Genome-wide multi-omics analysis reveals the nutrient-dependent metabolic features of mucin-degrading gut bacteria
Kyoung Su Kim,
Eunike Tiffany,
Ji-Young Lee,
Ara Oh,
Hyeon-Su Jin,
Ji-Sun Kim,
Jung-Sook Lee,
Myung Hee Nam,
Soo-Jong Hong,
Sowon Park,
Hong Koh,
Bong-Soo Kim,
Yun Kyung Lee,
Dong-Woo Lee
Affiliations
Kyoung Su Kim
Department of Biotechnology, Yonsei University, Seoul, Republic of Korea
Eunike Tiffany
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-Bio Science, Soonchunhyang University, Cheonan, Republic of Korea
Ji-Young Lee
Department of Biotechnology, Yonsei University, Seoul, Republic of Korea
Ara Oh
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-Bio Science, Soonchunhyang University, Cheonan, Republic of Korea
Hyeon-Su Jin
Department of Biotechnology, Yonsei University, Seoul, Republic of Korea
Ji-Sun Kim
Korean Collection for Type Cultures, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Republic of Korea
Jung-Sook Lee
Korean Collection for Type Cultures, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup, Republic of Korea
Myung Hee Nam
Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea
Soo-Jong Hong
Department of Pediatrics, Childhood Asthma Atopy Center, Humidifier Disinfectant Health Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Sowon Park
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
Hong Koh
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
Bong-Soo Kim
Department of Life Science, Hallym University, Chuncheon, Republic of Korea
Yun Kyung Lee
Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-Bio Science, Soonchunhyang University, Cheonan, Republic of Korea
Dong-Woo Lee
Department of Biotechnology, Yonsei University, Seoul, Republic of Korea
ABSTRACTThe 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.