"Odors have a power of persuasion stronger than that of words, appearances, emotions or will." 

These are the remarks of Patrick Süskind in his popular novel "Perfume: The Story of a Murderer." His words, although used to describe how the sense of smell is tied to human feelings about an object or a person, are widely confirmed in nature. Flowers produce fragrances as an evolutionary strategy to attract pollinators and ensure reproduction, and many species of insects, fish and mammals emit peculiar odors to attract mates. In fact, male brown lemmings can tell whether a female has ever mated simply by its odor.

Humans also emanate a range of smells, not all of which are pleasant. Take, for instance, the smelly armpits or the stinking foot! Body odor (BO) is a fairly common issue that affects people at some point in their lives, and more often than not, microbes are the root of the issue. Commensal microbes on the skin metabolize certain compounds in sweat and can produce foul-smelling odors. One can mask BO with deodorants and antiperspirants, but sometimes the odor can be an indication of an underlying disease.

Causes and Biochemistry of Body Odor

Humans have 3 types of sweat glands—apocrine, eccrine, sebaceous. While eccrine sweat glands are present in all skin types on the body, apocrine and sebaceous are restricted to certain locations. Body odor is primarily caused by apocrine sweat glands that become activated during puberty. These sweat glands develop in hairy regions like the armpits, genitals and scalp, where they secrete an oily fluid comprised of proteins, lipids and steroids. Contrary to popular belief, this viscous fluid (sweat) is naturally almost entirely odorless. It is only when members of the skin microbiota metabolize these secretions that they produce the malodorous byproducts, which cause body odor. In humans, armpits offer a moist, warm environment where microbes can thrive, making them a microbial hotspot.

The composition of the skin microbiota varies from one individual to another, and between locations on the same host; sometimes, even the left armpit can have a vastly different flora compared to the right. However, the major bacterial players that colonize the skin and produce body odor are similar. Some common skin bacteria that produce body odor include members of Corynebacterium, Staphylococcus and Cutibacterium genera.

The biochemistry behind the microbial conversion of sweat to malodorous products is still not completely understood. However, the odor can be largely attributed to the production of volatile organic compounds (VOCs), including volatile fatty acids and thioalcohols.

Key volatile fatty acids that contribute to body odor include 3-methyl-2-hexenoic acid (3M2H), which has a ‘goat-like’ odor, and 3-hydroxy-3-methylhexanoic acid (HMHA), which has a ‘cumin-like’ odor. These odorants are produced by some members of Corynebacterium, including Corynebacterium striatum, Corynebacterium jeikeium and Corynebacterium bovis. Other medium- and short-chain fatty acids also contribute to odor. If you have smelly feet, it is probably because Staphylococcus epidermis has degraded the leucine in your sweat to isovaleric acid, a cheesy-smelling compound.

Thioalcohols get their stinky odor from sulfur and, despite being present in only trace amounts, are some of the most pungent VOCs produced. 3-methyl-3-sulfanylhexan-1-ol (3M3SH) is a thioalcohol, produced by Staphylococcus hominis, which makes the underarms smell like rotten onions or meat. S. hominis encodes a proton-coupled oligopeptide transporter that imports the thioalcohol-conjugated precursor S-Cys-Gly-3M3SH into the cell, and subsequent catabolism results in the foul-smelling 3M3SH.

Factors Influencing Body Odor 

Several factors, including sex, genetics, age and diet can influence the type of odor that an individual emits. In fact, it has been suggested that, similar to a fingerprint, every individual’s body odor is unique and may be partly determined by genetics. Men have larger sweat glands and generally produce more sweat than women. This typically results in larger populations of Corynebacterium spp. and intensified cheese-like odor, due to the production of higher quantities of volatile fatty acids.

The underarm body odor has been linked to a gene called ABCC11, which encodes a protein that transports molecules across cellular membranes, including molecules in the sweat. If the ABCC11 gene is non-functional, sweat molecules are unable to cross the membrane barrier to reach the armpit. This starves bacteria on the other side of the skin surface, as they are unable to access or metabolize the organic compounds in the sweat. As a result, odorant substances are not produced. Loss-of-function ABCC11 mutation is fairly common in East Asian populations (80-95%).

The chemical nature of body odor has also been suggested to change with age. The characteristic "nursing home smell" of elderly people is thought to be associated with the presence of an unsaturated aldehyde, 2-nonenal. This compound has an unpleasant greasy and grassy odor and is produced upon oxidative degradation of ω7 unsaturated fatty acids in skin surface lipids.

De-odorizing Body Odor 

There aren’t many evidence-based guidelines to manage body odor, but deodorants and antiperspirants are commonly used to reduce or prevent it. Deodorants contain chemicals that kill skin flora and block production of stinky byproducts. Antiperspirants reduce the amount of sweat produced by clogging sweat glands. Many contain aluminum chloride, which creates a gel-like substance that forms a plug at the sweat ducts in the skin. Many deodorants and antiperspirants also contain antimicrobials, like propylene glycol, triclosan and benzalkonium chloride, which decrease bacterial abundance and result in an altered skin microbiome in the armpits. However, the modified microbiome can have unintended consequences as well. For instance, a study showed that the use of antiperspirants resulted in an increase in odor-producing Actinobacteria in some individuals.

While deodorants and antiperspirants do the minimum job of reducing bacterial load and their byproducts, respectively, a growing body of work is focusing on the use of probiotics and artificial microbial communities to reduce malodor. The field is still in its infancy, but one technique being developed is armpit microbial transplantation. In preliminary work, scientists used antibacterials to remove the armpit microbiome from a person with BO and replaced it with bacteria from the armpit microbiome of a healthy (related) donor. Comprehensive results on the efficacy and success of the procedure have yet to be published.

Body Odor and Diseases 

Certain medical conditions associated with metabolic imbalances can be diagnosed from odors that are emitted from the skin. For instance, trimethylaminuria is associated with a strong fish-like body odor. Phenylketonuria is associated with a musty odor, and hypermethioninemia is associated with in an odor akin to that of boiled cabbage.

Body odor profiles can also be used to diagnose diseases like malaria. Scientists collected samples of skin volatiles from more than 400 school children in malarial areas in Western Kenya and used them, in combination with predictive modeling, to identify asymptomatic malarial infections with 100% sensitivity. These studies still need to be replicated in diverse population settings, but the data offer hope of establishing skin volatile biomarkers as a robust, noninvasive strategy to identify asymptomatic malaria infections.

Additional research demonstrated that individuals with malaria have a unique blend of skin odors that makes them more attractive to mosquito vectors. Here, scientists examined the VOCs associated with socks collected from school children in Western Kenya. Data showed that children with malaria had elevated levels of aldehydes heptanal, octanal and nonal, compared to parasite-free individuals. Furthermore, the volatile compounds were detected by mosquito antennae, making malaria-infected children more prone to further attack by these insects. Whether these compounds are produced by the parasite or the skin microbiota has yet to be determined.

Conclusion 

It is now largely recognized that many compounds contributing to body odor originate from the skin microbiome, although we have a limited understanding of the underlying biochemistry. Defining the structural and molecular basis of odorless precursors, and the manner by which they are subsequently converted to odorant chemicals, can help inform the design of strategies to inhibit malodor formation.

Innovative therapies along the lines of armpit microbiota transfers may offer respite and psychological relief to people with chronic body odor conditions. At the same time, scientists are unraveling the role of odor in certain diseases. Leveraging this understanding will help in the development of rapid diagnostic tests, as well as treatments for a variety of pathogens and diseases.

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