The Human Holobiont: Enhancing Health and Preventing Disease

Investigating the relationship between the developing immune system and microbiomes to advance prevention and care

Full Project Name:The Human Holobiont: Enhancing Health and Preventing DiseasePrincipal Investigator:Nita H. Salzman, MD, PhD, PediatricsCo-Investigator:Calvin B. Williams, MD, PhD, PediatricsAward Amount:1,500,000

Award Date

July2021

Project Duration:60 Months

Project Description Narrative:

Humans exist as "holobionts," living in a relationship with vast microbial ecosystems that colonize on skin and mucosal surfaces. Called the "microbiome," these microbes exist in everyone, with the vast majority found in the gastrointestinal (GI) tract. In a healthy person, these microbes co-exist peacefully, and are essential to good health. Yet, some microbes can be harmful and promote disease such as autoimmune and inflammatory diseases, obesity and neuropsychiatric disorders while also creating susceptibility to infection or poor responses to therapies such as vaccinations or chemotherapy.

Through this award, investigators aim to advance understanding of how microbiomes become established within a developing immune system, and how this process contributes to systemic health in order to inform further study and future therapies for prevention and care across varying diseases.

Project Updates:

Engineered a strain of bacteria to allow the team to investigate immune responses
Created mice with a specific defect in immune regulation and showed that the mice have very early onset bowel inflammation
Demonstrated that byproducts produced by intestinal microbes change both gut development and production of intestinal antimicrobials via a novel pathway
Developed novel approaches to analyze small-volume blood samples from NICU patients
Disseminated findings through three published manuscripts and two academic presentations