The effects of locomotor activity on gastrointestinal symptoms of irritable bowel syndrome among younger people: An observational study.

Irritable bowel syndrome (IBS) is a common bowel disorder that manifests as unexplained abdominal pain or discomfort and bowel habit changes in the form of diarrhea, constipation, or alternating patterns of the two. Some evidences demonstrate that increased physical activity improves IBS symptoms. Hence, daily exercise is recommended in these patients. In this study, we aimed to investigate the relationship between physical activity and gastrointestinal symptoms in 101 university students (female = 78) with IBS. Participants were examined by Gastrointestinal Symptoms Rating Scale (GSRS), and gait steps were measured for 1 week using a pedometer. The association between the GSRS score and pedometer counts was determined by ordinal logistic modeling analysis. The ordinal logistic regression model for GSRS and locomotor activity showed a significant stepwise fit (z = -3.05, p = 0.002). The logistic curve separated GSRS score of 5 points (moderately severe discomfort) from 2 points (minor discomfort) by locomotor activity. The probability for daily locomotor activity to discriminate between 5 and 4 points of GSRS (i.e., likely to have reverse symptoms) decreased in accordance with increment of steps per day: 78% probability for 4000 steps, 70% probability for 6000 steps, 59% probability for 8000 steps, and 48% probability for 10000 steps. This study demonstrated that the severity of GSRS is associated with the amount of walking in younger people with IBS. These results may be used as a measure to determine the daily step count to reduce the severity of gastrointestinal symptoms in individuals with IBS.

Introduction

Irritable bowel syndrome (IBS) is a common bowel disorder that manifests as unexplained abdominal pain or discomfort and bowel habit changes in the form of diarrhea, constipation, or alternating patterns between the two [1, 2]. IBS is associated with reduced quality of life [3, 4], which may affect every day living activities. IBS is reportedly common in Japanese adults and is more prevalent in younger age females with low body mass index (BMI) [5]. We followed the treatment guidelines developed by the Japanese committee of Gastroenterology [6]. As some patients prefer non-medical management through diet and physical activity [7, 8], lifestyle modification is considered the initial management for IBS. A previous study has shown that increased physical activity improves gastrointestinal (GI) symptoms in patients with IBS [9]. In the National Health Promotion Movement in the 21st Century in Japan (Health Japan 21), the recommended amount of daily activity is equivalent to 9000 steps for men and 8500 steps for women aged 20–64 years [10]. Thus, it is desirable to achieve these targets in IBS patients.

Previous studies have reported that after a 12-week intervention, GI symptoms improved in physically active patients with IBS compared with physically inactive patients [7, 11]. Brief yoga poses and breathing intervention were feasible and safe adjunctive treatments in young patients with IBS, leading to reduced pain and GI symptoms [12]. Moreover, the IBS group had significantly improved symptoms of constipation compared to the usual care group at a 12-week follow-up after exercise [9]. Hence, physical exercise may be effective in attenuating IBS symptoms temporarily.

Adolescents reportedly present with a variety of IBS symptoms [13, 14] and physical activities [15, 16]. If the relationship between the severity of IBS symptoms and the amount of physical activities can be clarified, then the minimum amount of daily exercise to reduce IBS symptoms can be determined. However, to the best of our knowledge, no study has reported on the extent of the effects of daily activity on improving the GI symptoms of IBS. The research question of how activity level influences symptom severity is important to the management of IBS symptoms. Thus, we aimed to investigate the relationship between physical activity and GI symptoms among younger people with IBS and to estimate the extent of GI symptoms attenuated by achieving the recommended amount of daily activity as per Health Japan 21 [10].

Methods

Study design and ethical considerations

This was an observational study. This study was approved by the Ethics Committee in Saitama Prefectural University (No. 27157) and was conducted in accordance with the Declaration of Helsinki. Participants were informed that the purpose of this study was to investigate the relationship between GI symptoms and physical activity among participants with IBS during the informed consent procedure. Furthermore, they were instructed to measure their physical activity for 1 week using a Pedometer (LifeCorder GS, Suzuken, Tokyo), and to wear the pedometer for 1 week (except when taking a bath), and also to perform their daily life activities.

Participants

The inclusion criteria for study participants were as follows: (1) university students >20 years old and (2) students diagnosed with IBS symptoms according to Rome III criteria: recurrent abdominal pain or discomfort associated with two or more of the following: 1) improvement with defecation; and/or, 2) onset associated with a change in frequency of stool; and/or 3) onset associated with a change in form (appearance) of stool for at least 3 months in the last 6 months [17]. The exclusion criteria were (1) students taking medication for IBS treatment 12 weeks prior to the start of the study and (2) students in whom locomotor counts for 1 week could not be measured. The number of participants required for the analysis of this study was 67 as calculated by G* power [18], logistic regression a priori with an effect size of 0.8, an alpha error of 0.05, and a power of 0.8.

Data collection

From 2015 to 2018, we distributed 1240 copies of survey cooperation requests to university students annually between October to January. In this study, university students were recruited to investigate the relationship between IBS symptoms and physical activity, from autumn to winter. A request for recruiting collaborators in the survey was created, posted on the university bulletin board, and distributed to university students after class. A school medical doctor interviewed the students who read the distributed survey request form and confirmed the presence or absence of IBS symptoms according to the Rome III criteria.

The Rome III criteria are used to diagnose IBS symptoms, which include recurrent abdominal pain or discomfort, 3 days per month in the last 3 months (12 weeks), and are associated with two or more of the following three criteria: 1) improvement with defecation, 2) the onset is associated with a change in stool frequency, and 3) the onset is associated with a change in the stool form (appearance). To fulfil the criteria, symptom onset should occur 6 months prior to the diagnosis.

Informed consent forms were given to students who had IBS symptoms, and consent to measure the number of steps in 1 week and to investigate GI symptoms using the Gastrointestinal Symptoms Rating Scale (GSRS) [19, 20] was obtained. The GSRS is a disease-specific instrument of 15 items combined into 5 symptom clusters depicting reflux, abdominal pain, indigestion, diarrhea, and constipation. The GSRS has a seven-point graded Likert-type scale where “1” represents the absence of troublesome symptoms and “7” represents very troublesome symptoms.

Students responding to the survey carried pedometers (LifeCorder GS, Suzuken, Tokyo) about for 1 week, after which each individual’s weekly walking activity and digestive symptom scores were analyzed. Walking activity data that were recorded in LifeCorder GS were uploaded into a personal computer using an application Lifelyzer05 (Kenz, Tokyo). Participant’s GI symptoms were examined using the GSRS after pedometer counts.

Statistical analysis

Participants’ age, sex, physical activity, and GI symptoms were compared according to sex using χ2 test and Student’s t-test. The GSRS scores were derived from the total score and divided by 15 (i.e. the 15 item subscales). The average pedometer counts (steps/day) were calculated using all days of data collection. The association between the GSRS score and pedometer counts was determined by the ordinal logistic modeling analysis [21]. The relationship between GSRS score and pedometer counts (prediction probability g (x)) was estimated using ordinal logistic regression modeling (Eq 1) with the dependent variable as GSRS score (f (x), continuous variates 1 to 7) and the independent variable as pedometer counts for x (Eq 2). The principle of ordinal logistic regression modeling is to fit the probability (P) of multiple dichotomous responses (Eq 1): where x is the explanatory variable, β is the partial regression coefficient, and e is the residual between actual and predicted data. Therefore, for multilevel ordinal responses, the cumulative probability is calculated at each level to generate a simple regression. In this study, the probability of the cut-off point for each level of severity of GI symptoms based on the GSRS score (1|2, 2|3, 3|4, 4|5) was evaluated in association with the pedometer count. A sub-analysis was performed to investigate any gender difference. The level of statistical significance was set at 5%. All statistical analyses were performed using the R 3.5.2 software (R Foundation for Statistical Computing, Vienna, Austria).

Results

Of 663 participants who consented to enter the study, 103 university students (80 female) were diagnosed by school medical doctors to have IBS symptoms based on the Rome III criteria [17, 22], none of whom were taking medications for IBS. Of the 103 participants, two were excluded before the analysis because the step counts were not measured every day. Finally, data from 101 participants (female = 78) were analyzed (Fig 1). IBS subtypes, based on the frequency of symptoms in the participants, were constipation (n = 42), mixed type (n = 29), diarrhea (n = 25), and not classified (n = 5). All 101 participants completed the one-week step count and GSRS survey. The number of female students with IBS was higher than that of male students (x2 = 3.36, p < 0.01, V = 0.04). The BMI was 23 ± 3 for female participants and 21 ± 2 for male participants. No sex differences in age, one-week step count, and GSRS score were found (Table 1).

Fig 1

Selection process of the study population and study design.

The survey was distributed to a total of 1240 university students during the study period. Data from 101 students who met the inclusion criteria were collected and statistically analyzed.

Table 1

Participant characteristics.

	All	Female	Male	Statistics
Participants (n)	101	78	23	x2 = 3.36	p < 0.01	V = 0.12
Age (years)	20 ± 2	20 ± 2	20 ± 2	t = -0.59	p = 0.56	d = 0.09
Locomotor	8126 ± 2570	7627 ± 2426	8272 ± 2608	t = 1.37	p = 0.31	d = 0.26
GSRS score	2.6 ± .9	2.6 ± .9	2.7 ± .8	t = -0.77	p = 0.44	d = 0.11

The locomotor activity is the number of daily step counts measured using a LifeCorder GS pedometer that participants carried for 1 week. The Gastrointestinal Symptoms Rating Scale (GSRS) score is adjusted by dividing the total score by the number of questions.

Scatterplots of GSRS score and locomotor activity of the participants are presented in Fig 2a. The ordinal logistic regression model for GSRS and locomotor activity showed a significant stepwise fit (z = -3.05, p = 0.002; Fig 2b). The GSRS ranges from severe, to moderate, to minor discomfort. The threshold estimate assigned to severe is GSRS score of 5, to moderate GSRS score of 3 and to minor discomfort GSRS score of 2. Locomotor activity was a significant predictor in separating these thresholds with the estimate assigned to this logistic curve. Probability for daily locomotor activity to discriminate between GSRS scores 5 and 4 (i.e., likely to have severe symptoms) was decreased in accordance with increment of steps per day: 78% probability for 4000 steps, 70% probability for 6000 steps, 59% probability for 8000 steps, and 48% probability for 10000 steps (Fig 2b and S1 Table).

Fig 2

Logistic probability plots of the relationship between GSRS score and pedometer counts.

(A) Scatterplots of Gastrointestinal Symptoms Rating Scale (GSRS) scores and daily pedometer counts in university students with IBS (n = 101). GSRS scores range from 7 indicating “very severe discomfort” to 1 “no discomfort at all.” Plots were realigned by GSRS scores and the one-week pedometer counts in participants with irritable bowel syndrome (IBS). (B) Logistic curves separated by GSRS scores of 5 (moderately severe discomfort) and 2 (broken line: minor discomfort), GSRS scores of 5 and 4 (solid line), and GSRS scores of 4 and 3 (chain line) were in a stepwise fit. Ordinal logistic regression model, z = -3.05, stepwise fit p = 0.002.

Sub-analysis was performed separately to determine sex differences. We did not observe any significant difference in the results of the ordinal logistic regression analysis for the male participants (z = -1.81, p = 0.07), while that of female participants showed a significant difference (z = -2.44, p = 0.01), which was similar to the overall results of the ordinal logistic regression analysis (Fig 3). Probability for daily locomotor activity to discriminate between GSRS scores 5 and 4 was decreased in accordance with increment of steps per day: 79% probability for 4000 steps, 71% probability for 6000 steps, 62% probability for 8000 steps, and 52% probability for 10000 steps in female participants (Fig 3b). Especially, probability for daily locomotor activity to discriminate between GSRS scores 5 and 4 was 60% probability for 8500 steps per day in reference to necessary daily steps in healthy females recommended by the Health Japan 21 (S2 Table). [10]

Fig 3

Logistic probability plots of the relationship between GSRS score and pedometer counts in female participants.

(A) Scatterplots of Gastrointestinal Symptoms Rating Scale (GSRS) score and daily pedometer counts in female participants with irritable bowel syndrome (IBS) (n = 78). (B) Logistic curves separated by GSRS scores of 5 (moderately severe discomfort) and 2 (broken line: minor discomfort), GSRS scores of 5 and 4 (solid line), and GSRS scores of 4 and 3 (chain line) were in a stepwise fit. Ordinal logistic regression model, z = -2.44, stepwise fit p = 0.01.

Discussion

This study investigated the relationship between the number of daily step counts and GI symptoms by applying an ordinal logistic model to data collected from younger people with IBS. Our results indicated that locomotor activity and GI symptoms were correlated, and threshold levels of locomotor activity that could predict GI symptoms in IBS exist. We have also observed independent probabilities for IBS symptoms in relation to locomotor activity. Our findings suggest gender difference in the symptoms and its effects, which was predictable considering the female predominance of our cohort. On the ordinal logistic regression analysis data from the female participants were comparable to the overall results of the analysis, while the data from the male participants were not. Therefore, the results of this study can also serve as reference values for young female patients with IBS.

To the best of our knowledge, using a model formula to predict GI symptoms of IBS based on daily step counts is a novel method in this field. Therefore, we estimated the degree of attenuation of GI symptoms of IBS in our participants, especially in young females, by applying this formula to the recommended daily momentum in Healthy Japan 21 [10]. For example, probability for daily locomotor activity to discriminate between GSRS scores 5 and 4 was 60% probability for 8500 steps per day in reference to the recommended daily step counts for a healthy female according to the Health Japan 21. This result indicates that the equivalent number of steps recommended by Healthy Japan 21 may also be an effective target for patients with IBS.

Physical activity using a pedometer-based guideline could increase public health outcomes, [23, 24] with 3000 steps in 30 min (100 steps/min) considered as moderate-intensity activity [25]. Increased physical activity may improve IBS symptoms through different mechanisms [6, 8]. Mild physical activity enhances intestinal gas clearance and reduces symptoms in patients with bloating [26, 27]. To increase colon transit time in adults with chronic constipation [28], 30 min of daily walking is recommended to improve the defecation pattern [29]. A recent study demonstrated that inflammatory biomarkers [30] were attenuated after 24 weeks of moderate-intensity aerobic exercise [31]. Thus, routine physical activity may be a useful primary treatment modality in IBS.

This study has some limitations. (1) The participants in this study had mild IBS symptoms but were not taking medication. Since IBS improves with medications [32, 33] it is necessary to investigate whether there is a relationship between locomotor activity and digestive symptoms among patients taking medications. (2) Dietary therapy is effective in IBS [34, 35]. However, we did not investigate patients’ meal contents during the study period. It is unclear whether dietary contents affect the relationship between exercise and GI symptoms in IBS. Future studies are required to investigate such correlations. (3) This study did not use an index to estimate IBS symptoms other than GSRS. It is necessary to verify the relationship and effects using IBS-QOL [36] and other indicators. (4) The present analysis targeted younger people, and no stratification analysis was performed based on age. The recommended amount of locomotor activity differs between the young and elderly individuals in Health Japan 21 [10]. Thus, it is necessary to investigate the relationship between GI symptoms and daily effects of locomotor activity and to build a prediction model for elderly people. (5) There was no significant association between GI symptoms and locomotor activity in males with IBS in this study. There were gender differences in the symptoms of IBS [37] characterized by constipation and diarrhea. The Prevalence of IBS subtypes were similar to those in a previous study [38]; no IBS subtypes were included in our analysis. In addition, symptoms vary with age [39]; therefore, future studies with larger cohorts should be stratified by age and IBS subtype to further investigate the relationship between physical activity and digestive symptoms. (6) The purpose of the study was explained to the participants during the informed consent process. Thus, participants may have increased their physical activity during the study period since they were informed that IBS symptoms are affected by the amount of physical activity. It is unclear whether the information bias was influenced by the participants’ knowledge of the study aims. Therefore, the effect of the bias should be verified by a study examining the effects of information on the relationship between GI symptoms and physical activity among people with IBS. (7) This study used Rome III criteria, when the study was planned in 2015. The IBS diagnostic criteria were updated to ROME IV [40, 41], and the Japanese version of the questionnaire has not yet been published. In Rome IV, the evaluation of the symptoms has changed from that of Rome III, including the emphasis on the subjective experience of abdominal pain in IBS patients, and the demarcation between the constipation subtype of IBS and functional constipation. In subsequent studies, IBS diagnostic criteria should be based on ROME IV.

Based on our findings, increasing the daily step count to 9500 steps from 4000 steps will result in 50% reduction in the severity of symptoms. Previous studies have shown that exercise improves IBS symptoms [7, 11]. Current data has suggested the "degree" (amount) of physical activity required to attenuate IBS symptoms. The results of this study can provide the clinicians with information on how many steps to add to the current physical activity level among IBS patients that can reduce GSRS by 1 point. However, the effect of exercise on symptom improvement in IBS patients with mild to moderate discomfort is considered small. The effects of locomotor activity in decreasing GSRS scores should be determined in an intervention study in the future. It is recommended that patients with IBS exercise on a daily basis; however, there is no consensus on the type of exercise to be performed. In conclusion, the results of this study demonstrated that the amount of locomotor activity was related to GI symptoms in younger people with IBS by applying an ordinal logistic model. Furthermore, the results suggest that the amount of daily locomotor activity may attenuate IBS symptoms among younger people, especially female IBS patients. These results may be used as a measure to determine the daily step counts for reducing the severity of GI symptoms in individuals with IBS.

Target values for daily step counts in younger people with IBS.

Estimated probability rate for Gastrointestinal Symptoms Rating Scale (GSRS) score by ordinal logistic modeling in all participants in this study (n = 101). The Health Japan 21 recommended a daily activity level of 8500 steps/day for females and 9000 steps/day for males. IBS, irritable bowel syndrome.

(DOCX)

Click here for additional data file.

Target values for daily step counts in younger females with IBS.

Estimated probability rate for Gastrointestinal Symptoms Rating Scale (GSRS) score by ordinal logistic modeling. The Health Japan 21 recommended a daily activity level of 8500 steps/day for females. If a female patient with IBS walked only 4000 steps/day, she will attain GSRS score 5 with probability of 78.5%, while 8500 steps/day will reduce the probability to 59.7%. IBS, irritable bowel syndrome.

(DOCX)

Click here for additional data file.

(XLSX)

Click here for additional data file.

18 Mar 2020

PONE-D-19-33098

The effects of locomotor activity on gastrointestinal symptoms of irritable bowel syndrome: an observational study

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Reviewer #1: 1. The question of how activity level influences symptom severity is important to the management of IBS symptoms.

2. There were 1240 surveys distributed and 663 (53%) returned usable data. 103 of these had an IBS diagnosis and were included in the study. It is not clear whether the participation rate was influenced by the subject's knowledge of the study aims.

3.. Sex was predominantly female, with 78 females to 23 males. Sex was not a significant predictor. Should it be included in the analysis?

4. No instructions to subjects are included in the manuscript. These may influence the outcome of the data.

5. Among the predictor variables (age, sex, symptom severity, and activity), only activity level was significantly related to symptom severity. Age was restricted because the population were students. Although none of the predictor variables was related to symptom severity, an "ordinal logistic regression" method was used to control for overlapping classification of the predictors. The logic is not clear to me and should be explained. The supporting tables suggest that the data were analyzed by changes in activity level needed to move a subject from one severity classification to another on a 5-point scale. If this method appropriately controls for the classification overlap, the analysis shows a strong effect of age and sex on the severity of IBS symptoms.

6. There are some limitations to the study which should be explained: Age was limited by studying students. Sex is predominantly female; should the males be included in the analysis? Students receiving medications for IBS were excluded; does this bias the outcome?

7. Explain how this study extends previous studies of the effects of physical activity on IBS symptom severity. How should clinicians use the findings to manage patients?

8. Please explain the tables and figures. Are changes in activity level related to the baseline level of activity? Are the recommended changes achievable?

Reviewer #2: The aspect that the study addresses is important. Although the effect exercise on IBS is well documented, this study provides a quantitative measure of effect of walking on IBS symptoms. It will be helpful for management of this disease. The manuscript is well written. I have one main question.

What was the reason the authors used Rome III criteria for confirming IBS instead of Rome IV criteria? Please see the following three references given as example how using criteria Rome IV versus Rome III impacts studies.

(i) Am J Gastroenterol (2018) 113:1017–1025. https://doi.org/10.1038/s41395-018-0074-z

(ii) Lin and Chang; Clinical Gastroenterology and Hepatology Vol. 18, No. 2

(iii) https://doi.org/10.1111/nmo.13189

The authors need to address this in the manuscript as it may impact the conclusions drawn.

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Reviewer #2: No

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15 Apr 2020

Response to Reviewers

Reviewer #1 comments:

1. The question of how activity level influences symptom severity is important to the management of IBS symptoms.

Answer to comment 1:

We appreciate the reviewer’s helpful comments to improve our manuscript. This point is exactly our research question. Since this is a very important comment, we have added this sentence to the Introduction section. Please see page 4, lines 57-58 in the revised manuscript.

“The research question of how activity level influences symptom severity is important to the management of IBS symptoms.”

2. There were 1240 surveys distributed and 663 (53%) returned usable data. 103 of these had an IBS diagnosis and were included in the study. It is not clear whether the participation rate was influenced by the subject's knowledge of the study aims.

Answer to comment 2:

We value the reviewer for this important comment, it is better to calculate and compare the study participation rate of those who had IBS diagnosis before this survey and those who did not, but there was no data on this in this study. The results of this study may have been influenced by the information available to the participants about the relationship between gastrointestinal symptoms and physical activity. This is one of the limitation of this study. Therefore, we have added the information provided during the informed consent process to the participants in the Methods section. In addition, it was described as sixth limitation in the Discussion section.

Methods section, Study Design and Ethical Considerations subsection: P4, lines 67-71: “Participants were informed that the purpose of this study was to investigate the relationship between GI symptoms and physical activity among participants with IBS during the informed consent procedure. Furthermore, they were instructed to measure their physical activity for 1 week using a Pedometer (LifeCorder GS, Suzuken, Tokyo), and to wear the pedometer for 1 week (except when taking a bath), and also to perform their daily life activities.”

Discussion section: P12, lines 225-231: “The purpose of the study was explained to the participants during the informed consent process. Thus, participants may have increased their physical activity during the study period since they were informed that IBS symptoms are affected by the amount of physical activity. It is unclear whether the information bias was influenced by the participants’ knowledge of the study aims. Therefore, the effect of the bias should be verified by a study examining the effects of information on the relationship between GI symptoms and physical activity among people with IBS.”

3. Sex was predominantly female, with 78 females to 23 males. Sex was not a significant predictor. Should it be included in the analysis?

Answer to comment 3:

We value the reviewer for this comment. The prevalence of IBS is more common in females than in males, and being female is considered a risk factor in IBS [1, 2]．On the other hand, Bjorkman et al. reported that there was no gender difference with depressive symptom, pain, defecation frequency, effects on daily living, and dissatisfaction with bowel habits in IBS [3]. Therefore, we analyzed the relationship between gastrointestinal symptoms and locomotor activity by gender including all participants (including males). As a result, no significant fit was found in the logistic model in male (please see Results section, page 9, lines 161-165). These results may be related to gender differences in IBS pathology and differences in age and physical activity. Of course, the limitation of the analysis in this study was the small number of males. Therefore, we added this issue to the Discussion section as follows:

“There was no significant association between GI symptoms and locomotor activity in males with IBS in this study. There were gender differences in the symptoms of IBS characterized by constipation and diarrhea. The prevalence of IBS subtypes were similar to those in a previous study; no IBS subtypes were included in our analysis. In addition, symptoms vary with age; therefore, future studies with larger cohorts should be stratified by age and IBS subtype to further investigate the relationship between physical activity and digestive symptoms.” (page 12, lines 219-225:)

4. No instructions to subjects are included in the manuscript. These may influence the outcome of the data.

Answer to comment 4:

We agree with the reviewer about this comment. The results of this study may have been influenced by the knowledge of the participants about the relationship between digestive symptoms and physical activities. This is a limitation of the research. Therefore, we have added the information provided during the informed consent process to the participants in the Methods section. In addition, it was described as sixth limitation in the Discussion section.

Methods section, Study Design and Ethical Considerations subsection: P4, lines 67-71: “Participants were informed that the purpose of this study was to investigate the relationship between GI symptoms and physical activity among participants with IBS during the informed consent procedure. Furthermore, they were instructed to measure their physical activity for 1 week using a Pedometer (LifeCorder GS, Suzuken, Tokyo), and to wear the pedometer for 1 week (except when taking a bath), and also to perform their daily life activities.”

Discussion section: P12, lines 225-231: “The purpose of the study was explained to the participants during the informed consent process. Thus, participants may have increased their physical activity during the study period since they were informed that IBS symptoms are affected by the amount of physical activity. It is unclear whether the information bias was influenced by the participants’ knowledge of the study aims. Therefore, the effect of the bias should be verified by a study examining the effects of information on the relationship between GI symptoms and physical activity among people with IBS.”

5. Among the predictor variables (age, sex, symptom severity, and activity), only activity level was significantly related to symptom severity. Age was restricted because the population were students. Although none of the predictor variables was related to symptom severity, an "ordinal logistic regression" method was used to control for overlapping classification of the predictors. The logic is not clear to me and should be explained. The supporting tables suggest that the data were analyzed by changes in activity level needed to move a subject from one severity classification to another on a 5-point scale. If this method appropriately controls for the classification overlap, the analysis shows a strong effect of age and sex on the severity of IBS symptoms.

Answer to comment 5:

We appreciate the reviewer for these comments. We performed a stratified analysis of gender difference. Age was not adjusted for because all participants’ age categorized them in the younger age range, instead we described this as limitations of the study. In the title, we added "among younger people: ". In addition, a characteristic of the ordinal logistic regression model is that a linear function is applied to the logistic regression function. Equation 2 explains the f (x) part of Equation 1. Thus, we have added texts about the statistical analysis as follows:

“The relationship between GSRS and pedometer counts (prediction probability g (x)) was estimated using ordinal logistic regression modeling (Equation 1) with the dependent variable as GSRS (f (x), continuous variates 1 to 7) and the independent variable as pedometer counts for x (Equation 2). The principle of ordinal logistic regression modeling is to fit the probability (P) of multiple dichotomous responses (Equation 1):” (Methods section, Statistical Analysis subsection, page 6, lines 101-105)

In this study, the probability of the cut-off point for each level of severity of GI symptoms based on the GSRS score (1|2, 2|3, 3|4, 4|5) was evaluated in association with the pedometer count.” (Methods section, Statistical Analysis subsection, page 6, lines 109-111)

6. There are some limitations to the study which should be explained: Age was limited by studying students. Sex is predominantly female; should the males be included in the analysis? Students receiving medications for IBS were excluded; does this bias the outcome?

Answer to comment 6:

We appreciate the reviewer for these helpful comments. In the results of the ordinal logistic regression analysis performed in this study, only the factor ‘male’ was not a significant fit (z=-1.81, p=0.07, Figures), only being female was significant (z=-2.44, p=0.01), and no gender case was significant (z=-3.05, p=0.002). Please see the figure (not shown in this text) and the Results section on males. To clarify whether the gender difference was a confounding factor, male data were included in the analysis of this study. Our response to this comment of the reviewer is related to comment 4 of the reviewer. Please see our response to comment 4. In addition, since the participants in this study were young, we have changed the title to reflect the age.

7. Explain how this study extends previous studies of the effects of physical activity on IBS symptom severity. How should clinicians use the findings to manage patients?

Answer to comment 7:

We thank the reviewer for the pertinent question and agree with its relevance. Accordingly, we have added the following texts in the Discussion section:

Previous studies have shown that exercise improves IBS symptoms. Current data has suggested the "degree" (amount) of physical activity required to attenuate IBS symptoms. The results of this study can provide the clinicians with information on how many steps to add to the current physical activity level among IBS patients that can reduce GSRS by 1 point.” (Discussion section, page 13, lines 238-242)

8. Please explain the tables and figures. Are changes in activity level related to the baseline level of activity? Are the recommended changes achievable?

Answer to comment 8:

We appreciate the reviewer for these questions. This study was an observational study; gastrointestinal symptoms and pedometer counts were both obtained as baseline data. The number of steps is the data for one week, and the GSRS is the data after measuring the amount of walking. Please see revised manuscript in page 5, lines 93-96 and footnote in Table 1. In a further intervention study, it will be necessary to determine whether the gastrointestinal symptoms would improve as expected if the patient achieves the level of physical activity indicated in this study. The daily walk recommended by Health Japan 21 is 8,500 steps for a female and 9,000 steps for a male [4]. If the locomotor activity of IBS patient is low or does not reach the recommended level, according to Health Japan 21, the patient can be instructed to exercise to that extent. We added these texts in the Discussion section as follows:

“Previous studies have shown that exercise improves IBS symptoms. Current data has suggested the "degree" (amount) of physical activity required to attenuate IBS symptoms. The results of this study can provide the clinicians with information on how many steps to add to the current physical activity level among IBS patients that can reduce GSRS by 1 point.” (Discussion section, page 13, lines 238-242)

Reviewer #2 comment:

The aspect that the study addresses is important. Although the effect exercise on IBS is well documented, this study provides a quantitative measure of effect of walking on IBS symptoms. It will be helpful for management of this disease. The manuscript is well written. I have one main question.

9. What was the reason the authors used Rome III criteria for confirming IBS instead of Rome IV criteria? Please see the following three references given as example how using criteria Rome IV versus Rome III impacts studies.

(i) Am J Gastroenterol (2018) 113:1017–1025. https://doi.org/10.1038/s41395-018-0074-z

(ii) Lin and Chang; Clinical Gastroenterology and Hepatology Vol. 18, No. 2

(iii) https://doi.org/10.1111/nmo.13189

The authors need to address this in the manuscript as it may impact the conclusions drawn.

Answer to comment 9:

We appreciate Reviewer #2 for the useful comments provided to improve our manuscript. We have added these texts with recommended references in the revised manuscript as follows:

“This study used Rome Ⅲ criteria, when the study was planned in 2015. The IBS diagnostic criteria were updated to ROME Ⅳ, and the Japanese version of the questionnaire has not yet been published. In Rome IV, the evaluation of the symptoms has changed from that of Rome Ⅲ, including the emphasis on the subjective experience of abdominal pain in IBS patients, and the demarcation between the constipation subtype of IBS and functional constipation. In subsequent studies, IBS diagnostic criteria should be based on ROME Ⅳ.” (Discussion section, pages 12-13, lines 231-236)

References

1. Choghakhori R, Abbasnezhad A, Amani R, Alipour M. Sex-Related Differences in Clinical Symptoms, Quality of Life, and Biochemical Factors in Irritable Bowel Syndrome. Dig Dis Sci. 2017;62(6):1550-60. Epub 2017/04/05. doi: 10.1007/s10620-017-4554-6. PubMed PMID: 28374085.

2. Bijkerk CJ, Muris JW, Knottnerus JA, Hoes AW, de Wit NJ. Randomized patients in IBS research had different disease characteristics compared to eligible and recruited patients. J Clin Epidemiol. 2008;61(11):1176-81. Epub 2008/07/16. doi: 10.1016/j.jclinepi.2008.02.001. PubMed PMID: 18619799.

3. Bjorkman I, Jakobsson Ung E, Ringstrom G, Tornblom H, Simren M. More similarities than differences between men and women with irritable bowel syndrome. Neurogastroenterol Motil. 2015;27(6):796-804. Epub 2015/03/31. doi: 10.1111/nmo.12551. PubMed PMID: 25817301.

4. Nishi N, Okuda N. National Health and Nutrition Survey in target setting of Health Japan 21 (2nd edition). Journal of the Natlonal Institute of Public Health. 2012;6(5):399-408.

Submitted filename: 109_plosone_Response_to_Reviewers_3.docx

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1 May 2020

PONE-D-19-33098R1

The effects of locomotor activity on gastrointestinal symptoms of irritable bowel syndrome among younger people: an observational study

PLOS ONE

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Additional Editor Comments (if provided):

Few things in the methods should be clarified further.

Present briefly the Rome III criteria to diagnose IBS symptoms. Also, describe briefly the Gastrointestinal Symptoms Rating Scale (GSRS) and how it was used in the analysis.

Please describe briefly the process to obtain data from pedometer on physical activity, and how it was used in the analysis for e.g. average of all days of data or every day’s data, etc.

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Reviewers' comments:

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Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #1: 1. The authors have addressed the comments in my previous review, and the manuscript appears ready to be accepted for publication. However, there are a few minor points that should be addressed as listed below:

2. Figure 3 is identical to Figure 2, and the image described as Figure 3 in the manuscript does not exist. This oversight is easy to remedy.

3. On line 87, change the word "momentum" to "activity".

4. In lines 141 and 178, delete the word "fashion"; it is adequate without this word.

Reviewer #2: The authors addressed my question about using the Rome III criteria and revised the text and references accordingly.

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8 May 2020

Response to Academic Editor comments

Academic Editor comments:

Few things in the methods should be clarified further.

1. Present briefly the Rome III criteria to diagnose IBS symptoms.

Answer to comment 1:

We appreciate the academic editor for the helpful comments to improve our manuscript. We added the text to explanation the Rome Ⅲ criteria in our revised manuscript as follows:

“The Rome III criteria are used to diagnose IBS symptoms, which include recurrent abdominal pain or discomfort, 3 days per month in the last 3 months (12 weeks), and are associated with two or more of the following three criteria: 1) improvement with defecation, 2) the onset is associated with a change in stool frequency, and 3) the onset is associated with a change in the stool form (appearance). To fulfil the criteria, symptom onset should occur 6 months prior to the diagnosis.” (Methods section, pages 5-6, lines 92-96)

2. Also, describe briefly the Gastrointestinal Symptoms Rating Scale (GSRS) and how it was used in the analysis.

Answer to comment 2:

We agree with you regarding this comment. We have described about the GSRS and how it was used in the analysis as follows:

“The GSRS is a disease-specific instrument of 15 items combined into 5 symptom clusters depicting reflux, abdominal pain, indigestion, diarrhea, and constipation. The GSRS has a seven-point graded Likert-type scale where “1” represents the absence of troublesome symptoms and “7” represents very troublesome symptoms.” (Methods section, page 6, lines 99-102)

“The GSRS scores were derived from the total score and divided by 15 (i.e. the 15 item subscales). The average pedometer counts (steps/day) were calculated using all days of data collection. The association between the GSRS score and pedometer counts was determined by the ordinal logistic modeling analysis [21]. The relationship between GSRS score and pedometer counts (prediction probability g (x)) was estimated using ordinal logistic regression modeling (Equation 1) with the dependent variable as GSRS score (f (x), continuous variates 1 to 7) and the independent variable as pedometer counts for x (Equation 2). (Methods section, page 7, lines 110-116)

3. Please describe briefly the process to obtain data from pedometer on physical activity, and how it was used in the analysis for e.g. average of all days of data or every day’s data, etc.

Answer to comment 3:

We agree with you on this comment. We have described briefly the process of how to obtain data from the pedometer on the physical activity, and how it was used in the analysis as follows:

“Walking activity data that were recorded in LifeCorder GS were uploaded into a personal computer using an application Lifelyzer05 (Kenz, Tokyo).” (Methods section, page 6, lines 105-106)

“The average pedometer counts (steps/day) were calculated using all days of data collection.” (Methods section, page 7, lines 111-112)

Response to Reviewers

Reviewer #1 comments:

The authors have addressed the comments in my previous review, and the manuscript appears ready to be accepted for publication. However, there are a few minor points that should be addressed as listed below:

1. Figure 3 is identical to Figure 2, and the image described as Figure 3 in the manuscript does not exist. This oversight is easy to remedy.

Answer to comment 1:

We appreciate the reviewer’s helpful comments to improve our manuscript. We carefully checked and replaced Figures 2 and 3. The figures are very similar and at first glance they look the same, but they are different. For example, the number of scatter plots is different, and the logistic curves are slightly different. Please see the revised Figures 2 and 3.

2. On line 87, change the word "momentum" to "activity".

Answer to comment 2:

We agree with the reviewer about this comment and have changed the word "momentum" to "physical activity" for consistency with all other uses in the revised manuscript (Methods section, page 5, line 87).

3. In lines 141 and 178, delete the word "fashion"; it is adequate without this word.

Answer to comment 3:

We agree with the reviewer on this comment and have deleted the word "fashion" in the revised manuscript (Pages 9-11, lines 151-190).

Reviewer #2: The authors addressed my question about using the Rome III criteria and revised the text and references accordingly.

Answer to comment:

We would like to thank Reviewer #2 for carefully reviewing our manuscript and for the positive support of our research.

Submitted filename: 122_plosone_Response_to_Reviewers.docx

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19 May 2020

The effects of locomotor activity on gastrointestinal symptoms of irritable bowel syndrome among younger people: an observational study

PONE-D-19-33098R2

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Additional Editor Comments (optional):

Reviewers' comments:

21 May 2020

PONE-D-19-33098R2

The effects of locomotor activity on gastrointestinal symptoms of irritable bowel syndrome among younger people: an observational study

Dear Dr. Hamaguchi:

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