Rifaximin for Treatment of Bloating in Children and Adults With Cystic Fibrosis

Inclusion Criteria: 1. Confirmed CF diagnosis who are enrolled in the CFF registry. 2. Mild to severe symptom severity defined as abdominal Distention score ≥ 2 and/or bloating score ≥ 2 on a Likert Scale of 0-6) 3. Patient age ≥12 years and ≥ 30 kilograms (\~66.15 lbs) 4. Ability to provide informed consent or presence of legally authorized representative (LAR) 5. Ability to take drug or placebo by mouth (Pill must be intact. May not be opened, crushed, or modified to aid in ingestion) Exclusion Criteria: 1. Subjects who have previously been allergic to rifaximin or had a hypersensitivity to rifamycin or used rifaximin for any reason within three months (12 weeks) of the study start date 2. Subjects with FEV1 \< 40 (as measured within the last 12 months) will be excluded from the study given potential risks in subjects with advanced lung disease 3. Subjects who have received a new antibiotic for treatment of an acute pulmonary infection, or antibiotics for any other infection within 4 weeks prior to randomization or during the study period. Cyclic Antibiotics- Inhaled cyclic antibiotics are allowed at any timepoint. Oral or systemic cyclic antibiotics are exclusionary except for prophylactic antibiotics (e.g., azithromycin) which are allowed. New prophylactic antibiotics cannot be started within 4 weeks of randomization. 4. Subjects with a recent pulmonary exacerbation defined as 4 weeks prior to screening will not be enrolled 5. Subjects who are on probiotics will be asked to discontinue the use of probiotics 14 days prior to randomization as probiotics can alter the gut microbiome and cause bloating 6. Subjects with newly initiated cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatments within one month prior to the study 7. Subjects with new onset of distal intestinal obstruction syndrome (DIOS) or constipation 8. Subjects with advanced liver disease defined by: * portal hypertension and/or child Pugh B or C cirrhosis * or those with elevated liver enzymes-both AST/ALT \> 3 times the upper limit of normal at screening 9. Subjects with bilirubin or alkaline phosphatase elevations \> 2 times the upper limit of normal at screening will be excluded as this may be related to CFTR modulator use 10. Women of childbearing potential who are pregnant, trying to become pregnant, breastfeeding, or not using an acceptable method of contraception as described in Section 6.2. 11. Known clostridium difficile colitis. Colonization with c. difficile is not exclusionary.