MetaPhlAn 4 profiling of unknown species-level genome bins improves the characterization of diet-associated microbiome changes in mice
Paolo Manghi, Aitor Blanco‐Míguez, Serena Manara, Amir Nabinejad, Fabio Cumbo, Francesco Beghini, Federica Armanini, Davide Golzato, Kun D. Huang, Andrew Maltez Thomas, Gianmarco Piccinno, Michal Punčochář, Moreno Zolfo, Till Robin Lesker, Marius Bredon, Julien Planchais, Jérémy Glodt, Mireia Valles‐Colomer, Omry Koren, Edoardo Pasolli, Francesco Asnicar, Till Strowig, Harry Sokol, Nicola Segata
Abstract
Mouse models are key tools for investigating host-microbiome interactions. However, shotgun metagenomics can only profile a limited fraction of the mouse gut microbiome. Here, we employ a metagenomic profiling method, MetaPhlAn 4, which exploits a large catalog of metagenome-assembled genomes (including 22,718 metagenome-assembled genomes from mice) to improve the profiling of the mouse gut microbiome. We combine 622 samples from eight public datasets and an additional cohort of 97 mouse microbiomes, and we assess the potential of MetaPhlAn 4 to better identify diet-related changes in the host microbiome using a meta-analysis approach. We find multiple, strong, and reproducible diet-related microbial biomarkers, largely increasing those identifiable by other available methods relying only on reference information. The strongest drivers of the diet-induced changes are uncharacterized and previously undetected taxa, confirming the importance of adopting metagenomic methods integrating metagenomic assemblies for comprehensive profiling.