Is the microbiome as important for precision medicine as genetics?
The field of personalised medicine has been dominated by genetics, not surprising given our unique DNA footprints. However, studies have begun to point to the microbiome – the community of bacteria, viruses and microorganisms that inhabit the human body – as critical for functioning and metabolism, and therefore a perfect target. Could understanding the microbiome supplant genetics? Sally Turner finds out.
An increasing body of research has revealed that the microbiome has a fundamental impact on health. Metabolic, immune and neurological processes influence – and are influenced by – the vast colonies of microorganisms that inhabit the human body.
As the microbiome can be evaluated through DNA sequencing and readily modified by targeted interventions, it has been suggested that it should play a crucial role in the genetics-dominated field of personalised medicine.
The microbiome has the potential to transform preventative care and to reduce medical costs by enabling bespoke individual therapies based on finely-honed diagnostics.
“The microbiome is important to precision medicine because it is a highly personal and important facet of human health that nonetheless has universal principles and techniques that can be applied to foster a healthier system,” explains Thomas Kuntz, a researcher in the department of chemistry at the University of Chicago, and co-author of the key industry report ‘Introducing the microbiome into precision medicine’. “It hugely affects health in a multitude of ways both with and without consideration of external factors such as exercise, diet, drug interactions and so on.”
Kuntz continues to research microbiome applications, along with the report’s co-author Dr Jack Gilbert, faculty director of the Microbiome Center. Since the US Government launched the Precision Medicine Initiative in 2015, researchers have been keen to develop bespoke medical treatments based on genetic, environmental and lifestyle factors unique to the individual patient.
Kuntz and Gilbert have suggested several key areas where microbiome research could add value to the precision medicine approach. These include targeting impoverished and medically-underserved communities; enhancing the effectiveness of antibiotics, prebiotics and probiotics; and improving the metabolisation of drugs, and reducing adverse effects. At least 60 medications have been found to interact with the microbiome and a greater understanding of this area will lead to the development of more effective treatments.
In the wake of their recommendations, a study earlier this year, ‘Genetics or lifestyle: what is it that shapes our microbiome?’, from Israel’s Weizmann Institute of Science, revealed that the connection between health and the microbiome might be even greater than was first thought.
A host's genetics account for just 2% of the variation between populations.
Undoubtedly genetics plays a role in determining microbiome variation across populations and our genes may enable particular bacterial strains to thrive. However, the institute’s research had surprising results, indicating that a host's genetics account for just 2% of the variation between populations, and genes are less important in determining microbiome composition.
Instead it is diet and lifestyle that are the key influencers and our unique microbiomes grow and change with us throughout our lives. Though genetics is less of a determining factor, our unique colonies of fungi, bacteria and microorganisms are still able to interact with our genes to modify and influence many common health issues.
Going with the gut
A huge advantage microbiome science has over genetics is that it is far more mutable,” says Kuntz. “While technologies like CRISPR (a family of DNA sequences in bacteria and archaea) allow for changing of genetics, safe usage of that in humans is far off, but we already ‘edit’ our microbiomes even through changes in diet.”
Kuntz also argues that the possible dawn of a ‘post-antibiotic’ age would make microbiome interventions for diseases a dire necessity.
“Even if this does not come to pass,” he continues, “microbiome-based medicine for infection may be part of preventing overuse of antibiotics or even – as has been seen in clostridium difficile infections – something that outperforms antibiotics currently.”
A huge advantage microbiome science has over genetics is that it is far more mutable.
Understanding and implementing the correct changes in the microbiome (through diet or other means such as probiotics) is a lengthy and complicated process, but it is proving the efficacy, safety and economic viability of these interventions that is crucial to secure the necessary approvals to bring microbiome medicine to the global market.
“The latter is a current hurdle in fecal microbiota transplant (FMT) – the transplantation of fecal bacteria from a healthy person into a recipient,” says Kuntz. “FMT is possibly the easiest treatment to ensure a beneficial and large change in the microbiome, since understanding the inner workings is less important than the overall health status of the donor. This could be extremely helpful in a number of digestive diseases, which otherwise resist treatment.”
Perhaps the biggest issue facing microbiome precision medicine is to keep interest and funding high so that research can progress efficiently.
“Genomic medicine went through a significant bubble that when popped really limited the field despite its still promising applications to medicine,” explains Kuntz.
He believes the microbiome field faces a similar issue if it is considered a fad, or if a lack of immediate results is taken to indicate that results won’t eventually be forthcoming.
“So having enthusiasm and public support and knowledge – especially in traditionally underserved communities where microbiome driven disease may be highest – will be key to keeping the microbiome relevant,” he adds, “and ultimately having it implemented as standard, precision medicine.”
Research and development
Kuntz and Gilbert would like to see the standardisation and expansion of collection of microbiome samples for medicine and research. Making microbiome sampling a basic and integral part of personal health would not only increase its diagnostic potential they say, by simply reaching more people, it would also improve research if those samples could be properly identified and used for further large-scale epidemiological research.
“The price-point for taking microbiome samples is already low enough that this is possible, but collection protocols, public awareness, and reticence from healthcare providers remain as roadblocks,” says Kuntz. “A similar hurdle has faced genomic medicine for some time, but we are hopeful that microbiome medicine might overcome these issues more quickly.”
Collection protocols, public awareness, and reticence from healthcare providers remain as roadblocks.
In the longer term, the ultimate goal is to utilise this information along with further developing probiotic, prebiotic and microbiome targeting products to treat disease.
“This is further ahead due to the amount of research, especially on larger, more diverse cohorts, that must be first performed,” concludes Kuntz. “This isn’t to say some probiotic research won’t bear fruit sooner than ten to 15 years, but truly personalised therapies may take that long depending on what research breakthroughs are made and how research is handled now and in the future.”
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