Dysbiotic Scars following Chemotherapy

Treatment for acute leukemia involves repeated exposure to chemotherapies and associated antibiotics to treat and prevent infections in the immunosuppressed state. We have recently shown that repeated therapies result in an intestinal microbial community with lower resilience that is more susceptible to perturbations as treatments progress. Following cessation of treatments, the microbial community recovers its diversity, but it remains compositionally different from its original configuration. Our group, in collaboration with Dr. Armin Rashidi and others in the Division of Hematology, Oncology, and Transplantation, is working to understand the clinical and ecological significance of these changes.

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We have also identified specific states during treatment in which certain species of potential pathobionts - commensal bacteria that may become detrimental to the host in an imbalance, dysbiotic state - become dominant. We are working to characterize these states and evaluate the mechanism(s) by which keystone species in these states influence patient outcomes.

In August 2018, we received funding for this work through the Chainbreaker mechanism from the Masonic Cancer Center. In addition to other on-going projects, an interventional trial to supplement the intestinal microbiota using restorative microbiota therapy during leukemia treatments is planned.

Recent Publications

  • Rashidi A, Peled JU, Ebadi M, Ur Rehman T, Elhusseini H, Marcello LT, Halaweish H, Kaiser T, Holtan SG, Khoruts A, Weisdorf DJ, Staley C. 2022 Intestinal Blautia may protect against neutropenic fever in allogeneic transplant patients by augmenting the intestinal epithelium. Clin Infect Dis. in press. doi:10.1093/cid/ciac299
  • Rashidi A, Ebadi M, Rehman TU, Elhusseini H, Halaweish H, Holtan SG, Ramamoorthy S, Weisdorf DJ, Khoruts A, Staley C. 2022. Loss of microbiota-derived protective metabolites after neutropenic fever. Sci Rep. 2022 12(1), 6244. doi:10.1038/s41598-022-10282-0
  • Rashidi A, Ebadi M, Rehman TU, Elhusseini H, Halaweish HF, Kaiser T, Holtan SG, Khoruts A, Weisdorf DJ, Staley C. 2022 Lasting shift in the gut microbiota in patients with acute myeloid leukemia. Blood Adv. in press doi:10.1182/bloodadvances.2021006783
  • Rashidi A, Ebadi M, Rehman TU, Elhusseini H, Nalluri H, Kaiser T, Holtan SG, Khoruts A, Weisdorf DJ, Staley C. 2021. Gut microbiota response to antibiotics is personalized and depends on baseline microbiota. Microbiome 9(1), 211. doi:10.1186/s40168-021-01170-2
  • Rashidi A, Ebadi M, Ur Rehman T, Elhusseini H, Kaiser T, Ramamoorthy S, Holtan SG, Khoruts A, Weisdorf DJ, Staley C. 2021. Blood Adv. Altered microbiota-host metabolic crosstalk preceding neutropenic fever in patients with acute leukemia. 5(20), 3937-3950. doi:10.1182/bloodadvances.2021004973
  • Rashidi A, Ebadi M, Ur Rehman T, Elhusseini H, Nalluri H, Kaiser T, Holtan SG, Khoruts A, Weisdorf DJ, Staley C. 2021. Gut Microboes. Effect of COVID-19 precautions on the gut microbiota and nosocomial infections. 13(1), 1-10. doi:10.1080/19490976.2021.1936378
  • Rashidi A, Kaiser T, Ebadi M, Holtan SG, Rehman TU, Weisdorf DJ, Khoruts A, Staley C. 2020. Br J Haematol. Circulating bacterial DNA and neutropenic fever during anti‐leukaemia chemotherapy. 191(2), e55-e58. doi:10.1111/bjh.16994
  • Rashidi A, Maeser D, Kaiser T, Ebadi M, Rehman TU, Holtan SG, Weisdorf DJ, Khoruts A, Staley C. 2020. Br J  Haematol. Microbiome swings with repeated insults. doi:10.1111/bjh.16509
  • Rashidi A, Herman A, Staley C, Blazer BR, Weisdorf DJ. 2019. Br J Haematol. An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease. 189(5), 926-930. doi:10.1111/bjh.16458
  • Rashidi A, Kaiser T, Graizer C, Holtan SG, Rehman TU, Weisdorf DJ, Dunny G, Khoruts A, Staley C. 2019. Cancer. Gut dysbiosis during anti-leukemia chemotherapy versus allogeneic hematopoietic cell transplantation. 126(7), 1434-1447. doi:10.1002/cncr.32641
  • Rashidi A, Zhigang G, Kaiser T, Manias DA, Holtan SG, Rehman TU, Weisdorf DJ, Khoruts A, Dunny GA, Staley C. 2019. Vancomycin-resistance gene cluster, vanC, in the gut microbiome of acute leukemia patients undergoing intensive chemotherapy. Plos One. 14(10), e0223890 doi:10.1371/journal.pone.0223890
  • Rashidi A, Kaiser T, Graizer C, Holtan SG, Rehman TU, Weisdorf DJ, Khoruts A, Staley C. 2019. Specific gut microbiota changes heralding bloodstream infection and neutropenic fever during intensive chemotherapy. 34(1), 312-316. Leukemia. doi:10.1038/s41375-019-0547-0
  • Rashidi A, Kaiser T, Shields-Cutler R, Graiziger C, Holtan SG, Rehman T, Wasko J, Weisdorf DJ, Dunny G, Khoruts A, Staley C. 2019. Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia. Sci. Rep. 9(1), 6083. doi:10.1038/s41598-019-42652-6
  • Rashidi A, Kaiser T, Shields-Cutler R, Graiziger C, Ur Rehman T, Holtan SG, Weisdorf DJ, Knights D, Khoruts A, Staley C. 2019. Gut dysbiosis increases gut barrier damage during anti-leukemia chemotherapy: implications for acute graft-versus-host disease. Biol. Blood Marrow Transplant. 25(3), S142-143. doi:10.1016/j.bbmt.2018.12.433
  • Rashidi A, Kaiser T, Shields-Cutler R, Graiziger C, Ur Rehman T, Holtan SG, Weisdorf DJ, Knights D, Khoruts A, Staley C. 2019. Outpatient-to-inpatient transition causes marked dysbiosis in allogeneic hematopoietic cell transplantation recipients. Biol. Blood Marrow Transplant. 25(3), S47. doi:10.1016/j.bbmt.2018.12.124
  • Rashidi A, Kaiser T, Holtan S, Weisdorf D, Khoruts A, Staley C. 2018. Pre-transplant recovery of microbiome diversity without recovery of the original microbiome. Bone Marrow Transplant. 54, 1115-1117. doi:10.1038/s41409-018-0414-z