Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease

Abstract

Following allogeneic hematopoietic cell transplantation (allo-HCT), the gastrointestinal (GI) tract is frequently affected by acute graft-versus-host disease (aGVHD), the pathophysiology of which is associated with a dysbiotic microbiome. Since microbial composition varies along the length of the GI tract, we hypothesized that microbiome features correlate with the pattern of organ involvement after allo-HCT. We evaluated 266 allo-HCT recipients from whom 1,303 stool samples were profiled by 16S ribosomal gene sequencing. Patients were classified according to which organs were affected by aGVHD. In the 20 days prior to disease onset, GVHD patients had lower abundances of members of the class Clostridia, lower counts of butyrate producers, and lower ratios of strict-to-facultative anaerobic bacteria (S/F anaerobe ratio) compared to allograft recipients who were free of GVHD. GI-GVHD patients showed significant reduction in microbial diversity pre-onset. Patients with lower GI-aGVHD had lower S/F anaerobe ratios compared to those with isolated upper GI-aGVHD. In the 20 days after disease onset, dysbiosis was observed only in GVHD patients with GI involvement, particularly those with lower-tract disease. Importantly, Clostridial and butyrate-producer abundance, as well as S/F anaerobe ratio were predictors of longer overall survival; higher abundance of butyrate producers, and higher S/F anaerobe ratio were associated with decreased risk of GVHD-related death. These findings suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD.

Graft-versus-host disease complicated with small bowel obstruction in children: A case report

“…Burgos da Silva et al. showed that the preservation of fecal microbiome was correlated with reduced severity of GvHD ( 12 ).…”

Development of allogeneic hematopoietic stem cell transplantation in 2022: Regenerating “Groot” to heal the world

“…Growing evidence suggests a significant reduction in microbial diversity peri-GvHD, and the intestinal microbiome can serve as a target. 4 Pooled allo-microbiotherapy MaaT013 resulted in a 56% ORR in severe gastrointestinal aGvHD, while bacteremia was lower than the historical control (14% versus 31%–74%). As the United States approved the first fecal microbiota product for the prevention of Clostridioides difficile infection in 2022, it is anticipated that the microbiota will play an important role in controlling GvHDs.…”

Pathophysiology of gastrointestinal acute graft‐versus‐host disease and the potential role of glucagon‐like peptide 2

“…The commensal microbiota is frequently dysregulated and reduced in its diversity following allo-HCT, and dysbiosis has been shown to be associated with subsequent development of GI aGVHD in humans and mice. 45 Specific microbiome risk factors for aGVHD include the presence of certain bacteria such as enterococci and the loss of some bacteria from the Clostridia class. Anaerobic commensals, such as the Clostridia class, produce a class of microbiome-derived metabolites such as butyrate, propionate and acetate (short-chain fatty acids).…”

“…45 In addition to reduced use of antibiotics, dietary lactose depletion, which attenuates enterococci outgrowth, was shown to reduce aGVHD in mice; treatment with antibodies against poly-N-acetylglucosamine reduced aGVHD severity without impacting microbiome diversity. [45][46][47][48]…”