Odors and Infections

Many illnesses are associated with distinct odors. Especially those caused by infectious or opportunistic microbes inside the body or on its surfaces.  Body odor of someone infected with C. difficile, for example, can appear "swampy", Rotavirus gives sharply sweet putrid smell that some people associate with wet dogs. H. pylori can create a range of foul odors, and pseudomonas infections can smell like grapes and bitter almonds. 

Infections like C. difficile are usually linked to a general imbalance of the intestinal microbiota, often referred to as dysbiosis. This means that the odors could be coming from several microbial species, hence could be different for different individuals. Does it mean odor-based diagnostics will never be enough specific?

Not according to a 2-year-old beagle from Netherland, named Cliff. After just a little over two months of training, the beagle learned to identify the C. diff toxin by sniffing people or their samples. During one test, he was able to identify 25 out of 30 infected patients and 265 of 270 non-infected individuals. He also correctly identified 50 of 50 C. diff positive stool samples and 47 of 50 samples from people that did not have this infection. That's sensitivity of 100% for samples and 83-93% for sniffing the air around the patients, and a specificity of 94-100%! And it took him less than 10 minutes to accurately perform 300 diagnostic tests.  

Dogs already do the dirty work with detecting molds. They can examine an office building with 200 rooms in just 8 hours, a task that would take us several days of measuring  moisture, probably without any result. Electronic noses would be of great help and many years of research are finally being translated into useful technologies - to be integrated with refrigerators and mobile phones. But until we are able to build smart devices to detect odors without labor-intensive dog training, perhaps we could train our own nozzles. Studies have shown we do get better with practice. 


REFERENCES

Bomers MK, van Agtmael MA, Luik H, van Veen MC, Vandenbroucke-Grauls CM, & Smulders YM (2012). Using a dog's superior olfactory sensitivity to identify Clostridium difficile in stools and patients: proof of principle study. BMJ (Clinical research ed.), 345 PMID: 23241268

Poulton J, Tarlow MJ. (1987) Diagnosis of rotavirus gastroenteritis by smell. Arch Dis Child. 1987 Aug;62(8):851-2. PMID: 3662595

Arnaud Tognetti, Megan N Williams, Nathalie Lybert, Mats Lekander, John Axelsson, Mats J Olsson, Humans can detect axillary odor cues of an acute respiratory infection in others, Evolution, Medicine, and Public Health, Volume 11, Issue 1, 2023, Pages 219–228, https://doi.org/10.1093/emph/eoad016

Come out smelling like a rose

You are what you eat. And you smell like your food. Well, it's actually a bit more complicated - as we emit complex combinations of volatile chemicals produced from food by our own metabolic system as well as microbes that call us home. Same foods can be translated into a wide range of odors, depending on the individual. People exhibit a large variety of smells, much more diverse than animals or plants. Thanks to variations in our digestive enzymes, diets, supplements, medicines, perfumes, detergents, clothes, cars and a lot of other chemicals we are exposed to via different routes. And there are many ways to smell of a rose - for example, by putting a few petals in the pocket, wearing Sa Majeste La Rose or drinking rose oil.

As confirmed by gas-chromatograph mass spectrometry using a thermo desorption system and a selective ion mode (Akiyama et al., 2006), linalool, citronellol and geraniol, which are the main components of rose essential oil, are emitted from our palms after an oral intake of rose oil. The aroma starts to increase 30 minutes after ingestion and reaches its peak within an hour, then slowly decreases, wearing off more than 100 times in the next 6 hours. Citronellol seems to evaporate the fastest, and linalool lingers a little longer than the other two compounds, but, of course, this may very well differ for different individuals.

A new "functional food" - Deo Perfume Candy  - is an attempt to take the sciences of smells and foods to a whole new level by creating a sweet treat intended to make you smell good. The main active ingredient of this candies is Geraniol. It is extracted from rose oil, which in its turn is extracted from real rose petals - one gram of oil per two thousand petals. Small amounts of citric acid and tangerine oil are added for more flavor. An healthy food company Beneo partnered with Bulgarian candy maker, Alpi, to develop this nutricosmetics  treat. At present it is sold exclusively on Amazon and has already collected 5 reviews - ranging from a praise of the observed fresh-just-showered smell to complaints of the need to eat a buck load of candies to see some kind of effect. Does it really work? It might for some of us. With the right chemistry and metabolism, and the right combination of everything else. You can enter it in Aurametrix as Deo Perfume Candy and check back later to see how it worked for others. Or just log what you normally eat and wear to find how your body could react to Geraniol.

You might want to compare it with “Fuwarinka” or Otoko Kaoru's chewing gum - despite a name that translates to "man smell" it also contains rose-flavored geraniol. Although one tester reported to smell like an apple-flavored soap after chewing it.  You can also experiment with the "coming soon" edible perfume from Netherlands, and its mystery ingredient (transformed by the body enzymes and excreted through the skin’s surface through perspiration). There will be more to come.

The possibilities are endless and so are the human odor outcomes.

REFERENCES

AKIYAMA, A., IMAI, K., ISHIDA, S., ITO, K., KOBAYASHI, T., NAKAMURA, H., NOSE, K., & TSUDA, T. (2006). Determination of Aromatic Compounds in Exhalated from Human Skin by Solid-Phase Micro Extraction and GC/MS with Thermo Desorption System BUNSEKI KAGAKU, 55 (10), 787-792 DOI: 10.2116/bunsekikagaku.55.787

Studying body odor: one step at a time

Unpleasant body odors could be a sign of a disease. But even when the cause of the disease is known - an example is trimethylaminuria or TMAU - there are no one-size-fits-all solutions. Elimination of choline and other essential nutrients from diet can be harmful and unhelpful.  Everyone has their own unique needs, with individual combinations of foods, activities and optimal environmental conditions.

An earlier survey of about 100 body odor and halitosis sufferers indicated stress (34%), food (25%) and environment, including the weather and perfumed products (15%) as main triggers of odors. 23% of sufferers did not know what the trigger was.

Our study seems to have less unknowns. As you see from the picture, 60% of participants have both body odor and halitosis. Only 22% of participants were diagnosed with TMAU, one third has IBS, one third has environmental sensitivities (mostly pollen and mold allergies, but some have dust mite and pet allergies and chemical sensitivities). Over 60% of participants reported sensitivities to specific foods. Most frequent was lactose sensitivity.

It is known that a specific diet, infections and diseases have major impact on variations in human body odor.  Some of our early results on fatty and ammonia types of odors identified a few food ingredients and their maldigestion as potential causes. Our next posts on musty and smoky odors, as well as unpleasant odors in general will tell more.

e-mail to

 for more information

And stay tuned for results!

REFERENCES
Jan Havlicek, & Pavlina Lenochova (2008). Environmental effects on human body odour Chemical Signals in Vertebrates DOI: 10.1007/978-0-387-73945-8_19

Havlicek, J., & Lenochova, P. (2006). The Effect of Meat Consumption on Body Odor Attractiveness Chemical Senses, 31 (8), 747-752 DOI: 10.1093/chemse/bjl017

Moshkin M, Litvinova N, Litvinova EA, Bedareva A, Lutsyuk A, Gerlinskaya L. Scent Recognition of Infected Status in Humans. J Sex Med. 2011 Dec 6. doi: 10.1111/j.1743-6109.2011.02562.x.

What's that fatty odor?

Body odor is closely associated with diet. Deciphering the chemistry of human odor is not an easy task - only about 5% of odorous molecules are usually recovered from collection containers, and not all of the molecules are identified in complex spectra. Volatile fatty acids, alcohols, and aromatic ring compounds comprise a substantial fraction of smelly molecules, yet very little is known about the origin and factors controlling their production in humans. Fortunately for some (and not so fortunately for others), the human nose can capture and discriminate many smell signatures. Could this discrimination be used to connect the dots between diet and body odor? MEBO Research has just started an anonymous study using the Aurametrix health analysis tool to find out.

Aurametrix's knowledge base provides a wide selection of foods and symptoms, including different types of odors recognizable by the human nose. Participants in the study have been recording some of their food intake and activities on days when their symptoms are better or worse than average, entering items they suspect might be contributing to or alleviating their body odor on those days. The tool's analysis engine then lets them explore all the possible cause-effect relationships. In addition, Aurametrix performs automated analyses across the entire user community and displays cumulative results as "aggregate correlations." The figure on the right is an excerpt from these results.

Although the study has only just begun, the preliminary results already look very interesting. One example is fatty odor. Aurametrix linked several dietary chemicals to unpleasant "fatty odor" emanating from skin based on Aura entries of several participants. The top chemicals so far are:  Vitamin K1 (phylloquinone), Octadecanoic acid, FODMAPs, Beta-carotene,  Carbohydrates and Monosaccharides. Another interesting result (although there were fewer observations) is that Vitamin B12 obtained from diet seemed to help prevent fatty body odor.

• Could Vitamin K1 really contribute to "fatty" odor?  Could 6 observations derived from different users' Auras be just a coincidence? Vitamin K is proposed to increase production of alkaline phosphatase in intestines. This enzyme produces a number of different substances, some of which have a peculiar sweetish smell.  Chlorophyll, usually recommended to combat body odor and supposedly makes odor "sweeter," is an excellent source of vitamin K1. And so is Asparagus that gives urine a disagreeable odor.
• Octadecanoic (Stearic) acid was also linked to fatty odor in 6 observations. This saturated fatty acid is most abundant in animal fats and cocoa butter, and also in nuts and seeds (peanuts, flax), cheese, cookies and candies. Its smell is fairly mild, yet can be detected by the human nose (Bolton and Halpern, 2010). Besides, it slowly converts in the liver to heart-healthy oleic acid which has a faintly fatty odor with a hint of dead insects. It could also metabolize into other compounds and incorporate into liver lipids or follow alternative routes.
• FODMAPs, highly fermentable but poorly absorbed short-chain carbohydrates and polyols, were found to be an important dietary factor contributing to gastrointestinal symptoms. Perhaps FODMAPs, carbohydrates and monosacharides in particular could also contribute to odor in the absence of GI discomfort?
• Beta-carotene is another heart-healthy chemical with anticancerous properties important in human nutrition as a source of Vitamin A. Tobacco, tea, many spices and flowers owe their flavors to chemicals metabolized from beta-carotene. One of such chemicals is warm and woody beta-Ionone that smells of blackberry at lower concentrations and fatty-cheesy at higher concentrations.

The chemistry of odors and their origins is undoubtedly very complex. Yet, these preliminary results show that together we may find the answers to many health-related questions. With more participants, we'll soon connect the dots between diet and body odor. Want to participate? Write to:

References

Bolton B, & Halpern BP (2010). Orthonasal and retronasal but not oral-cavity-only discrimination of vapor-phase fatty acids. Chemical senses, 35 (3), 229-38 PMID: 20100787

Dunkel M, Schmidt U, Struck S, Berger L, Gruening B, Hossbach J, Jaeger IS, Effmert U, Piechulla B, Eriksson R, Knudsen J, & Preissner R (2009). SuperScent--a database of flavors and scents. Nucleic acids research, 37 (Database issue) PMID: 18931377

Colonoscopy for everyone! ..or Gonna Buy Me A Dog

New research from Japan brings good news: dogs can be almost as accurate as a colonoscopy exam.

In patients with colorectal cancer (CRC) and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99.

The sensitivity of canine scent detection of watery stool samples was 0.97 and the specificity was 0.99.

The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease.  

As simple as that: exhaling 100-200 ml into a breath sampling bag and storing it in a Ziploc bag at 4°C until a trained dog has a change to sniff it can be enough for diagnostics. Just one breath sample! And it was almost as good as a watery stool sample obtained during colonoscopy or this joyous examination itself.

There have been many research studies that dogs, rats and even moth can detect scents pertaining to human disease. Ordinary household dogs can be trained to distinguish breath odors (McCulloch et al 2006). For some cancers, sensitivity can be as high as 100% (Horvath et al 2008).

Unfortunately, sophisticated mass-spectrometry, gas chromatography and software tools interpreting the signals are still not as good as our four-legged friends that are never getting lost in the noise of disease-unrelated flavors.
But we are getting better in identifying specific chemicals responsible for various conditions - from alkanes  - such as pentane in breath of IBD patients and polystyrene foam or aromatic components of petroleum in cancer breath to blends of fatty acids like oleic and linoleic acids forming the smell of death.

Perhaps pet rats will find their use as pocket doctors before men-made sensors are developed to cope with infections, medical conditions, even fear and anxiety that also have a distinctive odor signature. In any case, Dr. Sonoda and his colleagues bring us a reassuring word that not every frequent visitor to the GI doctor's office will have to experience the joys of a colonoscopy.


Sonoda H, Kohnoe S, Yamazato T, Satoh Y, Morizono G, Shikata K, Morita M, Watanabe A, Morita M, Kakeji Y, Inoue F, & Maehara Y (2011). Colorectal cancer screening with odour material by canine scent detection. Gut PMID: 21282130


Other published literature on olfactory signatures in gastrointestinal disease:

Cheu HW, Brown DR, Rowe MI (1989) Breath hydrogen excretion as a screening test for the early diagnosis of necrotizing enterocolitis. Am J Dis Child 1989;143:156–9.

Pelli MA, Trovarelli G,, Capodicasa E, Breath alkanes determination in ulcerative colitis and Crohn's disease. Dis Colon Rectum 1999;42:71–6.

Pelton NS, Tivey DR, Howarth GS, A novel breath test for the non-invasive assessment of small intestinal mucosal injury following methotrexate administration in the rat. Scand J Gastroenterol 2004;9:1015–16.

Tibble JA, Sigthorsson G, Foster R, Use of surrogate markers of inflammation and Rome criteria to distinguish organic from nonorganic intestinal disease. Gastroenterology 2002;123:450–60.

Hormonal Manipulation of Olfactory Cues, or How to Lose a Guy in 10 days

Image via Wikipedia

Body odors are important cues used for social and sexual discrimination. As was shown many times, animals can easily smell age-, health- and genetics-related  differences.  Recent study of our large-eyed relatives, ring-tailed lemurs, demonstrate that drugs can alter body scents and change behavior.

Researchers examined changes in endocrine and  semiochemical profiles of sexually mature female lemurs treated with hormonal contraceptives during their breeding season. Genetic diversity and kinship were estimated using 11–14 microsatellite loci and pairwise genetic distances. Gas chromatography-mass spectrometry (GCMS) was used to detect the volatile compounds in odor. A rater blind to the treatments scored lemur male behavior in regards to female odors. 

The conclusion? Contraceptives change chemical ‘signature’, minimizing distinctiveness and genetic fitness cues. No more can the males determine which females are genetically and physically beautiful. All contracepted females lost their individuality and started to smell funny.  

What about hormones and chemicals in our food?  Maybe one day humans will wake up and realize that something is lost? May it will happen  sooner rather than later...

For those interested in helping with our research of human environmental malodor - check our studies or this call for collaboration.   



Jeremy Chase Crawford,, Marylène Boulet,, & Christine M. Drea (2010). Smelling wrong: hormonal contraception in lemurs alters critical female odour cues Proc. R. Soc. B published online before print July 28, 2010

Odor-prints: individual but genetic connections unclear

Odor is like fingerprints or facial features - it's unique.  Yet no single measurement could be easily applied to recognize an individual.

GC/MS measurements can be used to analyze mixtures of acids, alcohols, aldehydes, hydrocarbons, esters, ketones, and nitrogenous molecules in human odor. Complex algorithms mining patterns help to pinpoint the signatures. But could these signatures be easily derived from genetic makeups?

Recent article published in the Journal of Chemical Ecology looked at the usual suspects -  major histocompatibility locus (MHC) and found that these genes do not determine major patterns. 


Volatile carboxylic acids are the most diverse class of known axillary odorants, and the pattern of these acids is genetically determined. These acids  - like vast majority of human odorous compounds - are produced by human microbiome, in this case by skin bacteria. Odors of 12 families, comprising 3 to 6 siblings,were analyzed with comprehensive two-dimensional gas chromatography (GC x GC) and time-of-flight mass spectrometry (ToF MS). the analysis onfirmed the presence of individual signatures. but failed to find odors specific to HLA genes.

Even though paternally inherited HLA-associated odors were proposed to influence women odor preferences, genetic basis of odors may be more complicated than previously thought.

References

Natsch A, Kuhn F, & Tiercy JM (2010). Lack of Evidence for HLA-Linked Patterns of Odorous Carboxylic Acids Released from Glutamine Conjugates Secreted in the Human Axilla. Journal of chemical ecology PMID: 20623248

Thompson EE, Haller G, Pinto JM, Sun Y, Zelano B, Jacob S, McClintock MK, Nicolae DL, Ober C. (2010) Sequence variations at the human leukocyte antigen-linked olfactory receptor cluster do not influence female preferences for male odors. Hum Immunol. 2010 Jan;71(1):100-3. PMID: 19833159 
 
Jacob S, McClintock MK, Zelano B, Ober C (2002) Paternally inherited HLA alleles are associated with women's choice of male odor. Nature Genet 30: 175-179  PMID: 11799397  PDF