Investigating the mechanism of dietary fibre breakdown by the human and animal gut microbiota

The gut microbiota of many mammals, including humans and farmed animals, plays a critical role in the digestion of plant polysaccharides (often called dietary fibre) from crops and the products of this anaerobic fermentation (short chain fatty acids) provide both localised and systemic health benefits to the host. It is therefore important to understand the mechanisms by which key members of the gut microbiota interact with and degrade food/feed to inform both nutritional strategies to benefit host health, as well as facilitate development of novel crop traits aimed at maximising their health benefits (i.e. to develop varieties that are broken down more efficiently by the gut microbiota).
The mammalian gut is dominated by only two major phyla; the Gram negative Bacteroidetes and the Gram positive Firmicutes. While our lab and others have extensively characterised the glycan-degrading apparatus of gut Bacteroidetes, there is a major gap in our knowledge of how Gram positive members of the microbiota access plant polysaccharides, which is of critical importance if we are to have a detailed understanding of the interactions of the whole gut microbial community with dietary fibre. Furthermore, while the Bacteroidetes are well adapted to breakdown of the soluble fraction of dietary fibre, there is evidence the Firmicutes are more efficient at degrading the insoluble material, suggesting they occupy a distinct intestinal niche. In this project we aim to characterise the plant polysaccharide breakdown apparatus of several prominent Firmicute spp. isolated from both healthy human and domesticated animal guts. Initial screening for growth of a number of prominent gut Firmicutes (e.g Ruminoccus albus, Roseburia intestinalis), on pure forms of soluble and insoluble plant polysaccharides (e.g. cellulose, xylans, mannans, mixed linkage glucans, pectins) will enable us to identify the strains that grow most effectively on these substrates. RNAseq and/or proteomics approaches will be used to identify the degradative apparatus involved, including potentially novel enzyme families identified by distant homology detection, modelling based on detected homologs and follow-on structure-based function annotation through the rotation in the second supervisor's lab. The student will utilise a range of biochemical and cell biology techniques to characterise the main glycan degrading enzymes from these bacteria and their role in plant polysaccharide breakdown in the gut. Over the course of the project, interesting enzyme targets, as well as potentially proteins involved in surface glycan recognition, transport and signalling, will be advanced into structural studies to define the molecular basis for substrate specificity. The data generated will provide significant insight into the mechanism of fibre degradation by the microbiota and inform the development of new breeds of crop with altered polysaccharide structures designed to be broken down more effectively by gut microbes in both humans and farmed animals. These findings have the potential to contribute to more sustainable use of resources (especially feed) in farm animal production, as well as underpin the development of human plant-based foods with improved digestibility and thereby enhanced health benefits. The project fits squarely in to the 'Bioscience for sustainable agriculture' focus areas 'crop and farmed animal health' and 'food safety and nutrition'.