Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection

Table 1 Main clinical and experimental studies about the immunological mechanisms associated to fecal microbiota transplantation efficacy

Ref.	Model / clinical study	Main findings
Ekmekciu et al[57], 2017	Mice treated with antibiotic cocktail followed by FMT	Recovery of INF-γ, IL-17, IL-22 and IL-10 producer CD4+ T cells in intestinal LP. FMT failed to recover CD8+ T and B cells in LP after antibiotic exposure
Burrello et al[58], 2018	Mice treated with DSS followed by oral gavage of mucus and feces from healthy mice	Treatment increased Camp, S100A8, Muc1 and Muc4, reduced MHC-II+ cells and normalized populations of ILC-2, ILC-3, F4/80+ macrophages and CD11b+ Ly6G+ neutrophils
	In vitro stimulation of LPMCs stimulated with FMT or DSS-derived microbiota	FMT reduced IL-1β, TNF-α and IFN-γ and increased IL-10
	IL-10 receptor blockade in DSS mice prior of FMT treatment	Blockade of IL-10 resulted in reduction in colon length, increased weight loss and expression of IL-1β, TNF and IFNγ genes
Littmann et al[59], 2021	Use of different KO mice to evaluate B and T (CD8+, Th1, Th17 and Treg) cells	Treg cells play a pivotal role for FMT to achieve the effects against CDI
Monaghan et al[60], 2021	Multiomic analysis of fecal, sera and PBMC samples of patients with severe (n = 3) or fulminant (n = 1) CDI treated with FMT in 6 occasions plus fidaxomicin (severe cases) or vancomycin and metronidazole (fulminant case)	One patient (severe CDI) did not respond to treatment. The fulminant case responded after FMT in 10 occasions plus antibiotics. 78 features were identified differentiating responders to the non-responder. Non responsiveness was associated to higher levels of MMP-2, TWEAK, IL-26, sTNF-R1, sTNF-R2, effector memory CD8 T cells and circulation of senescent T cells; and lower TCR diversity repertoire, B cell and regulatory B cell frequencies

IL: Interleukin; FMT: Fecal microbiota transplantation; INF: Interferon; LP: Lamina propria; DSS: Dextran sodium sulfate; LPMCs: Lamina propria mononuclear cells; Muc: Mucin; TNF: Tumor necrosis factor; Treg: T regulatory; KO: Knockout; CDI: Clostridioides difficile infection; PBMC: Peripheral blood mononuclear cell; ILC: Innate lymphoid cells.