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.
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.
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.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dose-intensive cytostatic therapy and antibiotic treatment in allogeneic hematopoietic stem cell transplantation (allo-HSCT) cause severe abnormalities in a composition of gut microbiota as well as ...the emergence of antibiotic resistance. The data on the longitudinal recovery of major bacterial phyla and the expansion of genes associated with antibiotic resistance are limited. We collected regular stool samples during the first year after allo-HSCT from 12 adult patients with oncohematological disorders after allo-HSCT and performed 16SrRNA sequencing, multiplex PCR, conventional bacteriology and CHROMagar testing. We observed a decline in Shannon microbiota diversity index as early as day 0 of allo-HSCT (p = 0.034) before any administration of antibiotics, which persisted up to 1 year after transplantation, when the Shannon index returned to pre-transplant levels (p = 0.91). The study confirmed the previously shown decline in Bacillota (Firmicutes) genera and the expansion of E. coli/Shigella, Klebsiella and Enterococci. The recovery of Firmicutes was slower than that of other phyla and occurred only a year post-transplant. A positive correlation was observed between the expansion of E. coli/Shigella genera and blaKPC, blaCTX-M-1 and blaTEM (p < 0.001), Klebsiella spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaTEM, and blaSHV (p < 0.001), Pseudomonas spp. and blaNDM (p = 0.002), Enterococcus spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaSHV (p < 0.01). The correlation was observed between the expansion of Enterobacterales and and carbapenemase-positive CHROMagar samples (p < 0.001). Samples positive for carbapenem-resitant bacteria were at their maximum levels on day +30, and were gradually diminishing one year after allo-HSCT. From day +30 to +60, all isolated K. pneumoniae strains in fecal samples proved to be resistant to the main antibiotic groups (carbapenems, aminoglycosides, fluoroquinolones, third-generation cephalosporins). One year after HSCT, we documented the spontaneous decolonization of K. pneumoniae. The sensitivity of molecular biology techniques in the search for total and antibiotic-resistant Klebsiella seems to be superior to common bacteriological cultures. Future studies should be focused on searching for novel approaches to the efficient reconstitution and/or maintenance of strictly anaerobic microbiota in oncological patients.
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.
In order to address the upcoming crisis in the treatment of
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
phage from the
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
family, although its identity with the closest member of this family was not higher than 5%. The bacteriophage demonstrated lytic activity against all (
= 11)
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.
Inflammatory bowel diseases (IBD) and acute graft-versus-host disease (GVHD) are associated with persistent intestinal dysfunction preceded by gut bacterial dysbiosis. There are limited data on ...intestinal bacteriophages in these conditions. The aim of the present work was to detect associations between dominant intestinal bacteria by means of 16S rRNA gene sequencing, and some clinically significant viruses detected with a customized primer panel for NGS-based study. The clinical group included patients with Crohn's disease (IBD,
= 9), or GVHD (
= 6) subjected to fecal microbiota transplantation (FMT) from healthy donors. The stool specimens were taken initially, and 5 times post-FMT until day 120. Using NGS approach, we have found a higher abundance of
phylum in GVHD, especially, at later terms post-FMT. Moreover, we found an early increase of
and
abundance in GVHD, along with decreased relative content of
. Upon evaluation of intestinal phageome, the relative amount of
class was higher in GVHD. A significant correlation was found between
and
, thus suggesting their association during the post-FMT period. Moreover, the relative amounts of five
phage species showed distinct correlations with
and
ratios at different terms of FMT. In conclusion, parallel use of 16S rRNA gene sequencing and targeted NGS viral panel is a feasible and useful option for tracing specific viral strains in fecal microbiota. The developed array of viral primers may be extended to detect other phages infecting the clinically relevant bacteria.
Intestinal complications are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, only scarce data concern herpesvirus incidence in the colonic mucosa post-HSCT. Our ...purpose was to assess the frequency and clinical significance of cytomegalovirus (CMV), Epstein−Barr virus (EBV), human herpesvirus type 6 (HHV6), and herpes simplex virus (HSV) in the colonic mucosa post-HSCT. The study group included 119 patients of different ages, mostly with leukemias and lymphomas, subjected to allo-HSCT from haploidentical related (48%) or HLA-compatible donors (52%). In total, 155 forceps biopsies of the colonic mucosa were taken in cases of severe therapy-resistant intestinal syndrome post-HSCT. Most samples were taken from the descending, sigmoid, and transverse colon. Intestinal GVHD or local infections were assessed clinically and by histology. EBV, CMV, HSV, and HHV6 were tested in colonic mucosal lysates with commercial PCR assays. HSV was found in <8% of colonic samples, along with high HHV6 and CMV positivity (up to 62% and 35%, respectively) and a higher EBV incidence at 5−6 months post-HSCT (35%). For CMV and EBV, significant correlations were revealed between their rates of detection in blood and colonic mucosa (r = 0.489 and r = 0.583; p < 0.05). No significant relationships were found between the presence of herpesviruses and most patients’ characteristics. EBV positivity in colonic samples was correlated with delayed leukocyte and platelet recovery post-HSCT. Higher EBV frequency in the colonic mucosa was found in deceased patients (56% versus 21%, p = 0.02). The correlations among EBV positivity in the colon, lethality rates and delayed hematopoietic reconstitution suggest some relationship with systemic and local EBV reactivation post-transplant.
Relevance. The high incidence, prevalence and mortality in tuberculosis determines the relevance of improving clinical and organizational processes in terms of algorithmization. The aim of the study ...was to develop and evaluate the effectiveness of the clinical and organizational management algorithm for tuberculosis medical care at the regional level. Materials and Methods. The object of the study (2007-2021) were the tuberculosis medical care system of the Sverdlovsk region, Russian Federation. The scientific and methodological bases were Department of Health Organization, Drug Supply, Medical Technologies and Hygiene of the Peoples’ Friendship University of Russia topic SRW № 214791-3-000. The development of the algorithm was carried out on the basis of a scientifically proven universal clinical management system. The epidemiological tuberculosis author data and of Rosstat in the Sverdlovsk region for 2007-2020 were used - general and structural morbidity, prevalence, mortality, as well as the number of 3, 4 and 6 groups of dispensary registration of patients. The efficiency of the algorithm was evaluated by the dynamics of the complex of epidemiological indicators of tuberculosis. Research methods were applied: content analysis, analytical, statistical, comparative, expert. Significance was assessed using the t-White test. Differences in the compared parameters were considered significant at p0.05. Results and Discussion. The effectiveness of the developed algorithm for managing regional tuberculosis medical care, including the components of needs analysis, systematization, automation and telecommunications, interdisciplinary integration, resource provision and performance evaluation, was confirmed by a significant decrease in the Sverdlovsk region for the period 2007-2020 general incidence by 2.05 times (from 119.9 to 51.7 per 100 thousand of the population), the incidence of children 0-14 years old by 1.48 times (from 18.7 to 12.6 per 100 thousand children of the corresponding age), prevalence in the population by 1.8 times (from 258.6 to 143 per 100 thousand of the population) and mortality from tuberculosis by 2.675 times (from 21.4 to 8.02 per 100 thousand of the population) (p0.001). The COVID-19 pandemic (2020-2021) did not worsen the epidemiological situation for tuberculosis in the region. In 2020, an active form of tuberculosis was detected in 2201 people, which is 16 % less than in 2019 (p0.05). The prevalence of epidemiologically dangerous bacillary forms of the disease for the period 2019-2020 decreased by 15.4 %, from 73.2 to 61.9 per 100 thousand population (p0.05). Conclusion. Clinical and organizational management of tuberculosis medical care based on the algorithmization of scientifically evidence processes increases the effectiveness of therapeutic and preventive measures and the social and epidemiological well-being of the population.
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