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.

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

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.

Aims: Estrogen-dependent hyperplasia of myo- and endometrium manifests as uterine leiomyoma or adenomyosis. We studied possible associations between common polymorphisms of matrix metalloproteinase (MMP) genes and clinical features of uterine hyperplasia. Patients and Methods: One hundred seventy female patients with uterine leiomyoma (46.6±0.5 years) were observed. Clinical diagnosis was based on physical examination, ultrasonography, and histological data. MMP-1 (−1607 1G/2G, rs1799750) and MMP-3 (−1171 5A/6A, rs3025058) were genotyped with allele-specific polymerase chain reaction (PCR) of leukocyte DNA. Clinical and genetic data were evaluated using nonparametric statistics. Results: Distributions of MMP-1 and MMP-3 promoter alleles among patients and population controls were similar and corresponded to the Hardy–Weinberg equilibrium (HWE). Detectable tumor growth and adenomyosis were observed, respectively, in 71% and 55% of cases. Steady-state leiomyoma correlated with a higher prevalence of the MMP-1 1G/1G genotype (p=0.02 by χ² test). Accelerated tumor growth correlated with higher frequency of the MMP-1 2G allele [odds ratio (OR)=2.048, p=0.039, χ²=4.2611, confidence interval (CI)=(1.032–4.062)]. MMP-1 2G was also associated with multinodular growth [OR=3.561, p=0.01249, χ²=6.24, CI=(1.261–10.058)]. The MMP-1 2G allele tended to increase in patients with adenomyosis [OR=1.525, p=0.054, χ²=3.71, CI=(0.992–2.345)]. Conclusion: Our pilot study suggests that the 2G ⁻¹⁶⁰⁷MMP-1 genotype may be a potential risk marker of myo- and endometrial hyperplasia.

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).

Bacterial microbiota in stool may vary over a wide range, depending on age, nutrition, etc. The purpose of our work was to discriminate phyla and genera of intestinal bacteria and their biodiversity within a healthy population (North-Western Russia) compared to the patients with type 1 diabetes mellitus (T1DM). The study group included 183 healthy persons 2 to 53 years old (a mean of $26.5\pm 1.0$ years old), and 41 T1DM patients (mean age $18.2\pm 1.8$ years old). The disease onset was at $11\pm 1.5$ years, with a T1DM experience of $7\pm 1.5$ years. Total DNA was isolated from the stool samples, and sequencing libraries were prepared by amplifying the V3–V4 region of the 16S rRNA gene sequenced by Illumina MiSeq. Bioinformatic processing of NGS databases was adapted for microbiota evalutaion. Despite the broad scatter, the biological diversity for bacterial microbiota expressed as the Shannon index was significantly increased from younger to older ages in the comparison group, higher in adult healthy persons, with a trend for decrease in the Actinomycetota phylum which includes Bifidobacterium longum species. Similar but non-significant age trends were noted in the T1DM group. Concordant with the Bacillota prevalence in stool samples of diabetic patients, some anaerobic bacteria (Faecalibacteria, Lachnospira and Ruminococcae, Roseburia) were enriched in the T1DM microbiome against controls. Hence, correction of microbiota for Ruminococcus and Lachnospiraceae requires future search for new probiotics. Lower abundance of Actinomycetota and Bifidobacter in T1DM suggests potential usage of Bifidobacter-based probiotics in this cohort.