Effect of Ear Vagus Nerve Stimulator on Symptom Improvement and Intestinal Microbiome in Patients With Irritable Bowel
Phase: NA
Conditions: Irritable Bowel Syndrome
Sponsor: Huaping Xie

 
 
Study PROTOCOL 
 
(Effect of auricular vagus nerve 
stimulator on symptom improvement 
and gut microbiota in patients with 
irritable bowel) 
 
 
 
Version number: V3.0 
Version date: 2024.2.7 
 
 
 
Principal Investigator:  
Setting: Tongji Hospital, Tongji Medical College, 
Huazhong University of Science and Technology 

 
 
1. Research Background 
The human gut microbiota is one of the most abundant microbial communities on earth, 
containing highly diverse microbial communities that provide metabolic, immune, and protective 
functions and play a critical role[1-3] in human health. The gastrointestinal microbiome is 
influenced by a variety of factors, including neural stress, genetics, host physiology (host age, 
disease, etc.), and environmental factors such as living conditions and drug use. At the same time, 
the vagus nerve (VN) is considered to be a key component of the autonomic nervous system 
(ANS), which innervates most of the digestive tract and many GI organs such as esophagus, 
stomach, small intestine, and colon. It also innervates important organs[6] in the digestive system 
such as liver, pancreas, and gallbladder. The vagus nerve transmits excitation to the corresponding 
brain regions by sensing stimulation in the intestine, and regulates[5] the gut and brain 
bi-directionally through the "gut-brain axis". 
Recent studies have shown that VN has anti-inflammatory effects. This vagal function is 
mediated through a variety of pathways, some of which are still controversial. The first is the 
anti-inflammatory pathway of the hypothalamic-pituitary-adrenal axis, stimulated by the afferent 
fibers of the vagus nerve, where the adrenal gland releases cortisol, providing an important first line 
of innate defense against inflammatory infections and helping to restore home[7]ostasis. The second, 
called cholinergic anti-inflammatory pathway, releases acetylcholine (ACh) at synaptic junctions 
with macrophages through synaptic connections of enteric neurons mediated by vagal efferent 
fibers. Acetylcholine binds to the α-7-nicotinic acetylcholine receptor of macrophages and inhibits 
the release[8] of tumor necrosis (TNF)α, a proinflammatory cytokine. The last pathway is the splenic 
sympathetic anti-inflammatory pathway, where stimulation of splenic sympathetic nerves by VN 
leads to the distal release of acetylcholine by norepinephrine (noradrenaline). Finally, ACh inhibits 
TNFα release from splenic macrophages via α-7-nicotinic ACh receptors[9]. 
Irritable bowel syndrome (IBS) is a highly prevalent functional digestive disorder 
characterized[10] by chronic abdominal pain and altered bowel habits in the absence of biological or 
structural abnormalities. In the field of IBS, effective medical treatments are very limited[27], and 

patients are urgently looking for alternatives, including probiotics, hypnotherapy, osteopathic 
therapy, dietary changes, and fecal microbiota transplantation[11-14]. In recent years, with the 
continuous elucidation of the vagus nerve mechanism, IBS patients have become more and more 
interested in bioelectrical modulation. These patients are usually skeptical of traditional drug 
treatment and believe that drugs are easy to cause side effects. For the above reasons, vagus nerve 
stimulation (VNS) may be a promising option[15] for improving IBS symptoms.  
In fact, the interaction between the gut and nervous system seems to be one of the links of the 
brain-gut axis, which is mainly regulated by the autonomic nervous system. The anti-inflammatory 
effect of VNS has been demonstrated in previous studies, while low-grade intestinal mucosal 
inflammation[16,17] has been reported in IBS. In the gut, the vagus nerve is also the interface for the 
interaction between the microbiota and the mucointestinal tract, suggesting that there may be 
dys[18,19]biosis in VN in IBS. 
Vagus nerve stimulation (VNS) is currently used as a treatment option for many clinical 
conditions, such as heart failure[20], migraine[21], and inflammatory bowel disease[22]. VNS 
techniques are mainly divided into invasive (surgical implantation) and noninvasive 
(percutaneous)VNS techniques. Invasive VNS (iVNS) involves implantation of a programmable 
pulse generator device in the chest wall and placement of electrodes around the left (typical) 
cervical vagus nerve. As it stands, iVNS carries several potential risks, such as bradycardia and 
cardiac[23] arrest, localized infection[24] around the wound, etc. The transcutaneous VNS (tVNS) 
delivery system relies on the skin distribution of the vagal afferent nerve and intervenes in the 
external ear (auricular branch of the vagus nerve) or neck (cervical branch of the vagus nerve), 
which avoids the risk of surgical implantation of VNS delivery devices and promotes further 
research on the application of tVNS.  
In this study, the portable conchal stimulator produced by Ruizhenan Medical can accurately 
stimulate the conchal boat and stimulate the auricular vagus nerve percutaneously, giving full play 
to its therapeutic effect. Therefore, the purpose of this clinical trial is to use the conchial stimulator 
in patients with irritable bowel syndrome, and to explore whether it has a therapeutic effect on 
patients with irritable bowel syndrome. To explore the effect of tVNS therapy on irritable bowel 
syndrome (IBS) compared with drug therapy, hoping that the use of TVNS therapy can reduce the 
use of related drugs, or even replace drugs. 

Ruisen auricular concha vagus nerve stimulator can be used directly without installation. It is 
easy to carry and can be turned on at any time, without affecting daily work and life (as shown 
below). The current approved indications are as follows: for sleep disorders, anxiety, loss of appetite, 
fatigue as an adjunct treatment, and diabetes as an adjunct treatment. In foreign countries, concha 
vagus nerve stimulation has been approved for the adjuvant treatment of epilepsy and depression. At 
present, some hospitals in China have introduced new technologies for the treatment of disorders of 
consciousness, stroke rehabilitation, migraine, epilepsy, pain intervention and so on. 
 
Schematic illustration of the actual use of the auricular concha stimulator by the participants 
 
According to Mion, F et al. (2020), transcutaneous auricular stimulation of the left vagus nerve 
(taVNS) has been shown to improve symptoms of irritable bowel syndrome (IBS). In 12 patients 
with IBS, taVNS was applied for 6 months for at least 3 hours per day (preferably before bedtime), 
5 days per week, with continuous stimulation at a pulse width of 250 μs and a frequency of 30 Hz. 
Results Effective data were obtained in 9 patients (4 with diarrhea type and 5 with constipation type). 
IBS-SSS was significantly decreased at 3 and 6 months (baseline: 336, 3 months: 231[p = 0.0084]; 
The IBS-SSS decreased from 336 at baseline to 231 at 3 months [p = 0.0084], and 246 at 6 months 
[p = 0.0209][28]. 
According to the above research results, combined with the characteristics of the auricular 

conchae stimulator that is portable and does not affect daily life and work, this study aims to use 
auricular conchae stimulation with pulse width of 200μs, frequency of 30Hz, 3 hours a day for 8 
weeks to improve the clinical symptoms of patients with irritable bowel syndrome. 
2. Objectives of the study 
This study aimed to recruit a group of patients with irritable bowel syndrome (IBS) to use the 
Ruisenan portable auricular conic stimulator. (1) To observe the improvement of symptoms in 
patients with IBS; (2) To analyze the changes of gut microbiota in patients with irritable bowel 
syndrome; (3) verify whether the level of intestinal inflammation is reduced and find metabolic 
markers in the gut. 
3. Study design 
This was a randomized, double-blind study without placebo. Forty patients with 
physician-diagnosed IBS-D were recruited. The recruited patients were randomly assigned to 
undergo either real tVNS (transcutaneous vagus nerve stimulation) or sham TVNS (using the same 
device but without vagus nerve stimulation) at different times. 
4.Selection of subjects 
1、Eligibility Criteria 
1.1 Patients with colorectal cancer were excluded by colonoscopy within two years, and the 
clinical manifestations were diarrhea predominant irritable bowel syndrome, which met the Rome 
Ⅳ diagnostic criteria[25]. That is, recurrent abdominal pain or discomfort, occurring at least 3 days 
per month in the past 3 months, and meeting the following two or more points: 
(1) Improvement after defecation; 
(2) the change of the frequency of defecation; 
(3) The onset of the disease accompanied by changes in stool character (appearance). 
* Symptoms have been present for at least 6 months before diagnosis, and symptoms have met 
the above criteria for the past 3 months 
* Discomfort refers to non-painful discomfort. For pathophysiological studies and clinical 
trials, the frequency of pain/discomfort used for screening assessment is at least two days per week 
when selecting subjects for research. 

1.2 Patients with diarrhea and irritable bowel were mainly selected for enrollment. 
1.3 The enrolled patients with IBS were between 18 and 65 years of age and had a normal 
electrocardiogram before enrollment. 
1.4 Subjects were excluded from the study if they did not meet the requirements by having 
them fill out the questionnaire to assess the health status of the intestinal health-related 
questionnaire. 
2、Exclusion criteria 
(a) patients with other gastrointestinal diseases; (b) patients with a history of previous 
abdominal surgery, cardiovascular disease or serious illness; (c) in the past month, the participant 
has used medications that could affect the outcome of the study (e.g., probiotics, prebiotics, 
antibiotics, laxatives, prokinetic drugs); (d) pregnant women; And (e) patients enrolled in other 
clinical studies. 
5. Estimation of sample size 
Forty patients with diarrhea-predominant irritable bowel syndrome 
6.Study PROCEDURE 
Stool samples were collected from patients with diarrhea-type irritable bowel syndrome. The 
auricular concha-stimulator was used for 3 hours per day with a pulse width of 200μs and a 
frequency of 30Hz. Each patient was randomly selected for true stimulation or sham stimulation 
every 4 weeks for 8[28] weeks, resulting in a total of 4 groups, namely, true-true, true-false, false-true, 
and false-false (FIG. 2). Stool samples were collected on day 0, day 28 and day 56. Stool samples 
were collected two weeks after the end of the treatment. Patients completed questionnaires on day 0 
and every other 7 days thereafter, for a total of 11 questionnaire collections (Figure 1); the 
questionnaires are shown in Table 2. 

 
FIG. 1 Experimental design time schedule 
 
Figure 2 Schematic representation of patient randomization 
A questionnaire was used to determine whether the symptoms of patients with irritable bowel 
syndrome improved, and stool samples were collected on days 0, 28, 56, 63, and 70 for 16s 
sequencing analysis. To study the changes in intestinal microbial composition and intestinal marker 
metabolites in patients before and after the intervention of ear conchal stimulator. Continuous 
sampling survey was conducted 2 weeks after treatment to observe the long-term effect of tVNS 
treatment, and to explore whether the irritable bowel level of patients would return to the level 
before treatment or could be improved after stopping the stimulation. 
The study did not require recruitment advertisement, and the recruitment of subjects was 
completely voluntary. The possible risks in the process of the study were explained to the subjects, 
and the subjects signed the informed consent form after they agreed to participate in the study. A 
questionnaire survey was conducted on the volunteers who agreed to participate in the study to 

obtain their intestinal health and other health status. The subjects were screened according to the 
above selection criteria and exclusion criteria. The collected samples were named by number, and 
no personal information of the subjects was disclosed. The identity of the subjects was kept 
confidential throughout the study, only the number and disease phenotype were visible. Subjects 
may withdraw from the study at any time stage. 
The composition and structure of gut microbiota of the subjects will be analyzed. Subjects can 
keep informed of the progress of the experiment and analysis and obtain their own relevant data at 
any time. 
The auricular conchal stimulator used in this study was manufactured by Ruisenan Medical 
Company. The portable conchal stimulator used in this study was in the form of earphones, which 
was well accepted by patients. It is easy to use and can be used at night before going to bed without 
affecting the normal life of the participants. The contact point of the earphone was closely fitted to 
the left ear conchial boat, which precisely stimulated the conchial boat and gave full play to the 
therapeutic effect. The instrument has three optional modes to meet the needs of personalized 
treatment. 
The medical device registration certificate number of Ruisenan portable ear conchial 
stimulator is 20212090050, which meets the national standards for medical devices. The range 
(level) of Ruisenan portable auricular concha stimulator is 1-60; Frequency (Hz) range: 1-120; 
Pulse width (μs) range: 100, 200; Pulse on (off) time (s) range: 10-200. A variety of diseases can be 
treated by parameter adjustment, such as: sleep disorders, anxiety, depression, fatigue, pain, tinnitus, 
rehabilitation and so on. 
Product design diagram: 

 
The product inspection certificate is shown in Annex 1. 
 
7.Description of concha vagus nerve stimulator 
1、brand: Ruishan 
2、Model: tVNS501 
3、Core technical indicators: 
(1) The stimulation location should be the concha boat, which is enriched in the vagus nerve. 
(2) Built-in rechargeable lithium battery. 
(3) It has three output modes: ① Mode 1: randomly transform between pulse amplitude 0 level 
and set level, pulse width 200μs, pulse frequency in the range of 1-120Hz; ② Mode 2: pulse width 
200μs; The pulse frequency is 20Hz for 7s and 4Hz for 3s, alternating between the two. ③ Custom 
mode programmable: pulse width (100-2000μs), pulse frequency (1-120Hz), pulse on time 
(10-200s), pulse off time (10-200s). 
(4) The duration of stimulation can be set to 0-480min 
(5) The stimulation output amplitude can be set to 0-60 levels, and the current can be adjusted 
to 0-50mA. The current increases linearly with the increase of the output amplitude and can be 
adjusted freely. 
4、output waveform: 

 
 
 
5、Functions 
The current approved indications for concha-vagus nerve stimulation are as following: for the 
adjunctive treatment of sleep disorders, anxiety, loss of appetite, fatigue, and diabetes. In foreign 
countries, concha vagus nerve stimulation has been approved for the adjuvant treatment of epilepsy 
and depression. At present, some hospitals in China have introduced new technologies for the 
treatment of disorders of consciousness, stroke rehabilitation, migraine, epilepsy, pain intervention 
and so on. At the same time, a number of scientific research papers using the device are published 
every year, including the journal Brain Stimulation has also included research papers on the device. 
6、configuration requirements: no installation, direct use. It is convenient to carry, can be 
opened at any time to stimulate, and does not affect daily work and life. 
7、consumables: no consumables 
8、 Hospitals currently using the equipment of the same brand and model: 
General Hospital of the People's Liberation Army 
Sichuan West China Hospital 
Beijing Xuanwu Hospital 
Beijing Tiantan Hospital 

Shanghai Mental Health Center 
The First Affiliated Hospital of Zhejiang University School of Medicine 
Jiangsu Provincial People's Hospital 
Fujian Medical University Union Hospital 
The First Affiliated Hospital of Sun Yat-sen University 
Beijing Aviation General Hospital 
Xijing Hospital of Air Force Medical University 
The First Affiliated Hospital of Army Medical University 
Xiangya Boai Rehabilitation Hospital, Hunan Province 
People of Henan Province 
Anhui Provincial Hospital 
 
8. Possible risks and preventive measures 
1、Possible risks: 
① During the study period, if the patient's skin is allergic to the ear electrode, the use of the ear 
electrode can be immediately suspended, and the stopping date and time can be recorded. 
② If the current density of the electrode exceeds 2mA(r.m. s)/cm2, special attention should be 
paid to the use of the electrode. In case of discomfort, please stop using the electrode immediately or 
reduce the pulse amplitude. 
2、Preventive measures: 
If the symptoms of patients are not improved significantly after receiving otovagus nerve 
stimulation, the researchers of this experiment, as digestive specialists, will give further 
professional guidance, including drugs, psychological counseling, traditional Chinese medicine and 
other comprehensive programs, in order to improve the symptoms of patients. 
9. Data collection and statistical analysis 
The degree of pain, the frequency of diarrhea, and the degree of abdominal distension were 
used to evaluate the changes in the patient's irritable bowel status. The degree of pain refers to the 
use of psychometric practices to evaluate the patient's subjective feeling, which is also considered to 
be the main factor to evaluate the poor health-related quality of life (HRQL). The severity of 

irritable bowel syndrome was measured according to the Gastrointestinal Symptom Rating Scale for 
Irritable Bowel Syndrome (GSRS-IBS)[26]. On the GSRS-IBS scale, a score of 1 to 3 is defined as 
mild symptoms, a score of 4 or 5 as more severe, and a score of 6 or 7 as extremely severe[26]. 
Two-way analysis of variance (ANOVA) was used for statistical analysis. Two-sided t test was 
used for pairwise comparison, and p value was corrected for multiple comparisons. Kruskal-Wallis 
test was used for multiple group comparison. Spearman correlation analysis was used to determine 
the correlation between gut microbiota alterations and biological and pathological parameters 
related to constipation, with p values corrected by Benjamini-Hochberg method (Benjamini and 
Hochberg, 1995). A False Discovery Rate (FDR) threshold of 0.1 was used to consider the p value 
statistically significant. p < 0.05 or p < 0.01 was considered statistically significant. All rule plots 
were generated using GraphPad Prism version 8.0 (La Jolla, CA, United States). All statistical 
analyses were performed using GraphPad prismore and R(version 4.1.2,https://www.r-project.org/) 
10. References 
[1] R. Jumpertz, D. S. Le, P. J. Turnbaugh, C. Trinidad, C. Bogardus, J. I. Gordon, et al. Energy-balance 
studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J 
Clin Nutr, 2011, 94(1): 58-65 
[2] Z. Wang, E. Klipfell, B. J. Bennett, R. Koeth, B. S. Levison, B. Dugar, et al. Gut flora metabolism of 
phosphatidylcholine promotes cardiovascular disease. Nature, 2011, 472(7341): 57-63 
[3] J. R. Goldsmith, R. B. Sartor. The role of diet on intestinal microbiota metabolism: downstream 
impacts on host immune function and health, and therapeutic implications. J Gastroenterol, 2014, 49(5): 
785-798. 
[4] Bonaz B, Sinniger V, Pellissier S. Anti-inflammatory properties of the vagus nerve: potential 
therapeutic implications of vagus nerve stimulation. J Physiol. 2016; 594(20):5781-5790. 
doi:10.1113/JP271539 
[5]  Yu CD, Xu QJ, Chang RB. Vagal sensory neurons and gut-brain signaling. Curr Opin Neurobiol. 
2020; 62:133-140. Doi: 10.1016 / j.carol carroll onb. 2020.03.006 
[6] Chen Chen, JIN Yinchuan, Zhang Liang et al. [6] Chen C, Jin Y C, Zhang L, et al. Research progress 
of transcutaneous vagus nerve stimulation in the treatment of neurological and psychological diseases [J]. 
Stroke and neurological diseases, 2021, 38 (11) : 1043-1046. The DOI: 10.19845 / j.carol carroll nki 
zfysjjbzz. 2021.02619. 
[7]  Johnston GR, Webster NR. Cytokines and the immunomodulatory function of the vagus nerve. Br J 
Anaesth. 2009; 102(4):453-462. doi:10.1093/bja/aep037 
[8]  Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ. The cholinergic anti-inflammatory 
pathway: a missing link in neuroimmunomodulation. Mol Med. 2003; 9 (5 to 8) : 125-134. 
[9]  Matteoli G, Gomez-Pinilla PJ, Nemethova A, et al. A distinct vagal anti-inflammatory pathway 
modulates intestinal muscularis resident macrophages independent of the spleen. Gut. 2014; 
63(6):938-948. doi:10.1136/gutjnl-2013-304676 

[11]  Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel 
disorders. Gastroenterology130(5), 1480–1491 (2006). 
[12]  Wang Y, Zheng F, Liu S, Luo H. Research progress in fecal microbiota transplantation as treatment 
for irritable bowel syndrome.Gastroenterol. Res. Pract. 2019, 9759138 (2019). 
[13]  Shah K, Ramos-Garcia M, Bhavsar J, Lehrer P. Mind-body treatments of irritable bowel syndrome 
symptoms: an updated metaanalysis. Behav. Res. Ther. 128, 103462 (2019). 
[14]  Muller A, Franke H, Resch KL, Fryer G. Effectiveness of osteopathic manipulative therapy for 
managing symptoms of irritablebowel syndrome: a systematic review. J. Am. Osteopath. Assoc. 114(6), 
470–479 (2014). 
[15]  Ford AC, Harris LA, Lacy BE, Quigley EMM, Moayyedi P. Systematic review with meta-analysis: 
the efficacy of prebiotics,probiotics, synbiotics and antibiotics in irritable bowel syndrome. Aliment. 
Pharmacol. Ther. 48(10), 1044–1060 (2018).  
[16]  Bonaz B, Picq C, Sinniger V, Mayol JF, Clarencon D. Vagus nerve stimulation: from epilepsy to 
the cholinergic anti-inflammatorypathway. Neurogastroenterol. Motil. 25(3), 208–221 (2013). 
[17]  Borovikova LV, Ivanova S, Zhang M et al. Vagus nerve stimulation attenuates the systemic 
inflammatory response to endotoxin.Nature 405(6785), 458-462 (2000).  
[18]  Bonaz B, Bazin T, Pellissier S. The vagus nerve at the interface of the microbiota–gut–brain axis. 
Front. Neurosci. 12, 49(2018). 
[19]  Foster JA, Rinaman L, Cryan JF. Stress & the gut–brain axis: regulation by the microbiome. 
Neurobiol. Stress 7, 124–136(2017).  
[20]  De Ferrari GM, Crijns HJ, Borggrefe M, et al. Chronic vagus nerve stimulation: a new and 
promising therapeutic approach for chronic heart failure. Eur Heart J. 2011; 32 (7) : 847-855. The doi: 
10.1093 / eurheartj/ehq391 
[21]  Botha C, Farmer AD, Nilsson M, et al. Preliminary report: modulation of parasympathetic nervous 
system tone influences oesophageal pain hypersensitivity. Gut. 2015; 64(4):611-617. 
doi:10.1136/gutjnl-2013-306698 
[22]  Ghia JE, Blennerhassett P, Kumar-Ondiveeran H, Verdu EF, Collins SM. The vagus nerve: a tonic 
inhibitory influence associated with inflammatory bowel disease in a murine model. Gastroenterology. 
2006; 131 (4) : 1122-1130. The doi: 10.1053 / j.g astro. 2006.08.016 
[23] Asconape JJ, Moore DD, Zipes DP, Hartman LM, Duffell WH Jr. Bradycardia and asystole with the 
use of vagus nerve stimulation for the treatment of epilepsy: a rare complication of intraoperative device 
testing. Epilepsia. 1999; 40(10):1452-1454. doi:10.1111/j.1528-1157.1999.tb02019.x 
[24]  Fahy BG. Intraoperative and perioperative complications with a vagus nerve stimulation device. J 
Clin Anesth. 2010; 22 (3) : 213-222. The doi: 10.1016 / j.j clinane. 2009.10.002 
[25] Lacy BE, Patel NK. Rome Criteria and a Diagnostic Approach to Irritable Bowel Syndrome. J Clin 
Med. 2017; 6(11):99. Published 2017 Oct 26. doi:10.3390/jcm6110099 
[26]  Wiklund IK, Fullerton S, Hawkey CJ, et al. An irritable bowel syndrome-specific symptom 
questionnaire: development and validation. Scand J Gastroenterol. 2003; 38 (9) : 947-954. The doi: 
10.1080/00365520310004209 
[27]  Travers P, Lacy BE, Cangemi DJ. Irritable bowel syndrome - less irritable, or better 
treatments? . Curr Opin Gastroenterol. 2024; 27-40 (1) : 33. Doi: 10.1097 / MOG. 0000000000000987 
[28]  Mion, F., et al., Transcutaneous auricular vagus nerve stimulation for the treatment of irritable 
bowel syndrome: a pilot, open-label study. Bioelectronics in Medicine, 2020. 3(1): p. 5-12. 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 1. Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS). 
The 
following 
questions 
relate to the 
symptoms 
of irritable 
bowel 
syndrome. 
The severity 
or intensity 
of the 
following 
symptoms 
during the 
past 2 weeks 
No 
discomfor
t at all 
Slight 
discomfor
t 
Mild 
discomfor
t 
Moderate 
discomfor
t 
Moderate 
to severe 
discomfor
t 
Severe 
discomfor
t 
Very 
severe 
discomfor
t 
1 
2 
3 
4 
5 
6 
7 
1. Are you 
bothered by 
abdominal 
pain?  
 
 
 
 
 
 
 
2. Have you 
 
 
 
 
 
 
 

ever felt 
pain or 
discomfort 
in your 
abdomen 
that relieved 
with bowel 
movements?  
3. Have you 
been 
bothered by 
feelings of 
bloating?  
 
 
 
 
 
 
 
4. Are you 
bothered by 
gas?  
 
 
 
 
 
 
 
5. Do you 
suffer from 
constipation 
(difficulty 
defecating)?  
 
 
 
 
 
 
 
6. Do you 
suffer from 
diarrhea 
(frequent 
bowel 
movements)
?  
 
 
 
 
 
 
 
7. Do you 
have trouble 
having loose 
bowel 
movements?  
 
 
 
 
 
 
 
8. Do you 
have 
difficulty 
bowel 
movements 
because 
your stools 
are dry? 
 
 
 
 
 
 
 
9. Have you 
ever been 
bothered by 
 
 
 
 
 
 
 

the urgent 
need to 
defecate (the 
need to go to 
the toilet to 
defecate)?  
10. Do you 
have the 
feeling that 
your bowel 
movements 
are 
incomplete?  
 
 
 
 
 
 
 
11. Do you 
feel full 
soon after 
you start a 
meal?  
 
 
 
 
 
 
 
12. Do you 
still feel full 
long after 
you stop 
eating?  
 
 
 
 
 
 
 
13. Do you 
have 
significant 
abdominal 
swelling?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 2. Irritable Bowel Syndrome-Quality of Life Instrument (IBS-QOL) 

The following questions relate to the 
symptoms of irritable bowel syndrome. 
The severity or intensity of the following 
symptoms during the past week 
no 
A little 
bit 
More 
Quite a lot 
Totally so 
0 
1 
2 
3 
4 
1. I feel helpless because of my bowel 
movements 
 
 
 
 
 
2. The smell caused by my stool makes 
me feel embarrassed 
 
 
 
 
 
3. I worry about how much time I spend 
in the bathroom 
 
 
 
 
 
4. Because of my defecation problems, I 
feel vulnerable to other diseases 
 
 
 
 
 
5. I feel like I'm putting on weight 
because of my bowel problems 
 
 
 
 
 
6. I feel unable to organize my life 
because of my bowel problems 
 
 
 
 
 
7. I feel unhappy with my life because of 
my bowel problems 
 
 
 
 
 
8. I feel uncomfortable whenever I talk 
about my bowel problems 
 
 
 
 
 
9. I feel frustrated about having problems 
with my bowel movements 
 
 
 
 
 
10. I feel disconnected from those around 
me because of my bowel problems 
 
 
 
 
 
11. I have to watch how much I eat 
because of my bowel problems 
 
 
 
 
 
12. My sex life is not working because of 
my bowel movements 
 
 
 
 
 
13. I feel angry about my bowel 
movements 
 
 
 
 
 
14.1. I feel prone to irritating others 
because of my bowel problems 
 
 
 
 
 
15. I'm worried that my bowel problems 
are going to get worse 
 
 
 
 
 
16. I feel irritable and irritable because of 
my bowel movements 
 
 
 
 
 
17. I'm worried that people think I'm 
exaggerating my bowel problems 
 
 
 
 
 
18. Do I feel like I can't get anything 
done because of my bowel movements 
 
 
 
 
 
19. I have to avoid stressful situations 
because of my bowel problems 
 
 
 
 
 
20. My bowel problems have reduced my 
libido 
 
 
 
 
 

21. My bowel problems limit what I wear 
 
 
 
 
 
22. Because of my defecation problems, I 
have to avoid strenuous exercise 
 
 
 
 
 
23. Because of my defecation problems, I 
have to watch what kind of food I eat 
 
 
 
 
 
24. I have trouble getting along with 
unfamiliar people because of my bowel 
movements 
 
 
 
 
 
25. I feel slow to respond because of my 
bowel movements 
 
 
 
 
 
26. I feel unclean because of my 
defecation problems 
 
 
 
 
 
27.. It is difficult for me to travel long 
distances because I have problems with 
my bowel movements 
 
 
 
 
 
28. I feel frustrated that I can't eat what I 
want because of my defecation problems 
 
 
 
 
 
29. Being close to the bathroom is 
necessary because of my defecation 
problems 
 
 
 
 
 
30. My daily life revolves around my 
bowel problems. 
 
 
 
 
 
31. I worry about not being able to 
control my bowel movements 
 
 
 
 
 
32. I'm afraid I won't be able to defecate 
properly 
 
 
 
 
 
33. My bowel problems are affecting my 
relationships with those closest to me 
 
 
 
 
 
34. I feel like no one understands my 
bowel movements 
 
 
 
 
 
 
 
 
 
 
 
 
Attachment 1: 

 
 
 
 
 
 

Annex 2: