Human Skin Gas Profiles in PATM

People Allergic to Me (PATM) is a perplexing condition that has left both sufferers and medical professionals searching for answers. Thousands of individuals worldwide claim to experience PATM, leading to severe mental health challenges such as depression, anxiety, and suicidal tendencies. Despite its far-reaching impact, the underlying causes remain mysterious, with only a few scientific studies dedicated to understanding this condition. While a small subset of PATM sufferers has been diagnosed with TMAU, the majority remain without a diagnosis. 

A new study lead by Professor Sekine, recently published in Nature Scientific Reports, explores the human skin gas profiles to shed new light on PATM. 

The study included 44 subjects, divided into two groups: 24 without PATM (non-PATM) and 20 with PATM. The non-PATM group involved 13 male and 11 female participants (age: 18–59, 31 ± 13 years old). The PATM group comprised 12 male and 8 female participants (age: 19–53, average 39 ± 12 years old).

The non-PATM group had no known diseases, while the PATM group reported symptoms of PATM without other apparent diseases.

Researchers sought to understand the skin gas profile of people with and without PATM, potentially the source of body odor or other types of emissions. They measured the emission rate of 75 volatile compounds from the skin using a tool called a passive flux sampler (PFS) coupled with gas chromatography/mass spectrometry (GC/MS). PFS was designed to be convenient and unobtrusive, allowing people to use it on the go without any hassle.

Participants in the study were given a PFS device, similar in size to a bottle cap, to collect skin gas samples from their non-dominant forearm. They wore this device for an hour without any restrictions on their activities. The device was easily attached to the skin with a piece of surgical tape and didn't require any special preparation. After collecting the samples, PFS devices were sent to the laboratory and analyzed.

The PATM group exhibited significantly greater emission fluxes for a variety of chemicals, including some with offensive odors, and lower emissions of others, including some with more pleasant or neutralizing smells. 

Among the 75 measured skin gases, the PATM group exhibited significantly greater emission fluxes for chemicals like alcohol 2-ethyl-1-hexanol (2E1H), aldehyde isovaleraldehyde, hexanal, acetone, toluene, m,p-xylene, methyl mercaptan, ethyl mercaptan, and allyl methyl sulphide (AMS). These chemicals often have offensive odors and/or can lead to adverse health effects. The emissions of petrochemical 2E1H, and aromatic hydrocarbons (with benzene ring in their structure): toluene, and m,p-xylene were notably higher in the PATM group, with increases of approximately 12, 39, and four times, respectively.

Volatile organosulfur compounds such as methyl mercaptan (fecal odor, resembling smell of rotten cabbage or decaying vegetables), ethyl mercaptan (rotten fish, garlic, or onions), and Allyl Methyl Sulfide (AMS, garlic- or onion-like odor) were also significant. These compounds have extremely low odor thresholds and could easily alter body odor perception in PATM subjects. Bacteria in the oral cavity, such as Porphyromonas gingivalis and Anaerobic bacteria in the gut, such as Desulfovibrio species are producers of Methanethiol. 

Isovaleraldehyde contributes to body odor with a pungent fruit-like smell that can also contribute to aroma of beer and cheese. It can be sourced from metabolic breakdown of amino acids like leucine and valine, hence dietary intake, and microbial activity in the gut by methylotrophic yeasts. , species of Clostridium, Actinobacteria (Rhodococcus, Mycobacterium and Gordonia), Proteobacteria (Acetobacterium such as Gluconobacter oxydans), Odoribacteraceae, Ruminococcus gnavus, etc. These microbes are capable of producing  Isovaleraldehyde through anaerobic fermentation and the mevalonate-independent glyceraldehyde 3-phosphate/pyruvate pathway. 

Greater emission of acetone might indicate eating disorders in the PATM group, as it is influenced by fasting, starvation, or diet.

The PATM group had less skin release of various substances, including some types of alcohols, smell-related chemicals, and fruity-smelling compounds. Some of these chemicals are used in flavors or fragrances and are known to have a relaxing effect.

For example, α-pinene, β-pinene, and D-limonene have antifungal activities as well as abilities to decrease depression-like behavior and improve memory via an anti-neuroinflammatory mechanism under chronic restraint stress. 

D-limonene can be consumed through the diet by eating citrus fruits or drinking citrus-flavored beverages. Some fruity-smelling compounds are naturally found in fruits like peach and pineapple and contribute to sweet body scents. It can also be absorbed through the skin from personal care products containing citrus oils or inhaled from air.

Acetic acid smells like vinegar and is made by bacteria breaking down certain substances in sweat. It is linked to body odor in young adults. Lower skin emissions of acetic acid in the PATM group showed that sweating may not be the cause of their unique body odor. Acetic Acid is produced by acetic acid bacteria, such as Acetobacter and Gluconobacter species. Certain lactic acid bacteria, such as Lactobacillus, can also produce acetic acid.

The study also looked at benzaldehyde, which might come from toluene. People with PATM had much more skin emission of toluene but less of benzaldehyde.

The presence of benzaldehyde in the human body is typically at low levels, and its occurrence may vary based on factors such as diet, environmental exposure, individual metabolism, and gut microbiome composition. Almonds, apricots, and cherries are examples of foods that contain benzaldehyde or related compounds. Toluene is a common solvent used in various industrial and household products such as paints, glues, nail polish, and cleaning agents. Inhalation of fumes from these products can lead to toluene being present in the blood and tissues.

The ratio of toluene to benzaldehyde was much higher in the PATM group, and this ratio is seen as a key sign of PATM.

Air quality in terms of petrochemicals is worse in urban areas, high traffic areas, industrial workspaces, poorly ventilated interiors, newly constructed or renovated spaces, automotive interiors, salons and beauty parlors, households using cleaning products containing petrochemicals, such as certain detergents, aerosol sprays, and solvents, spaces with indoor smoking and even some healthcare facilities. 

Our previous study on breath VOC profiles in PATM, TMAU and MEBO (Alveolar Breath Test Study registered as NCT03451994) has unveiled intriguing insights into petrochemical metabolism, indicating that non-TMAU MEBO population may have difficulties with metabolizing environmental pollutants, while the Microbiome study (registered as NCT03582826) uncovered possible microbial sources of compounds that differentiate PATM, TMAU and MEBO from non-MEBO & non-PATM populations. Our findings align remarkably with Professor Sekine's work.

The synergy between these discoveries is shedding light on the underlying mechanisms and potential diagnostic markers. We will be publishing these complementary results soon, further contributing to the scientific community's knowledge of PATM, TMAU and MEBO.

Stay tuned for our upcoming publications, as we continue to unravel the mysteries of these conditions, working towards a future where this condition is better understood, diagnosed, and managed. 

REFERENCES

Sekine Y, Oikawa D, Todaka M. Human skin gas profile of individuals with the people allergic to me phenomenon. Sci Rep. 2023 Jun 10;13(1):9471. doi: 10.1038/s41598-023-36615-1. PMID: 37301918; PMCID: PMC10257688.