Halitosis and helicobacter pylori infection
Wenhuan Dou, MM, Juan Li, MM, Liming Xu, MM, Jianhong Zhu, PhD, Kewei Hu, MM, Zhenyu Sui, MM,
Jianzong Wang, MM, Lingling Xu, MM, Shaofeng Wang, MM
, Guojian Yin, PhD
Background: Halitosis is used to describe any disagreeable odor of expired air regardless of its origin. Numerous trials published
have investigated the relation between Helicobacter pylori (H pylori) infection and halitosis, and even some regimes of H pylori
eradication have been prescribed to those patients with halitosis in the clinic. We conducted a meta-analysis to deﬁne the correlation
between H pylori infection and halitosis.
Objectives: To evaluate whether there is a real correlation between H pylori infection and halitosis, and whether H pylori eradication
therapy will help relieve halitosis.
Methods: We searched several electronic databases (The Cochrane Library, MEDLINE, EMBASE, PubMed, Web of Science, and
Wanfangdata) up to December 2015. Studies published in English and Chinese were considered in this review. After a ﬁnal set of
studies was identiﬁed, the list of references reported in the included reports was reviewed to identify additional studies. Screening of
titles and abstracts, data extraction and quality assessment was undertaken independently and in duplicate. All analyses were done
using Review Manager 5.2 software.
Results: A total of 115 articles were identiﬁed, 21 of which met the inclusion criteria and presented data that could be used in the
analysis. The results showed that the OR of H pylori infection in the stomach between halitosis-positive patients and halitosis-negative
patients was 4.03 (95% CI: 1.41–11.50; P=0.009). The OR of halitosis between H pylori-positive patients and H pylori-negative
patients was 2.85 (95% CI: 1.40–5.83; P=0.004); The RR of halitosis after successful H pylori eradication in those H pylori-infected
halitosis-positive patients was 0.17 (95% CI: 0.08–0.39; P<0.0001), compared with those patients without successful H pylori
eradication. And the RR of halitosis before successful H pylori eradication therapy was 4.78 (95% CI: 1.45–15.80; P=0.01),
compared with after successful H pylori eradication therapy.
Conclusions: There is clear evidence that H pylori infection correlates with halitosis. H pylori infection might be important in the
pathophysiological mechanism of halitosis, and H pylori eradication therapy may be helpful in those patients with refractory halitosis.
Abbreviations: CBS =cystathionine b-synthase, CLO-test =campylobacter-like organism test, CSE =cystathionine g-lyase,
ENT =ears, nose, and throat, GERD =gastroesophageal reﬂux disease, H pylori =Helicobacter pylori, H2S =hydrogen sulﬁde, MM
=methyl mercaptan, UBT =urea breath test, VSC =volatile sulfur compounds.
Keywords: halitosis, Helicobacter pylori, meta-analysis
The term halitosis or bad breath is generally deﬁned to
describe any noticeable disagreeable odor of expired air
regardless of its origin.
The diagnosis of halitosis can always
be genuine halitosis, pseudo halitosis, and halitophobia.
a public social health problem, genuine halitosis is always
classiﬁed into physiological and pathophysiological illness,
which affects a signiﬁcant number of people around the world.
Research reveals that nearly 50% of the adult population has
The cause of the halitosis is often considered to be found in the
oral cavity. It was found that 80% to 90% of patients with
halitosis was caused by oral conditions, deﬁned as bad breath or
Halitosis usually results from deep caries,
pericoronitis, periodontal disease, exposed necrotic tooth pulps,
peri-implant disease, imperfect dental restorations, unclean
dentures, tongue coating, mucosal lesions, and factors causing
decreased salivary ﬂow rate.
The causative organisms from
halitogenic bioﬁlm on the posterior dorsal tongue, and/or within
gingival crevices/periodontal pockets are usually gram-negative
anaerobic bacteria. The basic pathophysiological process is
microbial degradation of sulfur containing amino acid sub-
strates, for example, methionine, cysteine, and cysteine.
Bacterial metabolism of these kinds of amino acids leads to
metabolites including many compounds, such as volatile sulfur
compounds (VSC), for example, hydrogen sulﬁde (H
Editor: Natale Figura.
WD, JL, LX, and JZ contribute equally in this meta-analysis.
The authors have no conﬂicts of interest to disclose.
Department of Gastroenterology, The Second Afﬁliated Hospital of Soochow
University, Suzhou, Jiangsu Province, People’s Republic of China.
Correspondence: Guojian Yin, Department of Gastroenterology, The Second
Afﬁliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s
Republic of China (e-mail: firstname.lastname@example.org); Shaofeng Wang, Department of
Gastroenterology, The Second Afﬁliated Hospital of Soochow University, Suzhou,
Jiangsu Province 215004, People’s Republic of China
Copyright ©2016 the Author(s). Published by Wolters Kluwer Health, Inc. All
This is an open access article distributed under the Creative Commons
Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Medicine (2016) 95:39(e4223)
Received: 5 April 2016 / Received in ﬁnal form: 29 May 2016 / Accepted: 20
Systematic Review and Meta-Analysis Medicine®
mercaptan (MM, CH
SH), dimethyl sulﬁde, and skatole,
The main odorants implicated in intraoral halitosis
are MM and H
About 10% to 20% of all genuine halitosis cases are attributed
to extra-oral diseases,
including upper and lower respiratory
tract disorders, gastrointestinal disorders, some systemic dis-
eases, metabolic diseases, medications, and cancer.
authorities have reported that the ears, nose, and throat (ENT)
are the most common sites of origin of extra-oral halitosis,
it is well established that various ENT disorders and symptoms
may be a manifestation of gastroesophageal reﬂux disease
(GERD). Poelmans et al
showed that patients with suspected
GERD-related ENT symptoms had a high prevalence of
esophagitis and this was associated with better response to
antisecretory therapy. Moshkowitz et al
found that halitosis
was a frequent symptom of GERD and might be considered an
extra-esophageal manifestation of GERD. Struch et al
clear evidence for an association between GERD and halitosis
and suggested treatment options for halitosis, such as proton
It was Tiomny et al
who ﬁrst showed the possible
connection between halitosis and Helicobacter pylori (H
pylori) infection in a case report. Since then, Hpylori
infection has been investigated with regards to a potential
relationship with halitosis in the past 20 years in many
studies, and inconsistent results from case reports, epidemio-
logical studies, randomized controlled trials, and quasir-
andomized controlled trials have been reported.
example, data from Ierardi et al
showed that Hpylori
eradication could resolve the symptom of halitosis. Serin
showed that halitosis was a frequent and treatable
symptom of Hpylori-positive nonulcer dyspepsia and
suggested an Hpylorieradication therapy for those patients
with halitosis. However, on the contrary, in Tangerman study
no association between halitosis and Hpyloriinfection was
found and he concluded that halitosis always originated
within the oral cavity and seldom or never within the
In order to clarify the possible relation between the H pylori
infection and the annoying halitosis, we conducted an exhaustive
review and meta-analysis of all the literatures related to this
subject to evaluate whether H pylori is a cause of halitosis and
whether eradication of H pylori can relieve it.
2.1. Search strategy
The Medical Ethics Committee of a 3-A hospital, the second
Afﬁliated Hospital of Suzhou University, Suzhou, China,
approved the study. Due to the review nature of the study,
informed consent was waived. A comprehensive, computerized
literature search was conducted in MEDLINE, PubMed, Web
of Science, and Wanfangdata from the beginning of indexing
for each database to December 2015, by 2 independent
investigators (GY and WD). Articles published in English and
Chinese were considered in this review. Search terms included:
“halitosis,”“bad breath,”or “malodor,”combined with
Helicobacter pylori,or“urea breath test.”The title and
abstract of eligible studies were then reviewed to exclude any
study that was irrelevant to the research question. After a ﬁnal
set of studies was identiﬁed, the list of references reported in the
included reports was reviewed to identify additional studies.
We did not include data presented only as abstracts at
2.2. Study selection and data extraction
Two review authors, Guojian Yin and Wenhuan Dou indepen-
dently assessed the abstracts of studies resulting from the
searches. Studies were included if they met the following criteria:
published as an original article; published as case reports, case-
control studies, cross-sectional studies, randomised/quasi-ran-
domised controlled trials, and comparative clinical experimental
trial; the relation between the incidence of halitosis and Hpylori
infection, or the incidence of halitosis before and after
eradication therapy of H pylori, were investigated in these
articles. Full text copies of any relevant and potentially relevant
studies, those appearing to meet the inclusion criteria, or for
which there were insufﬁcient data in the title and abstr act to make
a clear decision, were obtained. The full articles were assessed
independently by 2 review authors and any disagreement on the
eligibility of included studies was resolved through discussion
2.3. Statistical analysis
All studies were grouped and analyzed on the basis of study
design: Hpyloriinfection rates in patients with or without
halitosis (group 1); Halitosis rates in patients with or without
H pylori infection (group 2); Halitosis rates in infected
halitosis patients after the treatment with or without successful
H pylori eradication (group 3); Halitosis rates in Hpylori-
infected patients before and after successful H pylori eradica-
tion (group 4).
The Cochrane Q-statistic and the I
-statistic were used to
assess statistical heterogeneity between studies, and an I
of >50% or a Pvalue <0.05 for the Q-statistic was taken to
suggest signiﬁcant heterogeneity.
In the presence of heteroge-
neity, the random-effects model is recommended by the Cochrane
collaboration, because its assumptions account for the presence
of variability among studies.
As the included studies in each
subgroup were less than 10, the publication bias was not assessed
through Funnel plot or Begg test
and Egger tests in this
All statistical tests were 2-tailed, and a probability level of P<
0.05 was considered signiﬁcant. Results were presented in
accordance with the guidelines proposed by MOOSE.
(case-control studies, cross-sectional studies) and RRs (random-
ized controlled trials and quasi-randomized controlled trials, or
comparative clinical experimental trials) were used as the
reporting different risk estimates. All analyses were done using
Review Manager 5.2 software.
The search strategy generated 115 citations, of which 57 were
considered of potential value. Thirty-six of these 57 articles were
subsequently excluded from the meta-analysis for various
reasons (21 studies were excluded by inclusion criteria, 10
reviews, 4 meeting abstracts/summaries, and 1 comment). No
additional article was included from the reference of the included
21 articles even after an overall and careful inspection of those
references. In the ﬁnal analysis 21 articles (2 case reports, 1 cross-
sectional study, 13 case-control studies, 4 comparative quasi
clinical experimental trials, and 1 prospective nonrandomized
Dou et al. Medicine (2016) 95:39 Medicine
open-label trial) were included. Figure 1 shows the ﬂow-sheet of
these studies and their classiﬁcation by study design. Four
subgroups were further classiﬁed in the ﬁnal meta-analysis.
The characteristics of the studies are shown in Table 1. The
publication dates of the studies included in the meta-analysis
ranged from 1992 to 2015. The 21 studies were ranked as
moderate quality. A total of 5062 participants were involved in
these studies (2312 participants in group 1, 2052 participants in
group 2, 128 participants in group 3, and 570 participants in
3.1. Group 1 (n =7): H pylori infection rates in patients
with or without halitosis
Halitosis rates were associated with a statistically signiﬁcant
increase of H pylori infection as shown by the random-effects
model: Overall OR is 4.03 (1.41–11.50) with P<0.05 (Fig. 2).
Evidence of heterogeneity was shown between the studies: The I
was 89 and P<0.05. The random-effects meta-analysis was
therefore applied to minimize the effects of heterogeneity.
3.2. Group 2 (n =9): halitosis rates in patients with or
without H pylori infection
Hpyloriinfection rate were associated with a statistically
signiﬁcant increase of halitosis as shown by the random-
effects model: overall OR is 2.85 (1.40–5.83) with P<0.01
(Fig. 3). Evidence of heterogeneity was shown between the
studies: The I
was 87.20 and P<0.05. The random-effects
meta-analysis was therefore used to minimize the effects of
3.3. Group 3 (n =3): halitosis rates in H pylori-infected
halitosis patients after the treatment with or without
successful H pylori eradication
Compared with the halitosis rates of those H pylori-infected
halitosis patients without successful H pylori eradication after the
treatment, the halitosis rates of the patients with successful H
pylori eradication were lower with a statistical signiﬁcance:
overall RR is 0.17 (0.08–0.39) with P<0.0001 (Fig. 4). There
was no evidence of heterogeneity between the studies (the I
11.00 and P>0.05). The ﬁxed-effects meta-analysis was
therefore chosen to assess the overall RR effects.
3.4. Group 4 (n =5): halitosis rates in H pylori-infected
patients before and after successful H pylori eradication
Compared with the halitosis rates in those H pylori-infected
patients before the successful H pylori eradication, it was lower
after successful H pylori eradication therapy with a statistical
signiﬁcance: overall RR is 4.78 (1.45–15.80) with P<0.05
(Fig. 5). There was evidence of heterogeneity between the studies:
was 90 and P<0.05 suggesting evidence of heterogeneity.
Figure 1. The ﬂow sheet of the studies and the corresponding classiﬁcation by study design.
Dou et al. Medicine (2016) 95:39 www.md-journal.com
The characteristics of the included studies in this meta-analysis.
publication/country Study design Study type
Age, y, mean
or range Male, %
number Halitosis test
H pylori test
of H pylori UGID
Tiomny et al/1992/
Suggest a new explanation for halitosis based
on clinical experience of H pylori
Case report Unknown 50.0 4 Obvious to family members,
family physicians and
Double-drug for 4 weeks
Yes Unknown Unknown
Ierardi et al/1998/
Investigate the effects of H pylori eradicate
therapy on halitosis
45.3 (17–70) 50.0 58 Halimeter/ Organoleptic
Double-drug (omeprazole + amoxicillin)
for 14 days, and Triple-drug
(omeprazole+ clarithromycin +
metronidazole) for 10 days in
cases of eradication failure
Gasbarrini et al/
Evaluate the prevalence of H pylori
infection and gastrointestinal symptoms
in patients with IDDM
Case-control 35 ±11 43.1 116 Questionnaire (patients) UBT (stomach) —Unknown Unknown Unknown
Gasbarrini et al/
Compare the H pylori eradication rate in a group
of IDDM H pylori infected patients and in a
control group of infected dyspeptic patients
39±12 58.1 31 Questionnaire UBT (stomach) Triple-drug for 7 days for IDDM
patients (pantoprazol + amoxicillin +
Unknown Unknown Unknown
Shashidhar et al/
Evaluate safety and efﬁcacy of triple-drug
eradication therapy in symptomatic children
with H pylori infection
11 (1–25) 40.6 32 Questionnaire RUT/histology
Triple-drug for 2 weeks (lansoprazole
+amoxicillin + clarithromycin)
Yes Unknown Unknown
Werdmuller et al/
Compare the clinical presentations in relation to
HP infection in a consecutive series of
patients for gastroscopy
Case-control 50 (22–87) in H pylori
positive patients; 46
(13–83) in H pylori
46.5 404 Questionnaire Histology, Culture and
Gram stain, RUT, and
—No Unknown Unknown
Hoshi et al/2002/
Investigate the relationship between
gastrointestinal conditions and halitosis
Case-control 44.7 (21–77) in H
33.8 (18–67) in H pylori
73.9 46 Organoleptic UBT (stomach) –Unknown Unknown Unknown
Serin et al/2003/
Investigate the frequency of halitosis before and
after eradication therapy in patients with H
pylori-positive non-ulcer dyspepsia.
38.2 (20–70) 46.6 148 Questionnaire (both the
patients and their
Histology (stomach) Triple-drug eradication therapy
for 14 days
No No No
Candelli et al/2003/
Investigate the effects of H pylori infection on
gastrointestinal symptoms in young DM1
Case control 14.8 ±5.6 (6–21) 54.5 121 Questionnaire UBT (stomach) —Without known
Li et al/2005/China Analyze the clinical characteristics of dyspeptic
symptoms in patients
Case-control 49.5 (OD patients); 45.6
70.3 in OD
54.4 in FD
239 as OD;
543 as FD
Questionnaire Under endoscopy
—Yes Unknown Unknown
Adler et al/2005/
The correlation between halitosis and H pylori
infection on the mouth and the stoma
Case-control 56.5 (24–74) 32.4 124 Halimeter PCR (stomach) —Yes Unknown Yes
Katsinelos et al/
investigate the incidence and long-term outcome
of halitosis before and after eradication
therapy in patients with FD and H pylori
40.7 ±10.9 55.6 18 Questionnaire (both the
patients and their
Triple-drug eradication therapy for 10
days and quadruple-drug therapy
for 10days in cases of eradication
Antral gastritis (mild
Chen et al/2007/
Investigate the relationship between halitosis
and H pylori infection
Case-control 37 (18–64) 22.0 50 Organoleptic UBT/histology
—Unknown Unknown No
Suzuki et al/2008/
Study the relationship between oral H pylori
infection and halitosis
Case-control 45.3 ±15 42.0 326 Gas chromatography PCR (saliva) —No Unknown Yes
Lee et al/2009/Korea To evaluate the effect of Korea red ginseng
on H pylori-associated halitosis
Case report 47.7±10.4 (16–72) 44.3 88 Halimeter UBT (stomach) Triple-drug eradication therapy for 7
days or Red ginseng for 10 weeks
FD Unknown No
Tangerman et al/
Evaluate the possible relation between H pylori
Case-control 60 (H pylori +);
52.9 (H pylori -)
63.6 (H pylori +);
47.3 (H pylori -)
78 Organoleptic CLO-test /Histology/
—Yes Unknown Unknown
Dore et al /
Examine the role of H pylori in gastrointestinal
symptoms in children
Unknown (6–15) Unknown 1741 Questionnaire (both the
children and their
ELISA (stomach) —Unknown Unknown Unknown
Chen et al/2012/
Explore the relation between halitosis
and H pylori infection
Case-control 49.7 (halitosis + UGID);
41.6 (halitosis); 47.3
55.2 165 Questionnaire UBT (stomach) —Yes Unknown Unknown
Yilmaz et al/2012/
Compare the presence of H pylori infection in
children with and without halitosis
Case-control 8 (3–15) in halitosis
patients; 8 (3–15) in
50 108 Organoleptic Stool antigen test
—Unknown No No
HajiFattai et al/2015/
Relationship of halitosis with Gastric H pylori
Case-control 34.29 ±13.71 45.45 44 Organoleptic test RUT (stomach) —Unknown No No
Zaric et al/2015/
Eradication of gastric H pylori ameliorates
halitosis and tongue coating
Case-control 19–78 42.86 98 Organoleptic test Nestde-PCR Triple-drug eradication therapy
for 7 days
With dyspeptic Unknown Unkonwn
CLO-test =Campylobacter-like organism test (a rapid urease test), ELISA =enzyme-labeled immunosorbent assay, ENT=ear-nose-throat, FD =functional dyspepsia, H pylori =Helicobacter pylori, IDDM =insulin-dependent diabetes mellitus, OD =organic dyspepsia, PCR =polymerase
chain reaction, RUT =rapid urease test, UBT=urea breath test, UGID =upper gastrointestinal disease.
Dou et al. Medicine (2016) 95:39 Medicine
The random-effects meta-analysis was therefore chosen to
minimize the effects of heterogeneity.
The exact pathophysiological mechanism of halitosis is not
clear. The possible relationship between Hpyloriinfection
and halitosis was ﬁrst suggested by Marshall et al
The potential relation between halitosis and Hpyloriinfection
was further found by Tiomny et al
through a study of the
effects of Hpylorieradication therapy on halitosis. Since then,
a lot of studies have been focused on this controversial
In 2002, Hoshi et al
proved that the intensity of malodor of
mouth air was higher in H pylori-positive patients than in H
pylori-negative patients, and the levels of H
S and dimethyl
sulﬁde in mouth air were also signiﬁcantly higher in the H pylori-
positive patients than in the H pylori-negative patients. In 2005,
Adler et al
showed that the detection of H pylori by
histopathology in the gastric biopsies was positive in 80.43%
patients with halitosis and only 6.41% patients without halitosis
(P<0.01). However, all these studies were carried out in the
adults, the outcomes of the studies in the children were on the
contrary. No statistical signiﬁcance was reached between
halitosis-positive children and halitosis-negative children by
Dore et al
and Yilmaz et al.
Figure 2. H pylori infection rates in patients with or without halitosis.
Figure 3. Halitosis rates in patients with or without H pylori infection.
Figure 4. Halitosis rates in H pylori-infected patients with halitosis after treatment with or without successful H pylori eradication.
Dou et al. Medicine (2016) 95:39 www.md-journal.com
In this meta-analysis, we took all these studies into account
without considering the differences of age or sex between them.
The results showed that the OR (random model) of H pylori
infection between halitosis-positive patients and halitosis-nega-
tive patients was 4.03 (95% CI: 1.41–11.50; P=0.009). We also
did the meta-analysis of the risk of halitosis in the H pylori-
positive patients versus H pylori-negative patients. The results
showed that the OR (random model) of halitosis between
H pylori-positive patients and H pylori-negative patients was
2.85 (95% CI: 1.40–5.83; P=0.004).
But how does H pylori infection produce halitosis. By assessing
the VSC produced by 3 strains of H pylori (ATCC 43504, SS 1,
and DSM 4867) in broth cultures mixed with different sulfur-
containing amino acids in vitro, Lee et al
showed that H pylori
was capable of producing H
S and MM. Although the
production of VSC by H pylori was a little bit different among
different strains of H pylori and different sulfur-containing amino
acids, it was still the direct evidence that this microorganism can
contribute to the development of halitosis. It was suggested that
the VSC produced in the gastrointestinal tract could diffuse into
the lung air after being carried to the lungs via blood.
found that erosive changes in esophagogastroduodenal
mucosa were strongly correlated with increased VSC levels,
suggesting that H pylori-associated eroded and inﬂamed mucosa
might aggravate halitosis by making VSC diffusion much easier
into blood. It was also shown that in accordance with higher
levels of VSC produced in patients with erosive mucosal changes
and ulcerative changes, the enzymes cystathionine b-synthase
(CBS) and cystathionine g-lyase (CSE) prerequisite for VSC
generation were obviously highly induced.
On the contrary,
Hoshi et al
found that although levels of H
S and dimethyl
sulﬁde in mouth air were signiﬁcantly higher in H pylori-positive
patients than in H pylori-negative patients, which meant H pylori
did have some relation with halitosis, but no signiﬁcant difference
was observed in the exhaled breaths between the 2 groups, which
indicated the higher production of VSC in upper gastrointestinal
tract might be not the main source of halitosis. Although the role
of H pylori infection in the pathophysiological mechanism of
halitosis and the increase of VSC level is not clear, it may still be a
frequent contributor to the production of halitosis.
The oral HP infection has also been under investigation in the
past. In1989, H pylori was found in dental plaque by bacterial
In 1991, Desai et al
showed that H pylori was
detected in dental plaque and in gastric antral and body mucosa
in 98%, 67%, and 70%, respectively, of 43 consecutive patients
with dyspepsia. In 1996 in a group of 100 dyspeptic subjects,
H pylori was detected by campylobacter-like organism test
(CLO-test) in saliva, dental plaques, and gingival pockets in 84%,
100%, and 100% of cases and by the culture in 55%, 88%, and
100%, respectively. The presence of H pylori determined by urea
breath test (UBT) in the stomach in these subjects was 60%.
Whether the H pylori infection in the oral cavity correlates with
halitosis is not clear, further detailed investigation is needed.
In this meta-analysis we also evaluated the effect of Hpylori
eradication therapy on halitosis. The results showed that the RR
(ﬁxed model) of halitosis after successful Hpylorieradication in
the stomach in those Hpylori-infected halitosis-positive patients
was 0.17 (95% CI: 0.08–0.39; P<0.0001), compared with those
patients without successful H pylori eradication. We also did the
meta-analysis of the halitosis rates in Hpylori-infected patients
before and after successful H pylori eradication therapy.
The results showed that the RR (random model) of halitosis
before successful H pylori eradication therapy was 4.78 (95%
CI: 1.45–15.80; P=0.01), compared with the patients after
successful H pylori eradication therapy. These results all favor
successful Hpylorieradication therapy to treat those patients of
Interestingly, in 2011, Shalchi et al
took an further
comparative quasiexperimental clinical trial study of 33 halito-
sis-positive patients without oral diseases (17 H pylori-positive
patients and 16 H pylori-negative patients). All patients received
2-week’sH pylori eradication therapy regardless of H pylori
infection. She found that the RRs of halitosis resolution in H
pylori-positive group over H pylori-negative group were 2.8 and
3.3 respectively, and H pylori eradication could resolve halitosis
in a majority of patients. It was suggested that H pylori might be a
probable rather than a possible cause of halitosis.
In conclusion, there was a clear correlation between H pylori
infection and halitosis. H pylori might be a common contributor
to the production of halitosis. In those refractory halitosis-
positive patients without any oral/ENT/systemic diseases,
H pylori eradication therapy in the clinic may be helpful.
 Outhouse TL, Al-Alawi R, Fedorowicz Z, et al. Tongue scraping for
treating halitosis. Cochrane Database Syst Rev 2006;CD005519.
 Akos N, Zsolt B, Peter N, et al. Clinical importance and diagnosis of
halitosis. Fogorv Sz 2012;105:105–11.
 Arinola JE, Olukoju OO. Halitosis amongst students in tertiary
institutions in Lagos state. Afr Health Sci 2012;12:473–8.
Figure 5. Halitosis rates in H pylori-infected patients before and after successful H pylori eradication.
Dou et al. Medicine (2016) 95:39 Medicine
 van den Broek AMWT, Feenstra L, de Baat C. A review of the current
literature on aetiology and measurement methods of halitosis. J Dent
 Harvey-Woodworth CN. Dimethylsulphidemia: the signiﬁcance of
dimethyl sulphide in extra-oral, blood borne halitosis. Brit Dent J
 Chomyszyn-Gajewska M. Contemporary views on etiology and
pathogenesis of halitosis. Przegl Lek 2012;69:1293–6.
 Tangerman A, Winkel EG, de Laat L, et al. Halitosis and Helicobacter
pylori infection. J Breath Res 2012;6:017102.
 Poelmans J, Feenstra L, Demedts I, et al. The yield of upper
gastrointestinal endoscopy in patients with suspected reﬂux-related
chronic ear, nose, and throat symptoms. Am J Gastroenterol 2004;99:
 Moshkowitz M, Horowitz N, Leshno M, et al. Halitosis and
gastroesophageal reﬂux disease: a possible association. Oral Dis 2007;
 Struch F, Schwahn C, Wallaschofski H, et al. Self-reported halitosis and
gastro-esophageal reﬂux disease in the general population. J Gen Intern
 Tiomny E, Arber N, Moshkowitz M, et al. Halitosis and Helicobacter
pylori. A possible link? J Clin Gastroenterol 1992;15:236–7.
 Gasbarrini A, Ojetti V, Pitocco D, et al. Helicobacter pylori infection in
patients affected by insulin-dependent diabetes mellitus. Eur J Gastroen
 Ierardi E, Amoruso A, La Notte T, et al. Halitosis and Helicobacter
pylori: a possible relationship. Dig Dis Sci 1998;43:2733–7.
 Gasbarrini A, Ojetti V, Pitocco D, et al. Insulin-dependent diabetes
mellitus affects eradication rate of Helicobacter pylori infection. Eur J
Gastroen Hepat 1999;11:713–6.
 Shashidhar H, Peters J, Lin CH, et al. A prospective trial of lansoprazole
triple therapy for pediatric Helicobacter pylori infection. J Pediatr Gastr
 Werdmuller BF, van der Putten TB, Balk TG, et al. Clinical presentation
of Helicobacter pylori-positive and -negative functional dyspepsia. J
Gastroen Hepatol 2000;15:498–502.
 Hoshi K, Yamano Y, Mitsunaga A, et al. Gastrointestinal diseases and
halitosis: association of gastric Helicobacter pylori infection. Int Dent J
 Candelli M, Rigante D, Marietti G, et al. Helicobacter pylori,
gastrointestinal symptoms, and metabolic control in young type 1
diabetes mellitus patients. Pediatrics 2003;111(4 Pt 1):800–3.
 Serin E, Gumurdulu Y, Kayaselcuk F, et al. Halitosis in patients with
Helicobacter pylori-positive non-ulcer dyspepsia: an indication for
eradication therapy? Eur J Intern Med 2003;14:45–8.
 Li XB, Liu WZ, Ge ZZ, et al. Analysis of clinical characteristics of
dyspeptic symptoms in Shanghai patients. Chin J Dig Dis 2005;6:
 Chen X, Tao DY, Li Q, et al. [The relationship of halitosis and
Helicobacter pylori]. Shanghai Kou Qiang Yi Xue 2007;16:236–8.
 Katsinelos P, Tziomalos K, Chatzimavroudis G, et al. Eradication
therapy in Helicobacter pylori-positive patients with halitosis: long-term
outcome. Med Princ Pract 2007;16:119–23.
 Lee JS, Kwon KA, Jung HS, et al. Korea red ginseng on Helicobacter
pylori-induced halitosis: newer therapeutic strategy and a plausible
mechanism. Digestion 2009;80:192–9.
 Chi CJZXZBLLTMC. Analysis of 14C-urea breath test in patients with
halitosis. Labeled Immunoassays Clin Med 2012;19:154–6.
 Dore MP, Fanciulli G, Tomasi PA, et al. Gastrointestinal symptoms and
helicobacter pylori infection in school-age children residing in Porto
Torres, Sardinia, Italy. Helicobacter 2012;17:369–73.
 Shalchi R, Hosseini S, Gholipouri C. Helicobacter pylori and halitosis: a
comparative quasi-experimental clinical trial study. Afr J Microbiol Res
 Yilmaz AE, Bilici M, Tonbul A, et al. Paediatric Halitosis and
Helicobacter pylori infection. J Coll Physicians Surg Pak 2012;22:27–30.
 HajiFattahi F, Hesari M, Zojaji H, et al. Relationship of halitosis with
gastric helicobacter pylori infection. J Dent (Tehran) 2015;12:200–5.
 Zaric S, Bojic B, Popovic B, et al. Eradication of gastric Helicobacter
pylori ameliorates halitosis and tongue coating. J Contemp Dent Pract
 Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in
meta-analyses. BMJ 2003;327:557–60.
 Petitti DB. Meta-analysis and endocrinology. Endocrinol Metab Clin
North Am 1997;26:31–44.
 Janarthanan S, Ditah I, Adler DG, et al. Clostridium difﬁcile-associated
diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J
 Begg CB, Mazumdar M. Operating characteristics of a rank correlation
test for publication bias. Biometrics 1994;50:1088–101.
 Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis
detected by a simple, graphical test. BMJ 1997;315:629–34.
 Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational
studies in epidemiology: a proposal for reporting. Meta-analysis of
observational studies in epidemiology (MOOSE) group. JAMA 2000;
 Marshall BJ, Armstrong JA, McGechie DB, et al. Attempt to fulﬁl Koch’s
postulates for pyloric campylobacter. Med J Aust 1985;142:436–9.
 Adler I, Denninghoff VC, Alvarez MI, et al. Helicobacter pylori
associated with glossitis and halitosis. Helicobacter 2005;10:312–7.
 Lee H, Kho HS, Chung JW, et al. Volatile sulfur compounds produced by
Helicobacter pylori. J Clin Gastroenterol 2006;40:421–6.
 Kaji H, Hisamura M, Saito N, et al. Evaluation of volatile sulfur
compounds in the expired alveolar gas in patients with liver cirrhosis.
Clin Chim Acta 1978;85:279–84.
 Yoo SH, Jung HS, Sohn WS, et al. Volatile sulfur compounds as a
predictor for esophagogastroduodenal mucosal injury. Gut Liver
 Krajden S, Fuksa M, Anderson J, et al. Examination of human stomach
biopsies, saliva, and dental plaque for Campylobacter pylori. J Clin
 Desai HG, Gill HH, Shankaran K, et al. Dental plaque: a permanent
reservoir of Helicobacter pylori? Scand J Gastroenterol 1991;26:1205–8.
 Pytko-Polonczyk J, Konturek SJ, Karczewska E, et al. Oral cavity as
permanent reservoir of Helicobacter pylori and potential source of
reinfection. J Physiol Pharmacol 1996;47:121–9.
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