{"doi":"10.1093/infdis/jiad405","title":"Thinking Small, Stinking Big: The World of Microbial Odors","abstract":"Humans live embedded in an ecosystem of microbial life. Nowhere is this ecosystem more apparent to the naked eye (or, rather, nose) than in the world of microbially derived odors. From the fungal fragrances that sing of environmental mold to the bacterial bouquet that warns us off week-old leftovers, our air comprises a microbial miasma of information, ripe for research and exploration. Microbially derived odors, especially those produced by pathogens, can prove useful in the toolkit of both the microbe and the diagnostician. A rapidly increasing number of studies highlight the need for further understanding of these odors—their origins, their functions, and their utility in our hands. Microbial odors are mediated by volatile organic compounds (VOCs), small organic molecules with low boiling points, generally synthesized during the microbe's metabolism. Multicellular organisms typically detect VOCs via dedicated odor receptors, such as those in the vertebrate nose or on arthropod antennae. In the laboratory, individual VOCs produced by microbes can be characterized using gas chromatography/mass spectrometry, while the global fingerprint of microbial odors can be recognized through use of electronic nose technology. Which microbial VOCs mediate what odors—and to what purpose—are topics of ongoing investigation in the field. Why even care about the little smells of our microscopic neighbors? Specific odors have long been associated with human disease and have served well as rudimentary and noninvasive diagnostics. As early as 400 Bce, Hippocrates advised that students smell their patients’ breath to diagnose illness [1]. While our understanding of the underlying pathophysiology may have advanced in the millennia hence, conditions such as portal hypertension and diabetic ketoacidosis are readily recognized by their associated characteristic odors. Microbial pathogens tend to demonstrate more subtle odor profiles than these noninfectious conditions, as the odoriferous insult operates on far smaller orders of magnitude. This has not stopped us from seeking out new methods of detecting microbial infection by way of produced VOCs. Compared to other testing mechanisms, testing the odor profile of patients is minimally invasive. Additionally, as the testing relies on key metabolic products of the infection rather than easily mutated antigens, the prospect of microbial mutation away from diagnostic efficacy is far more remote. Detection of infection by way of scent has already proven possible thanks to both human technology and mammalian cooperation. In partnership with our four-legged friends, human clinicians have been able to pinpoint infections with startling accuracy on the basis of scent alone. African giant pouched rats (Cricetomys gambianus) in Tanzania and Mozambique have been successfully trained to sniff out and differentiate sputum samples from patients infected with tuberculosis, with greater accuracy than even trained human microscopists [2]. In Canada and the Netherlands, meanwhile, odor-sniffing dogs (Canis lupus familiaris) have been trained to identify Clostridium difficile in stool [3]. Preliminary studies additionally abound investigating the potential of canine assistance in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [4]. Manmade attempts are likewise promising, with breath tests for infections such as tuberculosis, SARS-CoV-2, and even malaria showing high sensitivity and accuracy [5]. Our ability to accurately and noninvasively pinpoint infection looks to be steadily improving, in part by detecting pungent pathogens. In the push and pull of host-pathogen competition, any evolutionary advantage over the adversary is liable to be maintained, and any disadvantage quickly discarded. Why, then, might pathogenic microbes release VOCs at all, if they might facilitate host detection and avoidance of infection? Microbial odors are not simply an inevitable byproduct of host metab","journal":"The Journal of Infectious Diseases","year":2023,"id":377621,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.939,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":28530,"name":"Audrey R. Odom John","orcid":"0000-0001-8395-8537","position":1,"is_corresponding":false},{"id":1089752,"name":"Tzvi Pollock","orcid":"0000-0001-8530-6751","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T01:16:40.346877Z","pmid":"37738417","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}