It is often said that DNA is what makes us who we are. In reality, only 10 per cent of about 37 trillion different cells in the human body are human cells – the rest belong to microbes from thousands of different species that co-exist within each of us.
Various parts of the body, such as the surface of the skin and lungs, have distinct microbial inhabitants, but it is in the gut which they mostly inhabit – and this has attracted much attention in biomedical research. These microbes include both beneficial and disease-causing bacteria. In a healthy individual, these “bugs” collaborate with us to aid digestion, produce vitamins and protect from the overgrowth of virulent pathogens. However, they are also associated with many disease processes, ranging from inflammation to cancer.
As we age, other factors in our environment – like our diet, stress, exercise and use of medications – alter and influence our microbiomes. In the last decade, research technologies have evolved and so too has the direction of research into the microbiome, unveiling its potential in human health.
In a healthy individual, these “bugs” collaborate with the body to aid digestion, produce vitamins and protect from the overgrowth of virulent pathogens.
Dr Sinead Corr, an assistant professor in microbiology in Trinity and the leader of College’s microbiome and mucosal immunity research group, says that advancements in microbiome research means that “we now know that the microbiome not only influences digestion, but also metabolic, hormonal and neurological processes”. Scientists also now understand that the composition and the function of the microbiome can be manipulated to benefit health and as a result, it has been an attractive therapeutic target, although not without its limitations.
Faecal Microbiota Transplantation (FMT) or “poop transplant”, was one of the first therapies that involved the usage of the gut microbiome. Corr explains that FMT works by “introducing a healthy faecal microbiome into patients”. This therapy has been successful in treating patients with the severe diarrhoeal infection called clostridioides difficile (C.diff), which can occur following antibiotic therapy. FMT is also the focus of therapeutic research for inflammatory bowel disease treatment.
Dr Natalia Muñoz Wolf, a research assistant professor in translational and respiratory immunology at Trinity, who is based in Tallaght Hospital, is investigating the impact of an imbalanced microbiota on Chronic Obstructive Pulmonary Disease (COPD), a respiratory illness.
In an email statement to The University Times, Muñoz Wolf describes her research, for which she received an Emerging Investigator Award from the Health Research Board in 2019: “The goal of my lab is to characterise the gut microbiome in COPD patients to understand if gut dysbiosis is linked to the more severe forms of COPD. This is the first step towards the development of microbiome-based therapies for management of COPD.”
The composition and the function of the microbiome can be manipulated to benefit health.
Referring to a recent US study from the University of Massachusetts, Muñoz Wolf said that the lung microbiome of patients with Acute Respiratory Distress Syndrome (ARDS) is abundant with gut bacteria. This, she says, has significant implications for coronavirus: “These are very important findings in light of the recent coronavirus pandemic where ARDS is prevalent in severe cases and raises the question as to whether modulation of the gut microbiome could be of benefit for ICU patients during the COVID-19 pandemic.”
Dr Stephen Lalor, assistant professor of pathology at UCD, adds that if the SARS-CoV-2 virus – which causes the illness we now know as coronavirus – was to behave like the influenza virus, there might be a potential for dietary or probiotic interventions. Furthermore, there is research ongoing about the microbiome in coronavirus patients.
“There have been, I think, two small studies that have really looked at the microbiome in COVID-19 patients”, he says. The findings of this research suggests that “there is potential for dietary or probiotic interventions”.
Other researchers are turning to metabolomics techniques, which involve chemical analysis of biomolecules produced by microbes. This allows researchers to essentially eavesdrop on how microbes are communicating with each other and with their host’s cells.
Speaking to The University Times, Dr Kenneth Mok, an associate professor of biochemistry in Trinity, explained the relationship between the gut microbiome and the brain: “If we know that there are certain metabolites that will foster a more healthy gut microbiota, then we can have the permeability of the blood-brain barrier adjusted.” This has implications for Alzheimer’s, for example, where the beta-amyloid protein plays a role and can cross the blood-brain barrier with harmful microbiota. Parkinson’s disease is another disorder subject to this line of research in being the forerunning neurodegenerative diseases that could be affected by the gut-brain relationship.
Another focus of microbiome research is the use of bacteriophages – viruses that infect bacteria. Corr says that their therapeutic potential lies in their capacity to select and destroy particular disease-causing bacteria while leaving beneficial bacteria unharmed: “Unlike probiotics which are non-specific, bacteriophages can target specific bacteria and harmful members of the microbiome.”
In Ireland, generally, there aren’t enough bioinformaticians with sufficient expertise to analyse all this data.
In the face of this exciting new research, microbiome researchers have several challenges ahead. The first is how to determine whether changes to the microbiome are a causative factor of disease processes – or merely a side effect.
“Research initially focused on associating changes in the microbiome or specific microbiome profiles with a particular health status”, Corr explains. “We need to be somewhat cautious in our interpretation of these findings, as many studies show associations rather than cause and effect.”
Lalor emphasises that the huge amount of data generated from these studies present a challenge to scientists: “In Ireland generally there aren’t enough bioinformaticians with sufficient expertise to analyse all this data, so we can send away samples to be analysed and sequenced.” However, Lalor adds that “there’s quite a bit of an individuality and a lack of consistency really in the data analysis”. To solve this problem, companies like Microsoft are investing in artificial intelligence to analyse these microbiome datasets in collaboration with pharmaceutical companies, to weed out important data sequences that show associations and causal effects for some of these diseases.
As researchers fight through the challenges, it is clear that the microbiome will bring very promising solutions to many diseases. For many, collaboration and a strong “bench-to-bedside” approach holds the key to driving research in this area forward. Backed by advancements in research technology, this diverse area of expertise continues to advance our understanding of an incredible array of diseases, and brings us ever closer to treating them.
