Enhanced cultured diversity of the mouse gut microbiota enables custom-made synthetic communities.

Microbiome research needs comprehensive repositories of cultured bacteria from the intestine of mammalian hosts. We expanded the mouse intestinal bacterial collection (www.dsmz.de/miBC) to 212 strains, all publicly available and taxonomically described. This includes strain-level diversity, small-sized bacteria, and previously undescribed taxa (one family, 10 genera, and 39 species). This collection enabled metagenome-educated prediction of synthetic communities (SYNs) that capture key functional differences between microbiomes, notably identifying communities associated with either resistance or susceptibility to DSS-induced colitis. Additionally, nine species were used to amend the Oligo-Mouse Microbiota (OMM)12 model, yielding the OMM19.1 model. The added strains compensated for phenotype differences between OMM12 and specific pathogen-free mice, including body composition and immune cells in the intestine and associated lymphoid tissues. Ready-to-use OMM stocks are available for 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.

Acids produced by lactobacilli inhibit the growth of commensal Lachnospiraceae and S24-7 bacteria.

The Lactobacillaceae are an intensively studied family of bacteria widely used in fermented food and probiotics, and many are native to the gut and vaginal microbiota of humans and other animals. Various studies have shown that specific Lactobacillaceae species produce metabolites that can inhibit the colonization of fungal and bacterial pathogens, but less is known about how Lactobacillaceae affect individual bacterial species in the endogenous animal microbiota. Here, we show that numerous Lactobacillaceae species inhibit the growth of the Lachnospiraceae family and the S24-7 group, two dominant clades of bacteria within the gut. We demonstrate that inhibitory activity is a property common to homofermentative Lactobacillaceae species, but not to species that use heterofermentative metabolism. We observe that homofermentative Lactobacillaceae species robustly acidify their environment, and that acidification alone is sufficient to inhibit growth of Lachnospiraceae and S24-7 growth, but not related species from the Clostridiales or Bacteroidales orders. This study represents one of the first in-depth explorations of the dynamic between Lactobacillaceae species and commensal intestinal bacteria, and contributes valuable insight toward deconvoluting their interactions within the gut microbial ecosystem.

The CIAMIB: a Large and Metabolically Diverse Collection of Inflammation-Associated Bacteria from the Murine Gut.

Gut inflammation directly impacts the growth and stability of commensal gut microbes and can lead to long-lasting changes in microbiota composition that can prolong or exacerbate disease states. While mouse models are used extensively to investigate the interplay between microbes and the inflamed state, the paucity of cultured mouse gut microbes has hindered efforts to determine causal relationships. To address this issue, we are assembling the Collection of Inflammation-Associated Mouse Intestinal Bacteria (CIAMIB). The initial release of this collection comprises 41 isolates of 39 unique bacterial species, covering 4 phyla and containing 10 previously uncultivated isolates, including 1 novel family and 7 novel genera. The collection significantly expands the number of available Muribaculaceae, Lachnospiraceae, and Coriobacteriaceae isolates and includes microbes from genera associated with inflammation, such as Prevotella and Klebsiella. We characterized the growth of CIAMIB isolates across a diverse range of nutritional conditions and predicted their metabolic potential and anaerobic fermentation capacity based on the genomes of these isolates. We also provide the first metabolic analysis of species within the genus Adlercreutzia, revealing these representatives to be nitrate-reducing and severely restricted in their ability to grow on carbohydrates. CIAMIB isolates are fully sequenced and available to the scientific community as a powerful tool to study host-microbiota interactions. IMPORTANCE Attempts to explore the role of the microbiota in animal physiology have resulted in large-scale efforts to cultivate the thousands of microbes that are associated with humans. In contrast, relatively few lab mouse-associated bacteria have been isolated, despite the fact that the overwhelming number of studies on the microbiota use laboratory mice that are colonized with microbes that are quite distinct from those in humans. Here, we report the results of a large-scale isolation of bacteria from the intestines of laboratory mice either prone to or suffering from gut inflammation. This collection comprises dozens of novel isolates, many of which represent the only cultured representatives of their genus or species. We report their basic growth characteristics and genomes and are making them widely available to the greater research community.