Genome-wide multi-omics analysis reveals the nutrient-dependent metabolic features of mucin-degrading gut bacteria

ABSTRACT

The prevalence and occurrence of mucin-degrading (MD) bacteria, such as Akkermansia muciniphila and Ruminococcus gnavus, is highly associated with human health and disease states. However, MD bacterial physiology and metabolism remain elusive. Here, we assessed functional modules of mucin catabolism, through a comprehensive bioinformatics-aided functional annotation, to identify 54 A. muciniphila genes and 296 R. gnavus genes. The reconstructed core metabolic pathways coincided with the growth kinetics and fermentation profiles of A. muciniphila and R. gnavus grown in the presence of mucin and its constituents. Genome-wide multi-omics analyses validated the nutrient-dependent fermentation profiles of the MD bacteria and identified their distinct mucolytic enzymes. The distinct metabolic features of the two MD bacteria induced differences in the metabolite receptor levels and inflammatory signals of the host immune cells. In addition, in vivo experiments and community-scale metabolic modeling demonstrated that different dietary intakes influenced the abundance of MD bacteria, their metabolic fluxes, and gut barrier integrity. Thus, this study provides insights into how diet-induced metabolic differences in MD bacteria determine their distinct physiological roles in the host immune response and the gut ecosystem.

KEYWORDS:

• Mucin-degrading bacteria
• genome annotation
• nutrient-dependent fermentation
• host immune response
• the gut ecosystem

Author’s contributions

K.S. Kim, E. Tiffany, J.Y. Lee, A. Oh, H.S. Jin, Y.K. Lee, and D.W. Lee formulated the research plan. K.S. Kim, E. Tiffany, J.Y. Lee, A. Oh, H.S. Jin, J.S. Lee, and M.H. Nam performed the experiments. K.S. Kim, E. Tiffany, A. Oh, M.H. Nam, B.S. Kim, Y.K. Lee, and D.W. Lee analyzed the data. K.S. Kim, Y.K. Lee, and D.W. Lee wrote the manuscript. S.J. Hong, H. Koh, B.S. Kim, Y.K. Lee, and D.W. Lee conceived, planned, supervised, and managed the study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The complete genome sequence of R. gnavus ATCC 29149 has been deposited in NCBI/GenBank under the accession number CP027002. The RNA-seq data generated in this study have been submitted to the NCBI BioProject database (https://www.ncbi.nlm.nih.gov/bioproject/) under accession number PRJNA967152. Annotation data sets and multi-omics data are available in Datasets and Supplementary File. Detailed materials and methods are available in Supplementary File.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2221811

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was partly supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) of Korea grant (2021M3A9I4021431 to DWL, 2021M3A9I4027993 to YKL, 2021M3A9I4023974 to BSK, and 2018M3A93056901 to MHN), funded by the Ministry of Science and ICT (MSIT), Republic of Korea. This work also partly supported by Bioindustrial Technology Development Program of Korea grant (200118770), funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea).