Since the outbreak of the COVID-19 pandemic, people have become more conscious of their sense of smell. Recent studies have revealed that smells, such as those emitted by ripening fruits or fermented foods, can cause changes in gene expression inside cells, beyond just the nasal area. This discovery has led scientists to ponder if inhaling volatile airborne compounds could be a potential treatment for cancer or a way to slow down neurodegenerative diseases. Although delivering medication through the nose is not a novel idea, more research is needed to fully comprehend the consequences of this discovery. It is essential to note that there may be unexpected health risks related to the tested compounds, so further studies are necessary.

“That exposure to an odorant can directly alter [the] expression of genes, even in tissues that have no odorant receptors, came as a complete surprise,” says Anandasankar Ray, a cell and molecular biologist at the University of California (UC) Riverside and senior author of the study.

The team conducted experiments on fruit flies (Drosophila melanogaster) and mice, exposing them to varying doses of diacetyl vapors for five days. Diacetyl is a volatile compound that is naturally released by yeast during fruit fermentation. It was widely used in the past to give foods like popcorn a buttery flavor and is sometimes present in e-cigarettes. It is also a by-product of brewing.

The team discovered that diacetyl can act as a histone deacetylase (HDAC) inhibitor in lab-grown human cells. As a result, it caused significant changes in gene expression in both flies and mice, affecting the cells in the brains of the animals, the lungs of the mice, and the antennae of the fruit flies.

HDACs are enzymes that help wrap DNA tightly around histones. If they are inhibited, genes can be expressed more readily. HDAC inhibitors are already used as treatments for blood cancer.

In subsequent experiments, the researchers discovered that exposure to diacetyl vapors effectively halted the growth of human neuroblastoma cells grown in a dish. Furthermore, it slowed the progression of neurodegeneration in a fly model of Huntington’s disease.

“Our important finding is that some volatile compounds emitted from microbes and food can alter epigenetic states in neurons and other eukaryotic cells,” Ray says. “Ours is the first report of common volatiles behaving in this way.”

The team studied the effects of diacetyl as a proof of concept, but given other research showing that inhaling diacetyl causes changes in airway cells and even a lung disease called obliterative bronchiolitis, or ‘popcorn lung’, “this compound may not be the perfect candidate for therapy,” Rays admits.

“We are already working on identifying other volatiles that lead to changes in gene expression,” adds Ray, who has founded two start-up companies and filed several patents based on his team’s work.

There are several limitations to the study. One reviewer pointed out that it falls short in providing a thorough analysis of the mechanisms that could explain how odors induce epigenetic changes in cells that are far from the nose. The study also did not explore whether prolonged or repeated exposure to commonly encountered odorants can have longer-term consequences. As the saying goes, it’s the dose that makes the poison.

The researchers note in their paper that, given our repeated exposure to particular flavors and fragrances, the findings outlined here highlight a new consideration for evaluating the safety of certain volatile chemicals that can cross the cell membrane. This work may have a more practical application in agriculture, as plants also contain HDAC enzymes and have been shown to exhibit a strong and sudden response to volatile chemicals in the air.

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