Clavel, Thomas

Numerous bacteria in the human gut microbiome remains unknown and/or have yet to be cultured. While collections of human gut bacteria have been published, none are publicly accessible. This is partly due to issues with the deposition of strains to public culture collections. We address these key issues (microbial unknowns, lack of public access to isolates) by proposing a framework that facilitates large-scale submission of isolates, exemplified by a rich collection of human gut isolates that is taxonomically described, functionally novel, and made publicly available. An innovative bulk strain submission system was established by large-scale generation and curation of persistent strain identifiers (https://straininfo.dsmz.de). This was used to create the Human intestinal Bacterial Collection (www.hibc.rwth-aachen.de), which contains 340 strains representing 198 species within 29 families and 7 phyla, of which 32 previously unknown taxa are taxonomically described and named. These included three butyrate-producing species of Faecalibacterium and new dominant species associated with health and inflammatory bowel disease. Plasmids were identified to be prolific within the HiBC isolates, with almost half (46%) of strains containing one or more plasmids (up to 6). Megaplasmids were identified within two strains, one of them is globally present within multiple Bacteroidales species. The strain submission framework and public collection of easily searchable and available gut bacterial isolates presented here will facilitate the work of many by enabling functional studies.

Microbiome research is hampered by the fact that many bacteria are still unknown and by the lack of publicly available isolates. Fundamental and clinical research is in need of comprehensive and well-curated repositories of cultured bacteria from the intestine of mammalian hosts. In this work, we expanded the mouse intestinal bacterial collection (www.dsmz.de/miBC) to 212 strains, all publicly available and taxonomically described. This includes the study of strain-level diversity, small-sized bacteria, and the isolation and characterization of the first cultured members of one novel family, 10 novel genera, and 39 novel species. We demonstrate the value of this collection by performing two studies. First, metagenome-educated design allowed establishing custom synthetic communities (SYNs) that reflect different susceptibilities to DSS-induced colitis. Second, nine phylogenetically and functionally diverse species were used to amend the Oligo-Mouse Microbiota (OMM)12 model [Brugiroux et al. 2016 Nat Microbiol]. These strains compensated for differences observed between gnotobiotic OMM12 and specific pathogen-free (SPF) mice at multiple levels, including body composition and immune cell populations (e.g., T-cell subtypes) in the intestine and associated lymphoid tissues. Ready-to-use OMM stocks are available to the community for use in future studies. In conclusion, this work improves our knowledge of gut microbiota diversity in mice and enables functional studies via the modular use of isolates.