Journal of Clinical Medicine Review The Role of Oral Microbiota in Intra-Oral Halitosis Katarzyna Hampelska 1,2, Marcelina Maria Jaworska 1 , Zuzanna Łucja Babalska 3 and Tomasz M. Karpi ´nski 3,* 1 Department of Genetics and Pharmaceutical Microbiology, Pozna´nUniversity of Medical Sciences, Swi˛ecickiego4,´ 60-781 Pozna´n,Poland; [email protected] (K.H.); rufi[email protected] (M.M.J.) 2 Central Microbiology Laboratory, H. Swi˛ecickiClinical´ Hospital, Pozna´nUniversity of Medical Sciences, Przybyszewskiego 49, 60-355 Pozna´n,Poland 3 Chair and Department of Medical Microbiology, Pozna´nUniversity of Medical Sciences, Wieniawskiego 3, 61-712 Pozna´n,Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-61-854-6138 Received: 27 June 2020; Accepted: 31 July 2020; Published: 2 August 2020 Abstract: Halitosis is a common ailment concerning 15% to 60% of the human population. Halitosis can be divided into extra-oral halitosis (EOH) and intra-oral halitosis (IOH). The IOH is formed by volatile compounds, which are produced mainly by anaerobic bacteria. To these odorous substances belong volatile sulfur compounds (VSCs), aromatic compounds, amines, short-chain fatty or organic acids, alcohols, aliphatic compounds, aldehydes, and ketones. The most important VSCs are hydrogen sulfide, dimethyl sulfide, dimethyl disulfide, and methyl mercaptan. VSCs can be toxic for human cells even at low concentrations. The oral bacteria most related to halitosis are Actinomyces spp., Bacteroides spp., Dialister spp., Eubacterium spp., Fusobacterium spp., Leptotrichia spp., Peptostreptococcus spp., Porphyromonas spp., Prevotella spp., Selenomonas spp., Solobacterium spp., Tannerella forsythia, and Veillonella spp. Most bacteria that cause halitosis are responsible for periodontitis, but they can also affect the development of oral and digestive tract cancers. Malodorous agents responsible for carcinogenesis are hydrogen sulfide and acetaldehyde. Keywords: halitosis; malodor; volatile sulfur compounds; hydrogen sulfide; microbiota; Fusobacterium; Porphyromonas; Prevotella; periodontitis; carcinogenesis 1. Introduction Halitosis is a common problem that manifests as an unpleasant and disgusting odor emanating from the mouth [1]. Malodor is mainly caused by putrefactive actions of microorganisms on endogenous or exogenous proteins and peptides. Oral malodor is an embarrassing condition that affects a large percentage of the human population. This condition often results in nervousness, humiliation, and social difficulties, such as the inability to approach people and speak to them [2–6]. Halitosis experiences from about 15% to 60% of the human population worldwide [7–12]. Halitosis can be divided into extra-oral halitosis (EOH) and intra-oral halitosis (IOH) [2,3,5]. The factors that increase the likelihood of halitosis include periodontal diseases, dry mouth, smoking, alcohol consumption, dietary habits, diabetes, and obesity. Halitosis can also be affected by the general hygiene of the body (i.e., dehydration, starvation, and high physical exertion), advanced age, bleeding gums, decreased brushing frequency, but also by stress [3,13–16]. Produced during stress, catecholamines and cortisol increased hydrogen sulfide production by sub-gingival anaerobic bacteria [17]. The medications which can cause extra-oral halitosis were categorized into 10 groups: acid reducers, aminothiols, anticholinergics, antidepressants, antifungals, antihistamines and steroids, antispasmodics, chemotherapeutic agents, dietary supplements, and organosulfur substances [18]. J. Clin. Med. 2020, 9, 2484; doi:10.3390/jcm9082484 www.mdpi.com/journal/jcm J. Clin.J. Clin. Med. Med.2020 2020, 9, ,9 2484, x FOR PEER REVIEW 2 of2 of18 17 More and more patients are struggling with bad breath and report this problem to their primaryMore andcare more practitioner patients arefor strugglingdiagnosis withand badmanagement breath and report[19,20]. this However, problem tomany their physicians, primary care practitionerdentists, and for biologists diagnosis andhave management insufficient knowledge [19,20]. However, regarding many the physicians, cause and dentists,biochemistry and biologists of this havedisease. insu ffi cient knowledge regarding the cause and biochemistry of this disease. InIn this this review, review, we we focused focused on on intra-oral intra-oral halitosis,halitosis, regardlessregardless of of classification. classification. 2.2. Classifications Classifications of of Halitosis Halitosis InIn the the literature, literature, mainly mainly threethree classificationsclassifications of of halitosis halitosis are are used, used, described described by by Miyazaki Miyazaki et etal., al., 19991999 [21 [21],], Tangerman Tangerman andand WinkelWinkel inin 20102010 [[22],22], and Aydin Aydin and and Harvey-Woodworth Harvey-Woodworth in in 2014 2014 [23] [23 ] (Figure(Figure1). 1). FigureFigure 1.1. ClassificationsClassifications of of halitosis halitosis [21–24]. [21–24]. MiyazakiMiyazaki et et al. al. divided divided halitosis halitosis as intra-oralas intra-oral (IOH) (IOH) and extra-oraland extra-oral (EOH) (EOH) [21]. Extra-oral [21]. Extra-oral halitosis canhalitosis be of can bloodborne be of bloodborne or non-bloodborne or non-bloodborne origin orig andin and covers covers about about 5–10% 5–10% of all all halitosis halitosis [22]. [22 ]. Bloodborne-relatedBloodborne-related causes causes include include diabetes diabetes metabolic metabo disorders,lic disorders, kidney kidney and and liver liver diseases, diseases, and certainand drugscertain and drugs food. and Non-bloodborne-related food. Non-bloodborne-related causes includecauses include respiratory respiratory and gastrointestinal and gastrointestinal diseases. Meanwhile,diseases. Meanwhile, pathological pathological conditions conditions in the oral in cavitythe oral are cavity responsible are responsible for 80–90% for 80–90% of IOH of [ 2IOH,3,25 ]. Both[2,3,25]. aerobic Both and aerobic anaerobic and bacteria anaerobic can bacteria be responsible can be forresponsible IOH. These for microorganisms IOH. These microorganisms tend to produce foul-smelling,tend to produce sulfur-containing foul-smelling, gases sulfur-containing called volatile gases sulfur called compounds volatile (VSCs)sulfur compounds [23,26]. (VSCs) [23,26].In the classification of Tangerman and Winkel [22], halitosis is classified as genuine and delusional. DelusionalIn the halitosis classification (monosymptomatic of Tangerman hypochondriasis; and Winkel [22], imaginary halitosis halitosis) is classified is a conditionas genuine in whichand patientsdelusional. believe Delusional that their halitosis breath is (monosymptomatic smelly and offensive. hypochondriasi The social pressures; imaginary of having halitosis) fresh smelling is a condition in which patients believe that their breath is smelly and offensive. The social pressure of breath increases the number of people that are preoccupied with this condition. However, the perception having fresh smelling breath increases the number of people that are preoccupied with this of oral malodor does not always reflect actual clinical oral malodor [27]. Self-perceived halitosis was condition. However, the perception of oral malodor does not always reflect actual clinical oral found to be more prevalent amongst males, particularly smokers, compared to females. However, malodor [27]. Self-perceived halitosis was found to be more prevalent amongst males, particularly there are no statistical differences when comparing with different age groups [28]. Genuine halitosis is smokers, compared to females. However, there are no statistical differences when comparing with further subdivided into physiological and pathological halitosis. Physiological halitosis (foul morning different age groups [28]. Genuine halitosis is further subdivided into physiological and breath, morning halitosis) is caused by saliva retention, as well as the putrefaction of entrapped food pathological halitosis. Physiological halitosis (foul morning breath, morning halitosis) is caused by particles.saliva retention, Meanwhile, as well intra- as and the extra-oral putrefaction causes of entrapped are responsible food forparticles. pathological Meanwhile, halitosis intra- [3,4 ,and19]. extra-oralAydin andcauses Harvey-Woodworth are responsible for dividedpathological pathologic halitosis halitosis [3,4,19]. into five types: Type 1 (oral), Type 2 (airway), Type 3 (gastroesophageal), Type 4 (blood-borne) and Type 5 (subjective). Moreover, it is Type 0 halitosis (physiologic odor), which can be a connection of the physiologic contributions of oral, J. Clin. Med. 2020, 9, 2484 3 of 17 J. Clin. Med. 2020, 9, x FOR PEER REVIEW 3 of 18 J. Clin. Med. 2020, 9, x FOR PEER REVIEW 3 of 18 J. Clin. Med. 2020, 9, x FOR PEER REVIEW 3 of 18 airway, gastroesophageal,Aydin and Harvey-Woodworth blood-borne, divided and subjective pathologic halitosis. halitosis into Any five combination types: Type of1 (oral), the above Type types Aydin and Harvey-Woodworth divided pathologic halitosis into five types: Type 1 (oral), Type 2 (airway),Aydin Typeand Harvey-Woodworth 3 (gastroesophageal), divided Type 4 pathologic (blood-borne) hali tosisand Typeinto five 5 (subjective). types: Type Moreover, 1 (oral), Type it is can be2 (airway), present Type in every 3 (gastroesophageal), healthy person [Type23]. 4 (blood-borne) and Type 5 (subjective). Moreover, it is Type2 (airway), 0 halitosis Type (physiologic3 (gastroesophageal), odor), which Type can 4