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Fecal microbial transplant in HSCT
While the addition of beneficial bacteria or their metabo- lites has been shown to ameliorate acute GvHD in ani- mal allo-HSCT models, many challenges remain con- cerning the role of the intestinal microbiota in allo-HSCT in humans. A substantial amount of basic research is being conducted aiming to better understand the place of microbiome changes in the pathogenesis of acute GvHD. In addition, a large population microbiome analysis is ongoing attempting to delineate the interplay between other factors, such as antibiotics and diet, and the micro- biota disruption, and to determine the optimal strategy allowing to preserve the microbiota intact.119 However, while these issues are still under investigation, clinical trials evaluating the efficacy of FMT and other above- mentioned interventions in the HSCT setting are under-
Figure 1. The multifactorial interplay between environmental factors, intestinal microbiota and tissue damage affects transplant-related outcomes. During allogeneic hematopoietic stem cell transplantation (allo-HSCT), condition- ing chemotherapy causes damage to the intes- tinal mucosa cells such as intestinal epithelial cells, intestinal stem cells, paneth cells and mucus producing goblet cells. Gut microbiota is already disrupted before allo-HSCT and due to prophylactic and systemic antibiotic therapy the microbiota disruption worsens with loss of butyrate producing bacteria and other beneficial commensals, along with increase in pathogenic bacteria such as Enterococcus. Depletion of bac- terial metabolites postpones epithelial cell repair and restoration of the mucus barrier. Pathogenic bacteria can disseminate through the damaged mucosa and cause blood stream infections, which will necessitate the administration of sys- temic antibiotics further disrupting the intestinal microbiota. This vicious cycle is associated with graft-versus-host disease (GvHD), increased mortality and diminished overall survival. The question remains whether fecal microbiota transplantation (FMT) and other interventions such as prebiotics and the use of antibiotics with less anti-anaerobic activity could eventually break the cycle and improve outcomes. IEC:– intestinal epithelial cells; ISC: intestinal stem cells.
way (Table 2). Joint efforts to further explore biological, correlative and recovery functions of the intestinal microbiota could ultimately lead to decreased transplant- related mortality, and even pave the way to personalized therapeutic strategies in HSCT.
Disclosures
No conflicts of interest to disclose.
Contributions
IH, DY-O and TZ wrote the paper.
Acknowledgements
The authors wish to thank Sonia Kamenetsky for her assis- tance in the preparation of this manuscript.
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