THE MICROBES THAT ARE KEY
TO OUR HEALTH

Professor Geraint Rogers

Institutes & Centres

Flinders Health and Medical Research Institute

Article published on 13 November 2020

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The microbes that are the sum of us.

What happens when an extremely ancient biological system comes face-to-face with a 21st century lifestyle? The results can be seen all around us, says Professor Geraint Rogers, in the diseases of affluence – diabetes, cancers and cardiovascular problems – all signs of our microbiome scrambling to keep up with the dramatic changes we have brought upon it.

The microbiome – the trillions of microbial communities that inhabit our bodies – has been with us always, but it is only relatively recently that we have discovered the close links between healthy microbiota and a healthy human.

To Professor Rogers the connection is unsurprising, so close is our relationship with the microbes that live on the skin and throughout our digestive tract.

“It's really symbiosis in a true sense,” Professor Rogers says. “These organisms have been picked up from the environment, live in a nice, warm, protected world of, for example, the gut. They have functionality, which is shared with our own genetic material, and this means that over time, if we have mutations in our own genes that cause us to lose the ability to make certain vitamins, for example, we can get those from the microbes in our gut.”

As those relationships develop, they create ties that bind us together – we need them and they need us.

“Those organisms become increasingly specialised to living on, or in, us and lose the ability to live outside of it,” says Professor Rogers, “so our fates become completely intertwined and rather than being separate entities, we are really one sort of metaorganism.”

For millennia this system operated without anyone noticing.

“Fast forward to the 17th and 18th centuries and the emergence of microbiology at a time when what killed people overwhelmingly was infectious diseases,” says Professor Rogers. “So we needed to devise a system to identify individual pathogens amongst all of this noise.”

And that’s what we did, cultivating colonies of bacteria in agar plates, studying them and learning how to eradicate or at least control them.

But the whole relationship between us and our microbiomes began to change in the second half of the 20th century.

“We got clean water, we got antibiotics, we got vaccines and for the first time in human history, we took control of infectious diseases to a large extent,” says Professor Rogers.

At the same time, agriculture’s Green Revolution meant we could produce as much food as we wanted. All of a sudden we were no longer dying from infections, nor starving to death. But with those out of the picture other ailments took centre stage – chronic heart disease, vascular disease and cancers associated with obesity and type 2 diabetes and associated conditions.

While it became increasingly clear that the effect of exposures to many of these hazards were mediated by the microbiome, we were ill-equipped to explain how. Our historic systems were good at identifying individual microbes but were not up to understanding the complex interaction of whole ecological communities with each other and the behaviour of the system.

“If you want to understand from the productivity of a forest, you need to understand the nitrogen cycles, you need to understand the sun, water systems, and so on. You can't understand the sum of the parts by looking at any one aspect in isolation. And that’s the same with us and our microbiomes,” says Professor Rogers.

Enter DNA sequencing and the realisation that the same technology that was used to sequence the human genome could sequence the genes in the microbiota. We could now identify all of the organisms in a microbial system, such as a stool sample.

Professor Geraint Rogers

“And then you could see what the characteristics and relative abundances of those organisms were and you could correlate that information with exposures or clinical outcomes, such as the correlation between people’s diets and the severity of vascular disease,” says Professor Rogers.

And the correlations that are still emerging are alarming, as our ancient biological systems, that served us so well for millennia, try to keep up with dramatic changes in our lifestyles.

For thousands of years, for example, we have eaten predominantly plant fibres and proteins. When the microbes in our gut ferment these, they produce metabolites that deliver an array of beneficial effects, from suppressing inflammation, to anti-inflammatory compounds, to protecting us against cancer.

“Over thousands of years, we've selected those bugs to do those functions,” says Professor Rogers.

“If you then go to a 20th century diet, which is saturated in fats and refined sugars which changes your gut microbiome, you lose the protective functions. And what’s more, these microbes produce metabolites that are pro-inflammatory and increase the risk of the development of things like obesity and type 2 diabetes.

“So it's a double hit, we've lost the much needed protection of an organ of our body and we've also inherited something that doesn't function properly.”

Combined with that, the modern over-use of antibiotics creates further dangers by wiping out beneficial microbes, and providing opportunities for pathogens to invade the niches that they leave behind.

The answer, says Professor Rogers, is as simple as it is elusive.

“We want to live in a very narrow band in the middle. Because if you go to developing countries, obviously there are horrific levels of infectious diseases and child mortality. But if you track the other way too far, then you go into chronic inflammatory diseases and immune mediated problems.

“It's trying to find the line that sits between those two and we've sort of lurched from one to the other.”

There is no more important time for creating a healthy microbiota than the period right at the beginning of life. From our first breath outside the womb we – and our immune systems – are on their own and we start to calibrate our immune systems to compile this list of friends and enemies – good microbes in our microbiome and pathogens which could kill us. Our metabolic systems also learn to account for the metabolites that they produce. And those calibrations stay with us for life.

“There's a plasticity in the first months of life, which we don't get back,” says Professor Rogers. His research has uncovered the problems that can flow from giving children antibiotics around birth that wipe out microbes and force a change in how the immune systems are set up, which is sort of tattooed into them and is there forever.

"We know these kids respond differently or less well to vaccinations. They're more likely to get inflammatory conditions like asthma, allergies, and auto-immune diseases. So you've got this sort of hyper immune response, because you haven't been exposed to lots of bugs, which have allowed you to calibrate yourself properly.”