Microbes and us

Over recent years the human gut microbiome – the trillions of microbes that live in our bodies – has been linked to a growing list of diseases and conditions from diabetes to autism and obesity. But although scientists have come to recognise our relationship with our companion microbes is vitally important, they are still only in the foothills of the research to discover its mechanics.

David Lynn, Professor of Systems Immunology at Flinders University’s College of Medicine and Public Health, is at the vanguard of that work, marrying his two great research interests – genomics and immunology – to build a holistic picture of this intimate relationship. It could lead to a range of better patient outcomes both at home and in some of the world’s poorest countries.

“My team is interested in microbes that infect you and cause disease; we’re also interested in vaccines against them and how they manipulate our immune systems,” Professor Lynn says. “But we're also interested in ‘good bacteria’, which may help infants respond more effectively to immunisation, or might help a cancer patient respond better to a particular drug.”

The microbiome can have a potent influence on immune development and particularly in early life. Professor Lynn’s earlier work showed that mice given antibiotics in early life, and then immunised with the same vaccines used to immunise infants, had lower antibody responses than mice that weren't treated with antibiotics, suggesting the microbiome is at fault.

Professor Lynn and his team have now taken that research into the clinic, with a large study in collaboration with the Women's and Children's Hospital in Adelaide, following more than 250 infants for the first 15 months of their life.

The researchers took stool samples at one and six weeks of life when the infants began getting their routine immunisations. Metagenomic profiling (which sequences the microbial DNA in stool samples) was used to establish the complete make-up of their nascent microbiomes.

“We then followed those infants taking blood samples at several time points – before they were immunised, a week later, a few months later, 12 months later and 15 months later,” Professor Lynn says.

About half the infants were exposed to antibiotics.

“Our results showing the impact of antibiotic exposure in infants on vaccine antibody responses will be published soon”. Professor Lynn says.

The team then correlated the results with differences in the infants’ microbiomes to identify particular bacteria that may be associated with good responses to vaccines.

Something similar could be at play with cancer treatments, with growing evidence that antibiotic treatments while on some immunotherapies – which encourage elements of the immune system to kill cancer cells – can be detrimental.

“If you take antibiotics while you're on those drugs or before them, a number of studies have shown your survival rate could be significantly impaired compared to someone who hasn't been on antibiotics,” says Professor Lynn.

The endgame to this research could be therapeutic techniques to enhance those bacteria which are helping our immune systems respond to infection, vaccines or cancer treatment.

Professor Lynn has his eye on two different settings for this.

“One is the developed world,” he says. “In Australia, we obviously have low infectious disease burden and so if antibody responses are lower in some infants, the consequences in terms of mortality are going to be much more limited – but still you would like to have protection lasting in all infants as much as possible.

“We're planning a future clinical trial to give infants who have had antibiotics in those critical first weeks of life a course of probiotics before their first immunisations. Clearly these probiotics wouldn’t be picked off a health food shop’s shelves and would themselves need to be tested in a randomised control trial, but that’s the next step”

Professor Lynn sees much broader implications in global health.

“Many of the vaccines we use can be up to 50% less effective in many developing countries,” he says. “Efficacy in Europe, Australia and America of the rotavirus vaccine, for example, is more than 95%, whereas in Malawi it can be less than 50%.”

There are multiple causative factors at play but Professor Lynn suspects one is the gut microbiome and the much higher use of antibiotics in low and middleincome countries.

“Malnutrition can also have profound effects on the gut microbiota, as can repeated intestinal infections, which are common in many of these countries,” says Professor Lynn.

Suitable interventions in these societies would need to be cheap and able to be made in very large number to be able to be implemented on a population scale.

“If we could develop an intervention that enhanced the efficacy of even one vaccine by five or 10%, you'd be talking about a big impact on disease mortality and morbidity in some of these settings. That's one of the goals that we're working toward.”