Novel Metagenomics Studies of the Gut, Virome and Fungome
Principle Investigator: Pooja Khandelwal, MD
Acute graft versus host disease (GVHD) is a life-threatening complication after a bone marrow transplant which manifests as a rash, large volume diarrhea, or jaundice. GVHD has a mortality rate of 30 to 50 percent and is associated with opportunistic infections, which include bacterial, viral, and invasive fungal infections. Blood stream infections result in antibiotic use which leads to disruption in the gut flora. This disruption of the gut flora is, in turn, associated with development of acute GVHD and additional infections, making this a vicious cycle.
The gut flora is composed of bacteria, fungi, and viruses. A growing amount of research exists on intestinal bacterial changes after bone marrow transplant and about how these changes cause GVHD or blood stream infections. No data exists about the role of fungi and viruses, even though children experience fungal infections and viral infections clinically.
We have hypothesized that changes in intestinal fungi and viruses will be associated with development of acute GVHD and infections in children undergoing a bone marrow transplant. We also hypothesized that the amount of human DNA present in stool samples from children will be a new way to identify children with acute GVHD and that more human DNA will be present in stool in severe forms of acute GVHD.
For this research, we are analyzing the intestinal fungi, viruses, and human DNA within our existing metagenomic shotgun sequencing data in 42 children after bone marrow transplant. We will confirm our findings in an additional group of 50 bone marrow transplant patients. We expect to identify important changes in intestinal fungi and viruses after transplant and plan to perform future interventional trials to modify the gut flora collectively as a novel strategy of reducing the incidence of acute GVHD and infections.