From the inception of the project to the current reporting period, we have made significant strides toward achieving our overarching goal of unravelling the complexities of the rumen microbiome to identify the most critical functions, structures, interactions, and metabolic outputs that sustain the host. Our work so far has been disseminated through 11 publications, several of which are high-impact articles in leading scientific journals.
Key Achievements and Results for the first two objectives of our proposal:
1.Top-Down Approach to Identify Essential Microbial Components:
1.1.Our investigations revealed functional redundancy across trophic levels, providing insights into the minimum requirements for a functioning rumen ecosystem (Sasson G, et al. ISMEJ 2022)
1.2.In our analysis of global patterns of microbial interactions, as detailed in Galai G, et al. (Ecography, 2024), we identified that regional processes shape the structure of rumen microbial co-occurrence networks this led to serendipity discovery of specific microbes and genes that are present in both the rumen and human microbiomes. This significant finding led to the identification of microbes that have been transferred from ruminants to humans (Moraïs S, et al. Science 2024), offering new insights into cross-species microbial transmission and its implications for human health. The methods developed through this research allowed us to examine global patterns of plasmidomes in the rumen microbiome as well as specific mechanism for bacterial mutualism (Moraïs S, et al. Nature Microbiology 2024), laying the foundation for studying plasmid dynamics in the human gut plasmidome and for pinpointing specific microbial consortia for in vitro experiments.
1.3 .We developed novel Methods for Plasmid-Associated Networks revealing fundamental patterns that can be applied for the design of minimum essential communities (Shapiro JT, et al. ISMEJ 2023 and Zorea A, et al. Nature Communications 2024).
1.4. In a publication currently in review in Nature microbiology, we show that exo-metabolites could be used to reproduce, in vitro, the natural successional dynamics of community assembly that takes place in the cow’s rumen. In particular exo-metabolites transiently consumed, such as pregnane steroids, ceramides, and triterpenoids, are needed to direct the assembly process and for specific microbes that are abundant and prevalent during the animal’s life to become metabolically active. These metabolites make community assembly robust to compositional variation, as seen in the deterministic convergence in composition of independent microcosms. Overall, we show in this work that metabolite supplementation can be an effective strategy for microbiome control.
1.5. Continuing to pursue our objectives without delays, we have identified specific consortia responsible for fiber degradation, which advances our understanding of how simplified microbial communities can replicate the functions of more complex ecosystems. We used serial-passage techniques to create stable microbial communities with reduced complexity, identifying 10-50 taxa essential for plant fiber degradation. We are preparing to publish these results, highlighting their interactions and connection to the host.
We also developed advanced nanoscale imaging methods to study microbial consortia, enhancing our understanding of microbial fiber degradation (Tatli M, et al. eLife 2022 and Wimmer BH, et al. microLife 2023).
2. To assemble minimum essential communities by using a bottom-up approach
2.1 Prior to community design, we mapped interaction networks among 80 representative rumen taxa and conducted metabolomic profiling, clustering taxa into functional groups to design minimum essential communities. This work is currently being summarised in a publication and will also use the knowledge accumulated during the creation of MS/MS spectral library resource (Mohanty I, et al. Cell (2024).
2.2 We identified specific rumen microbes with traits that enable them to be metabolically independent while also supporting other rumen microbes and the host. These microbes produce essential metabolites, such as amino acids and vitamins, and encode fiber-degrading enzymes crucial for host nutrition. Additionally, they engage in cross-feeding, providing other rumen microbes microbes with vital nutrients. This independence positions such microbes as foundational pillars of gut ecosystem stability and implicates that they should form a large basis of the minimum essential communities (publication submitted to Nature Ecology and Evolution).
2.3. We discovered a set of microbes that persist and dominate the adult rumen. They comprise 575 key species termed “founder microbes” that contribute to ecosystem stability through functional redundancy and code for essential functional versatility vital for the host's life, such as essential amino acid and vitamin synthesis. Notably, founder microbes exhibit dominance in gnotobiotic lambs, constituting 95% of the microbial abundance, which implies their indispensable role in sustaining ruminants life (publication in preparation).
2.4. Transplantation into Germ-Free Animals: We are finalizing results for the synthetic rumen consortia on fiber degradation and their transplantation into germ-free animals. Preliminary findings indicate that these minimal consortia can sustain host health and function.
Exploitation and Dissemination:
High-Impact Publications and Global Reach:
1. Our publications in prestigious journals such as Science, Cell, Nature Microbiology, and ISME Journal have ensured widespread dissemination of our findings.
2. Our recent findings, consolidated in the aforementioned Science paper, have been featured in press releases worldwide, increasing visibility and informing stakeholders about the potential applications of our research. The Altmetric Attention Score of this paper indicates that it received exceptional attention compared to other works published around the same time, ranking in the 99th percentile overall and the 95th percentile among science papers of the same age. This places our publication in the top 5% of all research outputs scored by Altmetric.
Presentations and Conferences: We have presented our results at various international conferences and workshops, fostering collaborations and discussions within the scientific community.
Advancement of Female Young Scientists:
The ERC grant has significantly advanced the careers of young female scientists in our team:
Dr. S. Moraïs and Dr. A. Zorea: Both have played pivotal roles in our groundbreaking research. The support from the ERC has been instrumental in propelling their careers, providing opportunities for leadership, publication in high-impact journals, and recognition within the scientific community.
