Described associations between specific microorganisms, the microbiota, and hematologic disorders
| Disease . | Implicated microbiota . | Reference . |
|---|---|---|
| Aplastic anemia | Aplastic anemia has been reported after infections with human parvovirus B19; hepatitis A, B, C, E, and G; CMV; EBV; echovirus 3; GB virus C; transfusion-transmitted or Torque teno virus; SEN virus; and non–A-E hepatitis viruses. | 50-52 |
| Megaloblastic anemia | Although changes in the microbiota have not yet been directly associated with this disease, cyanocobalamin (vitamin B12) is synthesized by several genera of intestinal bacteria. | 53 |
| Anemia of chronic inflammation | Hepcidin is a gene that is induced by infection and inflammation. Hepcidin-dependent changes in iron flux can induce anemia in chronic inflammatory states. | 54 |
| Gastric MALT lymphoma | Linked to infection with Helicobacter pylori. | 55 |
| Marginal zone lymphomas | HCV might provide the initial antigenic stimulus for B-cell clonal expansion. | 56 |
| HTLV-associated acute T-cell leukemia | Etiologically linked to HTLV-1 and with a distinct geographical distribution. | 57 |
| Burkitt lymphoma | A subset of the cases of this aggressive lymphoma, especially endemic cases in sub-Saharan Africa, is associated with EBV infection. | 58 |
| PTLD | PTLD after solid organ transplant and HCT is associated with EBV, which leads to uncontrolled B-cell proliferation and tumor formation. | 59 |
| Castleman disease | Human herpesvirus 8 (Kaposi sarcoma–associated herpesvirus) sequences have been described in some cases of multicentric Castleman disease. | 60 |
| ITP | Often secondary to persistent, often inapparent infections (eg, H pylori, CMV, or HCV). | 61 |
| Reactive thrombocytosis | Cytokines, such as IL-6, IL-1, and tumor necrosis factor, have been shown to promote in vivo and in vitro megakaryocytopoiesis, or production of platelets. Any inflammatory process such as bacterial infection, neoplasia, sepsis, multiple trauma, burns, or pancreatitis that elevates serum interleukin levels (especially IL-6), may increase the circulating platelet count. | 62 |
| GVHD | Loss of Paneth cells from GVHD results in decreased production of α-defensins. α-Defensins selectively kill noncommensal bacteria while preserving commensal microbiota. A decrease in the expression of α-defensins may thus result in the loss of microbial diversity. | 63 |
| Allo-HCT | The gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal microbiota with reduced diversity. The diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HCT recipients. Sequencing of free DNA in organ transplant recipients’ plasma revealed an expansion of Anelloviridae upon immunosuppression. There was a lower anellovirus burden in patients who suffer from graft rejection. A similar finding would be expected in the HCT population. | 64, 65 |
| Disease . | Implicated microbiota . | Reference . |
|---|---|---|
| Aplastic anemia | Aplastic anemia has been reported after infections with human parvovirus B19; hepatitis A, B, C, E, and G; CMV; EBV; echovirus 3; GB virus C; transfusion-transmitted or Torque teno virus; SEN virus; and non–A-E hepatitis viruses. | 50-52 |
| Megaloblastic anemia | Although changes in the microbiota have not yet been directly associated with this disease, cyanocobalamin (vitamin B12) is synthesized by several genera of intestinal bacteria. | 53 |
| Anemia of chronic inflammation | Hepcidin is a gene that is induced by infection and inflammation. Hepcidin-dependent changes in iron flux can induce anemia in chronic inflammatory states. | 54 |
| Gastric MALT lymphoma | Linked to infection with Helicobacter pylori. | 55 |
| Marginal zone lymphomas | HCV might provide the initial antigenic stimulus for B-cell clonal expansion. | 56 |
| HTLV-associated acute T-cell leukemia | Etiologically linked to HTLV-1 and with a distinct geographical distribution. | 57 |
| Burkitt lymphoma | A subset of the cases of this aggressive lymphoma, especially endemic cases in sub-Saharan Africa, is associated with EBV infection. | 58 |
| PTLD | PTLD after solid organ transplant and HCT is associated with EBV, which leads to uncontrolled B-cell proliferation and tumor formation. | 59 |
| Castleman disease | Human herpesvirus 8 (Kaposi sarcoma–associated herpesvirus) sequences have been described in some cases of multicentric Castleman disease. | 60 |
| ITP | Often secondary to persistent, often inapparent infections (eg, H pylori, CMV, or HCV). | 61 |
| Reactive thrombocytosis | Cytokines, such as IL-6, IL-1, and tumor necrosis factor, have been shown to promote in vivo and in vitro megakaryocytopoiesis, or production of platelets. Any inflammatory process such as bacterial infection, neoplasia, sepsis, multiple trauma, burns, or pancreatitis that elevates serum interleukin levels (especially IL-6), may increase the circulating platelet count. | 62 |
| GVHD | Loss of Paneth cells from GVHD results in decreased production of α-defensins. α-Defensins selectively kill noncommensal bacteria while preserving commensal microbiota. A decrease in the expression of α-defensins may thus result in the loss of microbial diversity. | 63 |
| Allo-HCT | The gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal microbiota with reduced diversity. The diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HCT recipients. Sequencing of free DNA in organ transplant recipients’ plasma revealed an expansion of Anelloviridae upon immunosuppression. There was a lower anellovirus burden in patients who suffer from graft rejection. A similar finding would be expected in the HCT population. | 64, 65 |
Allo-HCT, allogeneic HCT; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HCT, hematopoietic cell transplantation; HCV, hepatitis C virus; HTLV, human T-cell lymphotropic virus; ITP, idiopathic thrombocytopenic purpura; MALT, mucosa-associated lymphatic tissue; PTLD, posttransplantation lymphoproliferative disorder.