Clinical and immune effects of fecal microbiota transplantation in children with acute graft-versus-host disease

Abstract

Over last years, an important role of altered gut microbiota and its potential correction was suggested for pediatric cancer and autoimmune disorders. The data from last decade highlight sufficient influence of the main classes of gut bacteria (Firmicutes and Bacteroides) upon development of immune response in oncological disorders and autoagressive conditions, as well as role of their imbalance and its correction using fecal microbiota transplantation (FMT) approach. Our previous studies have shown a pronounced clinical effect of FMT, mostly, in adult patients with severe acute graft-versus-host disease (GVHD). The aim of this article was to present our own experience of FMT in children with intestinal form of GVHD resistant to conventional treatment. Materials and methods. A prospective single-center study included 7 patients aged from 3 to 10 years with severe intestinal GVHD developed after allogeneic he-matopoietic stem cell transplantation. Clinical effects of FMT were evaluated by conventional scales during 120 days after the procedure. Time-dependent changes of fecal microbiota were assayed, mainly, by the multiplex polymerase chain reaction (PCR) test-system. Results. We present our own experience of FMT in 7 children with intestinal GVHD and antibiotic-resistant colitis. Complete or partial response to the GVHD treatment was achieved in 6 cases (86%) by 120 days, in absence of serious adverse events following FMT. Since day +8 after TFM, increased amounts of B. fragilis gr., Faecali-bacterium prausnitzii and E. coli were registered in fecal microbiota (р< 0.048, р< 0.001, and р<0.048, respectively), in absence of differences for Bifidobacterium spp and Lactobacillus spp. Conclusion Combined therapy with immunosuppressive agents and FMT procedure in the patients with intestinal GVHD resistant to standard therapy is associated with pronounced clinical responses correlating with distinct changes of intestinal microbiota, with acceptable safety profile.