Analysis: researchers are taking effective microbes from the gut and growing them in a laboratory to use with sick patients and animals

Almost as soon as antibiotics were first used in the 1940s, resistant bacteria began to emerge. 80 years on, the global problem of antibiotic resistance is now one of the grand challenges facing society. We need new effective antibiotics - and we need them immediately. 

But like so many of nature’s bounties, we have squandered antibiotics to the point where we are in danger of returning to a pre-antibiotic era. Much of this waste has occurred in farming, where antibiotics have been used in huge amounts as growth promoters.  Almost everyone alive on earth today has grown up with antibiotics so it is difficult to imagine a world where routine surgeries can lead to fatal infections, where only a fraction of babies make it into adulthood and where epidemics can strike at a moments’ notice. 

From the RTÉ Brainstorm radio show, Ella McSweeney is joined by James Dooley from Ulster University and Sarah Delaney from Maynooth University, to look at the increase in antibiotic resistance

At the same time, it is only in recent decades that we have come to appreciate that humans are colonised by vast numbers of bacteria that are essential for our health, our "microbiomes". Think about the fact that mothers milk contains hundreds of sugars which the baby cannot digest, but which are easily consumed by bacteria within the baby’s gut. Why have we evolved to do this? Obviously, evolution has determined the importance of not only feeding baby, but also promoting the growth of a diverse and optimal microbiome.

So, we have a dilemma. We need more effective antibiotics, capable of efficiently killing bacteria in the human body and we also have a microbiome that we need to protect and nurture. 

At APC Microbiome Ireland, we have been tackling this problem for a number of years. Our approach is based on the fact that the microbiome is one of the most competitive microbial environments on the planet, with trillions of bacteria competing for limited resources. In the process, they develop strategies for outcompeting and even killing their neighbours, but in a very precise way that does not cause collateral damage to the rest of the microbiome. We have been trying to exploit these strategies to develop alternative antimicrobials that can kill targeted bacteria (the bad guys) while protecting the microbiome (the good guys).

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From RTÉ Radio 1's This Week, Justin McCarthy on the effect of the overuse of antibiotics on our collective ability to fight infection

These strategies can be as crude as conducting a faecal microbiome transplant, which does exactly what is says on the tin! A donor contributes a faecal sample, which is then introduced into the gut of a sick individual.  This has proved to be incredibly effective in the treatment of Clostridium difficile associated diarrhoea, an often fatal infection acquired in hospital which cannot be effectively treated with antibiotics. Recovery rates of close to 100% have been recorded for this somewhat yucky treatment option.

But what if we could isolate the most effective microbes from the gut and grow them up in a laboratory before reintroducing them to sick patients or animals? We have done this at APC Microbiome Ireland and we have shown in a series of published studies that individual bacteria, or mixtures of a few strains, can match antibiotics in treating salmonellosis in pigs, and can even treat full blown mastitis in milking cows. In some instances, we can even identify and isolate the bacterial weapons, the compounds they use to kill one another, and use those as purified preparations. Importantly, none of these treatments damage the microbiome.

Another research avenue is to use bacterial viruses to kill bacteria. Just as humans have viruses which infect us, bacteria can also fall prey to viral killers. These bacterial viruses are completely safe to humans, but kill bacteria in a very precise manner. We can isolate these viruses, grow them into high numbers, and then give them to a patient with an infection. Yes, in a somewhat ironic twist, we are giving patients viruses to cure them from an infection!

What we have shown - and continue to show - is that we can mine the microbiome for precise bacterial weapons that offer hope that we can prevent the return to a pre-antibiotic era, while still protecting our valuable microbiomes. In the near future, I confidently expect that people with serious and life threatening infections involving bad microbes will be treated with good microbes, which have been carefully selected to treat the disease and not damage the microbiome.

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RTÉ Brainstorm video on how antibiotic resistant infections could kill more people than cancer by 2050 if our overuse of antibiotics continues

As we work to develop these smart antimicrobials, it is important that we look after our dwindling stocks of effective antibiotics. We must find alternatives for animal husbandry, and make sure that patients don’t demand, and that doctors don’t oversubscribe, antibiotics. We should not use antibiotics for mild infections, or viral infections like colds and flu where they are completely ineffective. 

When you take an antibiotic, your microbiome may take a hit, but it will recover in the majority of cases. Microbes are the most evolved biological entities on the earth and they are resilient enough to cope with infrequent exposure to antibiotics. Therefore, if your doctor prescribes an antibiotic, you should always take it, and make sure you complete the course. Treating the immediate infection always takes precedence over protecting your microbiome, but hopefully in the future we will be able to do both.  

Professor Colin Hill will be discussing the next generation of antibiotics at UCC's Relevance To You series in Cork city-centre on Tuesday October 8th at 5.30pm. Admission is free but advance registering is essential.  

The views expressed here are those of the author and do not represent or reflect the views of RTÉ