Short Chain Fatty Acids as Predictors to Response of Acute Graft Versus Host Disease Treatment
Acute Graft Versus Host Disease (AGVHD) is a complication that affects nearly half of patients that undergo allogeneic stem cell transplant and is characterized by poor patient outcomes in many cases. AGVHD is caused by transplanted donor cells recognizing the host organs as foreign antigens and subsequently attacking them, usually the skin and lower gastrointestinal tract (LGI). Notably, the LGI consists of the gut microbiome, which plays important roles in aiding the immune system, so damage from chemotherapy and antibiotics could result in the LGI not being able to protect itself from further damage. One possible mechanism for this dynamic is the loss of short chain fatty acids (SCFA), which are produced by bacteria in the gut microbiome and are used as fuel by immune cells. While a loss of gut microbiome diversity has been observed in AGHVD patients, the potential implications of this loss and how they relate to SCFA levels has not yet been determined. Here we show that SCFA levels and other metabolic products could be used as biomarkers for potential treatment response. In particular, butyrate levels vary significantly between complete and partial responders (CR/PR) and non responders (NR) 14 days after steroid treatment. Our exploratory biomarker test indicated that the levels of other metabolic products vary greatly between CR/PR responders and NR. We also found that neither Total Parenteral Nutrition usage or Clostridium Difficile infection close to treatment affected SCFA levels. Our results indicate that SCFAs and other metabolic products can be used to determine the likelihood that patients will respond to AGVHD treatment. We believe that further research on a greater sample of high risk AGVHD treatments can confirm the insignificant differences in propionate and valerate levels in CR/PR and NR and identify the metabolic products that varied between the groups. Such evidence would indicate that SCFA levels should be evaluated in patients before hematopoietic cell transplants to determine a treatment plan that minimizes damage to the gut microbiome.