GastroIntestinal / Gastroenterology

Could probiotics evolve in the gut and cause harm?

New research in the journal Cell Host & Microbiome suggests that under certain conditions, probiotics can be harmful due to their ability to evolve once in the gut.
close up of woman's hands eating yogurt
For some people, probiotics may do more harm than good.

Probiotics are live microorganisms that play a key role in intestinal function.

They achieve this by helping create a healthful bacterial balance within the host’s gut.

Our bodies already contain around 1.5 kilograms of probiotic bacteria.

However, these microorganisms also occur in fermented foods such as yogurt, kimchi, miso, and some types of cheese.

Recently, much hype has surrounded the presumed health benefits of probiotics. Some of these benefits include aiding digestion, lowering blood pressure, improving cognitive function, and alleviating irritable bowel syndrome.

However, are probiotics an unmitigated good? As more and more people begin to consume them, emerging research cautions that probiotics may not work in the same way for everyone, and that some strains of probiotics may not even be safe.

Now, a new study offers a critical look at the therapeutic benefits of probiotics. Scientists from the Washington University School of Medicine in St. Louis, MO, have investigated the behavior of a strain of Escherichia coli in the intestines of mice.

Gautam Dantas, Ph.D. — a professor of pathology and immunology, molecular microbiology, and biomedical engineering at the university — led the new research.

How probiotics change inside the gut

Prof. Dantas and colleagues chose the probiotic E. coli Nissle 1917 because researchers believe it has anti-diarrheal properties.

They wanted to see how the bacterium behaves in mice’s digestive tracts, so they used rodents that had four different kinds of gut microbiome:

  • a microbiome that had no pre-existing bacteria
  • a microbiome with a limited, unbalanced range of bacteria, which often corresponds to an unhealthy microbiome
  • a normal gut microbiome
  • a normal gut microbiome treated with antibiotics

Prof. Dantas and colleagues fed the mice the probiotic and different diets. They designed one diet to mimic a normal one rich in fiber, another one to mimic a Western diet high in fat and sugars and low in fiber, and one to mimic the Western diet but with more fiber.

After 5 weeks, the researchers analyzed the rodents’ microbiomes. They found that the bacterium had changed to develop new characteristics.

Under certain conditions, the bacterium harmed the host, eating the protective layer that lines the intestine. Previous research has linked damage in this protective layer with irritable bowel syndrome.

“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,” reports first study author Aura Ferreiro.

“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.”

‘Using living things as medicine’ needs care

Experts are now developing probiotics into treatments for conditions such as inflammatory bowel disease, phenylketonuria (PKU), and necrotizing enterocolitis.

However, the results of the new study suggest that a probiotic that is beneficial to one person might adapt and become harmful in another.

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.”

Prof. Gautam Dantas

“There is no microbe out there that is immune to evolution,” continues Prof. Dantas. “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.”

To gain such an understanding, the researchers created a probiotic treatment for PKU, which is a metabolic condition that can cause brain damage.

In PKU, the body cannot degrade a substance called phenylalanine. Excessive levels of this substance eventually cause neurological damage. However, Prof. Dantas and team genetically modified the Nissle E. coli strain in a way that enabled it to break down phenylalanine and excrete it in the urine.

Using a mouse model of PKU, the researchers administered the genetically modified E. coli strain to the rodents. The treatment halved the levels of phenylalanine by the next day.

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