronic intestinal inflammation, such as occurs in inflammatory bowel diseases (IBD) in susceptible patients. 3.1 million people in the United States suffer from IBD, predominantly Crohn’s disease (CD) and ulcerative colitis (UC). The military is not spared from this illness. The peak incidence of IBD occurs between 18-40 years of age and 2/3 of active military personnel are within this age group. IBD is of concern to the military due to the disability it causes and its high costs in terms of lost work hours, chronic healthcare requirements, and diminished troop readiness. In addition, IBD is on the rise in the military, increasing two- to three-fold over the past two decades. Among Veteran populations, IBD represents one of the highest hospitalization rates, and IBD-associated colorectal cancer is on the rise in this population. These data define an urgent need for identifying novel, inexpensive therapies to treat this disease. The causes of IBD remain poorly understood, yet evidence indicates that there is an imbalance between the anti-inflammatory and pro-inflammatory cells in the intestinal mucosa related to the microbial environment of the intestine. Regulatory T cells are a critical type of immune cell that promotes balance in the intestinal immune response. We have demonstrated that human lactoferrin (hLF), a protein found in breast milk, activates anti-inflammatory, regulatory T cells in intestinal inflammation in mouse models of IBD. We and others have identified that hLF can alter the growth of bacteria in the intestine and that hLF can inhibit or treat infectious intestinal bacteria in the laboratory. These antibacterial effects have not been studied extensively in animals or humans. This study will determine how hLF activates these cells and will be one of the first to correlate the immune, microbial, and metabolic changes occurring in the intestine in response to this novel agent. In addition, this study will investigate the best method to administer hLF as well as the best formulation to use to attain the goal of treating intestinal inflammation. Upon conclusion of this study, we will understand the antimicrobial and anti-inflammatory potential of the naturally occurring protein hLF and better understand the mechanisms by which hLF acts to benefit a well-balanced immune system. Ultimately, this study will inform the development of hLF as a safe, effective, natural therapy for intestinal inflammation in humans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110312
Entities
People
- Edwin Dezoeten
Organizations
- United States Army
- University of Colorado Denver