Trends and developments in current and future gut microbiome research
The gut microbiome is a complex system of trillions of bacteria, fungi and other organisms that perform a number of roles in the body.
Though research into this area is relatively new, it has quickly become apparent just how essential the gut microbiome is in controlling biological processes such as digestion, immune responses and even how the nervous system communicates with the brain.
A recent interview with Atlantia Food Clinical Trials provides key insight into the role of the gut microbiome, the importance of current research in this area and details of some exciting new projects in microbiome research trial design and therapeutics development.
Could you start by telling our readers why gut microbiota is considered such a vital research area at the moment?
Research into the gut microbiota has only really taken place over the past 15 to 20 years.
Before that time, the scientific and medical communities largely regarded gut microbes as simply commensal bacteria that were regularly fed but did not have a specific function within our bodies.
However, we now know that these microbes actually have a central role in regulating the activity of organs and systems throughout the body.
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What are the specific factors that determine the make-up of our microbiota?
A wide range of factors are involved in determining the architecture or structure of gut microbiota.
In adults, the key determinant is diet. For example, maintaining a healthy diet that is rich in fruits, vegetables, fish, etc., will result in a person possessing a complex and relatively diverse microbiota.
In contrast, ongoing studies have clearly shown that a diet of fast food or otherwise highly processed food will prompt the architecture of the microbiota to alter, significantly impacting the diversity that is seen in more healthy gut microbiota.
Exercise is another key factor that impacts microbiota at a given time. There have been a number of published studies over the past 5 to 10 years which show that people who engage in aerobic exercise on a regular basis will generally exhibit a more diverse microbiota.
Specific factors can have a negative effect on the microbiota, besides diet. High levels of stress have been shown to impact the gut microbiota, and a range of medications can affect the microbiota, both negatively and positively.
It is important to remember that while there are a range of things that can influence the microbiota, diet is undoubtedly the dominant factor.
Which areas of microbiome research are you most interested in, and can you give any examples of recent developments in your field?
As a psychiatrist, I am very interested in how stress can influence overall mental health, particularly because stress is a key driver in anxiety and related disorders that are increasingly common throughout society.
I am very excited and intrigued by the potential to target gut microbiota to help alleviate symptoms of depression or anxiety. The most common treatment for depression at my clinic is either antidepressants or psychological therapies like cognitive behavioral therapy.
These approaches work well, but I think the research is also reaching a point where it may be possible to improve mental health and alleviate the symptoms of people with depression or anxiety by targeting the gut microbiome with appropriate therapeutic treatments.
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Is there the potential for microbiome research to support the development of therapeutic approaches to conditions such as Alzheimer’s disease?
The gut microbiota continues to be targeted in many ways as this research moves forward; for example, it can be targeted to treat a disease itself or to reduce the risk factors of a disease.
For complex disorders such as the increasing prevalence of dementing illnesses in western societies, we should be focused on targeting the gut microbiota to reduce the risk factors of dementia in the short- to medium-term.
For example, we know that reducing cholesterol and glucose levels can help lower the risk of dementing illnesses. This should be an immediate priority since we are currently a long way from being able to treat disorders like Alzheimer’s disease or Parkinson’s disease via microbial interventions.
We have known for a long time that Parkinson’s disease stems from the degeneration of dopamine neurons within the brain. Even if the disease does originate in the gut, if dopamine neurons in the brain are lost, intervention via the gut microbiome is unlikely to effectively treat Parkinson’s disease.
We can still use this targeted approach, however, to reduce risk factors for Parkinson’s disease and prevent its emergence, but I am not convinced that we will be able to reverse the symptoms of a disease like Parkinson’s disease or Alzheimer’s disease by targeting the gut microbiota.
What are the most important considerations when designing a gut microbiome-based research trial?
It is worth noting from the outset that while there have been some excellent preclinical studies in microbiome science, there remains a lack of robust research into the more clinical aspects of the microbiota.
I pride myself on designing and developing trials that are appropriate and sufficient enough to demonstrate an effect while being as cost-effective as possible for the client.
Anyone could devise an expensive study with a vast budget, but there have been historical issues in this area with poor research design and underpowered studies – whereby the number of participants recruited is not enough to accommodate the study design and ensure robust, reproducible results.
The considerations for a good microbiome study really depend on the phase of the study; for example, a very early-stage study would unlikely employ a random allocation parallel-group design, but this is ideal later on.
To move this entire field forward, we need to ensure that we deliver consistently and properly powered studies that confidently demonstrate the efficacy of products.
What is the impact of drugs on the gut microbiota?
It has been estimated that between 75% to 80% of commonly prescribed drugs throughout the US and Europe impact the gut microbiota in some way, with many of these adversely affecting the gut microbiota.
While antidepressants are prescribed to improve an individual’s mood state, these frequently have a negative impact on the gut microbiota. Proton-pump inhibitors also negatively impact the gut microbiota.
In contrast, medications such as lithium, which has been in use since the 1960s as a mood stabilizer in patients with bipolar illness or manic depression, have actually been shown to increase the diversity of the gut microbiota.
The important message for any clinician is that at least 75% of the drugs we use will impact the gut microbiota, so it is important to consider this when prescribing these.
There is increasing research into and focus on the gut-brain axis. As a specialist in this field, what new therapies do you foresee emerging in this area?
As a psychiatrist, I think one achievable goal within the next few years is the development of ‘psychobiotics’ – probiotics that are demonstrably effective in treating milder forms of anxiety and depression.
I hope to see this development, primarily due to its major societal impact. Depression is the most common disorder in modern society, with the World Health Organization reporting that depression has the highest level of morbidity around the world.
The advent of these ‘psychobiotics’ to treat milder forms of depression would offer major global benefits, potentially seeing fewer side effects than current antidepressants.
Antidepressants continue to be very effective for many people, but patients suffering from milder forms of depression prefer not to take these for a variety of reasons, despite their depression impacting their daily lives. An effective, proven natural alternative to antidepressants could offer considerable value to this group of patients.
About Atlantia Clinical Trials
Atlantia Clinical Trials Ltd is a CRO that specializes in conducting studies in foods, beverages and supplements for companies world-wide that want to scientifically validate their functional ingredients to support an: EFSA (European Food Safety Authority) Health Claim; FDA (Food & Drug Administration) Structure Function Claim; or General Product Marketing Claim.
Atlantia works with world leading scientists (among the top cited 1% internationally, in the areas of digestive health and functional foods) at the: APC Microbiome Institute in University College Cork, Ireland; Teagasc, Moorepark, Ireland and recognized centers of excellence globally.
Atlantia runs and operates its own clinic sites and conducts all studies to ICH-GCP standard (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use – Good Clinical Practice). Its team includes physician experts in digestive health, mental health (psychological stress and cognition), cardiovascular health, sports performance, metabolic disease, bone health, immune health and healthy ageing. The clinical team also includes project managers, research nurses, nutritionists, certified sports trainers and lab researchers.
Atlantia manages all elements from protocol design, placebo manufacture, recruitment, and study execution, to sample and data analysis, statistics and report/dossier preparation to provide a service which is technically, scientifically and clinically superior.
The clinical studies cover a broad spectrum of functional food and beverage categories, such as dairy, cereal, probiotic, different protein forms, infant-specific foods, vitamins/minerals, plant or marine extracts and medical foods.
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