Biology subjects

Predl, M.

Publications and source records attributed to Predl, M..

3 recordsLinked to original sources

bioRxiv2025

The geometry of cooperation: decoding microbial interactions

Bridging the gap between mechanistic models of metabolism and ecological theory remains a key challenge in understanding interactions within microbial communities. We propose a geometric framework for analyzing community metabolism, based on constraint-based modeling. By extending pathway analysis methods from single organisms to multi-species systems, we define the community metabolic space as the set of all feasible fluxes between species and their environment, conditional on growth rate and medium composition. Embedded within a nonlinear geometry, this space forms a polytope whose vertices represent the minimal building blocks of community metabolism from which every feasible solution can be constructed. Strikingly, these elementary community flux modes invite direct ecological interpretation - as specialist, commensalist, or mutualist modes of cooperation. Furthermore, we find that mutualism is either isotypic (arising from a minimal mutualistic behavior) or anisotypic (emerging from a combination of reciprocal commensalists). This distinction demonstrates that bidirectional cross-feeding alone is insufficient to determine the ecological interaction type. Our framework also offers significant potential for applications. Because it does not rely on optimization, powerful unbiased tools from metabolic engineering, such as production envelopes and minimal cut sets, may be extended to microbial communities. Taken together, this perspective aims to unify ecological and metabolic viewpoints by linking interaction types to the geometric structure of the community metabolic space, thereby laying the foundation for a deeper understanding of community structure, function, and design.

systems biology↗

bioRxiv2025

Elementary vectors reveal minimal interactions in microbial communities

Understanding microbial communities is essential for progress in ecology, biotechnology, and human health. In the last decade, constraint-based metabolic models of individual organisms have been combined to study microbial consortia. In this work, we present a geometric framework for characterizing all feasible microbial interactions. We project community models onto the key variables of interaction: exchange fluxes and community compositions. Based on this projection, we compute elementary composition/exchange fluxes (ECXs), extending the concept of minimal metabolic pathways from individual species to entire communities. Every feasible metabolic state of a community can be expressed as a combination of these elementary vectors. Notably, each ECX corresponds to a distinct ecological interaction type, such as specialization, commensalism, or mutualism. Finally, our geometric formulation enables the direct application of existing constraint-based methods, such as flux variability analysis and minimal cut sets, to microbial communities, providing a foundation for rational community design.

systems biology↗

bioRxiv2024

Expanding the cultivated human archaeome by targeted isolation of novel Methanobrevibacter strains from fecal samples

Archaea are integral components of the human microbiome but persist as understudied entities within the gastrointestinal tract (GIT), primarily due to the lack of cultured representatives for comprehensive mechanistic investigations. With only four Methanobrevibacter smithii isolates from humans available according to the Global Catalogue of Microorganisms (GCM), the existing cultures fail to adequately represent the observed diversity, as underscored by recent findings. This study introduces a targeted cultivation method for enriching methanogenic archaea from human fecal samples. Applied to 16 stool samples from healthy and diseased donors, the method aimed to genomically characterize the archaeal cultures and establish correlations with gastrointestinal disorders. The procedure combines methane breath testing, in silico metabolic modelling, media optimization, FACS, dilution series, and genomic sequencing through Nanopore technology. Additional analyses include co-cultured bacteriome, comparative genomics of archaeal genomes, functional comparisons, and structure-based protein function prediction of unknown differential traits. Successful establishment of stable archaeal cultures from 14 out of 16 fecal samples yielded nine previously uncultivated strains, eight of which were absent from a recent archaeome genome catalog. Comparative genomic and functional assessments of Methanobrevibacter smithii and Candidatus Methanobrevibacter intestini strains from diverse participant cohorts revealed features potentially associated with gastrointestinal diseases. This work substantially broadens the scope of available archaeal representatives for functional and mechanistic studies in the human GIT. The established protocol facilitates the cultivation of methanogenic archaea from nearly every human fecal sample, offering insights into the adaptability of Candidatus Methanobrevibacter intestini genomes in critical microbiome situations.

microbiology↗