The PKU microbiome

Phenylketonuria or PKU is an inborn error of metabolism associated with a "mousy" or "musty" odor. This odor is due to a buildup of phenylalanine substances in the body. Recent study explored gut microbiome in adults with PKU and found high levels of Bifidobacterium, Bacillus, Alistipes, Clostridium, Akkermansia, and Bacteroides, while much lower levels of Lactobacillus, Porphyromonas, Frisingicoccus, Blautia, and Faecalibacterium.

REFERENCES

Mancilla VJ, Mann AE, Zhang Y, Allen MS. The Adult Phenylketonuria (PKU) Gut Microbiome. Microorganisms 2021, 9, 530.

Body Odor and Skin Bacteria

Our bodies are rainforests of microbes feeding off the leftovers from our meals and contributing to a variety of body odors. 

Human skin is inhabited and re-populated depending on health conditions, age, genetics, diet, the weather and climate zones, occupations, cosmetics, soaps, hygienic products and moisturizers. All these factors contribute to the variation in the types of microbes. Population of viruses, for example, can include a mixture of good ones - like bacteriophages fighting acne-causing Propionibacterium  - and bad ones  - as highly contagious Mesles. Bacterial communities include thousands of species of Actinobacteria, Bacteroidetes, Cyanobacteria, Proteobacteria, and fungi Malassezia.

Nat Rev Microbiol. 2011 April; 9(4): 244–253.

Nat Rev Microbiol. 2011 April; 9(4): 244–253.

These microbes form communities and have active social lives, cooperating to our good and bad experiences. They converse chemically - in many specific dialects and in universal Esperanto-like languages some of which even we could listen to  - by sampling and understanding smells. 

Humans are among the smelliest animals. And very capable in telling smells apart,  even if the only difference in two molecules is that their structures are mirror images of one another. But unlike dogs that appreciate a garbage bin as much as we appreciate the smell of fresh flowers, we don't properly interpret smells and like to complain about body odors. As we don't know all that much about chemical nature of our surroundings and rely on context and psychological factors, like feeling an intrusion in our experiences of the world. 

Maybe we have something to learn from the science of smells? 

In  a recent review of axillary microbiota, German researchers gave a good lesson in organic chemistry, listing major chemicals, enzymes and microbes responsible for body odor. Let's take a look. 

As was also shown in previous studies, Staphylococcus and Corynebacterium spp. are the most abundant organisms colonizing moist areas and emitting chicken-sulfury, onion-like and clary-sage like odors. The strain of Staphylococcus haemolyticus is producing some of the most offensive sulfury smells. Corynebacterium jeikeium K411 is another species that can compete on the strength of the odor. 

The major odor-causing substances are sulphanyl alkanols, steroid derivatives and short volatile branched-chain fatty acids. 

Most common sulphanyl alkanol in human sweat, 3-methyl-3-sulfanylhexan-1-ol is produced by bacteria in several ways, particularly in glutathione biodetoxification pathway, from molecules synthesized after consuming proteins (due to aminoacids L-cysteine, L-glutamic acid and glycin). This chemical,  besides being a major descriptor of human sweat odor,  is also present in beers. Its S-enantiomer (75%) is described as a classical body odor (sweat) with onion-like tones. Interestingly, the opposite enantiomer, (R)-3-methyl-3-sulfanylhexan-1-ol, is fruity and grapefruit-like. 

Another set of molecules produced by Corinebacterium are most prominent in Caucasian men and some Asians. The odor is hircine - resembling of goats with fatty and cheesy notes or cumin-spice like. The food sources contributing to this odor are proteins and animal fats. 

Pheromones androstenol and androstenone, metabolites of sexual hormones, are also odorous. The latter is especially interesting as to some of us it smells like vanilla while to others is smells like urine.

Sweaty-feet and cheesy smelling isovaleric and propionic acids and sour-vinegary acetic acid are also adding to the spectrum of human odors.  They can smell different to different people too - some people have genetic makeup making them hypersensitive to these smells, but others are much more tolerant and forgiving. The food sources of sourish smells are protein-rich. Lactic acid is found in cheeses, yogurt, soy sauce, sourdough, meats and pickled vegetables. It can be also produced from the breakdown of carbohydrates during exercise and used as additional fuel. Glycerol is created from triglycerides found in fats and oils.  

So next time you are exposed to body odor, try to understand what could be causing it. It is not easy as it is a combination of many factors such as hormonal fluctuations, mental or physical stress, metabolism and microbes. It could be perfectly normal or result from a medical condition of the person who has the smell and your own olfactory abilities. But the smells are fascinating clues to health and  the basics can be learned by most everyone.

REFERENCES

Fredrich E, Barzantny H, Brune I, & Tauch A (2013). Daily battle against body odor: towards the activity of the axillary microbiota. Trends in microbiology, 21 (6), 305-12 PMID: 23566668

Grice EA, & Segre JA (2012). The human microbiome: our second genome. Annual review of genomics and human genetics, 13, 151-70 PMID: 22703178

Stevenson, R., & Repacholi, B. (2005). Does the source of an interpersonal odour affect disgust? A disease risk model and its alternatives. European Journal of Social Psychology, 35 (3), 375-401 DOI: 10.1002/ejsp.263

Troccaz M, Starkenmann C, Niclass Y, van de Waal M, Clark AJ.  ( 2004) 3-Methyl-3-sulfanylhexan-1-ol as a major descriptor for the human axilla-sweat odour profile.Chem Biodivers. 2004 Jul;1(7):1022-35. PMID: 17191896

Lenochová P, Vohnoutová P, Roberts SC, Oberzaucher E, Grammer K, Havlíček J (2012) Psychology of fragrance use: perception of individual odor and perfume blends reveals a mechanism for idiosyncratic effects on fragrance choice. (PMID:22470479) Free full text article  PLoS One [2012, 7(3):e33810]

Barzantny H, Brune I, Tauch A. (2012) Molecular basis of human body odour formation: insights deduced from corynebacterial genome sequences. Int J Cosmet Sci. 2012 Feb;34(1):2-11. doi: 10.1111/j.1468-2494.2011.00669.x. Epub 2011 Jul 25.  PMID: 21790661

The smell of Christmas

How does Christmas smell like? 

Like cinnamon! So say studies by European scientists  [1-3]. And even though the smell of cinnamon is described as "pungent" (besides "warm", 'sweet", and "spicy"), it fires up our brains, evoking a joyful Christmas mood and making us more generous. 

Cinnamon is classified as a stimulant. Smelling and tasting cinnamon could enhance attention and virtual recognition memory [4], at least in comparison to smells of peppermint, jasmine or cherries. In addition to its many healthy properties - like fighting E.coli in unpasteurized juices, lowering concentration of  fasting glucose, triglycerides, and total cholesterol - Cinnamon can make you feel fuller for longer [5]. So for those of us hoping to lose some weight - a cinnamon-flavored floss would be a good replacement for a Christmas desert.

Aggregate correlations - aka experience of the crowds analyzed in Aurametrix - tell many good things about Cinnamon. For example, that it led to less severe joint pain and helped with bad breath. Although - in higher concentrations - it was the reason of a yellowish skin.

Unfortunately for those with digestive problems, other Christmas-flavored foods seemed to have more side effects. Aurametrix correlations for Apple told that exceeding sensitivity thresholds could lead to gas, fecal and musty smell (was this why an apple a day kept the doctor away?). Too much orange was associated with bloating, indigestion and yellow stool. Pumpkin, on the other hand, lead to slightly better flavored gas!

With more daily observations entered by the users, Aurametrix will make more correlations between wellbeing and food flavors. But for now -

Merry Christmas! And let's smell some cinnamon!



REFERENCES

1. Seo HS, Buschhüter D, & Hummel T (2009). Odor attributes change in relation to the time of the year. Cinnamon odor is more familiar and pleasant during Christmas season than summertime. Appetite, 53 (2), 222-5 PMID: 19576937

2. Martin Lindström, Philip Kotler. Brand Sense: Sensory Secrets Behind the Stuff We Buy. Simon and Schuster, Feb 2, 2010

3. Idle JR. Christmas gingerbread (Lebkuchen) and Christmas cheer--review of the potential role of mood elevating amphetamine-like compounds formed in vivo and in furno. Prague.Med Rep. 2005;106(1):27-38.

4. Phillip Zoladz.  2003-2004 Allyn & Bacon Award Abstracts. Impact of the Chemical Senses on Augmenting Memory, Attention, Reaction Time, Problem Solving, and Response Variability: The Differential Role of Retronasal Versus Orthonasal Odorant Administration

5. Hlebowicz, J., Hlebowicz, A., Lindstedt, S., Bjorgell, O., Hoglund, P., Holst, J., Darwiche, G., & Almer, L. (2009). Effects of 1 and 3 g cinnamon on gastric emptying, satiety, and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and ghrelin concentrations in healthy subjects American Journal of Clinical Nutrition, 89 (3), 815-821 DOI: 10.3945/ajcn.2008.26807

6. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215–8.

7. Catherine Ulbricht, Erica Seamon, Regina C. Windsor, Nicole Armbruester, J. Kathryn Bryan, Dawn Costa, Nicole Giese, Joerg Gruenwald, Ramon Iovin, Richard Isaac, Jill M. Grimes Serrano, Shaina Tanguay-Colucci, Wendy Weissner, Heeja Yoon, and Jie Zhang. An Evidence-Based Systematic Review of Cinnamon (Cinnamomum spp.) by the Natural Standard Research Collaboration.  Journal of Dietary Supplements, December 2011, Vol. 8, No. 4 : Pages 378-454 (doi: 10.3109/19390211.2011.627783)