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) |