The fate of the gut microbiome following stem cell transplant

 Bone marrow prior to transplant

Bone marrow prior to transplant

Hematopoietic stem cell transplant (HSCT) is a difficult procedure that is usually administered to patients suffering from bone marrow or blood cancers such as multiple myeloma or leukemia.  Unfortunately, many patients who receive this treatment develop acute graft-versus-host disease (aGvHD), a multi-organ system immunologic disorder that is particularly detrimental to the gastrointestinal tract. 

In light of increasing evidence highlighting the importance of the symbiosis between the microbiome and human hosts, researchers set out to explore the fate of gut microbiota in pediatric patients who had undergone HSCT.  Specifically, phylogenetic profiles and functional properties were examined in a longitudinal analysis to develop a better understanding of the specific role the gut microbiome plays in patients who develop aGvHD following a HSTC procedure. 

Ten pediatric patients who had undergone HSTC, 5 of which had developed aGvHD, were selected for analysis.  The trajectory of the microbiota ecosystem was monitored using gene pyrosequencing of fecal samples, which were collected before, during, and after the HSTC procedure.  Collection and observation continued for 3 to 4 months.  Additionally, researchers examined short-chain fatty acid (SCFA) production samples in the patients as a measurement of microbiota metabolic activity.  Short-chain fatty acids are critical metabolites that microbiota require in order to maintain healthy physiology.  Healthy microbiota are critical toward educating the immune system and maintaining homeostasis.

Marked changes were observed in the gut microbiome populations of all 10 patients immediately following the HSTC procedure.  There was a massive invasion of new bacterial species following the procedure, with less than 10% of the original microbiota being conserved.  In particular, there was a significant loss in health-promoting bacterial species such as Faecalibacterium and Ruminococcus.  Two months after the procedures, the species richness and metabolic activities in the patients’ guts was restored. 

The patients who developed aGvHD experienced a major drop in health-promoting bacteria and higher abundances of invading bacteria as compared to non-aGvHD patients.  Interestingly, the gut microbiomes of the non- aGvHD patients contained significantly higher populations of Bacteroides phylum.  On top of this, Bacteriodes were the most abundant species observed among the original 10% of microbiota conserved through the HSTC operation. 

This study points to the importance of the gut microbiome in helping maintain healthy integrity of the gut immune system following a HSTC procedure.  The finding that having low Bacteriodes populations may be an unrecognized consequence that could lead to the development of aGvHD is particularly interesting.  Should these bacteria be as important as this data suggests, preventative microbiome-driven therapies could be explored with the aim of preventing post-HSTC procedural aGvHD onset.  A therapy that could maintain healthy Bacteriodes populations prior to HSTC operations could perhaps present a viable solution.  

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