Probiotic bacteria can damage the gut

Probiotics are living bacteria taken to promote digestive health, but a study on mice suggests they evolve in the gut and may become harmful over time.

Researchers from Washington University School of Medicine studied a strain of E. coli bacteria sold as an anti-diarrhoeal probiotic in Europe. After living in mice’s intestines for a few weeks, the bacteria gained the ability to damage the protective coating on the intestine, which has been linked to irritable bowel syndrome.

For the study, they used mice with four kinds of gut microbiomes: one with no pre-existing bacteria; one with a limited set of bacteria, characteristic of an unhealthy gut; a normal microbiome; and a normal microbiome after antibiotic treatment. Each mouse was given the probiotic E. coli Nissle (EcN) and fed a different diet consisting of either mouse chow, which mimics the natural mouse diet; high-fat, low-fibre diet similar to a Western diet; or a Western diet with fibre. After five weeks, the researchers took the bacteria from the mice’s guts and analysed the microbes’ DNA.

The mice’s diets and the make-up of their gut bacterial community influenced how much the probiotic evolved and in what ways.

“In-transit EcN accumulates genetic mutations that modulate carbohydrate utilisation, stress response and adhesion to gain competitive fitness, while previous exposure to antibiotics reveals an acquisition of resistance,” the study stated.

Graduate student and first author Aura Ferreiro said: “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.

“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 findings suggest that a probiotic that provides relief to one person could evolve to become ineffective or even harmful in another.

“If we’re going to use living things as medicines, we need to recognise 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,” said Gautam Dantas, senior author and Professor of Pathology and Immunology, Molecular Microbiology and Biomedical Engineering. “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.”

Probiotics are being developed as treatments for serious medical conditions such as inflammatory bowel disease and phenylketonuria (PKU), a metabolic disorder that causes neurological damage. The study insights could be used to not only better understand the safety of probiotics, but even potentially personalise probiotic-based medicine in future.

The research was published in Cell Host and Microbe.

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