Foot Odor Microbes
Introduction
By Heath Carmichael
What microbes are associated with foot odor? What benefits, if any, do these microbes have for humans? What metabolic processes do these microbes have that lead to the odors they produce? What diseases might be caused by these microbes?
Bromodosis is the medical term for having foot odor. Many people worldwide suffer from Bromodosis. Bromodosis is caused by microbes metabolizing dead skin cells from people's feet in to odorous acidic molecules. This is an even bigger problem for people who run because sweat provides an ideal growth environment for foot microbes. Some think that the odor is caused by sweat. This is untrue because sweat is odorless, but the microbes that live on feet grow better because of the moisture provided by sweat. Another contributor to foot odor is the type of socks that people choose to wear as well as how often one cleans their feet.
Microbial Metabolism
The smell on people's feet is caused by the breakdown of carbohydrates, fatty acids and peptides into smaller acids, most commonly acetic acid, propanoic acid, isobutyric acid and isovaleric acid (Fig 2). A study identified what microbes are to blame for the production of these smelly molecules. Propionibacteria and Staphylococcus were present in large amounts, but the amount did not change between smelly feet and feet that did not produce odor. Both these microbes are part of the normal human flora so their abundance is not unusual (Ara et al.). Propionibacteria is a gram positive actinobacterium that lives primarily in anaerobic conditions, so their main metabolic process is fermentation to produce lactic acid and propanoic acid (Bruggeman et al. 2004). However, the amount of Bacilli increased on odorous feet (Ara et al.) which implies that an increase in Bacilli could lead to an increase in odor. Staphylococcus aureus is a gram positive firmicute that can metabolize a number of different sugars to lactate using the Embden-Meyerhof-Parnas pathway and has been shown to produce acids that contribute to foot odor (Gillaspy et al. 2006). Staphylococcus epidermis has also been shown to produce lactic acid that contribute to sweat odor (Sawano 2000). Micrococci are gram positive actinobacteria that, when under anaerobic conditions, can produce acid from glucose (Kloos et al. 1975).
Another study showed that Bacillus subtilis natto (Fig 1) produces odors related to sweat by producing isobutyric and isovaleric acid from the amino acid leucine using a leucine dehydrogenase (Takemura et al. 2000). It was found that a similar leucine dehydrogenase is present in many microbes in the human flora (Ada 2006). One study tested the level of activity among different microbes by assaying the enzyme in many different microbial species (Oshima et al. 1978). It was found that the leucine dehydrogenase enzyme has the highest activity in Bacillus sphaericus (Fig 3). This enzyme is used to oxidize the L forms of leucine, valine, isoleucine, norvaline, norleucine, and aminobutyrate by removing the amine group from these amino acids and reducing NAD+ to NADH. The D enantiomers of these amino acids are capable of competitively inhibiting the leucine dehydrogenase enzyme. The removal of the amine group from these amino acids contributes to the odor produced by the bacteria that have the leucine dehydrogenase enzyme because NH3 and NH4+ have very distinct smells. While leucine dehydrogenase is most present in Bacillus sphaericus it is also found in many other types of Bacillus as well as in Corynbacterium (Oshima et al. 1978). Corynbacterium is gram positive actinobacterium that is chemoorganotrophic and a fermenter when under anaerobic conditions (Esteban et al. 1999). This ammonia production as well as the mixed acid fermentation that comes from other microbes present on feet that break down proteins, carbohydrates and fatty acids in dead skin cells are the main contributing factors to foot odor.
Prevention and Treatment of Bromodosis
Choice of footwear can play an important part in preventing bromodosis. Proper ventilation and consistent changing of ones footwear is necessary in order to prevent a buildup of moisture due to sweat. Sweat and moisture do not produce odor, but they produce an impeccable living and growth environment for microbes to inhabit and produce odorous metabolites. Wearing the same shoes consistently will lead to a buildup of moisture that provides an ideal environment for these microbes to grow in.
Proper foot hygiene is also necessary to reduce foot odor. By washing with antibacterial soap one can remove most of the microbes that produce odorous molecules. Removing dead skin helps as well because it removes the source of nutrients available for microbes to metabolize. Removing the source of amino acids and other nutrients is important in removing the oxidation products that produce odors.
Another way to prevent foot odor is to wear wool or cotton socks. Socks constructed of synthetic material like nylon and polyester provide less ventilation for people's feet and therefore increase the amount of sweat produced and retained. Wool or cotton socks are much better at providing ventilation for feet so less sweat is produced and retained. A study was done to test the amount of microbial growth on cotton t-shirts versus synthetic t-shirts. The results were that Firmicutes, Actinobacteria and Proteobacteria were found on both types of shirts, but Micrococci were found in a much higher abundance on synthetic t-shirts (Callewaerta et al. 2014). The anaerobic conditions on synthetic shirts were most likely due to the poor ventilation of these shirts compared to the ventilation of cotton t-shirts.
Health Benefits(Malaria Prevention)
Brevibacteria are another type of bacteria that is commonly associated with foot odors. They ingest dead skin cells and break down the amino acid methionine to methanethiol which produces an odor. This type of bacteria is also used in the production of cheese by metabolizing lactate to lactic acid as well as metabolizing casein proteins to amine and sulfur compounds (Rattray et al. 1999). What is interesting about this is that the odors associated with feet can also be associated with cheese. Common skin microbes play an important part in the production of cheese. A famous example is Propionibacterium freundenreichii, which is used to produce Swiss cheese. This bacterium breaks down the lactic acid produced by other microbes using fermentation to produce propanoic acid and carbon dioxide. The propanoic acid gives Swiss cheese its smell and flavor and the carbon dioxide production helps to give the cheese its characteristic holes (Button, Dutton. 2012). Researchers have used the similarity of skin odor producing microbes and cheese producing microbes to test the effectiveness of using types of cheese as attractants for mosquitos.
Mosquitos and other blood metabolizing insects are able to find their hosts by sensing chemical cues that come from their targets. Some attractants are Carbon Dioxide, from human's breath, volatile compounds from feces and urine such as octanol, as well as odorous acids like acetone and butanone (Knols, Meijerink. 1997). This research is of particular important for Africa, where malaria carrying mosquitos and tsetse flies are very common. In fact, the washing of ones feet with antibacterial soap changes the biting pattern of Anopheles gambiae, a malaria carrying mosquito (Fig 4). Malaria is a blood born virus carried by mosquitoes. A person is infected when they are bitten by a mosquito that carries the virus. The phage then replicates in the liver of human hosts and then attacks the host red blood cells. Some cases of malaria can be mild with symptoms like a fever, sweats and an enlarged liver. However, cases of malaria can be very severe and life threatening such as cases of cerebral malaria, severe anemia and acute kidney failure (CDC, “Malaria Disease”). Returning to the information that some of the bacteria on human feet are used to produce cheese, researchers have been testing the attraction of malaria mosquitos to cheese. Limburger cheese production most closely resembles the microbial community present on human feet and as a result malaria carrying mosquitos showed the highest affinity for this type of cheese.
This research has implications for public health because malaria and other insect pathogens have plagued sub-saharan Africa for many years. If widespread malaria mosquito traps could be constructed across the continent, diseases that come from these pathogens could be exterminated. One study shows that the number of mosquitos caught in traps using Limburger cheese increased when compared to a control compound used in traps (Knols, Jong. 1996). In 2015 over 214 million cases of malaria occurred worldwide and 438,000 people died because of this disease, many in sub-saharan Africa (CDC, “Malaria Disease”).
Other Foot Microbe Diseases
The bacterial growth environment present on feet can also lead to a number of infections that range from annoying to dangerous. Cellulitis, or staph infection, is a common infection on feet as a result of Staphylococcus aureus or Streptococci infecting layers of the skin (Mistry. 2013). These microbes are able to infect via cuts or breaks in the skin. Bacteria are able to infect deeper layers of the skin such as subcutaneous fat and the dermis. The result of this infection is usually an irritating rash, but can have more serious symptoms in immunocompromised people. People with diabetes are especially are at risk for more serious symptoms. They are at risk to develop foot ulcers, known as diabetic feet, as a result of infection. These ulcers can present as a hole in a persons foot(Fig 5). The feet are a particularly risky part of the body for some diabetics because of the ideal bacterial growth environment that exists on feet. Choice of footwear is even more important for people with diabetes because a lack of ventilation can cost them more than just odorous feet. If a foot infection becomes especially severe a person with diabetes may have parts of their toes or foot amputated as a way to stop the infection from spreading to the blood stream (Paola et al. 2015). For most people cellulitis is easily treated with antibiotics, but it is important to consistently wash one's feet with antibacterial soap after a cut opens in order to avoid infection because microbes that cause infection are also largely present in the normal human skin flora.
Another danger to human feet are fungal infections. Athlete's foot is a famous fungal infection and has similar symptoms to Cellulitis. Redness and itching are the major symptoms and the most likely areas of infection are between the toes and underneath the feet. The fungi that usually cause this disease are Epidermophyton, Trichophyton, and Microsporum (CDC, “Athletes Foot”). Athlete's foot is referred to as such because it is usually spread in locker rooms or public showers. Both of these environments contain plenty of moisture which produces excellent growth environments for these fungi and can be easily spread to the feet of people that come in to contact with the fungi. Once a person has become infected with Athlete's foot, they may treat it with antifungal creams and by keeping the foot very dry because maintaining a moist environment will only contribute to the growth of the fungi. It is common that people will wear sandals when they are infected with Athlete's foot in order to reduce the amount of moisture and make the living environment less beneficial for the fungi.
Toenails are excellent growth environments for microbes and fungi as well. Onychromycosis, or toenail fungus is a fungal infection located in the toenails. It is most commonly caused by dermatophyte fungi coming in to contact with a toenail. The symptoms are toenail discoloration, brittle texture, inflammation around or underneath the toenail, and an odor. Having hang nails or breaks in the skin close to the toenail can increase the likelihood of developing onychromycosis due to the fact that it provides a place for the fungi to infect. It is also possible to have fungal infections in the fingernails, but it is more common to have nail fungus in the toes. This is because there is less blood circulation to the toenails than fingernails so the body is less capable of fighting off fungal infection in the toes than in the fingers. Another reason is the living environment for microbes and fungi is much better on the toenails than on the fingernails. The moisture and darkness produce ideal conditions for these fungi to grow. Treatments are usually either oral antifungal drugs or antifungal nail creams that can be applied directly to the nails. In serious cases it is even possible for the nail to be removed surgically in order to more directly treat the fungi, but it can take a long time for a new nail to grow in its place. The prevention for nail fungus is very similar to the way that other foot problems are treated, consistent cleaning as well as reducing the moisture on the feet and nails (“Nail Fungus”. Mayo Clinic).
Foot Odor vs. Body Odor
Foot odor and body odor are similar in some ways, but different in many others. In both cases the odor is produced by bacteria consuming dead skin cells and proteins that are broken down to acids that have odorous smells. However, body odor is produced in the armpits or near the genitals where the apocrine sweat glands are located. These glands produce a different type of sweat than the sweat produced from the eccrine glands, which is where the sweat on human feet is produced. The sweat produced by apocrine glands has more proteins included in the sweat, where the eccrine glands produce sweat that is more watery (Freeman. 2010). This secretion of protein provides more material for microbes to metabolize. So why do some people with bromodosis have feet that smell much worse than their armpits or genital area smell? It is largely because of the lack of ventilation available for peoples feet because of the type of socks people wear and wearing the same pair of shoes constantly which creates a better living environment for microbes than armpits or genitals. Most people also are able to mask the odors produced on their armpits by wearing some type of deodorant, or washing their underarms with soap when they shower. It is less common for people to wear foot deodorant or wash their feet daily with soap which can make foot odor more prevalent for some people than armpit or genital odor.
Conclusion
In conclusion, bromodosis and other foot related infections and illnesses are mostly a result of a buildup of moisture on the feet that produce an ideal living environment for microbes to grow and produce putrid smelling acids. The majority of these acids come from normal skin flora microbes such as Propionibacteria, Staphylococcus, and Bacilli that perform fermentation on carbohydrates, proteins and fatty acids that come from dead skin cells on peoples feet. Lactic acid, acetic acid, propanoic acid and ammonia are common acids that produce odors and some of these acids are produced by the breakdown of proteins and amino acids by the leucine dehydrogenase present in many microbes on the human flora. The leucine dehydrogenase removes the amine group from proteins and breaks down the hydrocarbon skeleton to form other acids. Though foot odor might be annoying and off putting, there are some infections that can arise from the microbial community that flourishes on our feet. These infections can range from mild to dangerous. Cellulitis, or staph infection, is caused by Staphylococcus aureus or Streptococci infecting deeper layers of the skin through cuts or breaks in the skin on the feet. For most people cellulitis is just an annoying rash that is easily treated with antibiotics, but for people that are immunocompromised or have diabetes this infection can develop foot ulcers and may need to be amputated in order to prevent the infection spreading to the blood stream. Fungal infections are also somewhat common annoyances that take place on the feet. Things like athlete's foot or toenail fungus are fungal infections that are easily spread in public places where people are barefoot. Both of these diseases are annoyances that can be treated using antifungal creams and oral medications. These infections are more common on feet than on hands or fingers because of the impeccable growth environment present because of the amount of moisture on people's feet. A more serious disease that foot odor can attract is malaria. Pathogen carrying mosquitos are able to find their hosts based on chemical cues. The cues that arise from peoples feet as a result of the mixed acid fermentation make feet a common area that people are bitten by mosquitoes. Scientists have used the knowledge that Limburger cheese is produced using the same microbes that are present on the flora of human feet. They have tested the effectiveness of traps attracting phage carrying mosquitoes with the goal of capturing and eliminating malaria carrying mosquitoes. These tests have great possibilities to help humanity, especially in Africa because it could help capture and eliminate malaria carrying mosquitoes that have plagued Africa for many years. Prevention of bromodosis and other annoying feet related problems can be a simple task, but it does involve a level of effort that not all people will put in. Consistent washing of one's feet with antimicrobial soaps will go a long way to eliminate the odors that bacteria produce. Removing dead skin cells with a file is also an effective way to remove the starting material that these bacteria use to produce acids that make feet smell. Finally and maybe most importantly keep ones feet dry plays an important part in making the feet a less ideal growth environment for microbes. Not wearing the same pair of shoes every day and wearing socks that provide proper ventilation for ones feet help to eliminate the buildup of moisture that allow the proper growth environment for microbes to produce odors.
Reference
[1] Jessica C Zweers, Imrich Barák, Dörte Becher, Arnold JM Driessen, Michael Hecker, Vesa P Kontinen, Manfred J Saller, L'udmila Vavrová and Jan Maarten van Dijl. "Towards the Development of Bacillus subtilis as a Cell Factory for Membrane Proteins and Protein Complexes". Microbial Cell Factories. 2008. 7:10
[2] Katsutoshi Ara, Masakatsu Hama, Syunichi Akiba, Kenzo Koike, Koichi Okisaka, Toyoki Hagura, Tetsuro Kamiya, and Fusao Tomita. “Foot odor due to microbial metabolism and its control”. NCR Research Press. 2005.
[3]Luca Dalla Paola, Anna Carone, Lucian Vasilache, Marco Pattavina. “Overview on diabetic foot: a dangerous, but still orphan, disease”. European Heart Journal. 2015. A64-A68.
[4]Bart G. J. Knols and Jocelijn Meijerink. “Odors Influence Mosquito Behavior”. Science and Medicine. 1997. 4(5):56-63.
[5]M. Kanlayavattanakul and N. Lourith. “Body malodours and their topical treatment agents”. International Journal of Cosmetic Medicine. 2011. 30:298-311
[6]Niels O. Verhulst, Yu Tong Qiu, Hans Beijleveld, Chris Maliepaard, Dan Knights, Stefan Schulz, Donna Berg-Lyons, Christian L. Lauber, Willem Verduijn, Geert W. Haasnoot, Roland Mumm, Harro J. Bouwmeester, Frans H. J. Claas, Marcel Dicke, Joop J. A. van Loon, Willem Takken, Rob Knight, Renate C. Smallegange. “Composition of Human Skin Microbiota Affects Attractiveness to Malaria Mosquitoes”. PLoS ONE. 2011. 6(12):e28991
Sawano, K. 2000. Body odors. Jpn. J. Taste Smell Res. 45: 797–800.
Takemura, K., Andou, N., and Tsukamoto, Y. “Breeding of branched short-chain fatty acids non-producing natto bacteria and its application to production of natto with light smells”. J. Jpn. Soc. Food Sci. Technol. 2000. 47: 773–779.
[7]Toehihisa Oshima, Haruo Misono, and Kenji Soda. “Properties of Crystalline Leucine Dehydrogenase from Bacillus sphaericus”. Journal of Biological Chemistry. 1978. 253(16): 5719-5725.
[8]Chris Callewaerta, Evelyn De Maeseneirea, Frederiek-Maarten Kerckhofa, Arne Verliefdeb,c, Tom Van de Wielea and Nico Boona. “Microbial Odor Profile of Polyester and Cotton Clothes after a Fitness Session”. American Society for Microbiology. 2014. 80(21):6611-6619
[9]Julie E. Button, Rachel J. Dutton. “Cheese Microbes”. Current Biology. 2012. 22(17):587-589
[10]B.G.J. Knols, R. De Jong. “Limburger cheese as an attractant for the malaria mosquito Anopheles gambiae s.s.”. Parasitology Today. 1996. 12(4):159-161
[11]Rakesh D. Mistry, MD, MS. “Skin and Soft Tissue Infections”. Pediatric Clinics of North America. 2013. 60(5):1063-1082
[12]“Malaria Disease." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 07 Oct. 2015. Web. 24 Apr. 2016.
[13]“Athletes Foot.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 07 Oct. 2015. Web. 24 Apr. 2016.
[14]Shanna Freeman. "How to Get Rid of Foot Odor" 20 September 2010. HowStuffWorks.com. 24 April 2016.
[15]"Nail Fungus." - Mayo Clinic. N.p., n.d. Web. 24 Apr. 2016.
V. Chan, P. Sherman, B. Bourke., Bacterial genomes and infectious diseases (Totowa, N.J. : Humana Press, c2006).
Gillaspy, Worrell, Orvis, et al in Gram-positive Pathogens (eds Fischetti, V., Novick, R., Ferretti, J., Portnoy, D. & Rood, J.) 381-410 (ASM Press, Washington, D.C, 2006).
[16]Kloos, Wesley E., and Margaret S. Musselwhite. "Distribution and persistence of Staphylococcus and Micrococcus species and other aerobic bacteria on human skin." Applied microbiology 30.3 (1975): 381-395.
[17]Bruggemann H, Henne A, Hoster F, Liesegang H, Wiezer A, Strittmatter A, Hujer S, Durre P, Gottschalk G. The complete genome sequence of Propionibacterium acnes, a commensal of human skin. Science. 2004 Jul 30;305(5684):671-3.
[18]Rattray, Fergal P., and Patrick F. Fox. "Aspects of Enzymology and Biochemical Properties of Brevibacterium Linens Relevant to Cheese Ripening." Journal of Dairy Science, Volume 82, 1999, Pages 891-909.
[19]Esteban, J. et al. 1999. "Microbiological characterization and clinical significance of Corynebacterium amycolatum strains." European Journal of Clinical Microbial Infectious Diseases, 18: 518-521.
