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Int J Clin Exp Med 2019;12(6):7356-7364 www.ijcem.com /ISSN:1940-5901/IJCEM0085801

Original Article The relationships between hydrogen gas and gas and the symptoms of as determined by a breath test

Yiwen Huang1, Lin Jia2, Yao Liu2

Departments of 1Emergency, 2Gastroenterology, First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, China Received September 20, 2018; Accepted February 13, 2019; Epub June 15, 2019; Published June 30, 2019

Abstract: Objective: To explore the relationship between the breath levels of hydrogen and methane and the symp- toms of irritable bowel syndrome (IBS). Methods: Data from 76 IBS patients (40 males and 36 females) aged 30-53 years were analyzed retrospectively. Thirty healthy subjects who underwent a breath test (LBT) during the corresponding period were selected as the control group. The LBT results of both groups were statistically com- pared, and the correlation between the positive results and the clinical characteristics and symptom scores was analyzed. Results: The total positive rate of the LBT, and the volumes of hydrogen, methane, and total gas were significantly higher in the IBS group than they were in the healthy group (all P<0.05). Furthermore, the volumes of the individual gases and the total gas volume were higher in the LBT-positive compared to the LBT-negative patients (all P<0.05). IBS patients with constipation had a higher proportion of methane-positive patients than hydrogen- positive or hydrogen + methane positive patients (both P<0.05). In contrast, the diarrhea type IBS patients had significantly more hydrogen-positive patients than hydrogen + methane positive patients (P<0.05). The scores of constipation, abdominal distension and flatulence in LBT-positive IBS patients were higher than the scores of the LBT-negative patients (all P<0.05). The constipation and abdominal distension scores of the hydrogen-positive pa- tients were higher than those of the hydrogen-negative patients (both P<0.05), and the constipation score of meth- ane-positive patients was higher than the score of the methane-negative patients (P<0.05). A Pearson correlation analysis showed that the total gas volume in the IBS patients was positively correlated with constipation (r=0.425, P=0.011), abdominal distension (r=0.412, P=0.013) and flatulence (r=0.389, P=0.021), and their hydrogen volume correlated with abdominal distension (r=0.325, P=0.026) and distension (r=0.367, P=0.024), and their methane volume was positively correlated with constipation symptoms (r=0.458, P=0.009). Conclusion: The LBT-positive rate in IBS patients is higher than it is among healthy individuals. IBS patients with or constipation differed sig- nificantly in terms of the hydrogen-positive rate and methane-positive rate, indicating that the amount of hydrogen and methane produced during a LBT are correlated to the severity of specific symptoms. Therefore, the LBT has a diagnostic value in IBS and can be considered for its clinical diagnosis.

Keywords: Lrritable bowel syndrome, breath test, hydrogen, methane

Introduction den to patients and their families and a poor quality of life [3, 4]. Inflammatory bowel syndrome (IBS) is one of the most common and most studied intestinal The pathogenesis of IBS is not completely clear, disorders. Patients usually have one or more but most researchers consider IBS to be a het- persistent or indirect episodes of gastrointesti- erogeneous disease with multiple causes, such nal symptoms. Currently, the structural and bio- as abnormal intestinal motility, abnormal brain chemical abnormalities of the gastrointestinal and intestinal axis, intestinal dysbacteriosis, environment in IBS are not fully known [1, 2]. mental disorders, and genetic factors [5, 6]. The prevalence rate of IBS has been increasing Flatulence is the most common symptom of in recent years, a the current global prevalence IBS, with abdominal distension or other gas- rate of 12%, resulting in a heavy economic bur- related symptoms in 50% to 90% of patients, Relationships between hydrogen and methane gases and symptoms of IBS

Table 1. General data analysis University from April 2015 to November IBS Healthy 2017 were analyzed retrospectively. The t/χ2 P group (n=76) group (n=30) patients were 30-53 years old (average age Gender (n, %) 0.004 0.948 47.61±12.53 years), and included 40 males Male 40 (52.6) 16 (53.3) and 36 females. Thirty healthy subjects (16 males and 14 females, with an average age Female 36 (47.4) 14 (46.7) of 45.74±10.63 years) who underwent LBT Age (year) 47.61±12.53 45.74±10.63 0.734 0.464 at the same time were selected as controls. BMI (kg/m2) 22.81±2.52 21.92±2.15 1.743 0.084 The inclusion criteria were a) IBS diagnosed IBS-C (n, %) 23 (30.3) in accordance with the 2006 Rome III diag- IBS-D (n, %) 37 (48.7) nostic criteria, b) no usage of antibiotics, IBS-M (n, %) 16 (21.0) and other agents affecting gastro- Note: IBS, irritable bowel syndrome; IBS-C, chronic constipation; intestinal motility in the preceding 1 month, IBS-D, diarrhea; IBS-M, mixed type; BMI, body mass index. c) absence of thyroid disease or other com- plications that affect gastrointestinal motil- indicating a close relationship between intesti- ity, and d) [16]. Patients nal gas and IBS [7, 8]. In fact, IBS patients may with other digestive diseases, other infection have increased intestinal gas, a decreased gas sites, heart and kidney diseases, a history of tolerance and a reduced clearance rate com- gastrointestinal surgery, or incomplete clinical pared to healthy individuals [9]. Many studies data, and pregnant and lactating women were have reported that hydrogen and methane, the excluded. This study was approved by the Ethics main components of intestinal gas, are closely Committee of First People’s Hospital, Guang- related to IBS symptoms. For instance, the rate zhou Medical University and an informed con- of hydrogen production is significantly higher in sent was signed by the patients or their fa- IBS patients compared to normal controls. milies. Furthermore, since methane is known to have an inhibitory effect on intestinal transport, the Pre-LBT preparation detection of methane levels in exhaled air can be used to diagnose constipation type IBS [10, Twenty-four hours before the examination, the 11]. At present, the diagnosis of IBS relies on patients were instructed to strictly avoid foods symptomatology and various laboratory tests rich in cellulose and and to avoid such as barium meal and fiber colonoscopy, overeating. In addition, they fasted for 12 hours which have limitations such as low specificity or before the examination and were also not invasiveness [12]. Since intestinal bacterial allowed to take any sedatives during that peri- overgrowth is an important cause of IBS, the od. Right before taking the lactulose substrate, amount of hydrogen and methane produced by the patients rinsed their mouths thoroughly the intestinal bacteria from fermenting food and gargled. Two hours before and during the residues can be a useful indicator of the dis- examination, they were instructed to not exer- ease [13]. The lactose breath test (LBT) is a cise, to be relaxed and quiet, not to take a nap very effective and non-invasive method of mea- and also to avoid drinking and fasting, and to suring the amount of these intestinal gases, avoid interfering with intestinal peristalsis and and therefore the overgrowth of intestinal pulmonary ventilation. microflora. However, due to the inaccuracy of LBT, the incidence of intestinal bacterial over- Symptom scoring and LBT measurements growth in IBS patients has varied greatly across The severity of IBS symptoms including consti- studies. Therefore, it is necessary to further pation, diarrhea, abdominal pain, abdominal analyze the relationship between IBS and LBT distension, flatulence, tenesmus, and early [14, 15]. We retrospectively analyzed the case satiety in the last 7 days before the examina- data of 76 IBS patients in order to determine tion were analyzed using a self-testable scale. A the application value of LBT in IBS. visual simulation model was used to evaluate Materials and methods the severity and frequency of all the symptoms, which were scored from 0 to 6, with 6 indicating Patients and control subjects the most severe symptoms.

The data of 76 IBS patients who were admitted The patients ingested a 10 g lactulose syrup in First People’s Hospital, Guangzhou Medical mixture (Lactulose Oral Solution, 10 g/bag,

7357 Int J Clin Exp Med 2019;12(6):7356-7364 Relationships between hydrogen and methane gases and symptoms of IBS

Table 2. LBT results gher than 10 ppm with IBS group Healthy group a continuous increase t/χ2 P (n=76) (n=30) in methane content. LBT hydrogen + meth- Total positive rate (n, %) 57 (75.0) 11 (36.7) 13.744 <0.05 ane positive was de- H positive rate (n, %) 42 (55.3) 7 (23.3) 0.462 0.497 2 fined as meeting the CH positive rate (n, %) 11 (14.5) 4 (13.3) 0.490 0.484 4 previous two criteria at H2+CH4 positive rate (n, %) 4 (5.3) 0 (0.0) 0.475 the same time [17].

H2 volume (mL) 2234.52±987.57 1765.42±845.79 2.290 0.024

CH4 volume (mL) 1805.55±342.17 1587.46±175.43 4.305 <0.05 Statistical analysis Total gas volume (mL) 4040.12±428.63 3352.91±500.64 7.085 <0.05 SPSS 19.0 (Asia Ana- Note: LBT, lactose breath test; IBS, irritable bowel syndrome; H , hydrogen; CH , methane. 2 4 lytics Formerly SPSS China) was used to an- alyze all the data. The enumeration data were expressed as (n, %) and were compared using 2 an χ test. The_ measurement data were ex- pressed as x ± sd. Welch’s correction was adopted for those with uneven variances. The multigroup comparison was conducted using an ANOVA analysis, and the comparison between two groups was done using an SNK test. Pearson’s test was used for the correla- tion analysis. P<0.05 was considered statisti- cally significant.

Figure 1. LBT test gas volume results. *P<0.05; Results ***P<0.001. LBT, lactose breath test; IBS, irritable bowel syndrome. General data

Of the 76 IBS patients, 23 had chronic consti- Solvay Pharmaceuticals, Netherlands) in 200 pation (IBS-C), 37 had diarrhea (IBS-D), and 16 mL water. They were then asked to inhale deep- were of the mixed type (IBS-M). There were no ly and exhale slowly into a disposable collection significant differences between the IBS and bag. After exhalation, the gas was extracted healthy controls (n=30) in terms of gender, age, with a needle tube and injected into a respirom- or BMI (22.81±2.52 kg/m2 vs. 21.92±2.15 kg/ eter (Quintron-SC methane-hydrogen respirom- m2) (all P>0.05; Table 1). eter, Quintron, USA). The concentration of me- thane and hydrogen in the exhaled gas was LBT results recorded after the measured values were sta- ble. Exhaled air was collected like this every The total positive rate of LBT was significantly 20-minutes, and the experiment lasted 180 higher in the IBS patients compared to the minutes. Graphs of time vs methane/hydrogen healthy group (P<0.05). There were no signifi- concentration were plotted, and the area under cant differences in the positive rates of hydro- the curve was calculated as the volume of the gen, methane, and hydrogen + methane be- respective gas. tween the two groups (all P>0.05). However, the volumes of hydrogen and methane, and the Criterion for LBT hydrogen-positive total gas volume were all significantly higher in the IBS group than they were in the healthy The criterion for LBT hydrogen-positive was a group (all P<0.05; Table 2; Figure 1). hydrogen concentration within 90 minutes higher than the baseline 20 ppm, or the base- Gas volume analysis of IBS patients line value higher than 20 ppm with a continu- ous increase in hydrogen content. The criterion The hydrogen, methane and total gas volumes for LBT methane-positive was a methane con- of the LBT-positive patients were higher than centration within 90 minutes higher than the those of the LBT-negative IBS patients (all baseline of 10 ppm, or the baseline value hi- P<0.05). The hydrogen volumes of the IBS-D

7358 Int J Clin Exp Med 2019;12(6):7356-7364 Relationships between hydrogen and methane gases and symptoms of IBS

Table 3. Gas volume analysis of the IBS patients (mL) higher than that of the hydrogen + methane rate H volume CH volume Total gas volume 2 4 (P<0.05), but the propor- LBT positive (n=57) 2989.62±634.34 2347.27±547.53 5336.92±926.84 tions of both sub-groups LBT negative (n=19) 1479.39±311.41 1263.93±284.72 2743.33±588.64 were similar to the pro- T 9.953 11.101 14.212 portion of the methane- P P<0.05 P<0.05 P<0.05 positive patients (both

Note: LBT, lactose breath test; IBS, irritable bowel syndrome; H2, hydrogen; CH4, meth- P>0.05). For the IBS-M ane. patients, there was no significant difference be- tween the proportion of Table 4. Gas volume analysis of the IBS patients for each subtype (mL) hydrogen, methane and

H2 volume CH4 volume Total gas volume hydrogen + methane po- IBS-C (n=23) 1781.72±285.69* 2073.33±525.45 3855.02±834.51 sitive patients (all P> IBS-D (n=37) 2580.67±622.12 1525.63±217.59** 4106.34±713.81 0.05; Table 5). IBS-M (n=16) 2341.12±583.41 1817.93±336.36 4159.95±784.88 Symptom scores of IBS F 15.962 16.716 1.001 patients P P<0.05 P<0.05 0.373 Note: IBS, irritable bowel syndrome; IBS-C, chronic constipation; IBS-D, diarrhea; IBS-M, * There were no significant mixed type; H2, hydrogen; CH4, methane; compared with IBS-D and IBS-M, P<0.05; com- pared with IBS-C and IBS-M, **P<0.05. differences in the scores of abdominal pain, diar- rhea, tenesmus, or early and IBS-M patients were significantly higher satiety between the LBT-positive and LBT-negati- than the volumes of the IBS-C patients ve IBS patients (all P>0.05); however, the sc- (P<0.05), but the volumes of the IBS-D and ores of constipation, abdominal distension, IBS-M patients were statistically similar (P> and flatulence were significantly higher in the 0.05). The methane volumes of the IBS-C and LBT-positive patients (all P<0.05). The abdomi- IBS-M patients were significantly higher than nal distension and flatulence scores of the the volumes of the IBS-D patients (both P< hydrogen-positive IBS patients were higher 0.05), but there was no significant difference than the hydrogen-negative patients’ scores between the IBS-C and IBS-M patients (P> (both P<0.05), but there were no significant dif- 0.05). However, the total gas volume was not ferences in the scores of abdominal pain, diar- significantly different across the sub-groups rhea, constipation, tenesmus, or early satiety (P>0.05; Tables 3 and 4; Figure 2). (all P>0.05). The constipation score of the methane-positive IBS patients was higher than Correlation of the LBT results and the clinical the score of the methane-negative patients characteristics of the IBS patients (P<0.05), but there were no significant differ- ences in the scores of the common symptoms The hydrogen-positive, methane-positive and as listed above (all P>0.05; Tables 6-8). hydrogen + methane positive IBS patient sub- groups were similar in terms of sex and BMI (all Correlation analysis between LBT results and P>0.05). However, the methane-positive pa- IBS symptoms tients were older than the hydrogen-positive and hydrogen + methane positive patients A Pearson correlation analysis showed that the (both P<0.05), and the latter two sub-groups total gas volume of the IBS patients was posi- had similar ages (P>0.05). Within the IBS-C tively correlated with the scores of constipa- subtype, the proportion of methane-positive tion, abdominal distension, and flatulence (all patients was significantly higher than the pro- P<0.05). Furthermore, the volume of hydrogen portion of hydrogen-positive and hydrogen + was positively correlated with the scores of ab- methane patients (both P<0.05), but the latter dominal distension and flatulence (both P< two sub-groups were similar (P>0.05). In con- 0.05), while the volume of methane was posi- trast, in the IBS-C subtype, the proportion of tively correlated with the symptoms of consti- hydrogen-positive patients was significantly pation (P<0.05; Table 9; Figure 3).

7359 Int J Clin Exp Med 2019;12(6):7356-7364 Relationships between hydrogen and methane gases and symptoms of IBS

Methane has also been asso- ciated with gastrointestinal disorders such as chronic co- nstipation, constipation due to IBS and so on [20]. The bacteriological examination of biopsy specimens is the gold standard for the diagno- sis of bacterial overgrowth in the small intestines of IBS Figure 2. A. Gas volume analysis of IBS patients; B. Gas volume analysis of patients, but it has a low re- IBS patients for each subtype. *P<0.05; ***P<0.001; IBS-C, chronic constipa- producibility. Although the re- tion; IBS-D, diarrhea; IBS-M, mixed type; H2, hydrogen; CH4, methane; LBT, lactose breath test; IBS, irritable bowel syndrome. producibility of LBT can reach 90%, there is no unified dia- gnostic standard [17, 21]. Table 5. Correlations of the LBT results and the clinical characteris- In this study, the clinical da- tics of IBS patients ta of 76 IBS patients and 30 H +CH healthy controls were ana- H positive CH positive 2 4 2 4 positive χ2/F P lyzed retrospectively to ex- (n=42) (n=11) (n=4) plore the application of LBT Gender (n, %) 0.322 0.851 in the auxiliary diagnosis of Male 15 (35.7) 4 (36.4) 2 (50.0) IBS. Female 27 (64.3) 7 (63.6) 2 (50.0) Intestinal dysbacteriosis is Age (year) 43.43±7.23 54.14±6.77* 45.25±3.47 10.271 P<0.05 2 common in patients with IBS BMI (kg/m ) 21.63±2.55 23.53±2.72 23.34±2.31 2.790 0.070 [22]. We found that the total * IBS-C (n, %) 7 (16.7) 8 (72.7) 2 (50.0) 17.468 P<0.05 positive rate of LBT in IBS IBS-D (n, %) 25 (59.5) 3 (27.3) 0 (0.0) 7.781 0.020 patients was 75%, similar to IBS-M (n, %) 10 (23.8) 0 (0.0) 2 (50.0) 5.142 0.076 the 50%-80% rate observed Note: LBT, lactose breath test; IBS, irritable bowel syndrome; IBS-C, chronic consti- in previous studies [23, 24]. pation; IBS-D, diarrhea; IBS-M, mixed type; H , hydrogen; CH , methane; compared 2 4 In the healthy controls, the with hydrogen-positive patients and hydrogen + methane positive patients, *P<0.05. positive rate of LBT was 36.7%, which was significant- Table 6. Symptom scores of different results of LBT in IBS patients ly lower than the rate of the IBS patients. The total gas LBT positive LBT negative t P volume was also significantly Abdominal pain 1.85±0.67 1.70±0.64 0.853 0.397 higher in the IBS patients, Diarrhea 2.30±0.70 2.45±0.52 0.856 0.395 indicating extensive intesti- Constipation 2.03±0.52 1.55±0.61 3.335 <0.05 nal dysbacteriosis. Since in- Abdominal distension 3.48±0.67 2.30±0.64 6.720 <0.05 testinal bacterial overgrowth Flatulence 2.97±0.61 1.70±0.58 7.998 <0.05 is an important mechanism Tenesmus 1.91±0.55 1.76±0.79 0.450 0.768 of IBS, evaluating this over- Early satiety 2.33±0.70 2.09±0.76 1.264 0.210 growth can be an important Note: LBT, lactose breath test; IBS, irritable bowel syndrome. diagnostic basis for IBS [25]. Lactulose is routinely used as the substrate in LBT since Discussion it cannot be absorbed by the human body and can only be metabolized by intestinal bacteria Intestinal gases, mainly hydrogen and methane to produce hydrogen and methane [26]. produced by the colonic bacterial fermentation Although the volumes of hydrogen and meth- of food residues, is an important cause of IBS. ane in the exhaled air of IBS patients were high- Therefore, avoiding foods which can be metab- er than the volumes of the healthy controls, olized into high levels of hydrogen can effec- there were no differences in the positive rates tively improve the symptoms of IBS [18, 19]. of hydrogen, methane, and hydrogen + meth-

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significantly higher than Table 7. Symptom scores of the different results of H2 in the IBS patients those in the IBS-D patients and similar to those in the H positive H negative t P 2 2 IBS-M patients. These find- Abdominal pain 1.88±0.66 1.76±0.58 0.705 0.483 ings are similar to other Diarrhea 2.45±0.53 2.52±0.55 0.493 0.624 reports [27, 28]. Hydrogen Constipation 1.85±0.64 1.76±0.61 0.536 0.594 is the main component of Abdominal distension 3.09±0.72 2.52±0.63 3.072 0.003 intestinal gas in IBS-D Flatulence 3.01±0.71 2.55±0.65 2.490 0.015 patients, but methane is Tenesmus 2.18±0.55 2.15±0.53 0.207 0.836 the main component in the IBS-C patients [29]. We Early satiety 2.12±0.51 2.18±0.52 0.441 0.661 hypothesized therefore th- Note: LBT, lactose breath test; IBS, irritable bowel syndrome; H , hydrogen. 2 at the different IBS symp- toms are correlated to the type of the dominant intes-

Table 8. Symptom scores of the different results of CH4 in the IBS tinal gas. In recent years, patients many studies have associ- ated methane with consti- CH4 positive CH4 negative t P Abdominal pain 1.85±0.65 1.88±0.66 0.173 0.863 pation, and it can inhibit the intestinal transport Diarrhea 2.39±0.62 2.48±0.72 0.525 0.601 function [30]. Some stud- Constipation 2.36±0.52 1.75±0.61 4.227 <0.05 ies have shown that the Abdominal distension 2.76±0.64 2.67±0.63 0.526 0.601 small intestine migration Flatulence 2.79±0.68 2.63±0.66 0.893 0.375 complex motion frequency Tenesmus 2.15±0.51 2.30±0.49 1.118 0.267 of the IBS-D patients is Early satiety 2.09±0.51 2.27±0.54 1.310 0.194 faster than the frequency

Note: LBT, lactose breath test; IBS, irritable bowel syndrome; CH4, methane. of the IBS-C patients, which results in a gastric empty- ing delay, upper gastroin- Table 9. Correlation analysis between the LBT results and the IBS testinal symptoms and low- symptoms er esophagus motility dis- Total gas orders and other symptoms H volume CH volume volume 2 4 [31]. The analysis of the r P r P R P LBT results and the clinical Constipation score 0.425 0.011 0.458 0.009 characteristics of the IBS patients showed significant Abdominal distension score 0.412 0.013 0.325 0.026 differences in the ages of Bilge gas score 0.389 0.021 0.367 0.024 the hydrogen-positive, me- Note: LBT, lactose breath test; IBS, irritable bowel syndrome; H , hydrogen; CH , 2 4 thane-positive and hydro- methane. gen + methane positive pa- tients. The methane posi- ane in the LBTs of both groups. This may be due tive patients were older than the hydrogen posi- to the small sample size in our study. We will tive and hydrogen + methane positive patients, continue to follow up IBS patients, expand the which also confirms the association of meth- sample size, and verify our results. ane and constipation as older people are more likely to develop constipation [32]. There were no differences between the total gas volumes of the IBS-D, IBS-C, and IBS-M There were significant intra-group differences patients, but the volumes of hydrogen and in the proportion of hydrogen-positive, meth- methane were significantly different among the ane-positive and hydrogen + methane positive three subtypes. The hydrogen volumes in the patients. While the IBS-C subtype had a higher IBS-D patients were significantly higher than proportion of methane-positive patients, the the volumes in the IBS-C patients but similar to proportion of hydrogen-positive patients was those in the IBS-M patients. In contrast, the higher in the IBS-D subtype. This is also in methane volumes in the IBS-C patients were agreement with a previous study that showed

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Figure 3. Correlation analysis between the LBT results and the IBS symptoms. A. Correlation analysis of total gas volume and constipation scores (r=0.425, P=0.011); B. Total gas volume and abdominal distension score (r=0.412, P=0.013); C. Total gas volume and flatulence score (r=0.389, P=0.021); D. Hydrogen volume and abdominal disten- sion score (r=0.325, P=0.026); E. Hydrogen volume and flatulence score (r=0.367, P=0.024); F. Methane volume and constipation score (r=0.458, P=0.009). LBT, lactose breath test; IBS, irritable bowel syndrome; H2, hydrogen; CH4, methane. hydrogen and methane as the dominant intesti- consistent with a related report, the correlation nal gases of the IBS-D and IBS-C patients re- between the gas volumes and IBS symptom spectively. Furthermore, constipation, abdomi- scores was weak [35]. We hypothesize that the nal distension, and flatulence scores were high- severity of IBS symptoms is not only due to the er in the LBT-positive patients compared to the volume of the gases but is also a result of LBT-negative patients, and the abdominal dis- impaired gas transport and intestinal gas intol- tension and flatulence scores were higher in erance [36]. It is worth noting that the total gas the hydrogen positive patients compared to the volume is correlated with the symptoms scores, hydrogen negative patients, and the constipa- so it may be a more valuable diagnostic param- tion scores were higher in the methane-positive eter compared to the volumes of the individual patients compared to the methane-negative gases. The main limitation of this study was the patients. Some studies have reported that an small sample size, and our data has to be vali- excessive growth of intestinal bacteria, the severity of abdominal distension, and the flatu- dated by further studies on larger cohorts. lence are related to the volume of hydrogen in In conclusion, the LBT-positive rate in IBS pa- exhaled air [33]. In addition, the methane posi- tients was higher than the rate in healthy indi- tive rate in patients with rectocele constipation viduals. There were significant differences be- is higher than the rate in the non-constipation patients [34]. Both findings agree with our tween the hydrogen-positive and methane-pos- results. This association of the exhaled meth- itive rates in both the IBS-D and IBS-C patients, ane levels with constipation makes it a poten- indicating that the production of these gases tial target for the treatment of constipation. during LBT is related to the severity of the spe- cific symptoms. LBT has a diagnostic value in Our correlation analysis of LBT and IBS symp- IBS and can be potentially incorporated into the toms showed a positive correlation between routine clinical diagnosis of IBS. hydrogen volume and abdominal distension and flatulence, between methane volume and Disclosure of conflict of interest constipation symptoms, and between total gas volume and all three major symptoms. However, None.

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