Biology subjects

Olekhnovich, E. I.

Publications and source records attributed to Olekhnovich, E. I..

8 recordsLinked to original sources

bioRxiv2025

Non-Intestinal Microbial Signatures in Stool as Predictors of Cancer Immunotherapy Outcome

Despite the recognized role of the gut microbiome in modulating immune checkpoint inhibitor (ICI) efficacy, the ecological principles governing this relationship remain elusive. Moving beyond cataloging specific bacteria, we investigated whether general ecosystem properties determine clinical outcome. Through genome-resolved metagenomic analysis, we constructed a comprehensive catalog from 951 stool metagenomes and subsequently analyzed a curated subset of 624 samples from 11 multi-cancer cohorts. Our catalog comprises 3,816 non-redundant metagenome-assembled genomes (MAGs) and reveals key ecological determinants of ICI response. We found that clinical benefit is associated with an ecosystem dominated by prevalent, autochthonous taxa. A taxons prevalence in the population positively correlated with its association with positive outcome. Functionally, responder-associated microbes were enriched in genomic capacity for complex carbohydrate metabolism (including specialized mucin degradation) and amino acid biosynthesis. In contrast, non-response was characterized by enrichment of low-prevalence, exogenous (oral and food-derived) bacteria and a functional shift toward nucleoside metabolism, indicative of a dysbiotic state focused on replication. A log-ratio biomarker capturing this ecological shift provided generalizable predictive value across independent cohorts (mean AUC = 0.67 {+/-} 0.13). Our results support an ecological interpretation of the "Anna Karenina principle" in microbiomes: response is linked to a stable, functionally coherent microbial community, whereas non-response represents a destabilized state with high individual variability. This reframes the search for biomarkers from individual taxa to the assessment of ecosystem stability and metabolic competence, providing a foundation for microbiome-targeted strategies to improve cancer immunotherapy outcomes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/652660v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@f0c9edorg.highwire.dtl.DTLVardef@591c6eorg.highwire.dtl.DTLVardef@59863forg.highwire.dtl.DTLVardef@17c934d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

Bacteroides vesicles promote functional alterations in gut microbiota composition

Inflammatory bowel diseases are characterized by chronic intestinal inflammation and alterations of gut microbiota composition. Bacteroides fragilis, which secretes outer membrane vesicles (OMVs) with polysaccharide A (PSA), can moderate inflammatory response and possibly alter microbiota composition. In this research, we created a murine model of chronic DSS- induced intestinal colitis and treated it with Bacteroides fragilis OMVs. We monitored the efficiency of OMVs therapy by determining the disease activity index (DAI) and histological examination (HE) of the intestine before and after vesicles exposure. We also analyzed the microbiota composition using 16S rRNA gene sequencing. Finally, we evaluated the volatile compounds composition in animals stools by HS-GC/MS to assess the functional activity of the microbiota. As a result, we observed a more effective intestine repair after OMVs treatment according to DAI and HE. The metabolomic study also indicated the microbiota functional activity change, showing a predominance of phenol and pentanoic acid in the control group compared to the group treated with DSS (DSS) and the group treated with OMVs (DSS OMV). We also observed a positive correlation of these metabolites with Saccharibacteria and Hungatei Clostridium in the control group, whereas in the DSS group there was a negative correlation of phenol and pentanoic acid with Lactococcus and Romboutsia. According to metabolome and sequencing data, the microbiota composition of the DSS OMV group was intermediate between the control and DSS groups. It can be concluded that OMVs not only have an anti-inflammatory effect, but also contribute to the recovery of the microbiota composition.

microbiology↗

bioRxiv2023

Systemic Metabolic Depletion of Intestine Microbiome Undermines Melanoma Immunotherapy Effectiveness

Immunotherapy has proven to be a boon for patients grappling with metastatic melanoma, significantly enhancing their clinical condition and overall quality of life. A compelling connection was discovered between the composition of the intestinal microbiome and the effectiveness of immunotherapy substantiated in both animal models and human patients. Nonetheless, the precise biological mechanisms through which gut microbes influence melanoma treatment outcomes remain poorly understood. This study conducted a high-resolution metagenomic meta-analysis, employing cutting-edge bioinformatics techniques including genome-resolved metagenomics, strain profiling, comparative genomics, and metabolic reconstruction. According to the obtained results, the systemic metabolic depletion of the gut microbiome causes a lack of response to immunotherapy. Specifically, the presence of bacteria adept at utilizing polysaccharides, as well as those responsible for cobalamin, amino acids, and fatty acids production, decreased in patients who experienced unfavorable treatment outcomes. In contrast, patients who had successful outcomes after immunotherapy exhibited a prevalence of amino acids and cobalamin prototrophs, while autotrophy in these substances characterized the microbiomes of patients with unsuccessful outcomes. The metabolic reconstruction of short-chain fatty acid biosynthesis pathways did not differentiate bacteria linked to treatment outcomes based on their ability to produce acetate, butyrate, or propionate. However, the cobalamin-dependent Wood-Ljungdahl pathway of acetate synthesis was directly associated with immunotherapy effectiveness.

bioinformatics↗

bioRxiv2022

Reproducible stool metagenomic biomarkers linked to the melanoma immunotherapy positive outcome

The human gut microbiome plays an important role both in humans health and disease. Recent studies have shown the undeniable influence of gut microbiota composition on cancer immunotherapy efficacy. However, these researches show a lack of consensus in defining reproducible metagenomic markers for a positive immunotherapy outcome. Accordingly, extended published data re-analysis may help reveal clearer associations between the composition of the gut microbiota and treatment response. In this study, we analyzed 358 stool metagenomes from 5 studies published earlier: 210 metagenomes from melanoma patients with positive immunotherapy outcome, 148 metagenomes from melanoma patients with negative immunotherapy outcome. The biomarkers were selected by the group comparison of patients stool samples with different treatment responses (47 responders vs 55 non-responders, 102 metagenomes). Selected biomarkers were verified using the available data describing the influence of the fecal microbiota transplantation on melanoma immunotherapy outcomes (9 donors, 6 responders, 19 non-responders, 256 metagenomes). According to our analysis, the resulting cross-study reproducible taxonomic biomarkers correspond to 12 Firmicutes, 4 Bacteroidetes, and 3 Actinobacteria. 140 gene groups were identified as reproducible functional biomarkers, including those potentially involved in production of immune-stimulating molecules and metabolites. In addition, we ranked taxonomic biomarkers by the number of functional biomarkers found in their metagenomic context. In other words, we predicted a list of the potential "most beneficial" bacteria for a positive response to melanoma immunotherapy. The obtained results can be used to make recommendations for the gut microbiota correction in cancer immunotherapy, and the resulting list of biomarkers can be considered for potential diagnostic ways for predicting melanoma immunotherapy outcome. Another important point is the functional biomarkers of positive immunotherapy outcome are distributed in different bacterial species that can explain the lack of consensus of defining melanoma immunotherapy beneficial species between different studies.

bioinformatics↗

bioRxiv2020

Gut microbiota alterations due to fecal transplant

BackgroundFecal microbiota transplantation (FMT) is currently used to treat recurrent clostridial colitis and other diseases. However, neither the therapeutic mechanism of the FMT nor the mechanism that allows the donor bacteria to colonize the intestine of the recipient has yet been described. Moreover, FMT is a great model for studying the ecology of host-associated microbial communities. This creates the need for experimentation with approaches to metagenomic data analysis which may be useful to the interpretation of observed biological phenomena. MethodsHere the RECAST (Recipient intestinE Colonisation AnalysiS Tool) computational approach is presented, which is based on the shotgun reads sorting process in accordance with their origin in recipient metagenome. Using the RECAST algorithm, taxonomic/functional annotation, and machine learning, the shotgun metagenomic data from three FMT studies including healthy volunteers, patients with clostridial colitis and metabolic syndrome were analyzed. ResultsAccording to the analysis results, the colonizing and remaining microbial diversity in the post-FMT recipient metagenomic samples is clearly separated from the non-colonizers and lost. It is well explained by higher relative abundance in donor/pre-FMT recipient, Human Microbiome project metagenomes, and taxonomy. Moreover, the colonizing and remaining microbes are associated with lantibiotic and tetracyclines resistance genes. ConclusionBased on obtained results, the previously proposed "core" human gut microbiome concept may be elaborated. The top microbes of gut microbiota form "cores", which, moreover, are mutually integrable between humans. Also, we assume that redistribution of microbial diversity in post-FMT recipients metagenomes is due to competition of donor/recipient microbes and to host immunity. The associations of top gut microbes with lantibiotic/antibiotic resistance can be related to gut microbiota colonization resistance phenomena or anthropogenic impact.

bioinformatics↗

bioRxiv2019

Long-term impact of fecal transplantation in healthy volunteers

BackgroundFecal 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., Crohns 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.\n\nResultsWe 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.\n\nConclusionsThe 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.

microbiology↗

bioRxiv2018

Shifts in the gut microbiota structure caused by Helicobacter pylori eradication therapy

The human gut microbiome plays an important role both in health and disease. The use of antibiotics can alter gut microbiota composition, which can cause complications of various kinds. Here we report a whole genome sequencing metagenomic study of the intestinal microbiota changes caused by Helicobacter pylori eradication therapy. We have found the decrease in taxonomic alpha-diversity due to the therapy. The changes observed were more extensive for patients with duodenal ulcer and female ones. As well across the patients under the therapy we have detected the shifts in the metabolic potential and resistome. Seven KEGG pathways associated with quorum sensing, genetic Information processing and environmental Information processing were increased, while metabolic pathways related with metabolism of cofactors and vitamins and glycan biosynthesis and metabolism decreased. Changes in the resistome profile have also been identified. We observed perturbations in intraspecies structures, which were higher in group of patients under the therapy than in control group of people without treatment. The Eubacterium rectale pangenome extracted from metagenomic data were changed. We also isolated and sequenced Enterococcus faecium strains from two patients before and after eradication therapy. After the therapy this bacterium increased as the antibiotic resistance in vitro, as well the number of ARGs to macrolides and tetracyclines and metagenomic relative abundance in comparison with strains before therapy. In summary, microbial community demonstrated shift to reduce metabolic potential and to increased mechanisms, which mediate more survival condition through intraspecies perturbations.\n\nImportanceThe human gut microbiome plays an important role both in health and disease. The use of antibiotics can alter gut microbiota composition, which can cause complications of various kinds. H. pylori eradication therapy causes multiple shifts and alterations (including intraspecies changes) of the intestinal microbiota structure and leads to the accumulation of genes which determine resistance to macrolides. Since these changes are not the same for patients with various diseases, patients with duodenal ulcer may be further paid special attention for reducing side effects, such as antibiotic-induced dysbiosis. Also, study of antibiotic treatment in terms of its impact upon the human gut microbiota allows shedding light on of the complex processes that cause accumulation and spread of antibiotic resistance. An identification and understanding of these complicated processes may help to constrain antibiotic resistance spread, which is of great importance for human health care.

microbiology↗

bioRxiv2017

MetaCherchant - an algorithm for analyzing genomicenvironment of antibiotic resistance genein gut microbiota

Antibiotic resistance is an important global public health problem. Human gut human microbiota is an accumulator of resistance genes potentially providing them to pathogens. It is important to develop tools for identifying the mechanisms of how resistance is transmitted between gut microbial species and pathogens. We developed MetaCherchant - an algorithm for extracting the genomic environment of antibiotic resistance genes from metagenomic data in the form of a graph. The algorithm was validated on simulated datasets and applied to new \"shotgun\" metagenomes of gut microbiota from patients with Helicobacter pylori who underwent antibiotic therapy. Genomic context was reconstructed for several dominant resistance genes; taxonomic annotation of the context showed the species carrying the genes. Application of MetaCherchant in differential mode produced specific graph structures suggesting the evidence of possible resistance gene transmission within a mobile element that occurred as a result of the antibiotic therapy. MetaCherchant is a promising tool giving researchers an opportunity to get an insight into dynamics of resistance transmission in vivo based on metagenomic data.

bioinformatics↗