(P20-028-23) Genome-Wide Multi-Omics Analysis Reveals the Nutrient-Dependent Metabolic Features of Mucin-Degrading Gut Bacteria

Objectives: The prevalence and occurrence of mucin-degrading (MD) bacteria, as symbionts, play a crucial role in modulating the gut ecosystem. However, the physiological features of MD bacteria and their metabolic impacts on the host are still not clearly understood. We discuss the nutrient-dependent metabolic features of MD bacteria underlying diet-induced alterations of gut microbiota and how these affect host-microbe interactions in the human gut environment.

Methods: We performed comprehensive multi-omics analyses to investigate the distinct phenotypes of Ruminococcus gnavus and Akkermansia muciniphila under various culture conditions. To understand the physiological characteristics and metabolic features of both bacteria, we also analyzed their fermentation profiles on various mucus constituents and examined the effect of their fermentation products on host immune cells.

Results: We assessed functional modules of mucin catabolism, through a comprehensive bioinformatics-aided functional annotation, to identify 296 R. gnavus genes and 54 A. muciniphila 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. 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.

Conclusions: The reprogramming possibilities are complicated by variations in nutrient-specific MD capabilities. This study has revealed the context-dependency of MD bacteria, whose metabolism and host effects are altered by nutrient availability.

Funding Sources: This work was partly supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) of Korea grant (2021M3A9I4021431). 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).