Remote control: How do microbiota promote animal health?

Ever more people are enduring metabolic diseases like obesity, whilst older people are living in generally poor health. What if we could safeguard both healthy ageing and healthy metabolism?

Our gut bacteria regulate ageing and metabolism. As natural partners that assist with many functions that hosts can't perform alone, these microbes are a promising source of new therapies. Animals reared without bacteria live longer, but are obese. The challenge is therefore to understand how bacteria regulate both ageing and metabolism, and isolate just the mechanisms that can be used to promote long-term health by both measures.

A major issue is understanding how bacteria that live in the gut have widespread effects across other host tissues. This project will address this problem using flies to study processes that occur across animals. We will look at how specific bacterial genes regulate levels of hormones and nutrients in the fly, the tissues where those changes are important, and consequences for lifespan and metabolism. By doing this, we will evaluate how microbiota regulate host health, and whether we can precisely manipulate them to broadly improve health.

Ageing and declining metabolic health are dual healthcare crises. Worldwide, more than 1 in 3 adults are now overweight or obese, whilst the WHO projects that more than 30% of the population of Europe and many other parts of the world will be over 60 years old by 2045. Both obesity and age are major risk factors for health risks ranging from high blood pressure and gout to dementia and cancer: both worsen individual health and burden healthcare services. The microbiota are connected to both metabolic disease and ageing. These beneficial effects of microbiota, and the ease with which they can be manipulated, make an attractive theraputic target. This project aims to connect the microbiota with mechanisms of known relevance to both ageing and metabolic disease, with implications for healthcare, individuals and the private sector.

This project will potentially yield short and long-term benefits for:

1) Private sector
Therapies for microbiota and ageing are at the forefront of the present biomedical investment landscape. One goal of this work is to connect bacterial genetics and diversity to endocrine function, longevity and metabolic health, which is likely to be of direct and immediate commercial interest. IP may be of substantial economic value which could be rapidly developed via a start-up or licensing, and/or may be of broad commercial benefit to companies developing microbiome-centered therapies in the UK and globally.

2) Public healthcare services
The ageing population, and the increased load of general ill health it brings, is recognised as the NHS' greatest challenge. In the long term, research into the basics of the ageing process may bring treatments that impart substantial benefits for the general health, fitness and vigour of older people; which is anticipated to reduce the overall strain on the health system. Similarly, metabolic disease is on the rise. In 2012, the proportion of the NHS budget spent on diabetes care and complications was predicted to increase £12.9bn by 2035. Owing to a focus on the microbiome, this proposed work has particular potential for translation, which would indirectly decrease long-term costs to the healthcare system.

3) Older people and patients with metabolic conditions
Older people are an ever-increasing proportion of our society. The diseases of ageing such as heart disease, cancer and dementia cause immense personal suffering. Metabolic diseases such as obesity also cause substantial distress to patients via direct and secondary medical issues, as well as broader sociological issues such as access to employment. The ultimate goal of this research is to identify means to improve health in old age and overall metabolic health, which it is hoped will have long-term benefits for these groups.

4) Economy
In the long term this project stands to reduce the costs of healthcare both to individuals and healthcare systems, leading to general economic benefit. Furthermore, in the short term, this project will directly create two jobs.

5) Policy makers and third sector
The successful completion of this fellowship may contribute to influence on healthcare and research policy. Charities funding related research (e.g. Wellcome Trust, Rosetrees Trust) may be interested to support further research following the potentially broad scientific implications of this study.