Butyric Acid Supplementation for Gut Improvement After Cardiac Surgery in Kids

Safety will be measured by the combined incidence of adverse events (AE) and serious adverse events (SAE). These include allergic reaction, vomiting, diarrhea, abdominal distention, infection, hospitalization, or any other concern the families report. A Data Safety Monitoring Board (DSMB) will review and catalog the incidence and severity to determine study continuation. Investigators will evaluate each AE/SAE to determine the safety of the supplement in this age and participant population. AE and SAE definitions used according to FDA regulations.

A scoring system of 1-5 will be used to determine the severity of the AE after review by the DSMB. A cumulative score of 3 or greater will require cessation of the study for that individual. If an accumulation of 20 participants or more have a score >3 the study will be stopped. If an accumulation of SAE (score of 5) in 8 or more participants, the study will be stopped.

Tolerance will be measured by the incidence of nausea, inability to consume the supplement, or parental concern of intolerance. The tolerance scoring metric will be used to aggregate the listed criteria into a score for each participant. Each characteristic will receive a point. If a participant has a score of 2 or greater, it will be defined as intolerance. Participant study continuation will be discussed with the family in weekly calls during the supplementation period.

Safety will be evaluated through measurement of the white blood cell (WBC) count of the complete blood cell (CBC) count. Investigators will evaluate changes between the pre- and post-supplementation period CBC looking at changes in WBC count to quantify the incidence of leukocytosis (WBC > 15.0 x 10^9/L) and leukopenia (WBC < 6.0 x 10^9/L) after completing the supplement and prior to the surgery. Any participant that has a WBC count higher or lower than the values stated above will be documented.

Investigators will measure hematocrit between pre- and post-supplement time points to determine the effect of SunButyrate-TG. Investigators will evaluate changes between the pre- and post-supplementation period complete blood count (CBC) looking at changes in of anemia (hematocrit < 29%) or polycythemia (hematocrit > 45%) after completing the supplement and prior to the surgery. Any participant that has a hematocrit higher or lower than the values stated above will be documented.

Safety will be evaluated through measurement of the white blood cell (WBC) count of the complete blood cell (CBC) count. Investigators will evaluate changes between the pre- and post-supplementation period complete blood count looking at changes in platelet (PLT) count to quantify the incidence of thrombocytopenia (PLT < 30 x 10^9/L) or thrombocythemia (PLT > 750 x 10^9/L). Any participant that has a PLT count higher or lower than the values stated above will be documented.

Investigators will collect blood for a comprehensive metabolic panel before and after supplementation with SunButyrate-TG. Investigators will evaluate the changes in blood urea nitrogen (BUN) and Creatinine to determine evidence of renal impairment or acute kidney injury based upon Kidney Disease: Improving Global Outcomes (KDIGO) criteria (creatinine increase 1.5-1.9 times baseline or >0.3 mg/dL increase), or urine output < 0.5 mL/kg/h for 6-12 hours (excluding overnight for potty-trained children).

Investigators will collect blood and measure a comprehensive metabolic panel before and after supplementation for evidence of liver injury. Investigators will determine:

• Presence of acidosis (pH< 7.3)
• Elevation of transaminitis (AST/ALT > 3 x baseline)
• Elevation in INR (>2 if not on coumadin)
• Elevation in Bilirubin (>2 mg/dL)
• Elevation in alkaline phosphatase (> 2 x baseline)

If a participant meets any one of the above criteria, this will be considered evidence of liver injury and reported.

Changes to the gut microbiome will be measured before and after supplementation, as well as post-operatively. Investigators will measure improvement in alpha diversity and the number of short-chain fatty acids (SCFA) producing bacterial populations.

An improvement will be classified by an increase in alpha diversity of measurable OTU's by 12, Shannon diversity index (increase of 0.5), and Simpson diversity index (increase of 0.08), and specific number of SCFA producing organisms by 5 OTU's compared to the placebo group.

Investigators will measure metabolite profiles to evaluate the amount of short-chain fatty acids (SCFA) in the gut and plasma before and after supplementation with SunButyrate-TG. This will be classified by a statistically significant increase (p<0.05) in a list of 8 different SCFA. A positive increase in SCFA production will be classified by at least 1 SCFA being significantly increased following supplementation with SunButyrate-TG compared to the placebo group.

Investigators will measure 3 plasma markers of intestinal barrier function between pre- and post-supplement, as well as post-operatively. These markers are claudin-2, claudin-3, and intestinal fatty acid binding protein (FABP2). An improvement in gut barrier will be considered if there is a statistically significant reduction in the plasma marker of any of these at the post-supplementation, or post-operative time points compared to the placebo group.

Investigators will measure cytokine levels pre- and post-surgery to determine changes in cytokine profiles of a panel of 8 different cytokines, including TNF-alpha, IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, TGF-beta and IFN-gamma). An improvement in the cytokine profile will be considered if there is a statistically significant reduction in pro-inflammatory cytokines (IL-1, TNFa, IL-6, IL-4, or IL-8, IFN-gamma) or a significant increase in anti-inflammatory cytokines (IL-10 and TGF-beta) compared to the placebo group. These cytokines are measured together and will be considered a positive improvement in cytokine profiles if at least 2 pro-inflammatory cytokine values are reduced in conjunction with an increase in IL-10 and/or TGF-beta.

Investigators will evaluate immune cell profiles in participants before and after surgery. Investigators will evaluate shifts in neutrophils. A significant change will be considered if there is a reduction of greater than 5% total neutrophil count via flow cytometry.

Investigators will evaluate immune cell profiles in participants before and after surgery. Investigators will evaluate shifts in macrophages. A significant change will be considered if there is a reduction of greater than 5% total macrophage count via flow cytometry.

Investigators will evaluate immune cell profiles in participants before and after surgery. Investigators will evaluate shifts in T-regulatory cells (T-cell). A significant change will be considered if there is an increase of greater than 10% in T-regulatory cell count via flow cytometry.

Investigators will evaluate immune cell profiles in participants before and after surgery. Investigators will evaluate shifts in natural killer T-cells (NK T-cell). A significant change will be considered if there is a reduction of greater than 10% total NK T-cell count via flow cytometry.

Investigators will measure inflammatory genes using an ribonucleic acid (RNA) hybridization panel and evaluate the level of activation of these genes pre-and post-surgery to determine a decrease in inflammatory signaling following supplementation with SunButyrate-TG compared to placebo. These inflammatory gene profiles are identified as a panel are are unable to be separated out. The entirety of the inflammatory gene profile will be evaluated together to assess changes in inflammatory gene activation.