The Role of Bacterial Exopolysaccharides in the Maintenance of Healthy Human Gut Bacteria

Fermented health foods and beverages have gained popularity in recent years based on the benefits of probiotics for encouraging a healthy and diverse gut microbiota. Probiotics are live microorganisms that, when consumed in adequate amounts, confer a health benefit to the host. The microbes found in these health products are lactic acid bacteria (LAB) such as Lactobacillus and Bifidobacterium, which are also normal members of the microbiota. However, the ability of these organisms to colonise the adult gut is poor and the effects they have are transient; benefits are only apparent if the individual continues to consume the probiotic product. Within the context of enhancing the impact of these beneficial gut microbes, little attention has been given to the structurally diverse glycan exopolysaccharides (EPS) produced and excreted by lactic acid bacteria. EPS are high molar mass polysaccharides that are either loosely attached to the cell surface or excreted into the environment. They are classed into two distinct groups; homopolysaccharides and heteropolysaccharides. Homopolysaccharides are formed of a single type of monosaccharide repeating unit. By contrast, heteropolysaccharides are made up of two or more types of monosaccharide. Mostly LAB derived EPS belong to the heteropolysaccharide group. Since these glycans provide a potential carbon source for other members of the microbiota. Therefore, they have complex, multiple cascading effects on gut microbial populations. The Bacteroides phyla are the main polysaccharide degraders found in the microbiome, targeting mainly dietary polysaccharides. They employ polysaccharide utilisation loci (PUL) coregulated genes that upregulate in the presence of a particular glycan for their sense, capture, degradation and transport. Bacteroides and their respective PULs have been extensively studied in terms of dietary polysaccharide breakdown, such as how dietary carbohydrates xylan and rhamnogalacturonan II are degraded by members of this phyla. However, there is little biochemical data to describe how Bacteroides breakdown polysaccharides derived from other microbes. Structures of EPS are distinct from dietary glycans, offering the potential for discovery of novel enzymes, with potential biotechnological and therapeutic relevance. The relationship between the Bifidobacterium, the early colonisers of the infant gut, and the Bacteroidetes, secondary colonisers that appear before weening, is of significant interest. To understand how Bacteroides degrade and utilise EPS may provide insights into the arrival of Bacteroides into the infant gut microbiota and the development of the diverse adult microbiota as well as provide a route for therapeutic intervention. The project will assess the ability of Bacteroides to degrade LAB EPS using growth studies, microbial community profiling, recombinant protein technology and biochemical analysis of degradation products and enzyme activities. In collaboration with ThermoFisher Scientific in the UK and US, access to state of the art mass spectrometry methods will allow for the identification and characterisation of the complex carbohydrates. The information from this project will help to elucidate the carbohydrate-mediated relationships in the complex environment of the human gut.