The Role of Brain-Bone Marrow-Gut Interaction Following Major Trauma

February 4, 2026 updated by: University of Florida
Traumatic injury followed by critical illness provokes pathophysiologic changes in the bone marrow and the gut that contribute to persistent anemia and changes in the microbiome which significantly impact long-term recovery. This project will define the interactions between the stress, chronic inflammation, bone marrow dysfunction, and an altered microbiome which will provide a strong foundation for future clinical interventions to help improve outcomes following severe trauma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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. Our laboratory has conducted human 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 study 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.

Study Type

Observational

Enrollment (Estimated)

275

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32610
        • Recruiting
        • UF Health at Shands hospital
        • Contact:
        • Contact:
          • Jennifer Lanz, MSN
          • Phone Number: 352-273-5497
        • Principal Investigator:
          • Alicia Mohr, MD
      • Gainesville, Florida, United States, 32610
      • Gainesville, Florida, United States, 32610
        • Recruiting
        • UF Laboratory of Inflammation Biology and Surgical Science and Shands Hospital at UF
        • Principal Investigator:
          • Alicia L Mohr, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Acute Care Trauma ICU - Severe Blunt Trauma Orthopedic Injury Shock Orthopedic Clinic - Elective Hip Replacement

Description

Severe Trauma Cohort

Inclusion Criteria:

  1. All adults (age ≥18).
  2. Blunt trauma with an injury severity score > 15 and a long bone or pelvic fracture requiring open reduction internal fixation or intramedullary fixation
  3. Blunt trauma patients with shock, defined by either a systolic BP (SBP) <90 mm Hg or base deficit (BD) ≥5 meq or lactate ≥ 2 mmol/L or active red blood cell or whole blood transfusion within 6h or arrival

Exclusion Criteria:

  1. Patients not expected to survive greater than 48 hours
  2. Prisoners
  3. Pregnancy
  4. Previous bone marrow transplantation
  5. Patients receiving chronic corticosteroids or immunosuppression therapies
  6. Patients with End Stage Renal Disease
  7. Patients with any pre-existing hematological disease
  8. Surgery for repair of injury is greater than seven days after admission to the hospital for trauma
  9. Burn injury greater than 20% TBSA

Elective Hip Cohort

Inclusion Criteria

  1. All adults (age ≥55).
  2. Patient undergoing elective hip repair for non-infectious reasons.
  3. Ability to obtain Informed Consent prior to operation.

Exclusion Criteria

  1. Patients not expected to survive greater than 48 hours
  2. Prisoners
  3. Pregnancy
  4. Previous bone marrow transplantation
  5. Patients receiving chronic corticosteroids or immunosuppression therapies
  6. Patients with End Stage Renal Disease
  7. Patients with any pre-existing hematological disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Major Trauma Injury
Severe blunt trauma patients diagnosed with shock with a long bone or pelvic fracture requiring open reduction internal fixation or intramedullary fixation.
Other: Data and tissue collection
Collection of bone marrow, blood, feces, medical record data, and patient response surveys.
Elective Hip Replacement
Patients undergoing elective hip replacement surgery
Other: Data and tissue collection
Collection of bone marrow, blood, feces, medical record data, and patient response surveys.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Link the changes in HSPC and erythroid progenitor cell fate and function with sympathetic stress-induced changes establishing brain-bone marrow communication following trauma.
Time Frame: 3 years
The impact of the severity and duration of catecholamine secretion on the cellular biology of HSPCs and erythroid progenitor cells requires further detailed evaluation. At each stage of proliferation and differentiation, there is a complex interaction of cytokines, transcription factors, post-translational modification of histones, and miRs. Single-cell RNA-seq technologies using a novel second generation multi-omics technology, CITE-seq, will be used for identification of isolated HSPCs and erythroid progenitor cells. Such single cell sequencing technology is ideal for cell populations with a great deal of heterogeneity and is well-suited for bone marrow analysis. Isolated cells can then be characterized by their transcriptomic and epigenetic changes. We will also evaluate EVM cargo (specific proteins/RNA/miR) from both plasma and bone marrow to determine links to chronic stress exposure.
3 years
Determine the connection between changes in the microbiome with sympathetic stress-induced changes establishing gut-brain communication following trauma.
Time Frame: 3 years
Focusing on the effects of autonomic nervous system on gut function and immune responses, in the setting of sympathetic activation, a serial evaluation of the gut microbiota and their metabolic products (ex. SCFAs: butyrate, propionate, and acetate) will be performed in trauma patients. Correlation of microbial diversity and alterations of the taxonomic composition will be correlated with plasma markers of inflammation and clinical outcomes. Longitudinal study of the trauma pathobiome will elucidate clinical course patterns (recovery and CCI) with microbial composition. The unique biology of the microbiome in different sexes and age groups will require additional subgroup analysis.
3 years
Link changes in the microbiome with altered HSPC and erythroid progenitor cells fate establishing gut-bone marrow communication following trauma
Time Frame: 3 years
We will examine how stress-induced changes following trauma create a pathobiome that modulates HPSC differentiation and maintains altered erythroid progenitor function. The microbiota play a role in both lineage differentiation and also control systemic iron homeostasis by inhibiting intestinal absorption and increasing cellular iron storage. Bone marrow macrophages have a key role in late-stage erythropoiesis by supplying local iron to erythroblasts for hemoglobin production. Isolation of bone marrow macrophages and erythroblasts involved in EBIs and determination of local iron content will define microbiome-induced changes in terminal erythropoiesis.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Florida

Collaborators

National Institutes of Health (NIH)
National Institute of General Medical Sciences (NIGMS)

Investigators

  • Principal Investigator: Alicia Mohr, MD, University of Florida

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 24, 2025

Primary Completion (Estimated)

October 1, 2027

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

September 18, 2024

First Submitted That Met QC Criteria

September 18, 2024

First Posted (Actual)

September 20, 2024

Study Record Updates

Last Update Posted (Actual)

February 6, 2026

Last Update Submitted That Met QC Criteria

February 4, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB202400903
  • 1R35GM152216-01 (U.S. NIH Grant/Contract: NIH/NIGMS)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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