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Phenomics: a term used to describe the study of how our environments and lifestyles interact with our genes to influence our overall health and risk of disease as we go through life.

Examples of these gene-environment interactions include factors such as our diet, and whether we exercise, smoke, or live in cities or rural areas. These interactions are often affected by the bacteria and microbes that live in our environment and co-exist with us – for example, in our gut. The gut microbiome (a community of bacteria and other micro-organisms) is particularly of interest to researchers, as these microbes are one of the first sites of metabolism (chemical reaction) in the human system, given everything in our diet will interact with these bacteria.

Depending on the content and variability of this microbiome and how it first metabolises our diet, there will be changes in chemicals that we absorb through the gut wall. These changes are increasingly thought to impact our health and disease – for example, changes in the microbiome have been associated with the prevalence of diseases such as diabetes, obesity and dementia. However, often the underlying mechanism is not fully understood.

To attempt to find out more we can use a technique called metabolomics – an area of research in which I specialise. Metabolomics is a term used to describe the measurement of different chemicals and the changes in these chemicals that occur in our blood and urine. Certain chemicals are known to be produced and utilised by specific gut bacteria, so by measuring these we can quickly start to obtain a snapshot of the status of microbes in an individual’s gut. We study these chemical changes in a large number of people and aim to observe patterns that link certain chemicals with disease. By doing this this we can obtain insights into how these chemical signatures may play a role in specific disease outcomes. The larger the cohort, the more we can identify and trust these patterns, and therefore obtain a better understanding of the underlying mechanism of diseases.

What is becoming clearer from this research is that these chemical interactions are affecting an individual’s health at all stages throughout their life. For example, disturbances in the gut microbiome have been associated with an increased chance of mid-life diabetes, which in turn has been separately associated with an increased risk of dementia – which links back to the microbiome.

Understanding these links may be critical to finding new therapeutic targets and better managing disease outcomes, particularly when it comes to understanding disease-disease associations such as those observed in diabetes and dementia. 

To address this challenge, I have recently joined a new state-of-the-art research centre based in Perth, Australia, which will use samples from large human population cohort studies to acquire a chemical snapshot of the blood and urine of each person. My work will specialise in how these chemical changes impact healthy ageing and dementia. As part of this we will investigate the chemical changes that occur in an individual that lead to diabetes and the subsequent links to the microbiome and dementia.

An important consideration in our work is ensuring that results are replicated in multiple cohorts and population demographics to make sure that our findings are not an effect of an external influence – for example, how a sample has been collected. We therefore aim to work with international cohorts to validate our findings. We have ongoing collaborative projects that use cohorts from the DPUK Data Portal (such as the AIRWAVE population cohort) that will help validate and strengthen our findings and hopefully lead to a better understanding of these complex diseases.

Luke Whiley