University of Groningen
Tongue coating
Seerangaiyan, Kavitha
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Seerangaiyan, K. (2018). Tongue coating: It’s impact on intra-oral halitosis and taste. Rijksuniversiteit Groningen.
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TONGUE COATING
hygiene, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Layout design: Kavitha Seerangaiyan Cover design: Kavitha Seerangaiyan
Printed by: Ridderprint B.V (https://www.ridderprint.nl/) ISBN: 978-94-034-1074-6 (printed version)
hygiene, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Layout design: Kavitha Seerangaiyan Cover design: Kavitha Seerangaiyan
Printed by: Ridderprint B.V (https://www.ridderprint.nl/) ISBN: 978-94-034-1074-6 (printed version)
Tongue coating
It’s impact on intra-oral halitosis and taste
PhD thesis
to obtain the degree of PhD at the University of Groningen
on the authority of the Rector Magnificus Prof. dr. E. Sterken
and according to the decision of the Doctorate Board. This thesis will be defended in public on Wednesday 28 November 2018 at 11:00 hours
by
Kavitha Seerangaiyan
born on 7 September 1983 in Oddanchatram, India
Prof. E.G. Winkel
Prof. A.J. van Winkelhoff
Co-supervisor
Dr. P.J.W. Jüch
Assessment Committee
Prof. A. Vissink Prof. C. de Baat Prof. H. van der Mei
Tongue coating
It’s impact on intra-oral halitosis and taste
PhD thesis
to obtain the degree of PhD at the University of Groningen
on the authority of the Rector Magnificus Prof. dr. E. Sterken
and according to the decision of the Doctorate Board. This thesis will be defended in public on Wednesday 28 November 2018 at 11:00 hours
by
Kavitha Seerangaiyan
born on 7 September 1983 in Oddanchatram, India
Prof. E.G. Winkel
Prof. A.J. van Winkelhoff
Co-supervisor
Dr. P.J.W. Jüch
Assessment Committee
Prof. A. Vissink Prof. C. de Baat Prof. H. van der Mei
You are the creator of your own destiny
You are the creator of your own destiny
Chapter 1 1 General introduction.
13
Chapter 2
Tongue coating: its characteristics and role in intra-oral halitosis and general health: A review.
Chapter 3
33
The tongue microbiome in healthy subjects and patients with intra-oral halitosis.
Chapter 4 53
Untargeted metabolomic analysis of the bacterial tongue coating of intra-oral halitosis patients.
Chapter 5 77
Tongue cleaning increases the perceived intensity of salty taste.
Chapter 6 87
General discussion, conclusion and future prospective
Summary 95
Samenvatting 98
Acknowledgements
101
Chapter 1 1 General introduction.
13
Chapter 2
Tongue coating: its characteristics and role in intra-oral halitosis and general health: A review.
Chapter 3
33
The tongue microbiome in healthy subjects and patients with intra-oral halitosis.
Chapter 4 53
Untargeted metabolomic analysis of the bacterial tongue coating of intra-oral halitosis patients.
Chapter 5 77
Tongue cleaning increases the perceived intensity of salty taste.
Chapter 6 87
General discussion, conclusion and future prospective
Summary 95
Samenvatting 98
Acknowledgements
101
CHAPTER
1
General Introduction
CHAPTER
1
General Introduction
Introduction The tongue
The human tongue is a muscular organ situated in the floor of the mouth, covered with a mucous membrane. Its function is associated with chewing, swallowing, vocalization, and taste. Anatomically, the tongue can be distinguished into root, tip, and dorsal and ventral surfaces. The V-shaped sulcus terminalis on the dorsal surface separates the oral and pharyngeal parts of the tongue. The tongue surface consists of tiny protrusions called tongue papillae, which can be classified into four types: filiform, fungiform, circumvallate, and foliate papillae [1]. Filiform papillae, present at the anterior part of the tongue, have a core length of 0.5 mm with a central crater and uplifted borders. They are responsible for tongue anterior roughness. The foliate papillae are located at the edges, whereas the vallate papillae are located at the posterior tongue with 1 mm height and 2–3 mm diameter [2]. Fungiform papillae have a core length of about 0.5–0.8 mm. Fungiform, foliate, and circumvallate papillae contain the sensory cells involved in taste sensation [40].
Traditionally, visible aspects of the tongue have played an important role in oral and general health. The tongue is involved in various diseases such as vascular and lymphatic lesions (infantile hemangiomas and oral varices), reactive and inflammatory processes (hairy tongue, pigmented fungiform papillae of the tongue, benign migratory glossitis, and fissured tongue), infections (oral hairy leukoplakia, herpes simplex and varicella zoster virus infections, human papillomavirus, and candidiasis), premalignant lesions (leukoplakia and erythroplakia), malignant lesions (squamous cell carcinoma, Kaposi sarcoma, and lymphatic proliferative diseases), and signs of systemic conditions such as nutritional deficiency and systemic amyloidosis [3]. The tongue can reflect symptoms of systemic diseases and serves as a diagnostic indicator and for that reason is often called “a true mirror of the body.” For example, in HIV, the tongue is associated with specific symptoms, including a white patch with a corrugated or hairy appearance on the lateral tongue margin that represents hairy leukoplakia, which helps in early diagnosis of the infection [4]. Unlike other parts of the oral cavity, the patient can inspect the changes of the tongue easily and can misinterpret changes that they perceive. The involvement of the tongue in various disorders and diseases poses a diagnostic and therapeutic challenge to a general dental practitioner.
The tongue coating
In general, the coating is a characteristic feature of the tongue, comprising a thin white coat on the dorsal (middle and posterior) surface in healthy individuals [5]. The components of tongue coating are divided into i) cellular and ii) non-cellular. Cellular components are desquamated keratinized epithelial cells, bacteria and white cell
exudates. The non-cellular components contain proteins from saliva along with food debris and postnasal and gingival secretions [6].
Formation of the tongue coating
The formation of the tongue coating is thought to relate to proliferation and apoptosis of glossal epithelial cells [7]. A microscopic study on tongue ultrastructure indicated that the rate of multiplication of epithelial cells, quantity of desmosomes, and membrane-coating granules are responsible for tongue coating formation [8]. In addition, filiform papillae have a role in coating formation, based on the ultra-structural observation of tongue coating using transmission electron microscopy, which showed bacteria along with desquamated epithelial cells originating from the filiform papillae [9].
The medical significance of the tongue coating
In traditional Chinese medicine (TCM), the tongue and its coating play a vital role in disease diagnosis. According to TCM, the features of tongue coating such as color, thickness, and distribution represent the strength and depth of pathogenic factors [10]. According to TCM, the tongue is connected with other parts of the body such as heart, lung, liver, kidney, spleen, gall bladder, intestine (large and small), and stomach [10]. A change in the function of any of these organs is then reflected in the coating morphology and thus considered as an incidental symptom in Chinese medicine [11]. In ancient Greek medicine, tongue coating features could be a major symptom of acute, transient, or superficial conditions. In early (1828) western medicine, the amount of tongue coating and its color were considered in diagnosis of diseases like hepatitis and pneumonia and their progression [12]. Table 1 shows how tongue coating has been used in diagnosis. However, because of today’s advanced and sophisticated techniques, tongue coating–based diagnosis receives less attention.
Tongue coating Diseases
A coating on one side Lung infection on the corresponding side
Tongue with a lard-like coating Slow recovery in patients with fever Yellow coating Indicative of hepatitis and pneumonia Yellow coating on one side Hemiplegia or migraine
Table 1: Tongue coating in diagnosis of various diseases Examination of the tongue coating
Different features are used to describe the tongue coating and include thickness, area covered on the tongue surface, and discoloration. Traditionally, tongue coating is first
Introduction The tongue
The human tongue is a muscular organ situated in the floor of the mouth, covered with a mucous membrane. Its function is associated with chewing, swallowing, vocalization, and taste. Anatomically, the tongue can be distinguished into root, tip, and dorsal and ventral surfaces. The V-shaped sulcus terminalis on the dorsal surface separates the oral and pharyngeal parts of the tongue. The tongue surface consists of tiny protrusions called tongue papillae, which can be classified into four types: filiform, fungiform, circumvallate, and foliate papillae [1]. Filiform papillae, present at the anterior part of the tongue, have a core length of 0.5 mm with a central crater and uplifted borders. They are responsible for tongue anterior roughness. The foliate papillae are located at the edges, whereas the vallate papillae are located at the posterior tongue with 1 mm height and 2–3 mm diameter [2]. Fungiform papillae have a core length of about 0.5–0.8 mm. Fungiform, foliate, and circumvallate papillae contain the sensory cells involved in taste sensation [40].
Traditionally, visible aspects of the tongue have played an important role in oral and general health. The tongue is involved in various diseases such as vascular and lymphatic lesions (infantile hemangiomas and oral varices), reactive and inflammatory processes (hairy tongue, pigmented fungiform papillae of the tongue, benign migratory glossitis, and fissured tongue), infections (oral hairy leukoplakia, herpes simplex and varicella zoster virus infections, human papillomavirus, and candidiasis), premalignant lesions (leukoplakia and erythroplakia), malignant lesions (squamous cell carcinoma, Kaposi sarcoma, and lymphatic proliferative diseases), and signs of systemic conditions such as nutritional deficiency and systemic amyloidosis [3]. The tongue can reflect symptoms of systemic diseases and serves as a diagnostic indicator and for that reason is often called “a true mirror of the body.” For example, in HIV, the tongue is associated with specific symptoms, including a white patch with a corrugated or hairy appearance on the lateral tongue margin that represents hairy leukoplakia, which helps in early diagnosis of the infection [4]. Unlike other parts of the oral cavity, the patient can inspect the changes of the tongue easily and can misinterpret changes that they perceive. The involvement of the tongue in various disorders and diseases poses a diagnostic and therapeutic challenge to a general dental practitioner.
The tongue coating
In general, the coating is a characteristic feature of the tongue, comprising a thin white coat on the dorsal (middle and posterior) surface in healthy individuals [5]. The components of tongue coating are divided into i) cellular and ii) non-cellular. Cellular components are desquamated keratinized epithelial cells, bacteria and white cell
exudates. The non-cellular components contain proteins from saliva along with food debris and postnasal and gingival secretions [6].
Formation of the tongue coating
The formation of the tongue coating is thought to relate to proliferation and apoptosis of glossal epithelial cells [7]. A microscopic study on tongue ultrastructure indicated that the rate of multiplication of epithelial cells, quantity of desmosomes, and membrane-coating granules are responsible for tongue coating formation [8]. In addition, filiform papillae have a role in coating formation, based on the ultra-structural observation of tongue coating using transmission electron microscopy, which showed bacteria along with desquamated epithelial cells originating from the filiform papillae [9].
The medical significance of the tongue coating
In traditional Chinese medicine (TCM), the tongue and its coating play a vital role in disease diagnosis. According to TCM, the features of tongue coating such as color, thickness, and distribution represent the strength and depth of pathogenic factors [10]. According to TCM, the tongue is connected with other parts of the body such as heart, lung, liver, kidney, spleen, gall bladder, intestine (large and small), and stomach [10]. A change in the function of any of these organs is then reflected in the coating morphology and thus considered as an incidental symptom in Chinese medicine [11]. In ancient Greek medicine, tongue coating features could be a major symptom of acute, transient, or superficial conditions. In early (1828) western medicine, the amount of tongue coating and its color were considered in diagnosis of diseases like hepatitis and pneumonia and their progression [12]. Table 1 shows how tongue coating has been used in diagnosis. However, because of today’s advanced and sophisticated techniques, tongue coating–based diagnosis receives less attention.
Tongue coating Diseases
A coating on one side Lung infection on the corresponding side
Tongue with a lard-like coating Slow recovery in patients with fever Yellow coating Indicative of hepatitis and pneumonia Yellow coating on one side Hemiplegia or migraine
Table 1: Tongue coating in diagnosis of various diseases Examination of the tongue coating
Different features are used to describe the tongue coating and include thickness, area covered on the tongue surface, and discoloration. Traditionally, tongue coating is first
evaluated by visual examination from tip to root. The thickness of the coating is conveyed as none, thin (tongue body is visible), and thick (tongue body is not visible) [6]. These rather subjective criteria are not sufficient to accurately and reproducibly describe the amount of tongue coating, which has led to high inter- and intra-practitioner variation and underscores the need for a standard method [6]. In recent years, several authors have proposed tongue coating indices (e.g., Miyazaki et al. [13], Mantilla Gomez [5], Oho et al. [14], and Winkel et al. [15]). The Winkel Tongue Coating Index is generally considered a feasible method because of the simple evaluation criteria and easy interpretation of the scores [16].
Tongue coating in intra-oral halitosis
Halitosis is defined as a foul odor emanating from the mouth and can be classified into four types based on origin: transient or temporary halitosis, extra-oral halitosis, intra-oral halitosis, and pseudohalitosis (Fig. 1). Transient halitosis is temporary and caused by certain food intake (e.g., garlic) and morning bad breath that will disappear after breakfast and oral hygiene practices [17, 18]. Extra-oral halitosis (EOH) originates from a pathological condition outside the oral cavity and is categorized into blood-borne and non–blood-borne causes [18]. Non–blood-borne halitosis is caused by disorders in the nasal, paranasal, and laryngeal regions and the pulmonary or upper digestive tract. Blood-borne causes of EOH involve genetic causes [43], kidney and liver diseases, diabetes, metabolic disorders and certain certain drugs [18]. In case of blood-borne causes, gaseous compounds that originate from disorders in the body (e.g., hepatic cirrhosis) are exhaled via the lungs and the oral cavity [18].
Intra-oral halitosis (IOH) arises from the oral cavity and is responsible for 90% of halitosis cases. The consequences of IOH are often underestimated and can involve considerable impact on an individual’s social behavior and psyche. The current prevalence of IOH is not clear, but recent studies suggest a prevalence of 22% to 50% worldwide [21]. A survey carried out in the Netherlands in 2005 revealed that halitosis is among the top 100 greatest human health issues (TNS-NIPO) [19]. The physiological cause of IOH is strongly associated with tongue coating, whereas the pathological cause of IOH is gingivitis/periodontitis. These associations were demonstrated in a study involving 2000 patients in which a tongue coating was the cause for 51% of IOH, gingivitis/periodontitis was responsible for only 13%, and the combination was responsible for 22% of the cases. Other risk factors include stress and xerostomia [20].
In people with IOH, the amount of tongue coating is relatively high compared to those without it [22]. In daily life, a tongue coating is very thin because of the routine tongue movements during chewing and swallowing. Additionally, saliva
Fig. 1. Classification of Halitosis
production and dietary elements (e.g., fibrous foods) are strongly involved in cleansing the tongue. Factors that increase the amount of tongue coating are age and age-related. Elderly people often struggle to cope with oral hygiene and have an increased intake of soft food, with a reduced natural cleansing of the tongue by saliva and tongue movements. Among the several factors, oral hygiene has the strongest impact in the formation of coating. The factors outside the oral cavity such as gastrointestinal and liver diseases may also contribute to the thickness of the coating [23].
Tongue coating and volatile sulfur compounds
The tongue coating is believed to be the major source of volatile sulfur compounds (VSCs), which are key elements in IOH [24] [25]. VSCs are produced by anaerobic bacteria of the tongue dorsum that degrade sulfur-containing amino acids to VSCs [26]. The most common VSCs are hydrogen sulfide (H2S), methyl mercaptan
evaluated by visual examination from tip to root. The thickness of the coating is conveyed as none, thin (tongue body is visible), and thick (tongue body is not visible) [6]. These rather subjective criteria are not sufficient to accurately and reproducibly describe the amount of tongue coating, which has led to high inter- and intra-practitioner variation and underscores the need for a standard method [6]. In recent years, several authors have proposed tongue coating indices (e.g., Miyazaki et al. [13], Mantilla Gomez [5], Oho et al. [14], and Winkel et al. [15]). The Winkel Tongue Coating Index is generally considered a feasible method because of the simple evaluation criteria and easy interpretation of the scores [16].
Tongue coating in intra-oral halitosis
Halitosis is defined as a foul odor emanating from the mouth and can be classified into four types based on origin: transient or temporary halitosis, extra-oral halitosis, intra-oral halitosis, and pseudohalitosis (Fig. 1). Transient halitosis is temporary and caused by certain food intake (e.g., garlic) and morning bad breath that will disappear after breakfast and oral hygiene practices [17, 18]. Extra-oral halitosis (EOH) originates from a pathological condition outside the oral cavity and is categorized into blood-borne and non–blood-borne causes [18]. Non–blood-borne halitosis is caused by disorders in the nasal, paranasal, and laryngeal regions and the pulmonary or upper digestive tract. Blood-borne causes of EOH involve genetic causes [43], kidney and liver diseases, diabetes, metabolic disorders and certain certain drugs [18]. In case of blood-borne causes, gaseous compounds that originate from disorders in the body (e.g., hepatic cirrhosis) are exhaled via the lungs and the oral cavity [18].
Intra-oral halitosis (IOH) arises from the oral cavity and is responsible for 90% of halitosis cases. The consequences of IOH are often underestimated and can involve considerable impact on an individual’s social behavior and psyche. The current prevalence of IOH is not clear, but recent studies suggest a prevalence of 22% to 50% worldwide [21]. A survey carried out in the Netherlands in 2005 revealed that halitosis is among the top 100 greatest human health issues (TNS-NIPO) [19]. The physiological cause of IOH is strongly associated with tongue coating, whereas the pathological cause of IOH is gingivitis/periodontitis. These associations were demonstrated in a study involving 2000 patients in which a tongue coating was the cause for 51% of IOH, gingivitis/periodontitis was responsible for only 13%, and the combination was responsible for 22% of the cases. Other risk factors include stress and xerostomia [20].
In people with IOH, the amount of tongue coating is relatively high compared to those without it [22]. In daily life, a tongue coating is very thin because of the routine tongue movements during chewing and swallowing. Additionally, saliva
Fig. 1. Classification of Halitosis
production and dietary elements (e.g., fibrous foods) are strongly involved in cleansing the tongue. Factors that increase the amount of tongue coating are age and age-related. Elderly people often struggle to cope with oral hygiene and have an increased intake of soft food, with a reduced natural cleansing of the tongue by saliva and tongue movements. Among the several factors, oral hygiene has the strongest impact in the formation of coating. The factors outside the oral cavity such as gastrointestinal and liver diseases may also contribute to the thickness of the coating [23].
Tongue coating and volatile sulfur compounds
The tongue coating is believed to be the major source of volatile sulfur compounds (VSCs), which are key elements in IOH [24] [25]. VSCs are produced by anaerobic bacteria of the tongue dorsum that degrade sulfur-containing amino acids to VSCs [26]. The most common VSCs are hydrogen sulfide (H2S), methyl mercaptan
approximately 90% of VSCs in IOH. The important organic substrates for VSC production are cysteine and methionine from the saliva, gingival, and crevicular fluid and the tongue surface. In addition, bacterial degradation of diamines (tryptophan) produces indole and skatole, whereas degradation of polyamines (lysine and ornithine) can result in cadaverin and putresin [19]. The contribution of indole, skatole, cadaverin, and putresin to IOH is controversial [28].
The microbiome and the tongue coating
Several studies have demonstrated the relation between the tongue coating microbiome and IOH. An in vitro study showed that the production of oral malodor was associated with a shift in the microflora from Gram-positive to Gram-negative anaerobes [29]. Another in vitro analysis showed that certain oral bacterial species, when incubated with serum containing L-cysteine and L-methionine, produced mainly H2S and CH3SH [30]. Because the tongue dorsum has a surface area of
25 cm2 [36] with irregular topography from the presence of numerous fissures, crypts,
and papillae, it provides shelter for the tongue microbiome. Conventional anaerobic culture studies of IOH yielded isolated Peptostreptococcus anaerobius, Collinsella
aerofaciens, Eubacterium group, Actinomyces spp., Eikenella corrodens, Veillonella
spp., Fusobacterium nucleatum, pigmented Prevotella spp., Selenomonas spp.,
Actinomyces turicensis, Collinsella aerofaciens, Eubacterium saburreum, Eubacterium timidum, Prevotella tannerae, Campylobacter concisus, Campylobacter mucosalis, Leptotrichia buccalis, Selenomonas flueggei, and Centipeda periodontii
[31]. The anaerobic culture method had limitations in the cultivation of existent microbes, so the advent of sequencing-based technology has revolutionized medical research.
In culture-independent techniques, 16S rRNA sequencing of cloned genes from IOH samples showed the presence of Atopobium parvulum, Dialister spp., Eubacterium sulci, a phylotype of the uncultivated phylum TM7, Solobacterium
moorei, and a phylotype of Streptococcus, all highly associated with IOH [22].
Another study using 16S rRNA sequencing of tongue samples from patients with IOH showed the presence of Lysobacter-type species, S. salivarius, Prevotella
melaninogenica, Prevotella veroralis, and Prevotella pallens. These authors
concluded that the tongue microbiome in IOH has great species diversity and is complex [32]. The combination of anaerobic culture technique and amplification of 16S ribosomal DNA has revealed the presence of 32 species, including 13 non-cultivable species in halitosis patients [33].
Of interest, S. moorei was given more importance in several studies because of its presence in people with IOH compared to those without it. One such study revealed the presence of S. moorei only in participants with halitosis but not in any of
the control participants [33]. In a later study involving S. moorei, clinical factors of IOH (such as H2S, CH3SH, (CH3)2S, and total VSCs) and tongue coating indices
showed a significant correlation with each other [34]. However, quantitative polymerase chain reaction on tongue samples of IOH showed only a slight elevation of S. moorei in patients with IOH (98.8%) compared to controls (88.9%) [34]. The study showing that S. moorei produces VSCs also showed that S. moorei could produce VSCs from serum only in the presence of exogenous proteases such as pancreatic trypsin or Porphyromonas gingivalis gingipains [35]. These studies did not give further information on the crosstalk between the specific bacteria and IOH.
A study on the bacterial load of the tongue dorsum in participants with IOH showed a significant correlation between total bacterial load and IOH [26], but another study showed the opposite [37]. The authors of this latter study hypothesized that the tongue coating per se and not the bacteria was responsible for IOH [37]. Furthermore, the determination of the bacterial load before and after the tongue cleaning intervention showed no reduction in bacterial load [2]. The increase in certain bacterial species rather than the bacterial load was believed to be the responsible factor in the IOH. Based on this concept, a study showed an increase in H2S-producing bacteria in participants with IOH. Thus, IOH is probably caused by
bacteria of the oral cavity, and an increase in their number plays a role in IOH [38].
Intra-oral conditions affecting the tongue microbiome in IOH
The oral microbiome might change in composition, but we do not understand which factors initiate these changes. Altered physical parameters (environmental factors) such as pH, oxidation–reduction potential, or a low carbohydrate environment might play a role [29]. Previous studies on IOH focused more on microbial aspects rather than environmental factors. In vitro studies on microbes have demonstrated their ability to produce VSCs but did not reveal bacterial physiological changes. The cause of IOH is complex and may involve increased bacterial numbers along with metabolite-related factors [17]. Thus, a deeper understanding of bacterial flora dynamics and metabolites is required for developing an effective treatment strategy for IOH.
Treatment for tongue coating–related IOH
Treatment for IOH first involves VSC reduction. Tooth brushing, interdental cleaning, and tongue scraping, which reduce the total oral bacterial load including VSC-producing bacteria, can achieve this. These steps also reduce residual food matter and cellular debris from the gingiva and tongue coating. Mechanical approaches can reduce oral malodor, but their efficiency in treating chronic oral malodor is limited. Chemical treatment includes the use of mouth rinses. Effective mouth rinses contain
approximately 90% of VSCs in IOH. The important organic substrates for VSC production are cysteine and methionine from the saliva, gingival, and crevicular fluid and the tongue surface. In addition, bacterial degradation of diamines (tryptophan) produces indole and skatole, whereas degradation of polyamines (lysine and ornithine) can result in cadaverin and putresin [19]. The contribution of indole, skatole, cadaverin, and putresin to IOH is controversial [28].
The microbiome and the tongue coating
Several studies have demonstrated the relation between the tongue coating microbiome and IOH. An in vitro study showed that the production of oral malodor was associated with a shift in the microflora from Gram-positive to Gram-negative anaerobes [29]. Another in vitro analysis showed that certain oral bacterial species, when incubated with serum containing L-cysteine and L-methionine, produced mainly H2S and CH3SH [30]. Because the tongue dorsum has a surface area of
25 cm2 [36] with irregular topography from the presence of numerous fissures, crypts,
and papillae, it provides shelter for the tongue microbiome. Conventional anaerobic culture studies of IOH yielded isolated Peptostreptococcus anaerobius, Collinsella
aerofaciens, Eubacterium group, Actinomyces spp., Eikenella corrodens, Veillonella
spp., Fusobacterium nucleatum, pigmented Prevotella spp., Selenomonas spp.,
Actinomyces turicensis, Collinsella aerofaciens, Eubacterium saburreum, Eubacterium timidum, Prevotella tannerae, Campylobacter concisus, Campylobacter mucosalis, Leptotrichia buccalis, Selenomonas flueggei, and Centipeda periodontii
[31]. The anaerobic culture method had limitations in the cultivation of existent microbes, so the advent of sequencing-based technology has revolutionized medical research.
In culture-independent techniques, 16S rRNA sequencing of cloned genes from IOH samples showed the presence of Atopobium parvulum, Dialister spp., Eubacterium sulci, a phylotype of the uncultivated phylum TM7, Solobacterium
moorei, and a phylotype of Streptococcus, all highly associated with IOH [22].
Another study using 16S rRNA sequencing of tongue samples from patients with IOH showed the presence of Lysobacter-type species, S. salivarius, Prevotella
melaninogenica, Prevotella veroralis, and Prevotella pallens. These authors
concluded that the tongue microbiome in IOH has great species diversity and is complex [32]. The combination of anaerobic culture technique and amplification of 16S ribosomal DNA has revealed the presence of 32 species, including 13 non-cultivable species in halitosis patients [33].
Of interest, S. moorei was given more importance in several studies because of its presence in people with IOH compared to those without it. One such study revealed the presence of S. moorei only in participants with halitosis but not in any of
the control participants [33]. In a later study involving S. moorei, clinical factors of IOH (such as H2S, CH3SH, (CH3)2S, and total VSCs) and tongue coating indices
showed a significant correlation with each other [34]. However, quantitative polymerase chain reaction on tongue samples of IOH showed only a slight elevation of S. moorei in patients with IOH (98.8%) compared to controls (88.9%) [34]. The study showing that S. moorei produces VSCs also showed that S. moorei could produce VSCs from serum only in the presence of exogenous proteases such as pancreatic trypsin or Porphyromonas gingivalis gingipains [35]. These studies did not give further information on the crosstalk between the specific bacteria and IOH.
A study on the bacterial load of the tongue dorsum in participants with IOH showed a significant correlation between total bacterial load and IOH [26], but another study showed the opposite [37]. The authors of this latter study hypothesized that the tongue coating per se and not the bacteria was responsible for IOH [37]. Furthermore, the determination of the bacterial load before and after the tongue cleaning intervention showed no reduction in bacterial load [2]. The increase in certain bacterial species rather than the bacterial load was believed to be the responsible factor in the IOH. Based on this concept, a study showed an increase in H2S-producing bacteria in participants with IOH. Thus, IOH is probably caused by
bacteria of the oral cavity, and an increase in their number plays a role in IOH [38].
Intra-oral conditions affecting the tongue microbiome in IOH
The oral microbiome might change in composition, but we do not understand which factors initiate these changes. Altered physical parameters (environmental factors) such as pH, oxidation–reduction potential, or a low carbohydrate environment might play a role [29]. Previous studies on IOH focused more on microbial aspects rather than environmental factors. In vitro studies on microbes have demonstrated their ability to produce VSCs but did not reveal bacterial physiological changes. The cause of IOH is complex and may involve increased bacterial numbers along with metabolite-related factors [17]. Thus, a deeper understanding of bacterial flora dynamics and metabolites is required for developing an effective treatment strategy for IOH.
Treatment for tongue coating–related IOH
Treatment for IOH first involves VSC reduction. Tooth brushing, interdental cleaning, and tongue scraping, which reduce the total oral bacterial load including VSC-producing bacteria, can achieve this. These steps also reduce residual food matter and cellular debris from the gingiva and tongue coating. Mechanical approaches can reduce oral malodor, but their efficiency in treating chronic oral malodor is limited. Chemical treatment includes the use of mouth rinses. Effective mouth rinses contain
antibacterial agents that affect bacterial growth and neutralize bacterial VSCs. In-depth investigations into the mechanism of IOH formation is required to improve treatment of IOH effectively [39].
Tongue cleaning effect on taste perception
The primary sensory units of the taste system, the taste buds, are located in the taste papillae covering the tongue surface. Taste buds are embedded under the keratinous layer of the papillae with a taste pore exposed to the external milieu [40]. The five basic taste qualities are sweet, salty, sour, bitter, and umami. Among these qualities, sweet and salty tastes have a great impact on health-related problems. In particular, salt is a strong risk factor for hypertension, stroke, and obesity. According to the World Health Organization, human salt intake is high, ranging from 5–9 g/day, and the agency recommends reduction of salt intake [41]. The tongue-cleaning oral hygiene regimen significantly improves the salt taste sensation and might help to reduce salt intake [2, 42].
Aim of this thesis
In individuals with a healthy periodontium, tongue coating is the predominant cause for IOH, and anaerobic bacteria on the tongue dorsum produce VSCs that contribute to IOH. An improved understanding of the tongue microbiome will ultimately permit expansion of therapeutic strategies and is the aim of this thesis. Hence, the following research questions were formulated.
1. What is the impact of tongue coating in IOH, and what causes tongue coating formation?
2. What is the microbial composition of the tongue coating in IOH, and does the tongue microbiome induce coating formation?
3. Is IOH a related condition, is microbiome function metabolite-related, and how are they related to VSC production?
4. Does the removal of tongue coating increase taste perception?
Outline of the thesis
In chapter 1, a topical review is given on tongue coating, based on current knowledge, and its association with IOH. Also, the impact of tongue coating on general health is discussed.
In chapter 2, the tongue microbial composition in people with and without IOH is discussed, based on using 16S amplicon Illumina sequencing, an advanced sequencing technology, to study the microbiome.
In chapter 3, the formation of the tongue coating and the metabolic pathway involved in formation of VSCs is investigated using a non-targeted metabolomics approach, liquid chromatography–tandem mass spectrometry.
In chapter 4, the effect of removal of the coating by tongue cleaning and its relation to the intensity of salty taste perception is investigated.
In chapter 5, the formation of the tongue coating, the microbiome, and its metabolites in relation to IOH are summarized.
References
1. Jung HS, Akita K, Kim J-Y (2004) Spacing patterns on tongue surface-gustatory papilla. Int J Dev Biol 48:157–61.
2. Quirynen M, Avontroodt P, Soers C, et al (2004) Impact of tongue cleansers on microbial load and taste. J Clin Periodontol 31:506–510.
3. Mangold AR, Torgerson RR, Rogers RS (2016) Diseases of the tongue. Clin Dermatol 34:458–469.
4. Greenspan D, Greenspan JS (1996) HIV-related oral disease. Lancet 348:729– 733.
5. Mantilla Gómez S, Danser MM, Sipos PM, et al (2001) Tongue coating and salivary bacterial counts in healthy/gingivitis subjects and periodontitis patients; J Clin Periodontol 28:970–978.
6. Sterer N, Rosenberg M (2011) Breath odors of oral origin (oral malodor). Breath Odors, 5–17.
7. Huguley CM (1990) The tongue. clinical methods history physical laboratory examinations. editors: Walker HK, Hall WD, Hurst J, Chapter 130, Butterworths; Boston. doi: NBK236 [book accession]
8. Danser MM (2003) Tongue coating and tongue brushing: a literature review. Int J Dent Hyg 1(3):151-158.
9. Watanabe H (2006) Observation of the ultrastructure of the tongue coating. Kōkūbyō Gakkai zasshi J Stomatol Soc Japan 73:26–39.
10. Anastasi JK, Currie LM, Kim GH (2009) Understanding diagnostic reasoning in TCM practice: tongue diagnosis. Altern Ther Health Med 15:18–28.
11. Chen ZL (1987) Brief history of tongue inspection. Chin Med J (Engl) 100:38– 44.
12. Alan JD (1983) The tongue: the new role in oral health care, the old role in disease diagnosis. TIC 42:11–13.
13. Miyazaki H, Sakao S, Katoh Y, Takehara T (1995) Correlation between volatile sulphur compounds and certain oral health measurements in the general population. J Periodontol 66:679–684.
14. Oho T, Yoshida Y, Shimazaki Y, et al (2001) Characteristics of patients complaining of halitosis and the usefulness of gas chromatography for diagnosing halitosis. Oral surgery, oral Med oral Pathol oral Radiol
antibacterial agents that affect bacterial growth and neutralize bacterial VSCs. In-depth investigations into the mechanism of IOH formation is required to improve treatment of IOH effectively [39].
Tongue cleaning effect on taste perception
The primary sensory units of the taste system, the taste buds, are located in the taste papillae covering the tongue surface. Taste buds are embedded under the keratinous layer of the papillae with a taste pore exposed to the external milieu [40]. The five basic taste qualities are sweet, salty, sour, bitter, and umami. Among these qualities, sweet and salty tastes have a great impact on health-related problems. In particular, salt is a strong risk factor for hypertension, stroke, and obesity. According to the World Health Organization, human salt intake is high, ranging from 5–9 g/day, and the agency recommends reduction of salt intake [41]. The tongue-cleaning oral hygiene regimen significantly improves the salt taste sensation and might help to reduce salt intake [2, 42].
Aim of this thesis
In individuals with a healthy periodontium, tongue coating is the predominant cause for IOH, and anaerobic bacteria on the tongue dorsum produce VSCs that contribute to IOH. An improved understanding of the tongue microbiome will ultimately permit expansion of therapeutic strategies and is the aim of this thesis. Hence, the following research questions were formulated.
1. What is the impact of tongue coating in IOH, and what causes tongue coating formation?
2. What is the microbial composition of the tongue coating in IOH, and does the tongue microbiome induce coating formation?
3. Is IOH a related condition, is microbiome function metabolite-related, and how are they related to VSC production?
4. Does the removal of tongue coating increase taste perception?
Outline of the thesis
In chapter 1, a topical review is given on tongue coating, based on current knowledge, and its association with IOH. Also, the impact of tongue coating on general health is discussed.
In chapter 2, the tongue microbial composition in people with and without IOH is discussed, based on using 16S amplicon Illumina sequencing, an advanced sequencing technology, to study the microbiome.
In chapter 3, the formation of the tongue coating and the metabolic pathway involved in formation of VSCs is investigated using a non-targeted metabolomics approach, liquid chromatography–tandem mass spectrometry.
In chapter 4, the effect of removal of the coating by tongue cleaning and its relation to the intensity of salty taste perception is investigated.
In chapter 5, the formation of the tongue coating, the microbiome, and its metabolites in relation to IOH are summarized.
References
1. Jung HS, Akita K, Kim J-Y (2004) Spacing patterns on tongue surface-gustatory papilla. Int J Dev Biol 48:157–61.
2. Quirynen M, Avontroodt P, Soers C, et al (2004) Impact of tongue cleansers on microbial load and taste. J Clin Periodontol 31:506–510.
3. Mangold AR, Torgerson RR, Rogers RS (2016) Diseases of the tongue. Clin Dermatol 34:458–469.
4. Greenspan D, Greenspan JS (1996) HIV-related oral disease. Lancet 348:729– 733.
5. Mantilla Gómez S, Danser MM, Sipos PM, et al (2001) Tongue coating and salivary bacterial counts in healthy/gingivitis subjects and periodontitis patients; J Clin Periodontol 28:970–978.
6. Sterer N, Rosenberg M (2011) Breath odors of oral origin (oral malodor). Breath Odors, 5–17.
7. Huguley CM (1990) The tongue. clinical methods history physical laboratory examinations. editors: Walker HK, Hall WD, Hurst J, Chapter 130, Butterworths; Boston. doi: NBK236 [book accession]
8. Danser MM (2003) Tongue coating and tongue brushing: a literature review. Int J Dent Hyg 1(3):151-158.
9. Watanabe H (2006) Observation of the ultrastructure of the tongue coating. Kōkūbyō Gakkai zasshi J Stomatol Soc Japan 73:26–39.
10. Anastasi JK, Currie LM, Kim GH (2009) Understanding diagnostic reasoning in TCM practice: tongue diagnosis. Altern Ther Health Med 15:18–28.
11. Chen ZL (1987) Brief history of tongue inspection. Chin Med J (Engl) 100:38– 44.
12. Alan JD (1983) The tongue: the new role in oral health care, the old role in disease diagnosis. TIC 42:11–13.
13. Miyazaki H, Sakao S, Katoh Y, Takehara T (1995) Correlation between volatile sulphur compounds and certain oral health measurements in the general population. J Periodontol 66:679–684.
14. Oho T, Yoshida Y, Shimazaki Y, et al (2001) Characteristics of patients complaining of halitosis and the usefulness of gas chromatography for diagnosing halitosis. Oral surgery, oral Med oral Pathol oral Radiol
endodontology 91:531–534.
15. Winkel EG, Roldán S, Van Winkelhoff AJ, et al (2003) Clinical effects of a new mouthrinse containing chlorhexidine, cetylpyridinium chloride and zinc-lactate on oral halitosis. J Clin Periodontol 30:300–306. doi: 10.1034/j.1600-051X.2003.00342.x
16. Jung Y, Park K, Kim J (2009) A digital tongue imaging system for tongue coating evaluation in patients with oral malodour. Oral Dis 15:565–569. 17. Kleinberg I, Westbay G (1990) Oral malodor. Crit Rev Oral Biol Med 1:247–
259.
18. Seemann R, Conceicao MD, Filippi A, et al (2014) Halitosis management by the general dental practitioner-results of an international consensus workshop. J Breath Res 8:17101.
19. Bollen CML, Beikler T (2012) Halitosis: the multidisciplinary approach. Int J Oral Sci 4:55–63.
20. Quirynen M, Dadamio J, Van den Velde S, et al (2009) Characteristics of 2000 patients who visited a halitosis clinic. J Clin Periodontol 36:970–975.
21. Akaji EA, Folaranmi N, Ashiwaju O (2014) Halitosis: a review of the literature on its prevalence, impact and control. Oral Health Prev Dent 12:297–304. 22. Kazor CE, Mitchell PM, Lee AM, et al (2003) Diversity of bacterial
populations on the tongue dorsa of patients with halitosis and healthy patients. J Clin Microbiol 41:558–563.
23. Kojima K (1985) Clinical studies on the coated tongue. Japanese J Oral Maxillofac Surg 31:1659–1678.
24. Yaegaki K, Sanada K (1992) Biochemical and clinical factors influencing oral malodor in periodontal patients. J Periodontol 63:783–789.
25. Bosy A, Kulkarni G V, Rosenberg M, McCulloch CA (1994) Relationship of oral malodor to periodontitis: evidence of independence in discrete subpopulations. J Periodontol 65:37–46.
26. De Boever EH, Loesche WJ (1995) Assessing the contribution of anaerobic microflora of the tongue to oral malodor. J Am Dent Assoc 126:1384–1393. 27. Tangerman A (2002) Halitosis in medicine: a review. Int Dent J 52:201–206. 28. Tangerman A, Winkel EG (2010) Extra-oral halitosis: an overview. J Breath
Res 4:17003.
29. McNamara TF, Alexander JF, Lee M (1972) The role of microorganisms in the production of oral malodor. Oral surgery, oral Med oral Pathol 34:41–48. 30. Persson S, Claesson R, Carlsson J (1989) The capacity of subgingival
microbiotas to produce volatile sulfur compounds in human serum. Oral Microbiol Immunol 4:169–172.
31. Tyrrell KL, Citron DM, Warren YA, et al (2003) Anaerobic bacteria cultured from the tongue dorsum of subjects with oral malodor. Anaerobe 9:243–246. 32. Riggio MP, Lennon A, Rolph HJ, et al (2008) Molecular identification of
bacteria on the tongue dorsum of subjects with and without halitosis. Oral Dis 14:251–258.
33. Haraszthy VI, Zambon JJ, Sreenivasan PK, et al (2007) Identification of oral bacterial species associated with halitosis. J Am Dent Assoc 138:1113–1120.
34. Vancauwenberghe F, Dadamio J, Laleman I, Van Tornout I, Teughels W, Coucke W and Quirynen M (2013) The role of Solobacterium moorei in oral malodour. J Breath Res 7:46006.
35. Tanabe S, Grenier D (2012) Characterization of volatile sulfur compound production by Solobacterium moorei. Arch Oral Biol 57:1639–1643.
36. Collins LM, Dawes C (1987) The surface area of the adult human mouth and thickness of the salivary film covering the teeth and oral mucosa. J Dent Res 66:1300–1302.
37. Quirynen M, Mongardini C, van Steenberghe D (1998) The effect of a 1-stage full-mouth disinfection on oral malodor and microbial colonization of the tongue in periodontitis. A pilot study. J Periodontol 69:374–382.
38. Washio J, Sato T, Koseki T, Takahashi N (2005) Hydrogen sulfide-producing bacteria in tongue biofilm and their relationship with oral malodour. J Med Microbiol 54:889–895.
39. Slot DE, De Geest S, van der Weijden FA, Quirynen M (2015) Treatment of oral malodour. Medium-term efficacy of mechanical and/or chemical agents: a systematic review. J Clin Periodontol 42:S303–S316.
40. Gravina SA, Yep GL, Khan M (2013) Human biology of taste. Ann Saudi Med 33:217–222.
41. Organization World Health. WHO (2012) Sodium intake for adults and children. World Health Organ 2;56.
42. Seerangaiyan K, Jüch F, Atefeh F, Winkel EG (2018) Tongue cleaning increases the perceived intensity of salty taste J Nutr Health Aging doi: 10.1007/s12603-018-1030-8.
43. Pol A, Renkema GH, Tangerman A, Winkel EG, Engelke UF, De Brouwer APM, Lloyd KC, Araiza RS, Van Den Heuvel L, Omran H, Olbrich H, Oude Elberink M, Gilissen C, Rodenburg RJ, Sass JO, Schwab KO, Schäfer H, Venselaar H, Sequeira JS, Op Den Camp HJM and Wevers RA (2018) Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis Nat. Genet. 50 120–129
endodontology 91:531–534.
15. Winkel EG, Roldán S, Van Winkelhoff AJ, et al (2003) Clinical effects of a new mouthrinse containing chlorhexidine, cetylpyridinium chloride and zinc-lactate on oral halitosis. J Clin Periodontol 30:300–306. doi: 10.1034/j.1600-051X.2003.00342.x
16. Jung Y, Park K, Kim J (2009) A digital tongue imaging system for tongue coating evaluation in patients with oral malodour. Oral Dis 15:565–569. 17. Kleinberg I, Westbay G (1990) Oral malodor. Crit Rev Oral Biol Med 1:247–
259.
18. Seemann R, Conceicao MD, Filippi A, et al (2014) Halitosis management by the general dental practitioner-results of an international consensus workshop. J Breath Res 8:17101.
19. Bollen CML, Beikler T (2012) Halitosis: the multidisciplinary approach. Int J Oral Sci 4:55–63.
20. Quirynen M, Dadamio J, Van den Velde S, et al (2009) Characteristics of 2000 patients who visited a halitosis clinic. J Clin Periodontol 36:970–975.
21. Akaji EA, Folaranmi N, Ashiwaju O (2014) Halitosis: a review of the literature on its prevalence, impact and control. Oral Health Prev Dent 12:297–304. 22. Kazor CE, Mitchell PM, Lee AM, et al (2003) Diversity of bacterial
populations on the tongue dorsa of patients with halitosis and healthy patients. J Clin Microbiol 41:558–563.
23. Kojima K (1985) Clinical studies on the coated tongue. Japanese J Oral Maxillofac Surg 31:1659–1678.
24. Yaegaki K, Sanada K (1992) Biochemical and clinical factors influencing oral malodor in periodontal patients. J Periodontol 63:783–789.
25. Bosy A, Kulkarni G V, Rosenberg M, McCulloch CA (1994) Relationship of oral malodor to periodontitis: evidence of independence in discrete subpopulations. J Periodontol 65:37–46.
26. De Boever EH, Loesche WJ (1995) Assessing the contribution of anaerobic microflora of the tongue to oral malodor. J Am Dent Assoc 126:1384–1393. 27. Tangerman A (2002) Halitosis in medicine: a review. Int Dent J 52:201–206. 28. Tangerman A, Winkel EG (2010) Extra-oral halitosis: an overview. J Breath
Res 4:17003.
29. McNamara TF, Alexander JF, Lee M (1972) The role of microorganisms in the production of oral malodor. Oral surgery, oral Med oral Pathol 34:41–48. 30. Persson S, Claesson R, Carlsson J (1989) The capacity of subgingival
microbiotas to produce volatile sulfur compounds in human serum. Oral Microbiol Immunol 4:169–172.
31. Tyrrell KL, Citron DM, Warren YA, et al (2003) Anaerobic bacteria cultured from the tongue dorsum of subjects with oral malodor. Anaerobe 9:243–246. 32. Riggio MP, Lennon A, Rolph HJ, et al (2008) Molecular identification of
bacteria on the tongue dorsum of subjects with and without halitosis. Oral Dis 14:251–258.
33. Haraszthy VI, Zambon JJ, Sreenivasan PK, et al (2007) Identification of oral bacterial species associated with halitosis. J Am Dent Assoc 138:1113–1120.
34. Vancauwenberghe F, Dadamio J, Laleman I, Van Tornout I, Teughels W, Coucke W and Quirynen M (2013) The role of Solobacterium moorei in oral malodour. J Breath Res 7:46006.
35. Tanabe S, Grenier D (2012) Characterization of volatile sulfur compound production by Solobacterium moorei. Arch Oral Biol 57:1639–1643.
36. Collins LM, Dawes C (1987) The surface area of the adult human mouth and thickness of the salivary film covering the teeth and oral mucosa. J Dent Res 66:1300–1302.
37. Quirynen M, Mongardini C, van Steenberghe D (1998) The effect of a 1-stage full-mouth disinfection on oral malodor and microbial colonization of the tongue in periodontitis. A pilot study. J Periodontol 69:374–382.
38. Washio J, Sato T, Koseki T, Takahashi N (2005) Hydrogen sulfide-producing bacteria in tongue biofilm and their relationship with oral malodour. J Med Microbiol 54:889–895.
39. Slot DE, De Geest S, van der Weijden FA, Quirynen M (2015) Treatment of oral malodour. Medium-term efficacy of mechanical and/or chemical agents: a systematic review. J Clin Periodontol 42:S303–S316.
40. Gravina SA, Yep GL, Khan M (2013) Human biology of taste. Ann Saudi Med 33:217–222.
41. Organization World Health. WHO (2012) Sodium intake for adults and children. World Health Organ 2;56.
42. Seerangaiyan K, Jüch F, Atefeh F, Winkel EG (2018) Tongue cleaning increases the perceived intensity of salty taste J Nutr Health Aging doi: 10.1007/s12603-018-1030-8.
43. Pol A, Renkema GH, Tangerman A, Winkel EG, Engelke UF, De Brouwer APM, Lloyd KC, Araiza RS, Van Den Heuvel L, Omran H, Olbrich H, Oude Elberink M, Gilissen C, Rodenburg RJ, Sass JO, Schwab KO, Schäfer H, Venselaar H, Sequeira JS, Op Den Camp HJM and Wevers RA (2018) Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis Nat. Genet. 50 120–129
CHAPTER
2
Tongue coating: its characteristics and role in intra-oral
halitosis and general health-a review
Seerangaiyan K, Jüch F, Winkel EG. J Breath Res. 2018 Mar 6;12(3):034001.
CHAPTER
2
Tongue coating: its characteristics and role in intra-oral
halitosis and general health-a review
Seerangaiyan K, Jüch F, Winkel EG. J Breath Res. 2018 Mar 6;12(3):034001.
Abstract
Tongue coating (TC), a grayish white deposit on the tongue, is the main cause of intra-oral halitosis (IOH), a socially unacceptable condition. This review covers the general features of TC, including its formation and the factors that influence it. Volatile sulfur compounds (VSCs) are the principal elements of IOH, and TC and periodontal diseases are the two main sources of VSCs. This review covers the relationship between VSC, TC, and periodontal disease. We comprehensively discuss the methods employed to quantify TC, its microbial composition, its influence on general health and the importance in general medicine.
Keywords: Tongue coating (TC); halitosis; Intra-Oral Halitosis (IOH); Volatile
Sulfur Compounds (VSC); tongue microbiome
1. Introduction
Halitosis is commonly referred to as bad breath. It has a long history, dating back to 1500 BC, when Hippocrates, the ancient Greeks, and the Romans all mentioned it in their writings. In the modern world, halitosis has enormous impact on individual social and psychological well-being. Halitosis has no gender-specificity [1] and has been classified into four types: genuine halitosis (extra- and intra-oral halitosis), temporary or transient halitosis, pseudo-halitosis, and halitophobia [2]. Extra-oral halitosis (EOH) has a source outside the oral cavity, and intra-oral halitosis (IOH) has a source inside the oral cavity. Pseudo-halitosis is the case where no malodor is present, but the patient stubbornly believes he or she has halitosis. With halitophobia, the patient has been treated for genuine halitosis or counseled for pseudo-halitosis, but believes that his or her halitosis persists [2]. Among the different types of halitosis, nearly 90 percent are caused by IOH. The exact prevalence of IOH is not currently known, but according to previous studies, IOH affects 10-30% of the total population in United States [3] and China [4]. IOH is caused by pathological conditions (periodontitis and gingivitis) and physiological traits particularly tongue coating [TC]. Among other causes of IOH, TC is a major causative factor [5]. In general, TC is much more common than other tongue conditions, such as fissured tongue (associated with hyposalivation, candidiasis, diabetes mellitus, vitamin B deficiency, lichenoid reactions, and Sjögren syndrome) and depapillated tongue (indicative of nutritional deficiencies, xerostomia, local trauma, or candidiasis) [6]. The tongue is the mirror of the body, because it often provides information on systemic changes for diagnostic purposes [7]. For example, in the case of HIV, symptoms such as the presence of white patches that are corrugated, or hairy leukoplakia, which is a hairy appearance on the lateral tongue margin, helps in the early diagnosis of HIV [8]. However, the tongue receives little attention in the literature, and health care professionals have rather limited knowledge of TC and IOH [9]. This review provides an overview of the current knowledge of TC and its role in IOH.
2. The formation of tongue coating
There is no substantial evidence to explain the precise cause of TC formation. The TC consists of dead epithelial cells, bacteria, blood metabolites, secretions from the postnasal area and the gingiva, and saliva [10]. The tongue papillae, particularly the filiform papillae, comprise the specific structure involved in TC formation. Light and transmission electron microscopic studies on the TC revealed the presence of bacteria and exfoliated (desquamated) keratinized epithelium that originated from filiform papillae. Moreover, this exfoliated epithelium had degenerated [11]. The entrapment of food particles, saliva, and bacteria in between these filiform papillae can result in
Abstract
Tongue coating (TC), a grayish white deposit on the tongue, is the main cause of intra-oral halitosis (IOH), a socially unacceptable condition. This review covers the general features of TC, including its formation and the factors that influence it. Volatile sulfur compounds (VSCs) are the principal elements of IOH, and TC and periodontal diseases are the two main sources of VSCs. This review covers the relationship between VSC, TC, and periodontal disease. We comprehensively discuss the methods employed to quantify TC, its microbial composition, its influence on general health and the importance in general medicine.
Keywords: Tongue coating (TC); halitosis; Intra-Oral Halitosis (IOH); Volatile
Sulfur Compounds (VSC); tongue microbiome
1. Introduction
Halitosis is commonly referred to as bad breath. It has a long history, dating back to 1500 BC, when Hippocrates, the ancient Greeks, and the Romans all mentioned it in their writings. In the modern world, halitosis has enormous impact on individual social and psychological well-being. Halitosis has no gender-specificity [1] and has been classified into four types: genuine halitosis (extra- and intra-oral halitosis), temporary or transient halitosis, pseudo-halitosis, and halitophobia [2]. Extra-oral halitosis (EOH) has a source outside the oral cavity, and intra-oral halitosis (IOH) has a source inside the oral cavity. Pseudo-halitosis is the case where no malodor is present, but the patient stubbornly believes he or she has halitosis. With halitophobia, the patient has been treated for genuine halitosis or counseled for pseudo-halitosis, but believes that his or her halitosis persists [2]. Among the different types of halitosis, nearly 90 percent are caused by IOH. The exact prevalence of IOH is not currently known, but according to previous studies, IOH affects 10-30% of the total population in United States [3] and China [4]. IOH is caused by pathological conditions (periodontitis and gingivitis) and physiological traits particularly tongue coating [TC]. Among other causes of IOH, TC is a major causative factor [5]. In general, TC is much more common than other tongue conditions, such as fissured tongue (associated with hyposalivation, candidiasis, diabetes mellitus, vitamin B deficiency, lichenoid reactions, and Sjögren syndrome) and depapillated tongue (indicative of nutritional deficiencies, xerostomia, local trauma, or candidiasis) [6]. The tongue is the mirror of the body, because it often provides information on systemic changes for diagnostic purposes [7]. For example, in the case of HIV, symptoms such as the presence of white patches that are corrugated, or hairy leukoplakia, which is a hairy appearance on the lateral tongue margin, helps in the early diagnosis of HIV [8]. However, the tongue receives little attention in the literature, and health care professionals have rather limited knowledge of TC and IOH [9]. This review provides an overview of the current knowledge of TC and its role in IOH.
2. The formation of tongue coating
There is no substantial evidence to explain the precise cause of TC formation. The TC consists of dead epithelial cells, bacteria, blood metabolites, secretions from the postnasal area and the gingiva, and saliva [10]. The tongue papillae, particularly the filiform papillae, comprise the specific structure involved in TC formation. Light and transmission electron microscopic studies on the TC revealed the presence of bacteria and exfoliated (desquamated) keratinized epithelium that originated from filiform papillae. Moreover, this exfoliated epithelium had degenerated [11]. The entrapment of food particles, saliva, and bacteria in between these filiform papillae can result in
the formation of a thick coating [7]. The tongue is covered with keratinized and non-keratinized epithelial cells, and the balance between retaining and removing these cells influences TC formation [7]. A microscopic study on the ultrastructure of the tongue showed that the rates of epithelial cell multiplication and membrane-coating granule production were associated with TC formation [12].
3. The characteristics of tongue coating
Before visually studying TCs, it is of paramount importance to understand that the light source and the position of the patient during the examination [13] might influence the appearance and color of the TC. A TC is normally present in healthy people [14]. The normal TC is characterized by a thin, slightly moist, whitish substance, which is associated with the dorsal surface of the tongue. The normal TC may vary in color, thickness, moisture, and distribution, depending on the patient’s health [15]. Studies have indicated that there are wide variations in TC thickness and extent, depending on oral parameters, such as periodontal status and IOH. For instance, among subjects with good periodontal health, those with IOH were reported to have thicker TCs than those without IOH [16–18]. Subjects with periodontal disease had four times as much TC (estimated in terms of wet weight) compared to subjects with healthy periodontal tissues [10,19]. In periodontal disease, the TC thickness increases, due to the migration of leukocytes from periodontal pockets into the saliva, and subsequently, these cells are deposited onto the tongue surface [10].
4. Factors that affect tongue coating 4.1. The importance of age
The age of the individual influences the thickness of TC [14]. In elderly, TCs tend to be thicker and more discolored than the TCs of younger people. These age-related TC features might be related to a physical inability to cope with oral hygiene, increased intake of soft food, and a reduction in the natural cleansing of the tongue by saliva. Age might be related to changes in the nature of saliva or reduced salivary flow [20]. Furthermore, filiform papillae, which assist in TC formation, were found to increase with age, and fungiform papillae decreased with age [12]
4.2. The effect of diet on tongue coating
The thickness and color of the TC are affected by dietary conditions. Depending on the type of foods ingested, the appearance of the TC ranges from a water-like, clear solution to a viscous, pigmented, and mucous-like paste. Greasy foods that are rich in fat contribute to TC formation [21]. The TC may also become discolored after consuming colored or pigmented substances, including (1) foods such as chocolate and watermelon [21]; (2) drinks such as coffee [22] or red wine; (3) mouth rinses such as chlorhexidine [23]; (4) materials related to life style such as smoking [22]; and (5)
drugs [24]. Coffee and smoking often lead to a false impression of the quantity of TC [22].
In daily life, tongue movements involved in chewing and swallowing, saliva production, and dietary elements (e.g., fibrous foods) are involved in the cleansing of the tongue, which results in a normal, thin layer of TC. A soft diet, which we mostly consume when ill, might result in reduced tongue movements and less saliva secretion; Consequently, the thickness of the TC might increase [7].
4.3. Oral hygiene
Oral hygiene is the strongest influential factor in the formation of TC [22]. Natural mechanisms for cleansing the tongue might not necessarily remove the TC, when the coating is thick. In this scenario, mechanical tongue cleaning can remove debris, but often, tongue cleaning is not considered a routine oral hygienic procedure [21].
5. The importance of tongue coating in Western medicine
In earlier times, the TC received considerable attention. For instance, in 1828, Dr. Robert Froriep, a German physician-scientist and anatomist, described the importance of the quantity and color of the TC in diagnosing diseases. As scientific knowledge has grown, and improvements have been made in modern laboratory techniques and sophisticated instrumentation, the tongue and its coating have lost importance in the diagnosis of diseases [25]. In Western biomedicine, research on the TC has been scarce. In older individuals who are edentulous, aspiration pneumonia is a serious health problem. The presence of the TC has been considered a risk factor for aspiration pneumonia in people of 65 years or older. Hence, TC removal has been recommended in older individuals who are edentulous [26]. Moreover, thicker TCs were observed in patients with gastrointestinal and liver diseases, compared to healthy subjects [27]. Thus, more research on the TC is demanded in the field of biomedicine.
6. Tongue coating and volatile sulfur compounds in the oral cavity
IOH is mainly attributed to VSCs, particularly, hydrogen sulfide (H2S) and methyl
mercaptan (CH3SH), and to a lesser extent, dimethyl sulfide (CH3)2S. Together, H2S
and CH3SH contribute up to 90 percent of VSC content in the oral cavity [28];
(CH3)2S is mainly related to EOH, but in subjects with IOH, CH3SH can be
converted to (CH3)2S in the oral cavity [29]. The periodontal pockets and the TC are
the two main sources of VSCs. The relationship between VSCs, TC, and periodontal diseases has been studied by several research groups [10,19,28,30,31]. According to Tonzetich, the VSC concentration increases with the severity of periodontal disease [28]. Miyazaki et al. (1995) found a significant correlation between VSCs and the TC in all age groups, but found an association between VSCs and periodontal status only in older age groups. The study concluded that IOH was caused by the TC in young
