Table 2.

Summary of nearly 10 years of experimental studies investigating the association between alterations in the intestinal microbiota and aGVHD.

Year	Mouse model	Relative abundance alteration of microbiota	Relationship with aGVHD	Ref
2010	(Age- and sex-matched) Balb/c→C57B6(TLR-/-, MyD88-/-, TRIF-/- and WT)	● Bacteroides, Enterococcus ↑ ● Clostridia, Bifidobacteria, Bacillus, Lactobacilli↓	GVHD development is accompanied by shift towards proinflammatory bacterial species(enterobacteria, enterococci and Bacteroides/Prevotella).	(98)
2012	B10.BR→B6 Balb/c→B10.BR B6→BM12	● Clostridiales↓ ● Lactobacillales↑	Increased microbial chaos early after allo-HSCT is a potential risk factor for subsequent GVHD.	(99)
2012	(F) B6→B6D2F1 (F) C3H.Sw→B6 (F) B6-Ly5.1→B6D2F1	● Firmicutes, Bacteroidetes↓ ● E. coli↑	Diversity of the microbial community was significantly reduced in mice with GVHD.	(100)
2015	(F) B6→BALB.B (F) B6/SJL→BALB.B	● E. coli↑	Diversity of the microbial community was significantly reduced in mice with GVHD.	(101)
2016	(F) C57BL/6→129S1	● Erysipelotrichia, Enterococcus, Akkermansia↑ ● Clostridiales↓	Aggravated GVHD mortality was associated with imipenem-cilastatin or piperacillin-tazobactam treatment mice which lead to an increase in Akkermansia muciniphila.	(102)
2017	C57BL/6→B6D2F1 B6D2F1→B6D2F1	● Lactobacillus and another uncultured bacterium from Firmicutes↑ ● E. coli and another uncultured bacterium from Bacteroidetes↓	Improvement of aGVHD in animals treated with immunoglobulin may be mediated by reducing pathogenic bacteria such as E. coli and increasing probiotic bacteria such as Lactobacillus.	(103)
2017	BALB/c(WT, IL-17A -/-, IL-17RA -/-)→B6(WT, IL-17A -/-, IL-17RA -/-) BALB/c(WT)→B6(WT, IL-17RA/B/C-/-)	● Microbiome of WT mice shifted toward that of the IL-17RA/C–deficient mice during cohousing prior to transplant	IL-17–sensitive microbiota controls susceptibility to aGVHD with increased susceptibility to aGVHD transferred to WT mice via cohousing with IL-17RA or IL-17RC–deficient mice.	(57)
2019	(M) C57BL/6→BALB/c (M) C57BL/6→129S1/Sv (M) LP/J→C57BL/6	● Enterococcus↑	Enterococcus expands in mouse after allo-HSCT and exacerbates GVHD severity which is dependent on the lactose.	(104)
2019	(F) BALB/c→B6(WT and Nlrp6-/-) (F) C3H.sw→B6(WT and Nlrp6-/-)	● Verrucomicrobia, Proteobacteria, Bacteroidetes↑ ● Firmicutes↓	Host NLRP6 play a pathogenic role in aggravating GVHD which was independent of indigenous microbiota changes.	(105)