Understanding the Microbiome

Our gut is home to a large community of microbes and there is a growing realisation that this microbiome has an important influence on our health. At the Quadram Institute we are seeking to better understand the microbiome and uncover the mechanisms by which if affects health. With this increased understanding, we will be able to develop new therapies and treatments to combat diseases and maintain wellbeing throughout life.

A key step to unlocking the microbiome is to understand how these complex colonies initially establish themselves in the gut. We will better define how this happens, and the factors that affect the successful establishment of the gut microbiome, such as diet and antibiotic use, and elucidate how this impacts on health and regulating immune responses. We will define what constitutes a healthy gut and microbiome, which will allow us to understand how changes in this state lead to diseases, and from this suggest ways of preventing or treating these conditions.

The Quadram Institute is at the forefront of the interface between food, gut biology and health, and an important part of our research will involve understanding the interactions between food and the gut microbiota. Our studies encompass understanding how diet modulates the gut microbiota, and how this impacts health. We will also characterise how gut microbes metabolise food and what role these microbe-derived metabolites have in protecting health in the gut, and once they are absorbed into the body. A major focus will be on the role of gut microbes in breaking down starch and the implications of altering the rate of starch breakdown can have on health.

Our relationship with our microbiome is one that mutually benefits both. Within the Quadram institute, we will be researching how as the host we provide a suitable environment and nutrients that favour the correct establishment of appropriate microbial communities in the right place at the right time, with a focus on the mucus layer that lines the gut. This will integrate with our research into gut pathogens, to understand the role of the microbiome in preventing pathogenic infection.

We will build on our current work to understand the communication that happens between the microbiome and the host, and the mechanisms that convey this cross-talk. And we will be unlocking the ways in which the members of the microbiome communicate with each other, across different species, to mediate community interactions.

As well as advancing our fundamental knowledge, our efforts to understand the microbiome are aimed at linking this knowledge to the transition from a healthy to a diseased state, and then developing new therapies or treatments to counteract this. We will be studying what causes significant disease-causing changes in the microbiome, unpicking the complex interactions between the microbiome, the cells of the gut lining, the immune system and the host. We will be targeting diseases of the gut, such as IBD, as well as more systemic conditions related to dysbiosis in the microbiome.

A further aspect of this will be understanding how the gut links to the central nervous system – the gut-brain axis. We seek to elucidate the microbial cues capable of driving hunger and satiety responses that influence metabolic health. This is particularly important in the context of ageing. We also see a major decline in the composition of the microbiome as we reach old age; in the Quadram Institute we want to understand how this links to chronic age-related conditions, including dementia.

The Quadram Institute has brought together an interdisciplinary team, within the building and across the Norwich Research Park, with the range of expertise needed to understand the microbiome and to translate that knowledge into treatments for related diseases. Microbiologists will combine their knowledge of the basic biology of the bacteria, viruses and yeasts in the microbiome with computational and network biologists, to build up the best possible picture of the complexities contained in these communities. This will be complemented by expertise in microbial genomics, bioinformatics, mathematical biology and metagenomics within the Quadram Institute, as well as with our neighbours, the Earlham Institute. We have immunologists, gut biologists, food researchers and clinicians, all working under the same roof, providing insights into the interaction with our bodies and diet, and driving forward the translation of our research.

We are particularly interested in the microbiome in early life and in later life. Ongoing collaborations with the Norfolk and Norwich University Hospital are already guiding clinical practice, through our work on infants. We are also looking to study how the microbiome declines with age, working with volunteers from the local Norfolk population, to investigate links with age-related conditions such as mental decline and dementia.

Within the Quadram Institute we can study the microbiome at every level, from isolated genes, through to genomes, cells and microbial colonies, in vivo and in vitro and through advanced modelling systems, allowing us to characterise genes, individual microbial strains, and more complex ecosystems. But the interface within the Quadram Institute with the Regional Endoscopy Centre, and the Clinical Research Facility, means we can also study the microbiome in humans, and take our science from the lab to the clinic. We have established a faecal microbiota transplant service with the Norfolk & Norwich University Hospital, successfully treating patients infected with antibiotic resistant C. difficile. We want to explore how this can be improved, refined and expanded to other conditions, as well as other innovations, including prebiotics, probiotics, phage therapy, microbiome-promoting foods and ‘smart’ bacteria.