# The Role of Brain-Bone Marrow-Gut Interaction following Major Trauma

> **NIH NIH R35** · UNIVERSITY OF FLORIDA · 2024 · $457,500

## Abstract

ABSTRACT
Trauma remains the leading cause of death among people younger than 46 years of age and is the leading
cause of years of potential life lost among those younger than 65. With more lives saved, trauma morbidity has
increased, which has consequently revealed a lack of understanding of the impact of trauma survivorship on the
patients’ quality of life and long-term recovery. Severe injury when followed by chronic critical illness leads to
persistent anemia, and the use of blood transfusions is associated with a linear increase in infectious
complications. These conditions are due to prolonged bone marrow dysfunction associated with an exaggerated
catecholamine response, chronic stress, and systemic inflammation. The Principal Investigator (PI) has
demonstrated significant productivity over the last decade, especially in the last five years, in this research field.
The PI’s laboratory has conducted human and rodent research to establish that there are unique bone marrow
transcriptomic differences related to inflammation, the innate immune response, and known inhibitors of
erythropoiesis following trauma. The laboratory has also discovered that chronic stress after trauma contributes
to persistent anemia with impaired iron and erythropoietin function along with the prolonged loss of hematopoietic
stem progenitor cells (HSPC) from the bone marrow. Chronic stress after trauma also induces an altered
microbiome with decreased alpha and beta diversity and changes in microbial composition leading to a persistent
‘pathobiome’. All of these factors influence outcomes. We hypothesize that there is a unifying interaction between
stress, inflammation, and the microbiome and this has an overall role in the regulation of HSPC and erythroid
progenitor cell fate and function following trauma and critical illness. Therefore, the overarching goal for this
application is to build upon this foundation and expand our understanding of HSPC fate and function following
trauma, including examining interventions aimed at reducing stress/inflammation and restoring the microbiome,
thus, improving long-term outcomes. Severely injured patients with chronic critical illness at risk of long-term
morbidity as well as our novel preclinical rodent model of multicompartmental trauma and chronic stress will be
employed. We intend: (1) to directly link changes in HSPC and erythroid progenitor cell fate and function with
changes in the microbiota by examining specific mechanisms, including how stress-induced changes following
trauma create a pathobiome that maintains altered erythroid progenitor function. With these studies, we will (2)
explore the unique interplay of the microbiome, the stress response, and HSPCs and erythroid progenitor cell
fate in different cohorts of trauma, evaluating both age and sex; and (3) consider possible interventions that
restore the microbiome and/or reduce chronic stress/inflammation which reestablishes HSPC homeostasis to
improve bone marrow fun...

## Key facts

- **NIH application ID:** 10764574
- **Project number:** 1R35GM152216-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** ALICIA M MOHR
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $457,500
- **Award type:** 1
- **Project period:** 2024-09-10 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764574

## Citation

> US National Institutes of Health, RePORTER application 10764574, The Role of Brain-Bone Marrow-Gut Interaction following Major Trauma (1R35GM152216-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10764574. Licensed CC0.

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