Periodic Reporting for period 2 - EPYC (Evolution of pro- and eukaryotic commensals within the human gut)
Okres sprawozdawczy: 2022-08-01 do 2024-01-31
Problem being addressed:
The gut microbiome is important for human health, supporting nutrition, pathogen defence and immune self-regulation, with more than 200 species inhabiting each human gut. In recent years, studying genetic material from natural samples (metagenomics) led to notable breakthroughs in describing this microbial diversity, yet 50-90% of species are typically present at too low abundance to be specifically identified. Thus, most gut microbiome studies focused to date on dominant bacteria and very little is known of the highly diverse, yet low abundance, ‘elusive microbes’. Importantly, elusive microbes are an inherent part of ecosystem successions persisting at different ages of the host. I propose that niche adaptation and persistence are key indicators of a taxa’s importance to the gut ecosystem and host health. I will determine which microbes persist for years within a human, or even a family. This should be reflected in microbial genetic adaption, also indicating which genes are likely important to successfully colonize the human gut.
Why important for society:
This project will develop the next-generation of high-resolution metagenomics on an extended taxonomic range, ie, ability to identify more elusive microbes and at a greater scale, thereby enabling scientists to research microbial evolution in the human gut.
Overall objectives:
Our hypothesis is that that these elusive microbes are adapted to persist for multiple generations in the human host, indicating their importance, despite being largely ignored so far. To investigate this knowledge gap in EPYC, we will
(O1) Enable high-precision metagenomics of elusive microbes so they can be precisely identified
(O2) Estimate persistence of elusive microbe in human families
(O3) Describe their microbial genetics to understand why they persist in the human gut
The gut microbiome is important for human health, supporting nutrition, pathogen defence and immune self-regulation, with more than 200 species inhabiting each human gut. In recent years, studying genetic material from natural samples (metagenomics) led to notable breakthroughs in describing this microbial diversity, yet 50-90% of species are typically present at too low abundance to be specifically identified. Thus, most gut microbiome studies focused to date on dominant bacteria and very little is known of the highly diverse, yet low abundance, ‘elusive microbes’. Importantly, elusive microbes are an inherent part of ecosystem successions persisting at different ages of the host. I propose that niche adaptation and persistence are key indicators of a taxa’s importance to the gut ecosystem and host health. I will determine which microbes persist for years within a human, or even a family. This should be reflected in microbial genetic adaption, also indicating which genes are likely important to successfully colonize the human gut.
Why important for society:
This project will develop the next-generation of high-resolution metagenomics on an extended taxonomic range, ie, ability to identify more elusive microbes and at a greater scale, thereby enabling scientists to research microbial evolution in the human gut.
Overall objectives:
Our hypothesis is that that these elusive microbes are adapted to persist for multiple generations in the human host, indicating their importance, despite being largely ignored so far. To investigate this knowledge gap in EPYC, we will
(O1) Enable high-precision metagenomics of elusive microbes so they can be precisely identified
(O2) Estimate persistence of elusive microbe in human families
(O3) Describe their microbial genetics to understand why they persist in the human gut
Protocols were developed to build libraries of identifiable DNA sequences for low-input-DNA samples, to enable us to increase the accuracy of obtained DNA reads. We developed the necessary experimental lab infrastructure to specifically enrich normally underrepresented groups in the gut microbiome (O1).
We started the PEARL-AGE research study, recruiting participants in families to provide samples, obtaining all necessary ethics documentations and setting up the logistics to support this. We built computational pipelines that can track bacterial strains in metagenomic samples, important to understand how bacteria transfer between individuals, and to understand their persistence (O2).
We further built pipelines to resolve single genetic variations (SNVs) from metagenomes that will be used to estimate evolutionary trajectories of bacteria in metagenomes (O3).
We started the PEARL-AGE research study, recruiting participants in families to provide samples, obtaining all necessary ethics documentations and setting up the logistics to support this. We built computational pipelines that can track bacterial strains in metagenomic samples, important to understand how bacteria transfer between individuals, and to understand their persistence (O2).
We further built pipelines to resolve single genetic variations (SNVs) from metagenomes that will be used to estimate evolutionary trajectories of bacteria in metagenomes (O3).
The work supported by the ERC grant has enabled ten peer reviewed publications, that were supported by the ERC grant. For example, I argued in an invited opinion article, why we need a higher resolution in metagenomics (doi: 10.1128/mSystems.00881-21). We published a bioinformatic pipeline to support metagenomic analysis of labs with higher precision at lower computational demands, helping to democratize science (doi: 10.1186/s40168-022-01365-1 http://lotus2.earlham.ac.uk/). Furthermore, the lab described the typical persistence of a wide range of gut bacteria in a human cohort, proposing dispersal strategies for gut bacteria (doi: 10.1016/j.chom.2021.05.008).
These findings were also disseminated at scientific conferences and public engagement events, such as Pint of Science. We are also developing relationships with sequencing companies which is of mutual benefit in terms of expertise and the future impact of the project.
These findings were also disseminated at scientific conferences and public engagement events, such as Pint of Science. We are also developing relationships with sequencing companies which is of mutual benefit in terms of expertise and the future impact of the project.