Gut microbiota trajectory in pediatric patients undergoing hematopoietic SCT

Abstract

Acute GvHD (aGvHD) is the main complication of hematopoietic SCT (HSCT) during the treatment of hematological disorders. We carried out the first longitudinal study to follow the gut microbiota trajectory, from both the phylogenetic and functional points of view, in pediatric patients undergoing HSCT. Gut microbiota trajectories and short-chain fatty acid production profiles were followed starting from before HSCT and through the 3-4 months after transplant in children developing and not developing aGvHD. According to our findings, HSCT procedures temporarily cause a structural and functional disruption of the gut microbial ecosystem, describing a trajectory of recovery during the following 100 days. The onset of aGvHD is associated with specific gut microbiota signatures both along the course of gut microbiota reconstruction immediately after transplant and, most interestingly, prior to HSCT. Indeed, in pre-HSCT samples, non-aGvHD patients showed higher abundances of propionate-producing Bacteroidetes, highly adaptable microbiome mutualists that showed to persist during the HSCT-induced ecosystem disruption. Our data indicate that structure and temporal dynamics of the gut microbial ecosystem can be a relevant factor for the success of HSCT and opens the perspective to the manipulation of the pre-HSCT gut microbiota configuration to favor mutualistic persisters with immunomodulatory properties in the gut.Bone Marrow Transplantation (2015) 50, 992-998;

Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut

“…Temporal microbiota dynamics thus seemed to be linked to the gut condition of the patient. Beneficial bacteria such as Bacteroides, 5 Lactobacillus, 8 Bifidobacterium, and Faecalibacterium 14 were dominant in cases 1 to 3, 15 whereas Escherichia, which has been strongly correlated with GVHD in a mouse model, 9 was increased at the recurrence of aGVHD in case 4. The number of operational taxonomic units and diversity of the intestinal microbiota did not fully recover after FMT, even with apparent clinical response (supplemental Figure 2).…”

“…Indeed, the intestinal microbiota has been reported to be associated with the entire spectrum of aGVHD. 4,5,10 In summary, FMT was safely performed in SCT patients and offers promise as a potential treatment option for aGVHD. Further evaluation to confirm the safety and efficacy of FMT for aGVHD is warranted.…”

“…[4][5][6][7][8][9][10] Fecal microbiota transplantation (FMT) refers to infusion of a fecal suspension from a healthy donor into the gastrointestinal tract of a patient to restore a healthy microbiota and cure disease. Manipulation of the intestinal microbiota by FMT may influence the immune system and improve immune-mediated enteritis such as gut aGVHD.…”

The intestinal microbiota in allogeneic hematopoietic cell transplant and graft-versus-host disease

“…78 A longitudinal study of pediatric patients undergoing HCT showed that it often takes over 2 months after transplantation to regain intestinal diversity. 79 Lost diversity and intestinal domination of opportunistic bacteria have also been shown to precede blood stream infection (BSI) by the same pathogen in HCT patients. 55,80 As such, some investigators are exploring alternative antibiotic prophylactic strategies that may better preserve patient flora and maintain gut homeostasis.…”

The Gut Microbiota and Hematopoietic Stem Cell Transplantation: Challenges and Potentials

“…The decrease in diversity following allo-HSCT is often accompanied by the expansion of a single taxon. In most cases, at the onset of GvHD, an increase in the abundance of the members of the genus Enterococcus has been observed [17, 19]. This is frequently followed by BSI with vancomycin-resistant Enterococci and a decrease in the abundance of members of the order Clostridiales including Faecalibacterium spp.…”