Generally, halitosis is thought to be triggered by bacteria that are broken down into sulfur compounds.
But in many cases, the causes are unknown. In fact, between 0.5 and 3 percent of the general population has this less understood form of halitosis, called extraoral halitosis.
Certain illnesses that affect the nose, esophagus, or sinuses may be what causes it, but in some cases, the condition can even be bloodborne.
Study co-author Prof. Kent Lloyd, director of the Mouse Biology Program at University of California, Davis, explains the significance of understanding the causes of chronic bad breath, saying, "It's important to identify the cause of persistent halitosis, and differentiate [...] [between] relatively benign causes (e.g., gum disease) and the more morbid causes such as liver cirrhosis."
To this end, a few years ago, researchers started investigating. The efforts were led by Dr. Albert Tangerman, also of Radboud University, in collaboration with Ron Wevers, a professor of inborn errors of metabolism at the same university.
The scientists then discovered the sulfur compound methanethiol, which emanates a foul odor. As Prof. Wevers states, "Methanethiol is produced in large amounts in the intestines, and can originate from food. We believed that the protein responsible for getting rid of methanethiol was defective in these patients."
"However," he continues, "we could not find a lead for this in their metabolism. The process by which the body counteracts this compound was unknown. So at that point, we were stuck."
To move past this hurdle, Prof. Wevers, Dr. Tangerman, and colleagues looked for the culprit in their recently published study. Arjan Pol is the lead author of the new paper.
'Treatable' metabolism error is the culprit
Knowing that some bacteria can help to metabolize sulfur compounds, Pol and team examined bacteria and found a human protein that is responsible for converting methanethiol into other compounds.
The human protein is called selenium-binding protein 1 and the gene that encodes it is SELENBP1.
Pol and team examined the gene in five human patients with chronic extraoral halitosis and found that they all had a mutation of it. Additionally, the patients had increased levels of methanethiol in their blood.
To further validate their findings, the researchers used genetically engineered mice. They knocked out the SELENBP1 gene in the rodents, which resulted in increased blood levels of methanethiol and other foul-smelling sulfur compounds.
"While we didn't put our noses up to the mice's mouths, we did measure high amounts of some of these odor-forming chemicals in their blood, matching precisely what was found in the patients," Prof. Lloyd says.
"In conclusion," write the authors, "our experiments identified a novel enzyme activity of a human methanethiol oxidase. The enzyme is encoded by SELENBP1."
They add, "SELENBP1 mutations cause extraoral halitosis, an autosomal-recessive syndrome in which malodor results from [the] accumulation of sulfur-containing metabolites."
Pol and colleagues conclude:
"Our data reveal a potentially frequent inborn error of metabolism that results from MTO [methanethiol oxidase] deficiency and leads to a malodor syndrome [...] Theoretically, this syndrome may be an inborn error of metabolism that may be treatable through dietary measures."