Probiotics, delivered in pills or foods like yoghurt, have long been held up as a force for good in the body, but there may be a bit of a gray area between good and bad bacteria. A mouse study conducted at Washington University in St. Louis has now found that probiotics can evolve in the gut, becoming less effective or even turning against the host.
A growing body of research is revealing just how big a role the microbes in our gut play in our overall health, influencing our risk of cancer, diabetes and even depression. Probiotics are often recommended as a way to skew the balance back in our favor, and recent research has found new ways they could help, including "curing" certain food allergies and boosting the effectiveness of antibiotics.
But it's not all rosy for probiotics. Some people just don't have the guts for the good bacteria to take hold, or in the worst case scenario, they can grow out of control in the intestine and cause bloating and brain fogginess.
This delicate balance between good and bad bacteria is already an extremely complicated system, but it gets even more so when you remember that these creatures adapt over time, changing their abilities and effects in the body. The new study set out to quantify that.
"If we're going to use living things as medicines, we need to recognize that they're going to adapt, and that means that what you put in your body is not necessarily what's going to be there even a couple hours later," says Gautam Dantas, senior author of the study. "There is no microbe out there that is immune to evolution. This isn't a reason not to develop probiotic-based therapies, but it is a reason to make sure we understand how they change and under what conditions."
The researchers investigated how a probiotic known as E. coli Nissle (EcN) adapts to different conditions in the guts of mice. Different groups of mice started with different kinds of gut microbiomes and were fed different diets, and after five weeks the scientists examined the DNA of the probiotics in the gut to see how they'd changed under these various combinations.
The mice were given one of four types of gut microbiomes. A normal, healthy one with diverse bacteria; a normal biome that had been treated with antibiotics, killing off some species; a clean slate with no pre-existing bacteria; and a microbiome with limited diversity, mimicking an unhealthy gut.
Along with doses of the probiotic, these mice were then fed three different kinds of diets. One group ate regular mouse chow in the form of a high-fiber food designed to mimic a natural diet for the animals. Another was fed pellets high in fat and sugar and low in fiber, reminiscent of modern Western human diets. And the last group got the Western-style pellets with fiber supplements.
At the end of the five weeks, the DNA of the microbes was analyzed. The team found that, while there wasn't much evolution happening in the healthy mice, the probiotics in animals with less healthy microbiomes and diets had adapted quite a bit. On high-sugar diets, the probiotics evolved to feed on more types of sugars, and those that encountered antibiotics quickly developed resistance to them. Others even developed the ability to eat the intestinal lining, effectively turning against the host.
"In a healthy, high-diversity background we didn't capture a lot of adaptation, maybe because this is the background that Nissle is used to," says Aura Ferreiro, first author of the study. "But you have to remember that quite often we wouldn't be using probiotics in people with a healthy microbiome. We'd be using them in sick people who have a low-diversity, unhealthy microbiome. And that seems to be the condition when the probiotic is most likely to evolve."
The team says that understanding how probiotics evolve in the gut might lead to more personalized treatments based on an individual's microbiome, which could help treat a range of illnesses.
"Evolution is a given," says Dantas. "Everything is going to evolve. We don't need to be scared of it. We can use the principles of evolution to design a better therapeutic that is carefully tailored to the people who need it. This is an opportunity, not a problem."
The researchers then used the findings to design a potential probiotic treatment for a metabolic disorder known as phenylketonuria (PKU). People with this disorder are unable to metabolize phenylalanine, which can cause brain damage at high levels.
To experiment, the team gave EcN a gene that allowed the bacteria to break down phenylalanine. This was then given to mice that had been genetically engineered to not be able to process it, and sure enough, within a day phenylalanine levels had been cut in half in some mice.
The research was published in the journal Cell Host and Microbe, and the team describes the work in the video below.
Source: Washington University in St. Louis
