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 of synthetic communities (SYNs) allowed establishing custom strain consortia 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., induction of T-cell subtypes) in the intestine and associated lymphoid tissues. Ready-to-use OMM stocks from this work 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.
Bile acid (BA) metabolism is a complex system that encompasses a diverse mixture of primary and secondary, as well as conjugated and unconjugated BAs that undergo continuous enterohepatic circulation (EHC). Alterations in both composition and dynamics of BAs have been associated with various diseases; however, a mechanistic understanding of the relationship between altered BAs metabolism and related diseases is lacking. Computational modeling may support functional analyses of the physiological processes involved in the EHC of bile acids along gut the gut-liver axis. In this study, we developed a physiology-based model of murine BA metabolism describing synthesis, conjugation, microbial transformations, systemic distribution, excretion and EHC of BAs as well as an explicit representation of the host physiology at the whole-body level. For model development, BA metabolism of specific pathogen-free (SPF) was characterized in vivo by measuring BA levels and composition in various organs, expression of transporters along the gut and cecal microbiota composition. Interestingly, We found significantly different BA levels between male and female mice that could only be explained by adjusted expression of the hepatic enzymes and transporters in the model. Of note, this finding was in agreement with earlier experimental observations. The model for SPF mice could also describe equivalent experimental data in germ-free mice by specifically switching of microbial activity in the intestine. The here presented model hence allows functional analysis of BA metabolism in mice. In the future, the model may support the translation of results from mouse studies to a clinically relevant context through cross-species extrapolation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.