By Donald Brown, ND

Managing Director, Natural Product Research Consultants, Seattle, WA

Dr. Brown reports he is a retained consultant for Nature’s Way.

Source: Compare D, et al. Lactobacillus paracasei F19 versus placebo for the prevention of proton pump inhibitor-induced bowel symptoms: A randomized clinical trial. Digestive Liver Dis 2015;47:273-279.

Summary Points

  • The administration of a Lactobacillus paracasei strain (F19) twice daily and 3 times per week for 6 months appears to reduce the incidence of bowel symptoms (bloating and flatulence) and reduce changes in bowel habits (increased stool frequency and loose stools) but not abdominal pain in patients taking proton pump inhibitors.

Proton pump inhibitors (PPIs) have been reported in some but not all studies to cause small intestine bacterial overgrowth1 that may result in symptoms such as diarrhea, abdominal pain, and bloating. This randomized, double-blind, placebo-controlled trial included subjects ages 18 to 70 years with gastroesophageal reflux disease lasting more than 6 months and occurring at least three times weekly. Exclusion criteria included the use of PPIs or H2-antagonists for at least 2 consecutive weeks in the prior 3 months and the use of antibiotics or probiotics in the 4 weeks before the study.

All subjects were treated with pantoprazole (40 mg/day) for 6 months. While taking pantoprazole, subjects were then randomized to one of the following groups: 1) Lactobacillus paracasei F19 (LP-F19) bid for 3 days/week for 6 months; 2) placebo bid for 6 months; 3) LP-F19 bid for 3 days/week for the first 3 months followed by placebo 3 days/week bid for the following 3 months; or 4) placebo bid for 3 days/week for 3 months followed by LP-F19 bid for 3 days/week for the following 3 months. LP-F19 and placebo were delivered in sachets that were dissolved in water and taken right before meals. The active sachets contained 12 x 109 colony forming units (cfu) of LP-F19. Bloating, flatulence, abdominal pain, and bowel habits were assessed monthly. The primary endpoint was the percentage of subjects who developed clinically relevant bloating, flatulence, and abdominal pain at each monthly check-up. The secondary endpoints were: 1) changes in the mean score of bloating, flatulence, and abdominal pain at each monthly check-up, and 2) changes in the mean stool frequency/week and mean stool form at each monthly check-up.

One hundred subjects were randomized for the study with 25 in each arm. Mean age was 39 ± 10.4 years with 56 men and 44 women. In the parallel groups, the percentage of subjects developing clinically relevant bowel symptoms during the 6-month study was lower in the LP-F19 group compared to placebo. With regards to bloating, there were no significant differences between groups up to month 3. However, bloating was significantly lower in the LP-F19 group compared to placebo at months 4 (P = 0.038), 5 (P = 0.025), and 6 (P = 0.023). The rate of subjects developing flatulence was significantly lower in the LP-F19 group compared to placebo at all time points (P = 0.011). There was no significant difference between groups in terms of abdominal pain (P = 0.25). In the crossover groups, the percentage of subjects who developed clinically relevant bowel symptoms was lower during the LP-F19 phase compared to placebo for all three measures, bloating, and abdominal pain measured at 3 months. On the secondary endpoints for the parallel groups, the mean score of each symptom was lower for the LP-F19 group compared to placebo, and bowel habits (increased stool frequency and loose stools) changed significantly only in the placebo group. When the covariates time, LP-F19 treatment, and treatment by time interaction were considered, LP-F19 significantly affected the mean score of bloating (P = 0.02), flatulence (P < 0.0001), mean stool frequency/week (P = 0.016), and mean stool form (P = 0.02) compared to placebo. The mean abdominal pain score did not differ significantly over time. The same results were noted for the crossover groups. Adverse events are not reported in the paper.

The results of this multicenter trial suggest that concomitant use of probiotics (most likely lactobacilli strains) may reduce bowel symptoms such as bloating and flatulence but not abdominal pain in patients taking PPIs long-term. The four-arm design of the study was a bit of a head scratcher, and it is this reviewer’s opinion that that a two-arm parallel design with a larger cohort in each group would have been sufficient. An interesting note is the fact that probiotics were only used twice daily for 3 days/week during the study. According to the researchers, this was based on data showing LP-F19 survives intestinal transit and colonizes the intestinal tract for “long periods” after ingestion.2 It will be interesting in future clinical trials looking at probiotics for prevention of gastrointestinal symptoms consider not only probiotic potency (cfu/day) but also frequency of administration. Finally, clinicians should be asking if the rampant use of PPIs and subsequent small intestinal bacterial overgrowth might be one of the primary contributors to the rise in functional bowel disorders such as irritable bowel syndrome.

REFERENCES

  1. Lo WK, Chan WW. Proton pump inhibitor use and risk of small intestinal bacterial overgrowth: A meta-analysis. Clin Gastroenterol Hepatol 2013;11:483-490.
  2. Crittenden R, et al. Lactobacillus paracasei subsp. paracasei F19: survival, ecology and safety in the human intestinal tract – a survey of feeding studies within the PROBDEMO Project. Microb Ecology Health Dis 2002;Suppl 3:22-26.