The origins of the study go back 25 years, when a Dutch woman with smelly, never-ending bad breath visited Winkel's dental practice. The woman said her brother had the same halitosis problem.
Winkel obtained body fluid samples from the patient and sent them to Radboud University Nijmegen Medical Center for analysis. Albert Tangerman, Ron Wevers, and their colleagues found abnormally high concentrations of 4 sulfur-containing metabolites in the samples.
Two of the four are the volatile compounds dimethyl sulfide and methanethiol, which can originate from food and are produced in large amounts in the intestines. It is little wonder that the patient releasing these metabolites had bad breath.
"The odor of methanethiol is described as 'a distinctive putrid smell' and is also part of the smell of human flatus and of French cheese," co-author Huub Op den Camp of Radboud told Seeker. "The smell of dimethylsulfide resembles that released when cooking cauliflower or cabbage."
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Op den Camp specializes in the ecology and physiology of microorganisms. He, along with colleagues, next investigated bacteria that break down methanethiol. They discovered a protein, methanethiol oxidase, in the bacterium Hyphomicrobium that does so. The bacterium feeds on contamination in sewage, including sulfur compounds like methanethiol.
"Since we knew the genome of this bacterium, we were able to identify the gene" that encodes the methanethiol oxidase, Op den Camp told Seeker. "The next step was the exciting discovery that humans have an identical gene in their genome."
Op den Camp, lead author Arjan Pol, and their team achieved this latest feat after Wevers asked various colleagues from around the world if they knew of patients with chronic halitosis and especially if the bad breath seemed to affect multiple members of the same family. This led to the identification of three such families: a family in Germany, a Portuguese family, and a Dutch family.
The scientists took breath, blood, and urine from the patients, and determined that all had mutations in the SELENBP1 gene that encodes selenium-binding protein 1, which — as predicted — was found to be a methanethiol oxidase. Individuals harboring the mutation therefore cannot properly break down methanethiol, leading to the malodorous breath.
"In all patients, one of the mutations was maternally inherited and the other came from the father," Wevers said. "In the end, it will turn out that there will be equal numbers of males and females affected."
The mutation may even be more common than presently believed. The researchers calculate that about 1 in 90,000 people carry the mutation. For those who inherit the halitosis disorder, there is no cure, but they are advised to watch their diets to avoid foods that may further worsen the smell of their breath.
The halitosis perhaps affects nearby non-family members more than the patients themselves, since, as Wevers said: "They are used to having this smell around." It also does not seem to hurt their ability to taste food.
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A far more worrisome health issue came to the forefront during the research on bad breath, however.
Prior studies have found that SELENBP1 is a possible biomarker for disease progression in several cancers, such as those affecting the breasts, kidney, and colon. Additionally, methanethiol and dimethylsulfide have been identified in numerous of cancers.
"We think that this is the reason dogs can smell cancer, because both metabolites have been found in several cancer types," Wevers said. "Humans can certainly smell each of these, but the dog's nose is simply much better at that."
So far, there is no evidence that the patients with chronic halitosis who participated in the study are at increased risk for cancer. Nevertheless, since the presence of sulfur-containing metabolites has been linked to some cancers, the researchers plan to investigate the matter further.
In the future, the work could lead to new treatments for bad breath and might identify cancer drug targets.
A number of breath tests for certain cancers are already in the works. Earlier this year, breakthroughs were announced at the European Cancer Summit concerning breath tests for stomach and esophageal cancers. The simple and non-invasive tests, developed by scientists from Imperial College London and the Karolinska Institute in Sweden, were found to be 85 percent accurate.
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