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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(s):Calvin B. Williams, MD, PhD, PediatricsAward Amount:$1,500,000
Award Date
July2021
Project Duration:60 months

Project Summary:


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:


  • Continued to test modified bacterial strains in mice with a very specific defect in immune regulation and identified several key checkpoints that affect both the development of the immune system and response of the immune system to bacteria
  • Developed research tools to understand how bacteria communicate with the host, which will support the team to plan effective interventions to prevent damage to the microbiome or bolster its beneficial effects for the host
  • Developed a protocol to investigate how the microbiome of premature infants affects immune cell development
  • Leveraged over $560,000 to support continued research efforts
  • Disseminated project findings through 15 presentations and 10 publications to date

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