Bad breath isn’t just a question of having eaten too much garlic. The cause can also be genetic. The bodies of a small group of people seem incapable of converting methanethiol into an odourless gas. And the result is breath that smells like rotting cabbage. Researchers in Nijmegen published an article on this yesterday in Nature Genetics.

The story began about fifteen years ago in the lab for microbiology, where the microbiologists Arjan Pol and Huub Op den Camp were studying bacteria. One bacterium appeared to be very useful in purifying sewage water and gases that smelled like sulphur. The tiny organism destroyed the stench of methanethiol, a sulphurous gas with the penetrating smell of smelly feet and rotting cabbage. How? The bacterium has a protein that breaks down methanethiol and converts it into odourless gases.

The smell is comparable to the sulphurous odour in a kitchen where cauliflower is cooking – only much worse

On the opposite side of the Heyendaalseweg, Ron Wevers of Radboud university medical center received two samples of urine, one from a patient in Portugal and one from a Dutch patient. Wevers, a clinical chemist and a specialist in hereditary metabolic diseases, is often consulted by foreign colleagues. The two patients in question had the same problem: their breath smelled so foul that their social lives suffered. The smell is comparable to the sulphurous odour in a kitchen where cauliflower is cooking – only much worse.

Urine
Wevers and his colleague Udo Engelke brought the patients’ urine samples to the Goudsmit lab behind the Huygens building. This building houses NMR equipment (NMR is the abbreviation for Nuclear Magnetic Resonance), which can immediately chart scattered substances in the body. Wevers and Engelke discovered sulphur compounds in the urine that didn’t belong there. They assumed that the patients had a metabolic disease in which a protein – or more accurately, an enzyme, which is supposed to streamline the body’s metabolism – refused to do its job. Wevers: “If an enzyme fails to function and a substance can’t be broken down, that substance accumulates in the body.” The accumulated sulphur compounds in the bodies of these patients caused the smell.

Is there also a human variant of the enzyme that you found?

Wevers contacted Huub Op den Camp on the opposite side of the Heyendaalseweg. “Is there also a human variant of the enzyme that you found in the bacterium that breaks down methanethiol?” he asked. Op den Camp and Arjan Pol answered affirmatively. They had also found the gene in the bacterium that formed the base of the enzyme. And that gene had quite a resemblance to one of the human genes, namely SELENBP1. Indeed, this gene showed errors in the patients with the bad breath.

Mouse
Wevers and Engelke decided to do an experiment in which they bred a mouse with an error in the gene in question. Then microbiologist Arjan Pol showed that the mouse was also missing this particular enzyme. A German family with the same genetic error also became involved. The researchers in Nijmegen also found methanethiol in the breath of these patients, which had been transported to the Netherlands in five-litre bags.

This was enough proof to claim that the abnormal breath of the patients has a genetic cause. Because of an error in the SELENBP1 gene, they lack the related enzyme. And this was enough material for yesterday’s publication in Nature Genetics.

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On a diet

The specialist in hereditary metabolic diseases Ron Wevers has received reactions of relief from around the world. Finally, recognition for my problem, patients write. But he has no pill to offer them. “The only thing patients can do is to adjust their diet so that fewer sulphur compounds are released in the body. That’s a question of trial and error,” Wevers said. He recently had contact with a Dutch patient who said that her breath was better. “She adjusted her diet and now has fewer side effects.
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