Unlocking the gut microbiome’s secrets

Every decade or so science finds a new mountain to climb, and the gut microbiome is our latest Mount Kilimanjaro. But ascending the slopes will require a significant step change in data collection and analysis.

Unravelling the human genome has been widely credited as one of the biggest achievements in medical science – unravelling the gut microbiome, though, could be even more complicated.

While DNA is based on four nucleotide bases and is, largely, static, each of our guts is inhabited by a unique, shifting combination of trillions of bacteria.

Tracy Warren, CEO and co-founder of Astarte Medical, says: “You are born with your genome and it is something that you are, with some very rare exceptions, stuck with. The microbiome on the other hand is dynamic and it can be influenced. This is the new frontier.

“We should be cautious about how rapidly we are going to see true microbial therapies that affect large patient populations”

“When you look at all the influences, such as diet and environmental factors, I think it’s going to be a lot more difficult to unravel than the human genome. But the promise of being able to use it in a way that is therapeutically effective is getting people excited.”

Flurry of activity

It’s this potential, combined with a leap forward in technical capabilities, that has led to a flurry of research linking gut bacteria to everything from inflammatory bowel disease to autism and Alzheimer’s.

Part of the current interest has been driven by advances in technology, with techniques such as 16S ribosomal RNA and whole genome sequencing becoming, if not cost effective, then certainly more “cost favourable”.

But despite everything we have learned and terms such as “the gut-brain axis” moving into common parlance, Warren warns that we are only at the very beginning of the journey.

“Every decade or two in science, we find a new mountain to climb. This is our current Kilimanjaro, but I think we should be cautious about how rapidly we are going to see true microbial therapies that affect large patient populations,” she says.

“Through sequencing, we are starting to understand the community members, but, just like with the human genome, you need the reference base. At the moment, we’re building that base by scanning the communities and matching up the different bacteria or viruses. But only a fraction of what we know to exist has been indexed.”

All this means that when it comes to influencing the gut microbiome for therapeutic reasons, research is in its infancy, Warren says.

“In pharma trials you have safety studies, dosing schedules, screening for inclusion and exclusion criteria – but we don’t have any of that yet. Two people with similar demographics and health could take the same probiotic for the same amount of time, and one could feel better and the other not.

“At the moment, we don’t understand why. We don’t have enough of an indication of how to recruit the best patient or how long to treat them for. We just don’t understand all the mechanisms yet.”

Data integrity

Coherent data standards are another challenge, explains Warren, whose company has built a gut health monitoring system that helps doctors plan antibiotic and feeding strategies in premature babies while building a real-time microbiome dataset.

“A lot of the microbiome analysis I’ve seen presented has lacked standardisation. Sample prep in one lab could be very different to that in another, and 16S can’t be directly compared to whole genome sequencing, for example.

“We don’t have a standard way to generate data, which means that even if everyone did share their outputs, you couldn’t use that information to drive clinical outcomes. There’s just too much variability in how the samples are generated.”

Tracey Warren

There’s also a surge in Warren calls the “silver bullet” approach, driven by consumer interest, which includes companies offering microbiome screening services on a par with home DNA testing.

“It’s nice to know, but I’m not sure it’s scientifically as rigorous as it should be if someone is going to use that information to change course,” says Warren.

“On the other side of things, and this is certainly our campus, people are developing technologies to better drive the adoption of microbiome, by accelerating sampling and understanding.”

As technology moves forward and the field matures, it’s these evidence-based tools that Warren believes will unlock the huge potential.

“We need technology to catch up with the complexity of our biology. But if you were a data person, this is exactly where you would want to be working.”

Prevention vs. cure

While it is early days, there’s no denying that the microbiome is an exciting area of untapped potential.

Researchers might not know exactly how it works yet, but they can tell us that it’s connected to growth and development, as well as cognitive outcomes.

“It’s been linked to autism and there have been studies around Alzheimer’s and other late-in-life cognitive conditions.

“We certainly believe it has a huge influence on early neuro developmental conditions and developmental delays in children, as well as growth, weight and obesity,” explains Warren, adding that people often forget the gut is the largest organ of immunity.

“The potential not just for therapeutic intervention, but for using proper nutrition to prevent disease, is huge.”