Rifaximin Treatment in Bloating Predominant Functional Bowel Disorders

Bloating responder is defined as at least a 1-point reduction from baseline to week 2 in bloating symptom severity measured using a 7-point Likert scale for bothersomeness of bloating (range 0 to 6; higher scores indicate worse symptoms). Score categories are 0 = not at all, 1 = hardly, 2 = somewhat, 3 = moderately, 4 = a good deal, 5 = a great deal, and 6 = a very great deal.

Abdominal pain responder is defined as at least a 1-point reduction from baseline to week 2 in abdominal pain severity measured using a 7-point Likert scale for bothersomeness of abdominal pain (range 0 to 6; higher scores indicate worse symptoms). Score categories are 0 = not at all, 1 = hardly, 2 = somewhat, 3 = moderately, 4 = a good deal, 5 = a great deal, and 6 = a very great deal.

Change in IBS Symptom Severity Score (IBS-SSS) from baseline, assessing overall IBS symptom burden, abdominal pain, bloating, and bowel habit changes. The IBS-SSS scale ranges from 0 to 500, with higher scores indicating more severe IBS symptoms.

Change in Patient Assessment of Constipation-Symptoms (PAC-SYM) score, evaluating constipation-related symptoms, including stool consistency, discomfort, and straining. The PAC-SYM scale ranges from 0 to 48, with higher scores indicating worse constipation symptoms.

Overall treatment satisfaction, measured using a Visual Analog Scale (VAS) ranging from 0 to 10:

0 = Completely Dissatisfied 10 = Completely Satisfied Higher scores indicate greater satisfaction with treatment. The difference between baseline and post-intervention scores will be analyzed.

Change in Depression, Anxiety, and Stress Scores (DASS-21), a validated self-reported scale measuring psychological distress. The DASS-21 consists of three subscales:

Depression (0-21) Anxiety (0-21) Stress (0-21) Each subscale score ranges from 0 (normal) to 21 (severe symptoms), with higher scores indicating greater psychological distress. The total score is calculated by summing individual subscale scores.

Change in IBS-specific Quality of Life (IBS-QoL) score, which assesses the impact of IBS on daily activities, emotional well-being, and social functioning.

The IBS-QoL score ranges from 0 to 100, with higher scores indicating better quality of life.

Patient Assessment of Constipation Quality of Life questionnaire (PAC-QoL). The PAC-QoL is a 28-item patient-reported questionnaire assessing constipation-related quality of life over the previous 2 weeks. The overall score is typically reported as the mean item score and ranges from 0 to 4, with higher scores indicating worse constipation-related quality of life.

The quality of life of patients with FAB/D was measure with 36-Item Short Form Health Survey (SF-36). The SF-36 assesses health-related quality of life across 8 domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health. Each domain score is transformed to a 0 to 100 scale, with higher scores indicating better health status.

Change from baseline in stool microbiota alpha diversity, beta diversity, and taxonomic abundance measured by 16S rRNA sequencing.

Change from baseline in hydrogen gas production measured in part per million unit during lactulose hydrogen breath testing.

Change from baseline in methane gas production measured in part per million unit during lactulose hydrogen breath testing.

A positive lactulose hydrogen breath test is defined as either a rise in breath hydrogen of 20 ppm or more above baseline within 90 minutes or a breath methane concentration of 10 ppm or more at any time during the test after ingestion of 10 g lactulose. Breath samples are collected every 15 to 30 minutes for up to 180 minutes. Higher proportions indicate a worse outcome (more abnormal breath test results).

Frequency and dose of rescue medications used for breakthrough symptoms during the treatment period.

Incidence of treatment-emergent adverse events.

Exploratory analysis of whether baseline bloating symptom severity predicts treatment response. Baseline bloating symptom severity is assessed using a 7-point Likert scale for bothersomeness of bloating (score range 0 to 6; higher scores indicate worse symptoms). The association between baseline score and bloating responder status at 2 weeks will be evaluated using logistic regression and reported as an odds ratio. Bloating responder is defined as at least a 1-point reduction from baseline in bloating symptom severity score.

Exploratory analysis of whether baseline fecal microbiota alpha diversity predicts treatment response. Baseline stool microbiota is assessed using 16S rRNA sequencing. Alpha diversity will be assessed using the Shannon diversity index. The association between baseline Shannon diversity index and bloating responder status at 2 weeks will be evaluated using logistic regression and reported as an odds ratio. Bloating responder is defined as at least a 1-point reduction from baseline in bloating symptom severity score.

Exploratory analysis of whether baseline small intestinal bacterial overgrowth (SIBO) status predicts treatment response. Baseline SIBO status will be assessed using a lactulose hydrogen-methane breath test after ingestion of 10 g lactulose, with breath samples collected every 15 to 30 minutes for up to 180 minutes. A positive SIBO diagnosis is defined as a rise in breath hydrogen of 20 parts per million or more above baseline within 90 minutes. The association between baseline positive SIBO status (yes/no) and bloating responder status at 2 weeks will be evaluated using logistic regression and reported as an odds ratio. Bloating responder is defined as at least a 1-point reduction from baseline in bloating symptom severity score.

Exploratory analysis of whether baseline intestinal methanogen overgrowth (IMO) status predicts treatment response. Baseline IMO status will be assessed using a lactulose hydrogen-methane breath test after ingestion of 10 g lactulose, with breath samples collected every 15 to 30 minutes for up to 180 minutes. A positive IMO diagnosis is defined as a breath methane concentration of 10 parts per million or more at any time during the test. The association between baseline positive IMO status (yes/no) and bloating responder status at 2 weeks will be evaluated using logistic regression and reported as an odds ratio. Bloating responder is defined as at least a 1-point reduction from baseline in bloating symptom severity score.