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2844. Butyrogenic Bacteria After Acute Graft vs. Host Disease Associate with the Development of Steroid Refractory GVHD
- Source :
- Open Forum Infectious Diseases
- Publication Year :
- 2019
- Publisher :
- Oxford University Press (OUP), 2019.
-
Abstract
- Background Steroid refractory acute graft- vs. -host-disease (GVHD) after hematopoietic cell transplantation (HCT) is highly morbid with limited treatment options. Murine studies show protection from GVHD with butyrate exposure but direct exposure of stem/progenitor cells to butyrate inhibits colonic stem cell proliferation. Methods Stool samples were collected weekly in a cohort of HCT recipients (n = 210) undergoing allogeneic transplant, and underwent 16S rRNA sequencing to determine the number and relative abundance of butyrogens. Dissociated primary human colonoid cell aggregates (200,000 per well) were plated onto collagen IV-coated transwells (0.4 µm pore size, 0.33 cm2, PET) in stem cell medium for 24 hours. From 24 hours onwards, the basal-lateral chamber was switched to differentiation medium; the apical chamber was Hanks Buffered Salt Solution (HBSS), HBSS with 10 mM butyrate sodium salt early (24 hours onwards) or late (72hours onwards). Trans-epithelial electrical resistance was measured daily. Results Retrospective chart review identified 27 recipients who developed acute GVHD of the gut, stratified to be either steroid refractory GVHD (failed to respond to 2 mg/kg of methylprednisolone) or responsive. The presence of butyrogens in the gut microbiome after the onset of severe acute GHVD of the gut associated with increased risk of steroid refractory GVHD (Figure 1; P < 0.05). Direct exposure of human colonic stem/progenitor cells to butyrate inhibits the development of trans-epithelial electrical resistance; exposure after differentiation had no inhibition of barrier formation (Figure 2; P < 0.05 by T-test). Conclusion Butyrogens may help prevent the development of acute GVHD of the gut, but once severe GVHD has developed may inhibit recovery due to the loss of crypt architecture exposing colonic stem cells to microbe-produced butyrate with impaired differentiation and cell replacement. Disclosures All Authors: No reported Disclosures.
- Subjects :
- biology
business.industry
medicine.medical_treatment
Hematopoietic stem cell transplantation
medicine.disease
biology.organism_classification
Transplantation
Abstracts
Infectious Diseases
Graft-versus-host disease
Oral Abstracts
Oncology
Methylprednisolone
Immunology
medicine
Stem cell
business
Host disease
Steroid refractory
Bacteria
medicine.drug
Subjects
Details
- ISSN :
- 23288957
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Open Forum Infectious Diseases
- Accession number :
- edsair.doi.dedup.....d4848ef749e50b8c8cb1547e9c92fc25