BackgroundFecal 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.ResultsWe 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.ConclusionsThe 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.

Background: Fecal microbiota transplantation (FMT) is now approved for the treatment of refractory recurrent clostridial colitis, but a number of studies are ongoing in inflammatory bowel diseases, i.e., Crohn's disease, nonspecific ulcerative colitis, and in other autoimmune conditions. In most cases, the effects of FMT are evaluated on patients with initially altered microbiota. The aim of the present study was to evaluate effects of FMT on the gut microbiota composition in healthy volunteers and to track long-term changes. Results:We have performed a combined analysis of three healthy volunteers before and after FMT with frozen capsules, followed by evaluation of their general condition, adverse clinical effects, changes of basic laboratory parameters, and several immune markers. Intestinal microbiota samples were evaluated by 16S rRNA gene sequencing (16S seq) and shotgun sequencing (or whole-genome sequencing -WGS). The data analysis demonstrated the 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 and systemic inflammatory response in one volunteer. Conclusions:The FMT procedure leads to significant long-term changes of the gut microbiota in healthy volunteers with the shift towards donor microbiota composition, being relatively safe 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.

Objective: to evaluate trends of survival in nine index malignant neoplasms (iMNs), which are screened at the first stage of the Dispanserization of certain groups of the adult population (DCGAP), on data of the Arkhangelsk regional cancer registry over a period 2006-2019. Materials and methods. We compared two seven-year periods 2006-2012 and 2013-2019, before and after the introduction of the DCGAP. The 1- and 5-year cancer-specific survival (CSS) rate was calculated using the life table and Kaplan-Meier methods with an assessment of the differences by log-rank. Cox regression analysis with sequential input was used to identify possible causes of differences in survival between periods and independent prognostic factors. Results. 37197 cases were selected for analysis. 5-year CSS estimates in 2013-2019 compared with the previous seven-year period significantly increased for all nine iMNs, by from 2.5% [2006-2012, 12.5% ​​(95% confidence interval (CI) 11.4-13.6%) vs 2013-2019, 15.0 (95% CI 13.7-16.5%)] in lung cancer up to 12.6% [2006-2012, 31.0% (95% CI 28.6-33.4%) vs 2013-2019, 43.6 (95% CI 40.8-46.2%)]. Correction for the stage (possible effect of screening) in the Cox model has led to a decrease in the hazard ratio (HR) of death from cancer of the colon, rectum, breast, kidney by 38-64%, no change for other iMNs; while for cervical cancer, it has increased. Adjustment for the variable "treatment method" led to a 34-100% decrease in the HR in the Cox model for all iMNs, except for prostate cancer. Conclusion. The increase in survival estimates for nine iMNs in 2013-2019 can be explained to a large extent by improved access to cancer-directed treatment and its quality; the contribution of DCGAP is possible in renal, breast and colorectal cancer. Key words: malignant neoplasms, screening, dispensarization of certain groups of the adult population, survival

In recent years, the important role of disturbances in the intestinal microbiota and its possible correction in children with oncological and autoimmune diseases has been established. The aim of the article is to review the literature data on the issue and to describe own experience of fecal microbiota transplantation (FMT) in children with an intestinal form of acute graftversus-host disease (GVHD). Materials and methods of research: a prospective single-center study included 7 patients aged 3 to 10 years with gut GVHD developed after transplantation of allogeneic hematopoietic stem cells (allo-HSCT). The clinical effects of FMT have been studied in children using rating scales during 120 days after this procedure. Time-dependent changes in the composition of fecal microbiota were assessed by the method of multiplex polymerase chain reaction test-system (PCR). Results: the literature data show a significant role of the content and ratio of of the main bacterial classes of Firmicutes and Bacteroides in the development of the immune response in cancer and autoimmune processes, as well as the possibility of correcting disorders using FMT. The first-hand experience of FMT in children with gut GVHD and antibiotic-resistant colitis is presented. Complete or partial response to GVHD therapy after 120 days was achieved in 6 (86%) patients in the absence of serious adverse events after FMT. From day +3 after FMT, increased amounts of B. fragilis gr., F. prausnitzii and E. coli were registered in fecal microbiota (p<0,048, p<0,001, p<0,048, respectively) in the absence of differences in Bifidobacterium spp. and Lactobacillus spp. Conclusion: the combination of systemic immunosuppressive therapy with FMT in patients with intestinal forms of GVHD resistant to standard therapy is accompanied by pronounced clinical responses and typical changes in the composition of the intestinal microbiota in the absence of serious adverse events.