We all have a gut microbiome: a population of bacteria that lives in harmony with our body and provides a vital role in assisting our immune system to protect our body from harmful pathogens. An individual’s microbiome is unique, much like a fingerprint. Only now are we beginning to understand the importance and extent of the roles that this plays in all aspects of our health – from gut health to the more recently discovered impacts on the gut-brain axis and how this can mediate feelings of anxiety and depression. Recent studies have also suggested a microbial component implicated in early onset dementia. It will be exciting to see how research in this fascinating field develops in the near future.
A benevolent microbiome is one that responds swiftly to insult and stress in a timely and sustainable way; such insults could range from trauma to metabolic or endocrine issues. Our understanding of the microbiome is not currently extensive enough to define what makes up such a microbiome – we have knowledge of some of the species present and we can identify which are most abundant: Bifidobacterium and Lactobacillus, but we are still far from being able to provide a definition due to its vast and complex nature. However, it is widely accepted that a diverse microflora is best and a microbiome dominated by just one or two genus or species will normally result in dysbiosis. Such difficulties may make it worth considering what a ‘bad’ microbiome looks and what might be considered a pathogen. This has also proven difficult since much of the microbiome relies on a careful homeostatic dynamic between microbe and host, and what might be harmful to one individual may not be to another. Difficulties also surround the fact that the microbiome is different for each individual, and there are multiple genetic, host factors and species involved. Despite this, a normal hallmark of pathogenic species is the production of a toxin.
In the past, an over reliance on rodent models used in this research has hindered the reliability of results, and consequently, wild extrapolations have been made. It is hoped that in the future, it will be possible to stimulate human tissue interactions in vitro, which will help overcome this problem. Insufficient understanding of the biology and mechanisms involved at a molecular level has led to many failed studies, and as a result, a decline in investment. Pharma’s key interest currently is in understanding the mechanisms, biomarkers and metabolites that affect disease, and the search to find a molecule produced by an adverse microbiome and understand how it causes disease. It is also important to understand the link between nutrition, lifestyle and our microbiome. We are already aware of certain drug-food interactions and their effects on efficacy, such as the relationship between statins and grapefruit. Lifestyle factors such as diet, flossing, physical activity and whether a baby is bottle fed or breast fed also impact the diversity of our microbiome. Understanding these interactions will be vital to further developments.
It is hoped that understanding of the gut microbiome will, in time, be applied in precision medicine. In future, it may be possible to reduce the population treated with certain drugs with no benefit, or to identify individuals for either inclusion or exclusion in clinical trials. However, these restrictions cannot be made based on the current information available and if excluding people, there needs to be incontrovertible evidence before these restrictions are made. The future may also see microbiome derived therapies or drugs as well as prescription of probiotics. Faecal microbiota transplant is currently being used to treat dysbiosis and return homeostasis to the gut flora, and is becoming a key treatment for Clostridium difficile infections. There are other suggestions that the microbiome could be used to improve vaccine efficiency, and studies have shown a correlation between increased vaccine outcomes and a diverse microbiome. There is clearly still more understanding needed before these ideas can be widely applied but there are exciting new discoveries and treatments just around the corner.
This blog post is a follow up to a session at Genesis 2019.
Written by Ellie Brian
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