Carbapenem Antibiotics Promote Mucus Degradation By Bacteroides and Aggravate Graft-Versus-Host Disease

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for graft-versus-host disease (GVHD). The gastrointestinal tract has been identified to be a primary target of allogeneic donor T cells in allo-HSCT. The intestinal microbiota is known to interact with the host immune system and has been found to be an important modulator of GVHD. Broad-spectrum antibiotics such as carbapenems are often used in allo-HSCT patients to treat infections but have been found to increase the risk for intestinal GVHD, possibly via bystander depletion of beneficial commensal bacteria. However, whether loss of beneficial commensal bacteria is mechanistically sufficient to aggravate intestinal GVHD is not known. To examine this further, we utilized a mouse model of GVHD to study the effects of meropenem, a commonly used carbapenem in allo-HSCT patients.