Background: Fecal microbiota transplantation (FMT) has been recently approved by FDA for the treatment of refractory recurrent clostridial colitis (rCDI). Success of FTM in treatment of rCDI led to a number of studies investigating the effectiveness of its application in the other gastrointestinal diseases. However, in the majority of studies the effects of FMT were evaluated on the patients with initially altered microbiota. The aim of our study was to estimate effects of FMT on the gut microbiota composition in healthy volunteers and to monitor its long-term outcomes. Results: We have performed a combined analysis of three healthy volunteers before and after capsule FMT by evaluating their general condition, adverse clinical effects, changes of basic laboratory parameters, and several immune markers. Intestinal microbiota samples were evaluated by 16S rRNA gene and shotgun sequencing. The data analysis demonstrated profound shift towards the donor microbiota taxonomic composition in all volunteers. Following FMT, all the volunteers exhibited gut colonization with donor gut bacteria and persistence of this effect for almost ∼1 year of observation. Transient changes of immune parameters were consistent with suppression of T-cell cytotoxicity. FMT was well tolerated with mild gastrointestinal adverse events, however, one volunteer developed a systemic inflammatory response syndrome. Conclusions: The FMT leads to significant long-term changes of the gut microbiota in healthy volunteers with the shift towards donor microbiota composition and represents a relatively safe procedure to the recipients without long-term adverse events.

Aim.Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD). Materials and methods.The prospective single-center study in R.M. Gorbacheva institute included 27 patients with GI GVHD after allogeneic stem cell transplantation. 19 patients received FMT, 8 patients received placebo. Clinical scales for GI autoimmune diseases were used to evaluate response. Microbiome alterations were assessed with multiplex PCR. Results.After FMT higher overall bacterial mass (р=0.00088), higher bacterial numbers ofBifidobacteriumspp. (р=0.021),Escherichia coli(р=0.049) andBacteroides fragilisgr. (р=0.000043) compared to placebo group. Also higher bacterial mass was observed in patients with clinical response (р=0.0057). The bacterial mass after procedure in non-responders was compared to the placebo group (р=0.31). Partial response of GVHD was achieved faster in the FMT group compared to placebo (median 4 days vs 48 days,p=0.014). Complete response was observed in 8 (42%), 14 (74%) and 16 (84%) at 30, 60 and 90 days respectively, while in the placebo group only 0%, 1 (13%) and 4 (50%) achieved complete response at the same time points. The incidence and severity of adverse events was comparable between FMT and the placebo group. Conclusion.FMT in patients with refractory GI GVHD was associated with favorable clinical outcomes and recovery in certain marker bacterial populations. Multiplex PCR can be used to assess an engraftment of a donor microbiota. FMT in GI GVHD was not associated with life-threatening adverse events, but further studies are required to validate clinical efficacy.

In order to address the upcoming crisis in the treatment of Klebsiella pneumoniae infections, caused by an increasing proportion of resistant isolates, new approaches to antimicrobial therapy must be developed. One approach would be to use (bacterio)phages and/or phage derivatives for therapy. In this study, we present a description of the first K. pneumoniae phage from the Zobellviridae family. The vB_KpnP_Klyazma podovirus, which forms translucent halos around the plaques, was isolated from river water. The phage genome is composed of 82 open reading frames, which are divided into two clusters located on opposite strands. Phylogenetic analysis revealed that the phage belongs to the Zobellviridae family, although its identity with the closest member of this family was not higher than 5%. The bacteriophage demonstrated lytic activity against all (n = 11) K. pneumoniae strains with the KL20 capsule type, but only the host strain was lysed effectively. The receptor-binding protein of the phage was identified as a polysaccharide depolymerase with a pectate lyase domain. The recombinant depolymerase protein showed concentration-dependent activity against all strains with the KL20 capsule type. The ability of a recombinant depolymerase to cleave bacterial capsular polysaccharides regardless of a phage’s ability to successfully infect a particular strain holds promise for the possibility of using depolymerases in antimicrobial therapy, even though they only make bacteria sensitive to environmental factors, rather than killing them directly.

The pilot clinical study presented demonstrates the possibility, safety, and effectiveness of oral microbiota transplantation from a healthy donor to a patient with neuroblastoma to prevent chemotherapy-induced oral mucositis. A 6-month-old patient with a diagnosis of retroperitoneal neuroblastoma was treated according to the NB 2004 protocol. Due to the development of severe oral mucositis, it was decided to perform oral microbiota transplantation. During the next 3 chemotherapy cycles and conditioning regimen before autologous hematopoietic cell transplantation (auto-HCT), the patient was repeatedly injected per os with donor saliva from her healthy mother. Oral microbiota transplantation was shown to effectively prevent the development of oral mucositis after chemotherapy, and only grade 1 oral mucositis developed after auto-HCT. In all loci of the oral cavity, there was a decreased abundance of bacteria from the Staphylococcaceae, Micrococcaceae, and Xanthomonadaceae families. Conversely, there was an increase in the relative abundance of Streptococcaceae and certain other bacterial taxa. In conclusion, the transplantation of maternal saliva in this patient prevented severe mucositis and was accompanied by a compositional change of the patient’s oral microbiota. No adverse events due to the transplantation of maternal saliva were noted.

Bacteroides fragilis – потенциальный маркер эффективной трансплантации микробиоты при лечении острой реакции «трансплантат против хозяина»Bacteroides fragilis is a potential marker of effective microbiota transplantation in acute graft-versus-host disease treatment

In this single-center analysis, we evaluated the trends in 5185 hematopoietic cell transplantations performed between 1990 and 2022. The study group comprised 3237 allogeneic (alloHCT) and 1948 autologous (autoHCT) hematopoietic cell transplantations. In the multivariate analysis, there was an improvement in event-free-survival (EFS) after autoHCT (HR 0.6, 95% CI 0.4–0.7, p < 0.0001) due to reduced cumulative incidence of relapse in the last five years (56% in 2010–2014 vs. 38% in 2015–2022). An improvement in EFS after alloHCT over time was observed (HR 0.33, 95% CI 0.23–0.48, p < 0.0001), which was due to reduced non-relapse mortality. No difference in cumulative relapse incidence was observed over the last decade for allografted patients. Survival after autoHCT improved in Hodgkin’s disease (HR 0.1, 95% CI 0.1–0.3), multiple myeloma (HR 0.4, 95% CI 0.2–0.7) and solid tumors (HR 0.2, 95% CI 0.2–0.4), while after alloHCT, improvement was observed in acute myeloid leukemia (HR 0.3, 95% CI 0.1–0.5), acute lymphoblastic leukemia (HR 0.2, 95% CI 0.1–0.5), Hodgkin’s disease (HR 0.1, 95% CI 0.0–0.4), non-Hodgkin’s lymphomas and chronic lymphocytic leukemia (HR 0.2, 95% CI 0.0–0.6), inborn diseases (HR 0.2, 95% CI 0.2–0.4) and acquired aplastic anemia with matched related donors and matched unrelated donors (HR 0.3, 95% CI 0.2–0.8).