Microbiome and diversity indices during blood stem cells transplantation - new perspectives?

Objective: The human body is colonized by bacteria, fungi and viruses. Resident commensal bacteria are a fundamental line of resistance to colonization by exogenous microbes. They actively regulate the production of nutrients by the host through a negative feedback mechanism, in order to prevent the availability of nutrients for potential pathogens. While only a small fraction of these microorganism may be pathogenic, the relationship between host and commensal microbiome is now studied as a whole, impacting several aspects of the host biology. Some studies have made clear the progresses in examining the role of microbiome on transplants and graft versus host disease (GVHD) severity and its pathogenesis: the risk of complications from allogenic hematopoietic stem cells transplantation (HSCT) is greater with the highest mortality if a patient has a lower bacterial diversity in the gut prior to the transplantation process beginning. Microbiota-associated molecular patterns are directly recognized by pathogen recognition receptors. The development of molecular methods has greatly expanded our knowledge of the composition and function of the microbiome in health and disease, shortening the response times vs. microbiological culture tests. The gut flora can make the difference when it comes to allo-HSCT. The aim of the study was to monitor microbiome of 10 children during allo-HSCT.

Methods: Oral specimens and gut faecal microbiome (100 grams) samples were collected at 2, 16, 24 days. The samples were analysed by polymerase chain reaction and primary sequencing was done. To calculate the biodiversity of microbiome the Shannon index and the Observed species index were chosen.

Results: Our study suggests some differences in the diversity indices (DIs) in 5 children affected by GVHD vs. not affected. The DIs in oral and faecal specimens show in all patients a diminution in the post-transplant phase with an improvement in species diversity after 16 days from the transplant. The Observed species index in faeces specimens after 16 days was higher in patients which had not GVHD; moreover, patients with GVHD showed a deterioration at 24 days. Oral specimens after 24 days showed a parallel trend in the two groups. The Shannon index shows a downward trend in faeces specimens of the children with GVHD at 24 days; the children without GVHD recover a good trend of entropy. Oral specimens at 24 days show low entropy in the two groups. Very aggressive bacterial species as Cronobacter and Routella in the faeces specimens of a child had not serious consequences for disease status: Cronobacter were not present 24 days after transplantation.

Conclusions: The data show the microbial metabolome could have an impact on patients with GVHD vs. no GVHD. A better understanding of the role of the oral and gut microbiome in GVHD can give directions to move towards the development of innovative approaches for preventing GVHD following allo-HCT, reducing also antibiotic therapy.