2022 Impact Factor
2022 Impact Factor
,1 Panyavee Pitisuttithum,2,6 Jarongkorn Sirimongkolkasem,4,6 Pakkapon Rattanachaisit,5,6 Sureeporn Jangsirikul,6 Tanisa Patcharatrakul,3,6 and Sutep Gonlachanvit3,6*
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Abdominal bloating, one of the common complaints from patients with functional gastrointestinal disorders (FGID), is characterized by fullness, flatulency, and increased abdominal pressure sensation. Patients with FGIDs such as irritable bowel syndrome (IBS), functional bloating, functional dyspepsia, and functional constipation commonly have abdominal bloating with a prevalence of 40-76%, which may affect their quality of life.1 Various mechanisms of abdominal bloating in FGID have been proposed,2 including increased gas production from colonic bacterial fermentation, visceral hypersensitivity, gut dysmotility, or carbohydrate malabsorption.3
Diets rich in fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) can contribute to bloating symptoms by increasing intestinal gas production, osmotic load and increased intestinal transit time, causing abnormal intestinal contractions and intestinal hypersensitivity.4 The low FODMAP diet is one of the effective non-pharmacological treatments for patients with IBS, which can relieve bloating symptoms and improve overall gastrointestinal (GI) symptoms. A meta-analysis of IBS patients showed a significant improvement in bloating (OR, 1.75; 95% CI, 1.07-2.87) and overall symptoms (OR, 0.44; 95% CI, 0.25-0.76) after low FODMAP diets.5 Since up to 50% of the patients did not respond to a low FODMAP diet,5 the implementation of a low FODMAP diet is associated with higher healthcare utilization and a high level of patient cooperation, the prediction of low FODMAP responsive patients is therefore essential to treatment success by increasing physicians’ confidence in recommending a low FODMAPs diet for suitable patients and enhancing patients’ compliance.
We hypothesized that a low FODMAP diet would not improve bloating symptoms in patients with low baseline breath hydrogen levels because the pathophysiology of bloating in these patients is not associated with increased intestinal gas production by FODMAPs. Therefore, this study aims to assess the role of a spot hydrogen breath test in predicting the response to a low FODMAPs diet and the response rate of a low FODMAPs diet in patients with bloating associated with various FGIDs.
This prospective study was conducted in a gastroenterology outpatient clinic from October 2020 to February 2022. Patients 18-70 years of age diagnosed with FGIDs, including IBS, functional constipation, functional dyspepsia, and functional diarrhea using Rome IV criteria6 with bothersome bloating symptoms for more than 6 months were included. Exclusion criteria were previous GI tract surgery or GI tract malignancy. The participants with possibly on a low in FODMAPs diet (less than 7 items of high FODMAP diet items per week), gluten-free or vegan diet were excluded from the study. Patients with antibiotics or prebiotics used within 4 weeks before dietary advice and who did not have breakfast or lunch were also excluded from the study. All participants needed to have stable medical conditions without treatment modification at least 4 weeks before study enrollment.
On enrollment day, all subjects were asked to complete GI symptoms questionnaires. The average severity of upper and lower GI symptoms a week prior to enrollment day, including abdominal bloating, abdominal pain, and overall GI symptoms, was assessed using a 0-10 cm visual analog scale. The IBSseverity scoring system was assessed in patients with IBS. A breath sample was collected 2 hours after the patient’s usual lunch (Supplementary Table 1). Then, participants were asked to complete the next 7-day food diary to capture their habitual diets.
At the second visit (day 0), a dietitian implemented the structural individual low FODMAPs dietary advice according to the patient’s recorded food diary. A glucose hydrogen breath test was done to exclude small intestinal bacterial overgrowth. The patients were instructed to follow the dietary advice for 4 weeks and complete the food diary during the last 7 days of the study.
At week 4 of the study, the participants were appointed to the outpatient clinic to collect the spot breath test and to complete the abdominal bloating, abdominal pain, and overall GI symptoms questionnaires.
The spot postprandial breath samples were collected 2 hours after the patient’s usual lunch, based on a previous study from our center showing that gas production increased at 2 hours after high FODMAP lunch7 but not breakfast. Before collecting the specimen, participants were asked to use chlorhexidine mouthwash before collecting breath samples. Two breath samples were collected and analyzed for hydrogen, methane, and carbon dioxide concentrations (QuinTron Instrument Company, Inc, Milwaukee, WI, USA). Smoking and extensive exercise were not allowed within 2 hours before the breath test. The spot gas level was the average from 2 breath samples in both hydrogen and methane.
The low FODMAP dietary advice was performed according to our previous study of the structural individual low FODMAPs dietary advice (SILFD) in IBS.8 High FODMAPs items were identified from each patient’s baseline 7-day food diary. A well-trained dietician advised patients to avoid high FODMAPs consumption and modify their recipe and menu with the available low FODMAPs items. The examples of Thai food menus using low FODMAPs ingredients were distributed in the pamphlets and provided to the patients.
The severity of GI symptoms, including abdominal pain, discomfort, bloating, overall GI symptoms, bowel movement frequency, and stool characteristics, was recorded and assessed using a 0-10 cm visual analog scale at baseline, and the average of 7 days of those symptoms before the end of the study. Responders were defined as those with at least a 30% decrease in abdominal bloating severity during the fourth week compared to the baseline.
The sample size was calculated using the efficacy of SILFD8 with at least 30% reduction of abdominal bloating compared with baseline with 90% power at α = 0.05, indicating at least 27 subjects. The data were analyzed using SPSS software for Windows (version 22.0; IBM Corp, Armonk, NY, USA). Categorical parameters were analyzed using Student’s t test for normal distributed data and Mann-Whitney U test for non-normal distributed data. Data are expressed as mean ± SD or as median with interquartile range. Statistical significance was defined by a P-value < 0.05.
The study was conducted following the declaration of Helsinki and approved by the Ethics Committee of our hospital (IRB 345/63). The study protocol was registered under the Thai Clinical Trial Registry (TCTR20220901003).
Total of 56 patients were eligible for this study. Eighteen patients were excluded. The Supplementary Results section shows the inclusion process details (Supplementary Figure). In summary, a total of 38 patients were enrolled. The mean age of included patients was 52.7 ± 13.8 years, with 78% female.
The average baseline number of high FODMAP diet items per week was 10 (9-12) items per week. The prevalence of each FGID and GI symptoms severity scores are shown in Table 1. Twenty-one patients (55.2%) were classified as responders to dietary advice. The responders’ baseline GI symptoms, bloating, and abdominal pain severity scores were not significantly different from the non-responder group (P > 0.05). Participants’ average GI symptoms severity scores at baseline and after dietary advice are shown in supplementary section (Supplementary Tables 2 and 3).
Table 1 . Baseline Patients’ Profiles Before Low Fermentable Oligo-, Di-, Mono-saccharides, and Polyoles Dietary Advice Compared Between Responders and Non-responders
| Baseline patients’ characteristic before dietary advice | All patients (N = 38) | Responders (n = 21) | Non-responders (n = 17) | P-value |
|---|---|---|---|---|
| Age (yr) | 52.6 ± 13.8 | 54.5 ± 14.0 | 50.4 ± 13.6 | 0.230 |
| Female | 30 (78) | 19 (90) | 11 (64) | 0.110 |
| IBS | 22 (56) | 12 (57) | 10 (58) | 0.920 |
| Functional constipation | 6 (16) | 5 (20) | 2 (13) | 0.540 |
| Functional bloating | 5 (14) | 1 (3) | 4 (24) | 0.110 |
| Functional dyspepsia | 5 (14) | 4 (20) | 1 (5) | 0.340 |
| Bloating severity (0-10) | 3.5 (3.1-7.1) | 5.0 (2.5-7.8) | 4.1 (3.1-7.3) | 0.710 |
| Abdominal pain severity (0-10) | 0.0 (0.0-2.5) | 0.0 (0.0-2.1) | 0.0 (0.0-3.7) | 0.240 |
| Overall GI symptoms (0-10) | 3.5 (2.5-7.5) | 3.5 (2.3-7.5) | 4.0 (2.7-7.2) | 0.960 |
| High FODMAP items per 7 days | 10.0 (9.0-12.0) | 11.0 (10.0-16.5) | 12.5 (8.5-13.5) | 0.780 |
IBS, irritable bowel syndrome; GI, gastrointestinal; FODMAP, fermentable oligo-, di-, mono-saccharides, and polyols.
Data are expressed as mean ± SD, n (%), or median (interquartile range: quartile1-quartile3).
The baseline spot intestinal gas levels after lunch in responders were higher than non-responders (hydrogen 9.5 [3.3-17.3] parts per million [ppm] vs 4.5 [3.3-6.3] ppm, P < 0.05; methane 3 [1.8-4.0] ppm vs 1.5 [1.0-3.0] ppm, P = 0.06; responders vs on-responders, respectively) (Fig. 1). The area under the curve for predicting low FODMAPs dietary advice responsiveness using baseline hydrogen level was 0.692 (95% CI, 0.51-0.86; P < 0.05), with the best cutoff at 8 ppm with a sensitivity of 66.7% and a specificity of 82.4%. The positive predictive value was 79.1%, the negative predictive value was 71.2%, and the accuracy was 74.5% for predicting the response. The area under the curve for predicting low FODMAPs dietary advice responsiveness using baseline methane levels was 0.682 (95% CI, 0.51-0.85; P = 0.060), with the best cutoff at > 2.25 ppm with a sensitivity of 71.4% and specificity of 70.6%. The positive predictive value was 70.8%, the negative predictive value was 71.2%, and the accuracy was 71% (Fig. 2). The prevalence of patients with either baseline hydrogen levels > 8 ppm or baseline methane levels > 2.25 in the responder group was significantly higher than in the non-responder group (Table 2).
Figure 1. Spot hydrogen levels (A) and spot methane levels (B) compared between responders and non-responders. ppm, parts per million. *P < 0.05.
Figure 2. Receiver operating characteristics curve of spot hydrogen and methane breath test for predicting response to a low fermentable oligo-, di-, mono-saccharides, and polyols (FODMAP) dietary advice. Hydrogen level > 8 parts per million (ppm) (bold line) identified patients as low FODMAP responders (area under the curve [AUC], 0.692; 95% CI, 0.51-0.86; P < 0.05). Methane level > 2.250 ppm (dash line) identified patients as low FODMAP responders (AUC, 0.68; 95% CI, 0.51-0.85; P = 0.060).
Table 2 . Baseline Hydrogen and Methane Levels and Prevalence of Patients at the Cutoff Levels Comparing Between Responders and Non-responders
| Baseline hydrogen and methane levels and prevalence of patients at the cutoff levels | All patients (N = 38) | Responders (n = 21) | Non-responders (n = 17) | P-value |
|---|---|---|---|---|
| Breath hydrogen levels (ppm) | 5.3 (3.4-15.0) | 9.5 (3.3-17.3) | 4.5 (3.3-6.3) | 0.045 |
| Breath methane levels (ppm) | 2.5 (1.0-3.7) | 3.0 (1.7-4.0) | 1.5 (1.0-3.0) | 0.060 |
| At cutoff H2 level > 8 ppm | 17 (44) | 14 (66) | 3 (17) | 0.010 |
| At cutoff CH4 level > 2.25 ppm | 20 (52) | 15 (71) | 5 (30) | 0.010 |
| At cutoff H2 > 8 ppm and CH4 > 2.25 ppm | 16 (42) | 14 (66) | 2 (11) | 0.010 |
| At cutoff H2 > 8 ppm or CH4 > 2.25 ppm | 21 (55) | 15 (71) | 6 (35) | 0.030 |
ppm, parts per million; H2, hydrogen; CH4, methane.
Data are expressed as median (interquartile range: quartile1-quartile3) or n (%).
After dietary advice, the hydrogen levels significantly decreased in the responder group (P < 0.05). Also, the methane levels in the responder group tended to decrease (P = 0.06). In contrast, hydrogen and methane levels in non-responders between baseline and after dietary advice were not significantly different (Fig. 1).
There was no difference in the baseline numbers of high FODMAP items per week between responders and non-responders (P = 0.780). At fourth week after dietary advice, food diaries for 7 days of both responders and non-responders showed a significant decrease in their high FODMAPs items intake compared to their baseline items (responders 11 [10-16.5] vs 4 [4-8] items per week, P < 0.05; non-responders 12 [8.5-13.5] vs 6 [3.5-7.5], items per week, P < 0.05). There was no significant difference in the numbers of high FODMAPs between both 2 groups after dietary advice (P = 0.430). List of menu before and after dietary advice are presented in supplementary section (Supplementary Table 4).
There were 22 IBS patients enrolled in the study. Sixteen patients with non-IBS were diagnosed with functional constipation (6 patients), functional bloating (5 patients), and functional dyspepsia (5 patients). Twelve IBS patients (55%) and 9 non-IBS patients (56.3%) were responders. There were 6 patients with constipation-predominant IBS (IBS-C) and 6 patients with unclassified IBS (IBS-U) in the responder group. Five patients with IBS-C, one patient with diarrhea-predominant IBS (IBS-D), 1 patient with mixed IBS, and 3 patients with IBS-U were classified as non-responders. Among IBS patients, the baseline hydrogen and methane levels in the responders tended to be higher than the non-responders (hydrogen: 11.8 [3.3-20.3] ppm vs 4.3 [2.5-5.5] ppm, P = 0.120; methane: 2.5 [1.8-4.0] ppm vs 1.5 [1.0-2.5] ppm, P = 0.150). In IBS-C patients, the baseline hydrogen and methane levels were higher in the responders but did not reach statistical significance (hydrogen: 13.3 [4.5-25.1] ppm vs 3.3 [2.1-5.3] ppm, P = 0.127; methane: 3.3 [2.1-5.3] ppm vs 2 [1-4] ppm, P = 0.330). Also, in IBS-U subgroup, the baseline hydrogen level and methane level were higher in responders without statistical significance (hydrogen: 8.8 [1.8-24.2] ppm vs 2.8 [1-3] ppm, P = 0.429; methane: 2.2 [1.2-3.3] ppm vs 0.8 [0-1] ppm, P = 0.286). Among non-IBS patients, the baseline hydrogen and methane levels in responders tended to be higher than non-responders (hydrogen: 9 [5-16.8] ppm vs 4.5 [3.5-5.7] ppm, P = 0.170; methane: 3 [1.8-3.8] vs 1.5 [1.0-3.5] ppm, P = 0.250). At fourth week after dietary advice, the bloating severity was significantly improved in both IBS and non-IBS subgroups (IBS: 5 [3.2-7.5] to 0 [0-1.8]; non-IBS 4.4 [1.6-7.7] to 1.2 [0.0-2.7], both P < 0.05). There was also significantly improvement of bloating symptoms in both responder group of IBS-C subgroups (7 [5.0-7.5] to 0.7 [0.0-1.6], P < 0.05) and IBS-U subgroup (3.6 [2.4-8.0] to 1.2 [0.0-2.4], P < 0.05). The overall GI symptoms and abdominal pain severity in both IBS and non-IBS subgroups were lower than baseline but did not reach statistical significance. The number of high FODMAPs diet items in both IBS and non-IBS subgroups significantly decreased from baseline and was not different between groups (IBS patients: 11 [7-14] items to 5 [3-8] items; non-IBS patients: 10 [6-15] items to 5 [4-7] items; both P < 0.05).
Previously, many predictor tools were proposed to predict the response to a low FODMAPs diet, but none was used as the standard method before low FODMAP dietary recommendations. Our study showed that a spot-breath hydrogen level after lunch of more than 8 ppm and methane of more than 2.25 ppm could predict the response to low FODMAPs dietary advice in FGID patients with bloating symptoms with high sensitivity and specificity. This simple point-of-care test would facilitate a low FODMAPs recommendation for this group of patients.
The previous study in our laboratory showed that the increased hydrogen and methane concentrations in breath samples were observed after lunch by a high FODMAPs meal but not after breakfast and were associated with bloating symptoms. This phenomenon might be explained by an incomplete absorption of carbohydrate moved from the ileum into the large bowel, stimulated by lunch ingestion. Gas production and bloating severity after breakfast were lower due to the overnight absorption of intestinal gas into the circulation.7 So, the baseline hydrogen and methane levels after lunch probably predict dietary responsiveness. Our study showed that a spot breath test after lunch or the second meal of the day could be a promising and convenient tool to predict the response to the low FODMAP diet. It can be performed as an outpatient procedure, and results were instantly analyzed before implementing the dietary advice. In this study, 55 percent of patients with bloating symptoms were classified as responders, a similar efficacy as the previous study in IBS patients with SILFD protocol.8 The numbers of high FODMAPs items recorded by the patients’ food diary were significantly reduced from baseline in both responders and non-responders and replaced by commonly available low FODMAPs items. The numbers of high FODMAP items 4 weeks after advice were not significantly different between groups. The spot breath hydrogen levels after lunch at 4 weeks after dietary advice in the responder group were significantly decreased from baseline (P < 0.05), while the baseline and after-treatment levels of non-responders were not significantly different even though the number of high FODMAP items was significantly decreased. The finding suggests intestinal gas contributes to bloating symptoms, especially in patients with high baseline gas levels. The discrepancy between the numbers of high FODMAP items and breath hydrogen levels in the non-responders at baseline may be explained by the difference in intestinal gas generation and homeostasis between responders and non-responders, which warrants further research study. In patients with low hydrogen and methane levels, their bloating symptoms may be associated with other factors, such as visceral hypersensitivity and altered gut flora. These patients are unlikely to respond to low FODMAPs dietary advice even though they could reduce the high FODMAP diet intake. In this study, some patients with high baseline hydrogen levels did not respond to low FODMAPs dietary advice. Different thresholds of visceral perception may explain this finding, or the meals on the test day differed from their usual diet.
Previous studies demonstrated the predictors of a low FODMAP diet response in IBS patients.9 Two studies identified that the low FODMAP diet responders had a higher amount of fecal saccharolytic bacteria, for example, Bacteroides, Ruminococcaceae, and Faecalibacterium prausnitzii than non-responders.10 However, there were heterogeneities among these studies due to multiple ethnicities, diet consumption, and age. In addition, bacterial identification is costly and inconvenient. A volatile organic compound in feces was also studied but failed to be demonstrated as a predictor of response to a low FODMAP diet.11 These findings may not ease identifying who will likely benefit from a low FODMAP diet.
To our knowledge, no RCT has demonstrated the efficacy of low FODMAPs implementation in other FGIDs except IBS patients. In our study, other FGIDs patients with bloating symptoms had bloating and overall GI symptoms improvement after low FODMAP dietary advice. Subgroup analysis in patients without IBS demonstrated a significant improvement in bloating symptoms after low FODMAPs implementation. The pathophysiology of bloating symptoms may be different between FGIDs. However, increased intestinal gas probably plays a common role. Our data also showed promising evidence to support the importance of categorizing FGIDs as a symptom-based diagnosis rather than a group of symptoms or syndrome-based diagnosis when considering the treatment option.
There are some limitations of this study. First, the meals at breakfast and lunch on the test day were not well-controlled and may not represent the participants’ usual diet. Some participants had their meals at the hospital with limited food choices. We presented the recorded meals on test day before baseline breath sample collection in the supplementary material section (Supplementary Table 1), which does not suggest a correlation between the numbers of high FODMAPs items in the breakfast and lunch and breath hydrogen and methane levels. Future studies with good instruction to the participants to take their usual diet for breakfast and lunch may enhance the accuracy of the spot hydrogen breath test for predicting the response to a low FODMAP diet. Second, the sample size was relatively small. During the Coronavirus disease 19 pandemic, collecting breath samples could generate aerosol infectious droplet particles. Twelve patients were lost to follow-up due to the pandemic outbreak and did not have post-advice breath test results, but this did not affect the study’s power and validity. Although this study is a pilot study, the sample size was calculated based on our previous study evaluating the effectiveness of a low FODMAP dietary advice on IBS symptoms, including bloating and intestinal gas production.8
In this study, we used the SILFD protocol8 and demonstrated that low FODMAP diet improves bloating symptoms in IBS patients and other FGIDs patients.8 The protocol that we used is only the FODMAP restriction phase. Further clinical applications of spot breath test to the other phases of FODMAP implementation12,13 such as reintroduction phase or personalization phase could generalize the utility of spot breath test. Moreover, studies on the cost-effectiveness of using a spot breath test as a tool before initiating a low FODMAP diet in an outpatient setting and research to clarify whether other gases or mechanisms besides hydrogen and methane caused the bloating symptoms in non-responders are warranted.
In conclusion, the low FODMAPs diet improves bloating symptoms in IBS patients and other FGIDs patients. A higher baseline breath hydrogen level was associated with bloating improvement after low FODMAPs dietary advice. A spot breath test after lunch is a simple point-of-care test possibly helpful in managing patients with bloating.
The authors thank Miss Boonumpai Kamonsakpitak and Miss Wachinee Promjampa for patient enrollment and contributions to our study.
This study was partly supported by the Ratchadapiseksompotch Fund (CUGR631403047), Chulalongkorn University. The study funders had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.
Note: To access the supplementary tables and figure mentioned in this article, visit the online version of Journal of Neurogastroenterology and Motility at http://www.jnmjournal.org/, and at https://doi.org/10.5056/jnm22214.
None.
Sutep Gonlachanvit and Tanisa Patcharatrakul: concept, design, and critical revision of the article for important intellectual content; Pochara Somvanapanich, Panyavee Pitisuttithum, Jarongkorn Sirimongkolkasem, Pakkapon Rattanachaisit, Sureeporn Jangsirikul, and Tanisa Patcharatrakul: data collection; Sutep Gonlachanvit, Pochara Somvanapanich, Panyavee Pitisuttithum, and Tanisa Patcharatrakul: data analysis and interpretation; and Sutep Gonlachanvit, Pochara Somvanapanich, and Panyavee Pitisuttithum: manuscript drafting. All authors had access to the study data and reviewed and approved the final manuscript.
Author ORCID Information
Pochara Somvanapanich Panyavee Pitisuttithum Sutep Gonlachanvit |
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