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

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.