Patients with gastrointestinal (GI) acute graft-versus-host disease (GVHD) may show patterns of microbial dysbiosis that are detectable in stool samples at the approximate onset of GVHD. Additionally, indicators of microbial health from prior to GVHD onset appeared associated with better survival outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) in this study. Results were reported in the journal Blood.
Acute GVHD of the GI system often occurs after allo-HCT and is associated with microbial dysbiosis. Lower-GI (LGI) tract involvement is also associated with worse outcomes, whereas upper-GI (UGI) tract involvement shows greater responses to treatment, the study investigators explained. “We hypothesized that unique patterns of microbial dysbiosis correlate with organ-specific intestinal involvement in GVHD and consequently influence GVHD outcomes after allo-HCT,” the investigators stated in their report.
In this study, the research team analyzed stool samples obtained from 266 patients who underwent allo-HCT. They profiled the samples using 16S ribosomal gene sequencing to characterize the composition of the intestinal microbiome in patients and identify patterns by organ involvement of acute GVHD in patients.
A total of 1303 stool samples were obtained from the patients in this study. In the 20-day period before GVHD onset, patients with GVHD showed reduced abundance of microbes from the class Clostridia, compared with patients who did not develop GVHD. Patients with GVHD also showed lower levels of microbes associated with butyrate production in the 20 days before disease onset in addition to lower ratios of strict-to-facultative anaerobic bacteria (S/F anaerobe ratio) than did patients without GVHD.
Patients who had acute GVHD of the LGI tract had lower S/F anaerobe ratios prior to disease onset, compared with patients who had acute GVHD isolated to the UGI tract. In the 20 days following GVHD onset, patients with GI involvement had a lower S/F anaerobe ratio than did patients without GVHD, and this phenomenon was more pronounced in patients with LGI involvement.
The research team also characterized factors that appeared significantly related to better survival outcomes. Longer overall survival was predicted by greater amounts of Clostridia and butyrate producers, in addition to a higher S/F anaerobe ratio. Lower risks of GVHD-related mortality were linked to a greater amount of butyrate producers and a higher S/F anaerobe ratio.
“In conclusion, we found significant associations between microbial diversity, the abundance of butyrate producing taxa and the S/F anaerobe ratio with GI-GVHD, particularly LGI-GVHD,” the study investigators reported. They also considered the study’s findings to suggest the intestinal microbiome may have use as a biomarker for outcomes with GVHD in allo-HCT recipients.
Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Burgos da Silva M, Ponce DM, Dai A, et al. Preservation of fecal microbiome is associated with reduced severity of graft-versus-host disease. Blood. Published online August 15, 2022. doi:10.1182/blood.2021015352