Gut Microbiome Dysfunction in Sepsis and Trauma Survivors

Gastrointestinal microbiome dysfunction has been demonstrated to be a culprit of various systemic dysfunctions in peripheries such as cardiovascular, nervous, endocrine and musculoskeletal systems. The topic of microbiome dysfunction after sepsis and trauma injury is understudied but may be responsible for persistent systemic inflammation clinically observed in sepsis and trauma survivors. Therefore, the objective of this project is to investigate the gut microbiome after acute phase of sepsis or severe trauma injury and compare it with 108 age-matched healthy population controls

The investigators hypothesize that alterations of the gut microbiota will correlate with persistent systemic inflammation in sepsis and trauma survivors compared to existing healthy population controls. This research group will collect stool samples from 108 sepsis survivors and 108 trauma survivors (groups of ages 18-45, 46-64, and \>65; male and female; n=18 per age + sex cohort) admitted to the surgical intensive care unit between day 7 and 28 of hospital admission, as well as 3 and 6 months after their sepsis or trauma event. The investigators will perform 16S rRNA DNA sequencing on the isolated bacterial DNA from these samples and bioinformatic analysis to determine microbiota alterations between time points and between sepsis and control cohorts. In addition, the investigators will draw 20ml of blood to isolate plasma.

Trauma Subgroup for traumatic brain injury (TBI) pilot study: Our team will enroll 15 additional trauma injury patients with traumatic brain injury. This subgroup will have an added stool (if available) and blood sample collection after initial injury (+ 5 days). The additional sample will be compared to the sample collected at 14-21 days and follow up samples at 3 and 6 months. The results will be associated with Glasgow Outcome Scale Extended at 3 and 12 month time points and the recorded discharge Rancho Los Amigos scale score from the medical record. The specific aims will be: Aim 1 - define the impact of persistent systemic inflammation on the gastrointestinal microbiota in sepsis and trauma survivors and Aim 2 - identify microbial genes associated with persistent systemic inflammation in sepsis and trauma survivors compared to normal controls. Trauma Subgroup Aim: Pilot study to test the hypothesis that changes in the microbiome towards pathogenic microbe is associated with worsened outcomes in trauma injury patients with TBI (traumatic brain injury).

Eligibility Criteria:
Sepsis Population

Inclusion Criteria

1. Admission to the 46, 77, 87, 4 East, 4 West, or 24-5 ICUs where clinical care can be managed by the critical care organization guided by standard operating procedures.
2. Age ≥18 years
3. Meets Sepsis 3 criteria at time of sepsis diagnosis
4. Has remained in ICU for 14 days (+/- 7 days) following sepsis diagnosis.
5. Ability to obtain patient/LAR informed consent.
6. Is receiving adequate nutritional intake: oral or enteral nutrition.

Exclusion Criteria

1. Severe traumatic brain injury with unencumbered assessment of GCS equaling 3 on admission to intensive care unit
2. Refractory shock (i.e., patients who are expected to die within 12 hours).
3. Uncontrollable source of sepsis (e.g. irreversible disease state such as unresectable dead bowel).
4. Patient or patient's family are not committed to aggressive management of the patient's condition.
5. Known HIV infection with CD4 count \<200 cells/mm3.
6. Organ transplant recipient on immunosuppressive agents.
7. Known pregnancy.
8. Prisoners.
9. Institutionalized patients j Inability to obtain informed consent.

k) Burn injury greater than 20% TBSA (total body surface area)

Trauma Population

Inclusion Criteria

1. All adults (age ≥18 to 54) require both:

a. Blunt and/or penetrating trauma patient with i. Hemorrhagic shock defined by:

1. Systolic BP (SBP) ≤ 90 mmHg or 2. Mean arterial pressure ≤ 65 mmHg or 3. Base deficit (BD) ≥5 meq or 4. Lactate ≥ 2 or 5. Active red blood cell or whole blood transfusion within 6 hours of arrival

b. Injury Severity Score (ISS) greater than or equal to 15

2. All adults (age 55 and older) require:

a. Either hemorrhagic shock defined by: i. Systolic BP (SBP) ≤ 90 mmHg or ii. Mean arterial pressure ≤ 65 mmHg or iii. Base deficit (BD) ≥5 meq or iv. Lactate ≥ 2 or v. Active red blood cell or whole blood transfusion within 6 hours of arrival

OR

b. Injury Severity Score (ISS) greater than or equal to 15. 3. Ability to obtain Informed Consent

Exclusion Criteria

1. Patients not expected to survive greater than 48 hours.
2. Prisoners.
3. Pregnancy.
4. Previous bone marrow transplantation.
5. Patients with End Stage Renal Disease.
6. Patients with any pre-existing hematological disease (e.g. hemochromatosis, myelodysplastic syndrome, hematologic cancers)
7. Burn injury greater than 20% TBSA
8. Severe traumatic brain injury with unencumbered assessment of GCS equaling 3 on admission to intensive care unit.

Trauma TBI subgroup (15 participants)

Inclusion criteria will be:

1. Any adult age 18 or older with any traumatic bleed (intracerebral hemorrhage, subarachnoid hemorrhage, intraparenchymal hemorrhage, subdural hematoma, cerebral epidural hematoma) and any GCS (Glasgow Coma Score).

Exclusion criteria is the same used for the trauma cohort.

Healthy Control

Inclusion criteria will be:

1. All adults (age ≥18)
2. Ability to obtain Informed Consent prior to blood collection.

Exclusion Criteria will be:

1. Current, chronic steroid use
2. Pregnancy
3. Current or recent (within 7 days) use of antibiotics.