Table 1.

Summary of studies investigating how microbiota changes affect GVHD (structured by phylum).

Bacterium	Role in GVHD	Species	References
PROTEOBACTERIA
Escherichia coli	Murine GI GVHD was accompanied by flora shifts toward E. coli and this increase was significantly associated with GVHD severity and mortality.	Mouse	Heimesaat et al. (27)
FIRMICUTES
Enterococcus spp.	Expansion post-transplantation and association with increased GI GVHD severity in allo-HCT patients.	Human	Holler et al. (24)
	Associated with increased GVHD severity in mice and in patients in three different centers. Aggravation of GVHD in a murine MHC-disparate model.	Human/Mouse	Stein-Thoeringer et al. (28)
Lactobacillus johnsonii	GVHD was accompanied by increase in Lactobacillales and decrease in Clostridiales in mice and patients. Ampicillin treatment before allo-HCT resulted in reduced survival in GVHD mouse models. L. johnsonii reintroduction prevented increased GVHD lethality and pathology and prevented Enterococcus expansion in mice.	Human/Mouse	Jenq et al. (29)
Lactobacillus rhamnosus GG	Oral administration reduced translocation of enteric bacteria and acute GVHD in a murine model.	Mouse	Gerbitz et al. (30)
	Randomized trial of probiotic treatment in 31 allo-HCT recipients. The trial was terminated when interim analysis did not detect an appreciable probiotic-related change in the gut microbiome or incidence of GVHD.	Human	Gorshein et al. (31)
Lactobacillus plantarum	Ongoing clinical trial aiming to prevent GVHD by orally-administered L. plantarum in children undergoing allo-HCT. Preliminary results demonstrated safety and feasibility.	Human	Ladas et al. (32)
Clostridiales spp.	Clinical trial (64 patients, stool analyzed 12 days after BMT) showing that Blautia is associated with reduced GVHD-related mortality. Data were confirmed in a 2nd cohort with 51 patients.	Human	Jenq et al. (33)
	Oral gavage with Clostridia spp. reduced GVHD severity and mortality in murine mouse models.	Mouse	Mathewson et al. (34)
	Depletion of Clostridia spp. was associated with increased GVHD in 15 pediatric allo-HCT patients. Treatment with clinda-mycin depleted Clostridia and exacerbated GVHD in mice, while Clostridia supplementation reduced murine GVHD severity.	Human/ Mouse	Simms-Waldrip et al. (35)
BACTEROIDETES
Barnesiella spp.	Barnesiella spp. conferred protection against Enterococcus domination in allo-HCT patients and mice.	Human/ Mouse	Ubeda et al. (36)
Bacteroides/Prevotella spp.	Bacteroides/Prevotella spp. increased during GI GVHD in mice.	Mouse	Heimesaat et al. (27)
VERRUCOMICROBIA
Akkermansia muciniphila	Allo-HCT recipients (n = 857) as well as GVHD mice treated with broad-spectrum antibiotics showed increased GVHD severity. Imipenem-cilastatin treatment caused destruction of the colonic mucus layer and expansion of Akkermansia muciniphila in mice.	Human/Mouse	Shono et al. (20)