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Noninvasive probe monitors health of friendly gut bacteria

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Picture: Bacteria in a petri dish.
Photography courtesy of Nicola Fawcett/Wikimedia
  • The community of bacteria that live in the gut, known as the gut microbiota, play a pivotal role in illnesses such as cancer, diabetes, obesity, depression, and inflammatory bowel disease.
  • The aim of probiotic and prebiotic supplements is to restore a healthy balance to the microbiome, but their effects are difficult to study.
  • Researchers have developed a probe that can measure the activity level of an enzyme produced by bacteria that is key to their health-promoting effects.
  • A female volunteer swallowed two capsules containing the probe, which monitored the microbial health of the entire length of her digestive system.

The gut microbiota is the community of bacteria, fungi, viruses, and other microorganisms that make their home in the human digestive tract.

In recent years, scientists have discovered an astonishing range of interactions between the gut microbiota and human health. These include effects on mood, eating disorders, and immunity.

A recent study reported by Medical News Today also found associations between particular bacterial species and the risk of developing diabetes, heart disease, and obesity.

Bacteria in the gut produce an enzyme called bile salt hydrolase (BSH) that may be essential to many of their beneficial effects.

For example, scientists have linked high BSH activity to decreased inflammation, reduced blood cholesterol levels, and protection against colon cancer and urinary tract infections.

Scientists still know surprisingly little about the complex interactions between the diet, the gut microbiota, and BSH activity.

Recently, an international team of researchers set out to study the effects of prebiotics — insoluble dietary fibers that promote the growth of “friendly” bacteria — on the activity of BSH.

They also wanted to develop a clinical test for assessing the enzyme’s activity in people with inflammatory bowel disease.

Microbiologists currently use indirect techniques to gauge the enzyme’s activity, for example by analyzing fecal samples or culturing bacteria in the lab. But these efforts do not reflect the diversity of bacteria and the chemical complexity of their natural environment, which varies according to where they live in the gastrointestinal tract.

So the team, led by researchers at the University of Missouri, in Columbia, and the Swiss Federal Institute of Technology, in Lausanne, developed a noninvasive chemical probe that measures the activity of BSH along the entire length of the gut.

They have published their findings in the journal Science Advances.

The probe relies on a natural compound called luciferin, which emits light in the presence of oxygen, and the enzyme luciferase, which originates in fireflies.

To create the probe, the researchers chemically “caged” the luciferin by combining it with a small molecule that shields it from luciferase.

They designed the cage so that only the enzyme BSH can liberate the luciferin molecule from the probe. As a result, the amount of light that a fecal sample produces in the presence of luciferase is proportional to the amount of BSH along the length of the gut.

The scientists first tested their probe on samples in the lab. A female volunteer then swallowed two capsules containing the probe, and these successfully measured the enzyme’s activity as they passed through her gut.

“Until now, we have not had any ways to noninvasively monitor activity in the intact gastrointestinal tract, given the unique chemical environment, variable distribution, and highly dynamic nature of the gut microbiota,” says Dr. Elena Goun, an associate professor in the university’s department of chemistry and the senior author of the paper.

In another experiment, in mice, the team used the probe to test the ability of different types of prebiotic supplement — inulin and fructo-oligosaccharides (FOSs) — to boost the production of BSH.

They discovered that inulin produced no significant change in BSH levels in the animals’ guts, but FOSs doubled these levels.

Dr. Goun explains the significance of her team’s results:

“Prebiotics are often used in combination with probiotics to enhance their functions in the body. […] We show, for the first time, that certain types of prebiotics alone are capable of increasing [BSH] activity of the gut microbiota, which, among other health benefits, has been shown to decrease inflammation, reduce blood cholesterol levels, and protect against colon cancer and urinary tract infections.”

The senior researcher adds that there could also be important cost benefits, as prebiotics are less expensive to produce and store than probiotics.

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