Periodic Reporting for period 4 - FunKeyGut (Illuminating Functional Networks and Keystone Species in the Gut)
Reporting period: 2021-10-01 to 2022-09-30
We live in an intimate symbiosis with our gut microbiota, which provides us services such as vitamin production, breakdown of dietary compounds, and immune training. Sequencing-based approaches that have been applied to catalogue the gut microbiota have revealed intriguing discoveries associating the microbiome with diet and disease. The next outstanding challenge is to unravel the many activities and interactions that define gut microbiota function.
The gut microbiota is a diverse community of cooperating and competing microbes. These interactions form a network that links organisms with each other and their environment. Interactions in such a “functional network” are based partially, though not exclusively, on food webs. Certain “keystone species”, such as Rumonicoccus bromii, are thought to play a major role in these networks. Though some evidence exists for the presence of keystone species, their identity and activity remains largely unknown. As keystone species are vital to networks they are ideal targets for manipulating the gut microbiota to improve metabolic health and protect against enteropathogen infection.
Given the complexity of the gut microbiota, networks can only be elucidated directly in the native community. This project aimed to identify functional networks and keystone species in the human gut using novel approaches that are uniquely and ideally suited for studying microbial activity in complex communities. Using state-of-the-art methods such as stable isotope labeling, Raman microspectroscopy, and secondary ion mass spectrometry (NanoSIMS) we will illuminate functional networks in situ. This will allow us to identify what factors shape gut microbiota activity, reveal important food webs, and ultimately use network knowledge to target the microbiota with prebiotic/probiotic treatments rationally designed to promote health.
The gut microbiota is a diverse community of cooperating and competing microbes. These interactions form a network that links organisms with each other and their environment. Interactions in such a “functional network” are based partially, though not exclusively, on food webs. Certain “keystone species”, such as Rumonicoccus bromii, are thought to play a major role in these networks. Though some evidence exists for the presence of keystone species, their identity and activity remains largely unknown. As keystone species are vital to networks they are ideal targets for manipulating the gut microbiota to improve metabolic health and protect against enteropathogen infection.
Given the complexity of the gut microbiota, networks can only be elucidated directly in the native community. This project aimed to identify functional networks and keystone species in the human gut using novel approaches that are uniquely and ideally suited for studying microbial activity in complex communities. Using state-of-the-art methods such as stable isotope labeling, Raman microspectroscopy, and secondary ion mass spectrometry (NanoSIMS) we will illuminate functional networks in situ. This will allow us to identify what factors shape gut microbiota activity, reveal important food webs, and ultimately use network knowledge to target the microbiota with prebiotic/probiotic treatments rationally designed to promote health.
In this project we developed bioinformatics analyses to describe the biological and ecological properties of putative keystone taxa in the human gut microbiota. We also developed and applied a multi-modal single cell analysis and sorting workflow to determine which microbes are active under specific environmental or nutrient conditions. This workflow was applied to determine key species occupying specific niches of interest, with a particular focus on dietary polysaccharides that have been proposed as candidate prebiotics. We also evaluated the interaction between dietary and host-derived nutrients in shaping the composition and activity of the gut microbiota. These results have been communicated to the scientific community via presentations at international conferences and have, or will be, published in peer-reviewed scientific journals.
The established multi-modal single cell analysis and sorting workflow to determine which microbes are active under specific conditions is a powerful approach that is generalizable to many questions in human microbiome research as well as environmental microbiology, and even to eukaryotic cell biology and immunology. It is anticipated that the tools and approaches developed here will help to give deeper insights into a number of important biological questions.