Abstract
Halitosis is a common and ignored condition, but in some, it is a disease-associated health problem, suggestive of overt disease conditions and hasaffected about 25–30% of world’s population, bothering nonmedical social disturbance in many people. Although two kinds, pseudohalitosis and halitophobia, are also concerned, genuine halitosis originated from the oral cavity, such as gingivitis, caries, and poor oral hygiene, in 80% and the remaining 20% are extraoral sources of halitosis, which should not be ignored because of stigmata suggestive of overt tissue dysfunctions, for instance, poor nutrition and hygiene, alcohol abuse, smoking, and systemic illness such as chronic obstructive pulmonary disease, liver cirrhosis, diabetes mellitus, and chronic renal diseases. In this chapter, Helicobacter pylori (H. pylori)–associated halitosis as one of the extragastric manifestations is introduced. Since diagnostics of halitosis includes subjective methods (examiner’s sense of smell) and objective methods (instrumental analysis), under the hypothesis of a possible relationship between H. pylori infection and objective halitosis, the real levels of volatile sulfur compounds (VSCs) in the breath showed significant correlation between VSC levels and the degree of H. pylori–associated erosive gastritis as well as gastric cancer. These findings are further validated through either measuring H2S level in gastric juices of H. pylori–infected gastritis or checking the expressions of cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) responsible for H2S generation in biopsied stomach. The eradication of H. pylori significantly ameliorated halitosis, accompanied with significant reductions in gastric H2S levels (p<0.01). Korean red ginseng was very effective in either reducing H. pylori–associated H2S or alleviating halitosis in patients with H. pylori–associated chronic atrophic gastritis. Conclusively, H. pylori infection demonstrates to have an important relationship with the development of halitosis, and its eradication could possibly promote the improvement of this condition.
Keywords
- Halitosis
- Helicobacter pylori
- volatile sulfur compounds
- hydrogen sulfide
- gastritis
- gastroesophageal reflux disease
1. Introduction
1.1. Halitosis, pseudohalitosis, and halitophobia
Halitosis is a very common and unpleasant condition, affecting around 1/4–1/3 of the general population, which can be classified into the following three conditions, genuine halitosis, pseudohalitosis, and halitophobia based on their pathogenesis [1, 2]; genuine halitosis is usually related to an organic pathology, such as periodontitis, gingivitis, gastritis, and other systemic illness, and malodor molecules such as volatile sulfur compounds (VSCs) that arise usually from bacterial interactions generate the basis of oral malodor, such as hydrogen sulfide (H2S), methyl mercaptan (CH3SH), and dimethyl sulfide [(CH3)2S]. In addition, sulfur compounds, short-chain fatty acids, such as butyric acid (CH3CH2CH2COOH), propionic acid (CH3CH2COOH), and valeric acid (C5H10O2), diamines, including cadaverine [NH2(CH2)5HN2] and putrescine [NH2(CH2)4HN2], 1-proxy-2-propanol, phenyl compounds, such as indole, skatole, phyridiene, alkalines, ketones, and nitrogen-containing compounds, such as urea [(NH2)2CO2] and ammonia (NH3), may contribute to malodor of halitosis [3, 4]. When the concentration of these molecules in halitotic breath exceeds a threshold detected by objective methods, genuine halitosis can be diagnosed. Furthermore, pathologies of the tongue, poor oral hygiene, deep caries, and postnasal drainage are primarily associated with halitosis, in which condition, species such as
Halitosis relevant with practical clinical problems can be classified into the following two clinical situations according to origin, one is oral halitosis, around 90% in all, and the other is extraoral halitosis, remaining 10% among whole halitosis [9]. Since VSCs are responsible for halitosis irrespective of origin, in case of extraoral halitosis, VSCs generally generated from the body, travel to the lung through the vascular system, and pull out through breath from the alveoli. As another systemic diseases causing extraoral halitosis, liver disease, such as cirrhosis, hepatoma, and hepatic failure, uremia from end-stage renal disease, and metabolic disorder, such as diabetic ketoacidosis and other kinds of metabolic disorders had been reported. Also, excess food intake (food factors) like garlic or onion can be common etiology for halitosis [10, 11]. Among these system diseases, it must be kept in mind that halitosis can be a clue symptom suggestive of serious cancers, especially gastric, liver, and pancreatic cancer. Furthermore, halitosis can be one of the prominent extragastric manifestations suggestive of
2. Halitosis provoked by gastrointestinal (GI) diseases
Apart from oral cavity, the GI tract diseases caused halitosis as presenting symptoms, though physician and patients still abusively believe that halitosis originates from the oral cavity or stomach. For instance, almost all patients suffering from some erosive changes in esophago-gastric organ, halitosis might be very common and earliest manifestation. In our earlier investigation [15], almost all patients with GERD or some degree of erosive gastritis, real levels of VSCs were significantly increased. Other examples of clinical diseases, such as pyloric stenosis, duodenal obstruction, aorto-enteric anastomosis, pharyngeal pouches, Zenker’s diverticulum, and hiatal hernia, usually led to halitosis as usual clinical manifestations. Especially, GERD, achalasia, or other malabsorption syndromes may cause halitosis accompanied with other symptoms of retching and flatulence. In cases of intestinal obstruction, halitosis may be detectable because the first sign noticed to either patient’s relatives or physician. Halitosis is usually noted after consuming dietary products, such as garlic, onions, and some spiced foods cause transient unpleasant odor or halitosis [14]. Yoo
3. Hydrogen sulfide (H2S) biogas: Good, bad, ugly in its biology, and halitosis
Although biologic gas such as H2S as principal gas molecule is responsible for causing halitosis, there are contradictory biological implications of three major biogas, nitric oxide (NO), H2S, and carbon monoxide (CO), in anti-inflammatory substances, promoting resolution of inflammatory processes, imposing several situations, including ischemic-reperfusion injury, cardioprotection, sepsis, hemostasis, fibrosis, pancreatitis, separately, but sometimes interacting each other [19, 20]. Interestingly, H2S stands for dual functions, inflammatory mediator or anti-inflammatory mediator [21], gaseous intracellular transducer implicated in either abnormal pathology or normal physiology [22], positioning homeostasis as friend or foe [23]. H2S and their responsible enzymes, cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE), played good or bad, but ugly biological implications dependent on cellular context and disease conditions.
Though many new technologies to detect endogenous H2S production and to develop novel H2S-delivery compounds have been invented [24], simple gas with complex biology of good, bad, and ugly aspect, in this chapter, the way to detect VSCs, the implication of H2S among VSCs, and their regulations will be introduced. The Halimeter (Interscan corporation, Chatsworth, CA, Figure 1A) and OralChroma (Abimedical corporation, Kanagawa, Japan) are electronic devices available to detect some of the VSCs in expired air easily in clinic. These two devices are a portable gas chromatograph featuring easy to handle, lower cost, higher performance, time saving, fast results, very accurate, and reproducible even compared with conventional gas chromatographs. However, the limitation is that they limitedly target three gases: H2S, CH3SH, and (CH3)2S. With the Halimeter measurement, the total amount of VSCs in
3.1. H2S as dual-edged sword, is it neurotransmitter or inflammatory mediator?
H2S is a well-known toxic gas that is synthesized from the amino acids, cysteine and homocysteine, by two enzymes, CBS and CSE [30, Figure 1C]. Like other biogas, CO or NO, H2S is a signaling molecule implicated in either physiological actions of the cardiovascular or digestive system or pathophysiological actions in homeostasis, proliferation, and apoptosis of vascular smooth muscle cells, insulin release, nociceptive effects, cytoprotection, but contradictory action of inflammatory mediators, for instance, pancreatitis, chronic obstructive pulmonary disease, joint inflammation, sepsis, and
4. Halitosis as one of extragastric manifestations of H. pylori infection (Figure 3)
There were two translational studies confirming the association between
5. Amelioration of troublesome halitosis through suppressing H. pylori –associated H2S with natural products
Lee
In conclusion, though the solution of halitosis problems must include the reduction of the intraoral bacterial load and/or the conversion of VSCs to nonvolatile substrates [50], targeting both etiologic organism removal and VSCs generating enzyme suppression seems to be very ideal modality of halitosis treatment (Figure 3), in which KRG seems to ideal product to deserve in clinic.
Acknowledgments
This study was supported by the grant from the Korea Society of Ginseng, funded from the Korea Ginseng Corporation (2012).
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