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. 2021 Mar 16;12:644982. doi: 10.3389/fimmu.2021.644982

Table 3.

Summary of human studies investigating the association between the microbiota and GVHD in the past 10 years.

Year Patients Relative abundance alteration of microbiota Outcomes Ref
2012 18 adult patients (8 GVHD vs. 10 non-GVHD) ● In GVHD patients:

  • Lactobacillales↑

  • Clostridiales↓

 GVHD group had decreased stool microbial diversity, microbial chaos early after transplantation is a potential risk factor for subsequent GVHD. (99)
2014 80 adult patients ● In GVHD patients:

  • Enterococcus, Streptococcus, Lactobacillus↑

 Increased mortality from GVHD was associated with lower diversity of microbiota at engraftment, which showed a strong predictive effect on mortality. (123)
2015 115 adult patients ● In GVHD patients:

  • Blautia↓

 Increased abundance of commensal bacteria belonging to the Blautia genus is associated with reduced lethal GVHD and improved OS. (124)
2017 29 pediatric patients ● In GVHD patients:

  • Enterobacteriaceae, Enterococcus↑

● In non-GVHD patients:

  • anti-inflammatory Clostridia(AIC), Bacteroidetes, Bifidobacterium ↑

 Exposure to antianaerobic antibiotics clindamycin lead to depletion of Clostridia species which is associated with GVHD in pediatric HSCT patients. (125)
2017 66 adult patients (52 GVHD vs. 14 non-GVHD) ● In GVHD patients:

  • oral Actinobacteria, oral Firmicutes↑

  • Lachnospiraceae↓

 The stool microbiota at neutrophil recovery post-HSCT is predictive of subsequent development of aGVHD. (126)
2018 81 adult patients (32 GVHD vs. 49 non-GVHD) ● In GVHD patients:

  • Enterobacteriaceae↑

  • Lachnospiraceae, Ruminococcaceae↓

 Intestinal microbiota might induce aGVHD by influencing the Treg/Th17 balance. (68)
2019 141 adult patients (83 grade 0-I aGVHD vs. 58 grade II-IV aGVHD) ● In GVHD patients:

  • Proteobacteria, Gammaproteobacteria, Enterobacteriaceae↑

  • Firmicutes, Clostridia, Lachnospiraceae, Peptostreptococcaceae, Erysipelotrichaceae, Blautia, Lachnoclostridium, Erysipelatoclostridium, Eubacterium↓

 GVHD group had lower diversity of microbiota.
The AIM score defined as microbiota diversity of 4 bacterials (Lachnospiraceae, Peptostreptococcaceae, Erysipelotrichaceae, Enterobacteriaceae) was positively correlated with aGVHD grade and could be predictive of the development of aGVHD.		 (127)
2019 1325 adult male patients ● In GVHD patients:

  • enterococcal↑

 Expansion of enterococcal was associated with GVHD and mortality which can be driven by lactose. (104)
2020 70 patients (35GVHD vs. 35 non-GVHD) ● In GVHD patients:

  • Lachnospiraceae, Blautia, Ruminococcaceae↓

 Microbiota alterations were highly specific of GI aGVHD severity with lower bacterial biomass, a-diversity and decreased butyrate. (128)
2020 1362 adult patients from 4 centers ● In GVHD patients:

  • Enterococcus, Klebsiella, Escherichia, Staphylococcus, Streptococcus↑

 Patterns of microbiota disruption during allo-HSCT were similar across transplantation centers and geographic locations which were characterized by loss of diversity and domination by single taxa, lower diversity was associated with higher risks of TRM and death attributable to GVHD. (129)

OS, overall survival; AIM score, accumulated intestinal microbiota score; TRM, transplant-related mortality.