Microbiota long-term dynamics and prediction of acute graft-versus-host-disease in pediatric allogeneic stem cell transplantation

Abstract

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) exhibit changes in their gut microbiota and are experiencing a range of complications, including acute graft-versus-host disease (aGvHD). It is unknown if, when, and under which conditions a re-establishment of microbial and immunological homeostasis occurs. It is also unclear whether microbiota long-term dynamics occur at other body sites than the gut such as the mouth or nose. Moreover, it is not known whether the patients microbiota prior to HSCT holds clues to whether the patient would suffer from severe complications subsequent to HSCT. Here, we performed integrated host-microbiota analyses of the gut, oral, and nasal microbiotas in 29 children undergoing allo-HSCT. The bacterial diversity decreased in the gut, nose, and mouth during the first month and reconstituted again 1-3 months after allo-HSCT. The microbial community composition traversed three phases over one year. Distinct taxa discriminated the microbiota temporally at all three body sides, including Enterococcus spp., Lactobacillus spp., and Blautia spp. in the gut. Of note, certain microbial taxa appeared already changed in the patients prior to allo-HSCT as compared to healthy children. Acute GvHD occurring after allo-HSCT could be predicted from the microbiota composition at all three body sites prior to HSCT, in particular from Parabacteroides distasonis, Lachnospiraceae NK4A136 sp. and Lactobacillus sp. abundances in the gut. The reconstitution of CD4+ T cells, TH17 and B cells was associated with distinct taxa of the gut, oral, and nasal microbiota. This study reveals for the first time bacteria in the mouth and nose that may predict aGvHD. Surveillance of the microbiota at different body sites in HSCT may be of prognostic value and could assist in guiding personalized treatment strategies. The identification of distinct bacteria that have a potential to predict post-transplant aGvHD might provide opportunities for an improved preventive clinical management, including a modulation of microbiomes. The host-microbiota associations shared between several body sites might also support an implementation of more feasible oral and nasal swab sampling-based analyses. Altogether, the findings suggest that both, host factors and the microbiota, could provide actionable information to guiding precision medicine.