Deciphering the molecular mechanisms of inter-species bacterial communication in the gut microbiome

• Applicant: Professor Dr. Kai Papenfort
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 564323947

The complex ecosystem of hundreds of bacterial species in the mammalian gut microbiota significantly influences host health. These bacterial communities must continuously adapt to host-imposed environmental changes, such as diet and medication variations. Failure to adapt can lead to microbiota imbalances with adverse health outcomes for the host (dysbiosis), however, the mechanisms by which gut microbes modulate their functions in the host remain largely unexplored. Research performed by us and others revealed that bacterial communication through chemical signals, i.e. quorum sensing, plays an important role in microbial interactions, however, the functions of quorum sensing in complex, multispecies gut communities are only poorly understood. In this project, we aim to investigate how microbial communication systems within the mammalian gut microbiome regulate microbiota functions, and ultimately how these processes influence community dynamics and resilience against environmental perturbations such as changes in host diet and pathogen invasion. Focusing on Bacteroides thetaiotaomicron, one of the most prevalent bacterial species in the human gut, and our recently identified pyrazinone quorum sensing signals, we will use molecular genetics, analytical chemistry, and mouse models, to: (i) identify the molecules and signaling pathways involved in sensing and responding to this novel class of quorum sensing signals in B. thetaiotaomicron, (ii) unravel how quorum sensing influences collective microbial behaviors and community dynamics in gut microbiota communities, determine the relevance of these behaviors in microbiota colonization, and in response to changes in host diet, and (iii) examine how interspecies communication influences microbiota functions and colonization resistance towards the major human pathogen, Vibrio cholerae. By decoding the chemical lexicon and signaling pathways responding to quorum sensing signals in B. thetaiotaomicron, we will contribute to a better understanding of how microbial communication affects microbiota community dynamics and function in the gut, and how these processes can promote the adaptation to fluctuating and adverse conditions, including dietary changes and pathogen defense. Understanding these mechanisms will improve our ability to prevent microbiota imbalances and devise innovative approaches for managing dysbiosis effectively.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2474: Illuminating gene functions in the human gut microbiome
• International Connection: Portugal
• Cooperation Partner: Professorin Dr. Karina Xavier