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Table 2 The published clinical trials of microbiota intervention in the treatment and prevention of aGVHD

From: Roles of the intestinal microbiota and microbial metabolites in acute GVHD

Interventions

Number of patients

Outcomes

References

Antibiotics

 Optimization of Antibiotic

140 HSCT recipients including intervention cohort and control cohort

The first prospective multicentre study aims to address the effect of two antimicrobial therapy strategies on intestinal microbiota. Faecal microbiota and clinical outcomes including GVHD incidence and severity will be compared between both cohorts.

[104]

Prebiotics

 RS and GFO

Prebiotic group: 49

Control group: 142

RS and GFO administration mitigated mucosal injury and reduced the incidence of aGVHD. RS and GFO intake maintained the gut microbial diversity and preserved butyrate-producing bacterial population

[105]

 FOS

Prebiotic group: 15

Control group: 16

FOS was safe and well-tolerated at 10 g per day in allo-HSCT patients. Community-level gut microbial composition was only different on transplant day (day 0) between FOS and controls, 5 days after intake of FOS. The incidence of aGVHD (grades I-IV) and overall survival at 1 year were not associated with the administration of FOS

[106]

 Glutamine

Prebiotic group: 27

Control group: 26

Glutamine administration decreased GVHD related mortality

[107]

Probiotics

 Lactobacillus Rhamnosus GG

Probiotic group: 20

Control group: 11

The abundance of Lactobacillaceae family and Lactobacillus genus were not affected by probiotic administration. The administration of Lactobacillus Rhamnosus GG did not affect the gut microbiota or the incidence of aGVHD

[108]

 Lactobacillus plantarum strains 299 and 299v

Probiotic group: 30

Administration of Lactobacillus plantarum was safe and feasible in children and adolescents undergoing HCT

[109]

FMT

 Related or spouse donor

4 patients with GI aGVHD (SR, n = 3; steroid-dependent, n = 1)

FMT was safe and effective in all patients, with 3 CR and 1 PR. The dynamic of microbiota seemed to be linked to the gut condition of the patients. FMT also increased the peripheral effector regulatory T cells

[110]

 Unrelated or related donor

3 patients with SR GI aGVHD

All three patients responded clinically to FMT, with 2 CR and 1 PR

[111]

 Unrelated donor

8 patients with SR GI aGVHD

FMT was safe and effective in most patients, with 4 CR, 1 PR and 1 remission

[112]

 Related donor

1 patient with SR GI aGVHD

FMT restored the intestinal microbial diversity, with the improvement of diarrhea and colonoscopy findings

[113]

 Unrelated donor

2 patients with SR GI aGVHD

FMT resulted in 1CR and 1 PR

[114]

 Unrelated donor

1 patient with SR GI aGVHD

The diversity and structure of the intestinal microbiota after FMT was restored and the patients was cured

[115]

 Unrelated donor

15 patients with GI aGVHD (SR, n = 6; steroid-dependent, n = 9)

10 patients showed CR, accompanied by an increase in intestinal microbial diversity and increased abundance of butyrate-producing bacteria

[116]

 Unrelated donor

41 patients with SR GI GVHD

FMT group: 23

Control group:18

Clinical remission was significantly greater in FMT group than in control group. FMT group showed a higher overall survival and lower mortality rate. No differences were observed in the occurrence of any other side effects

[117]

 Unrelated donor

11 patients with aGvHD

FMT was effective in the treatment of GVHD and in the decolonization of GI tract from antibiotic-resistant bacteria

[118]

  1. RS, resistant starch; GFO, glutamine, fiber, and oligosaccharides; SR GI aGVHD, steroid-resistant gastrointestinal acute GVHD; CR, complete responses; PR, partial response