Search bioRxiv⌕ Search

Biology subjects

Maistrenko, O. M.

Publications and source records attributed to Maistrenko, O. M..

6 recordsLinked to original sources

A census of hidden and discoverable microbial diversity beyond genome-centric approaches

Cataloguing Earths biodiversity remains one of the most formidable challenges in biology, and the greatest diversity is expected to reside among the smallest organisms: microbes. Yet the ongoing census of microbial life is hampered by disparate sampling of Earths habitats, challenges in isolating uncultivated organisms, limited resolution in taxonomic marker gene amplicons, and incomplete recovery of metagenome-assembled genomes (MAGs). Here, we quantified discoverable bacterial and archaeal diversity in a comprehensive, curated cross-habitat dataset of 92,187 metagenomes. Clustering 502M sequences of 130 marker genes, we detected 705k bacterial and 27k archaeal species-level clades, the vast majority of which was hidden among unbinned contigs. At deeper taxonomic levels, we estimate that 10 archaeal and 145 bacterial novel phyla and around 80k novel genera are discoverable in current data. We identified soils and aquatic environments as novel lineage recovery hotspots, yet predict that discovery will remain in full swing across habitats as more data accrues. Finally, we show that prokaryotic diversity follows power laws, confirming century-old hypotheses on clade size patterns and suggesting that novel lineages arise within common (and fractal) evolutionary patterns, comparable to those among eukaryotic clades and viruses, along the full depth and breadth of the Tree of Life.

microbiology↗

C. difficile is overdiagnosed in adults and a commensal in infants

Clostridioides difficile is an urgent threat in hospital-acquired infections world-wide, yet the microbial composition associated with C. difficile, in particular in C. difficile infection (CDI) cases, remains poorly characterised. To investigate the gut microbiome composition in CDI patients, we analysed 534 metagenomes from 10 publicly available CDI study populations. We then tracked C. difficile on a global scale, screening 42,900 metagenomes from 253 public studies. Among the CDI cohorts, we detected C. difficile in only 30% of the stool samples from CDI patients. However, we found that multiple other toxigenic species capable of inducing CDI-like symptomatology were prevalent. In addition, the majority of the investigated studies did not adhere to the recommended guidelines for a correct CDI diagnosis. In the global survey, we found that C. difficile prevalence, abundance and biotic context were age-dependent. C. difficile is a rare taxon associated with reduced diversity in healthy adults, but common and associated with increased diversity in infants. We identified a group of species co-occurring with C. difficile exclusively in healthy infants, enriched in obligate anaerobes and in species typical of the healthy adult gut microbiome. C. difficile in healthy infants was therefore associated with multiple indicators of healthy gut microbiome maturation. Our analysis raises concerns about potential CDI overdiagnosis and suggests that C. difficile is an important commensal in infants and that its asymptomatic carriage in adults depends on microbial context.

microbiology↗

Drivers and Determinants of Strain Dynamics Following Faecal Microbiota Transplantation

Faecal microbiota transplantation (FMT) is an efficacious therapeutic intervention, but its clinical mode of action and underlying microbiome dynamics remain poorly understood. Here, we analysed the metagenomes associated with 142 FMTs, in a time series-based meta-study across five disease indications. We quantified strain-level dynamics of 1,089 microbial species based on their pangenome, complemented with 47,548 newly constructed metagenome-assembled genomes. Using subsets of procedural-, host- and microbiome-based variables, LASSO-regularised regression models accurately predicted the colonisation and resilience of donor and recipient microbes, as well as turnover of individual species. Linking this to putative ecological mechanisms, we found these sets of variables to be informative of the underlying processes that shape the post-FMT gut microbiome. Recipient factors and complementarity of donor and recipient microbiomes, encompassing entire communities to individual strains, were the main determinants of individual strain population dynamics, and mostly independent of clinical outcomes. Recipient community state and the degree of residual strain depletion provided a neutral baseline for donor strain colonisation success, in addition to inhibitive priority effects between species and conspecific strains, as well as putatively adaptive processes. Our results suggest promising tunable parameters to enhance donor flora colonisation or recipient flora displacement in clinical practice, towards the development of more targeted and personalised therapies.

microbiology↗

Polarization of microbial communities between competitive and cooperative metabolism

Resource competition and metabolic cross-feeding are among the main drivers of microbial community assembly. Yet, the degree to which these two conflicting forces are reflected in the composition of natural communities has not been systematically investigated. Here, we use genome-scale metabolic modeling to assess resource competition and metabolic cooperation potential in large co-occurring groups, with up to 40 member species, across thousands of habitats. Our analysis revealed two distinct community types, clustering at opposite ends in a trade-off landscape between competition and cooperation. On one end lie highly cooperative communities, characterized by smaller genomes and multiple auxotrophies, reminiscent of the black queen hypothesis. At the other end lie highly competitive communities, conforming to the red queen hypothesis, featuring larger genomes and overlapping nutritional requirements. While the latter are mainly present in soils, the former are found both in free-living and host-associated habitats. Community-scale flux simulations showed that, while the competitive communities can better resist species invasion but not nutrient shift, the cooperative communities are susceptible to species invasion but resilient to nutrient change. In accord, we show, through analyzing an additional independent dataset, the colonization of the human gut by probiotic species is positively associated with the presence of cooperative species in the recipient microbiome. Together, our analysis highlights the bifurcation between competition and cooperation in the assembly of natural communities and its implications for community modulation.

microbiology↗

Disentangling the impact of environmental and phylogenetic constraints on prokaryotic strain diversity

Microbial organisms inhabit virtually all environments and encompass a vast biological diversity. The pan-genome concept aims to facilitate an understanding of diversity within defined phylogenetic groups. Hence, pan-genomes are increasingly used to characterize the strain diversity of prokaryotic species. To understand the interdependency of pan-genome features (such as numbers of core and accessory genes) and to study the impact of environmental and phylogenetic constraints on the evolution of conspecific strains, we computed pan-genomes for 155 phylogenetically diverse species using 7000 high-quality genomes. We show that many pan-genome features such as functional diversity and core genome nucleotide diversity are correlated to each other. Further, habitat flexibility as approximated by species ubiquity is associated with several pan-genome features, particularly core genome size. In general, environment had a stronger impact on pan-genome features than phylogenetic signal. Similar environmental preferences led to convergent evolution of pan-genomic features in distant phylogenetic clades. For example, the soil environment promotes expansion of pan-genome size, while host-associated habitats lead to its reduction.

genomics↗

Extensive Transmission of Microbes along the Gastrointestinal Tract

The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.

microbiology↗