Abstract
The gut microbiome is a new target for therapeutics. In vitro high-throughput culture models could provide time-and-cost saving solutions to discover microbiome responses to drugs. Unfortunately, there has been no report of in vitro models capable of maintaining functional and compositional profiles resembling the in vivo gut microbiome. Here, we developed and validated a high-throughput culturing model named Mipro to maintain individuals’ microbiomes. The Mipro model quintupled viable bacteria count while maintained the functional and compositional profiles of individuals’ gut microbiomes. Comparison of taxon-specific functions between pre -and-post culture microbiomes showed Pearson’s correlation coefficient r of 0.83 ± 0.03. Moreover, the Mipro model also exhibited a high degree of in vitro – in vivo correlation (Pearson’s r of 0.68 ± 0.09) in microbial responses to metformin in mice fed a high-fat diet. Mipro provides a highly simulated gut microbiome for high-throughput investigation of drug-microbiome interactions.
- List of abbreviations
- ANOVA
- analysis of variance
- BCM
- basal culture medium
- CA
- cholic acid
- CDCA
- chenodeoxycholic acid
- COG
- Clusters of Orthologous Groups
- DCA
- deoxycholic acid
- FDR
- false discovery rate
- FSC
- forward scatter
- KEGG
- Kyoto Encyclopedia of Genes and Genomes
- KO
- KEGG Orthology
- LC-MS/MS
- liquid chromatography-tandem mass spectrometry
- LCA
- lowest common ancestor
- LFQ
- lable-free quantification
- MiPro
- Maintenance of gut microbiome Profiles
- OD
- optical density
- PCA
- principle component analysis
- PCoA
- principal coordinates analysis
- PLS-DA
- partial least squares – discriminant analysis
- SSC
- sideward scatter