The long and winding road of fecal microbiota transplants to targeted intervention for improvement of immune checkpoint inhibition therapy.

There is ample evidence for the beneficial effect of FMT on the outcome of ICI therapy for cancer, especially melanoma. The optimal treatment schedule, as well as donor selection criteria, still must be worked out. Progress is being made in the unraveling of the mechanisms by which microbiota and their metabolites (butyrate and the tryptophan metabolite indole-3-aldehyde) interact with the mucosal immune system of the host. A better understanding of these mechanisms contributes to improving FMT outcomes and developing novel therapeutic approaches. It will allow the identification of key bacterial species which mediate the effect of FMT. Promising species are Faecalibacterium prausnitzii, Eubacterium rectale, and three Bifidobacterium species (B. adolescentis, B.bifidum, and B. longum), because they are important direct and indirect butyrate producers, which could form the basis of targeted microbiota therapy.