Dataset Information

Continuous pre- and post-transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wild-type mice.

ABSTRACT:

Objective

The gut microbiome plays a key role in the development of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. Here we investigate the individual contribution of the pre- and post-transplant gut microbiome to acute GVHD using a well-studied mouse model.

Design

Wild-type mice were cohoused with IL-17RA^{-/ -} mice, susceptible to hyperacute GVHD, either pre- or post-transplant alone or continuously (i.e., pre- and post-transplant). Fecal samples were collected from both WT and IL-17RA^{-/ -} mice pre- and post-cohousing and post-transplant and the microbiome analyzed using metagenomic sequencing.

Results

Priming wild-type mice via cohousing pre-transplant only is insufficient to accelerate GVHD, however, accelerated disease is observed in WT mice cohoused post-transplant only. When mice are cohoused continuously, the effect of priming and exacerbation is additive, resulting in a greater acceleration of disease in WT mice beyond that seen with cohousing post-transplant only. Metagenomic analysis of the microbiome revealed pre-transplant cohousing is associated with the transfer of specific species within two as-yet-uncultured genera of the bacterial family Muribaculaceae; CAG-485 and CAG-873. Post-transplant, we observed GVHD-associated blooms of Enterobacteriaceae members Escherichia coli and Enterobacter hormaechei subsp. steigerwaltii, and hyperacute GVHD gut microbiome distinct from that associated with delayed-onset disease (>10 days post-transplant).

Conclusion

These results clarify the importance of the peri-transplant microbiome in the susceptibility to acute GVHD post-transplant and demonstrate the species-specific nature of this association.

SUBMITTER: Bowerman KL

PROVIDER: S-EPMC7524395 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Continuous pre- and post-transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wild-type mice.

Bowerman Kate L KL Varelias Antiopi A Lachner Nancy N Kuns Rachel D RD Hill Geoffrey R GR Hugenholtz Philip P

Gut microbes 20200113 4

<h4>Objective</h4>The gut microbiome plays a key role in the development of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. Here we investigate the individual contribution of the pre- and post-transplant gut microbiome to acute GVHD using a well-studied mouse model.<h4>Design</h4>Wild-type mice were cohoused with IL-17RA<sup>-/ -</sup> mice, susceptible to hyperacute GVHD, either pre- or post-transplant alone or continuously (i.e., pre- and po ...[more]

PMID: 31928131

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Dataset Information

Continuous pre- and post-transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wild-type mice.

Objective

Design

Results

Conclusion

Publications

Continuous pre- and post-transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wild-type mice.

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