Ringel Y, Ringel-Kulka T, Maier D, et al. Probiotic bacteria lactobacillus acidophilus NCFM and bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders—a double-blind study. J Clin Gastroenterol. 2011 Mar 22. [Epub ahead of print]
Double-blind, placebo-controlled, randomized clinical trial. Study duration totaled 14 weeks, including a 2-week run-in period, an 8-week intervention period, and a 4-week follow-up.
Sixty eligible patients with non-constipation functional bowel disorders (FBD) who met the Rome III criteria for non-constipation IBS, functional diarrhea, or functional bloating.
Study Medication and Dosage
Sixty patients were randomized into 2 parallel intervention arms: an active probiotic arm and a placebo arm. During the 8-week intervention period, the active probiotic arm (n=31) received a pill twice daily consisting of a equal blend of Lactobacillus acidophilus NCFM and Bifidobacterium animalis sp. lactis Bi-07, yielding 1x1011 CFU per pill, whereas the placebo arm (n=29) received placebo pills consisting of microcrystalline cellulose.
Assessments were made at 4 and 8 weeks of the intervention period. The two primary endpoints were global relief of GI symptoms and a satisfaction survey. Secondary endpoints included change in specific functional GI symptoms (ie, abdominal pain, abdominal bloating, postprandial symptoms), stool frequency, stool consistency, severity of symptoms, global well-being, and a health-related quality of life questionnaire.
Although the two primary endpoints were inconclusive, severity of abdominal bloating, a secondary endpoint, was reduced in the active probiotic arm compared with the placebo group at 4 weeks (4.10±3 vs 6.17±3, respectively, P=0.009) and at 8 weeks (4.26±3 vs 5.84±3, respectively, P=0.06). Analysis of pre- and post-intervention change in bloating severity scores yielded a significant improvement in the active probiotic arm compared with the placebo group at 4 weeks (-1.58 vs 0.95, respectively, P=0.02) and at 8 weeks (-1.4 vs 0.6, respectively, P<0.01), representing a 15% reduction in clinical bloating symptoms. Analyses on a non-constipated irritable bowel syndrome (IBS) subgroup showed similar results. Importantly, genetic analysis of the fecal microbiota confirmed the presence of the test probiotic strains in the intervention group. There were no differences between the groups at baseline or at the end of the 8-week intervention in regards to fecal analysis for inflammation biomarkers. Finally, there were no differences in adverse events between the intervention and placebo groups.
According to the Rome III Diagnostic Criteria Functional Gastrointestinal Disorders (FGIDs), functional bloating is categorized under functional bowel disorders (FBDs) with IBS, functional constipation, functional diarrhea, and unspecified functional bowel disorders.1,2 Interestingly, bloating symptoms overlap with other FGIDs, as up to 96% of IBS patients report this symptom. In a previous study of 337 subjects, Ringel and colleagues reported that bloating was the second-most bothersome symptom among IBS patients after abdominal pain and the third most important reason to seek medical care.3 Yet, the authors note, a current lack of mechanistic understanding yields few effective treatment options.
Probiotics are, as defined by the Food and Agriculture Organization of the United Nations (FAO) as, “live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host.”4 Widely used for managing gastrointestinal symptoms, probiotics' effects on bloating symptoms specifically is an area of research interest, but results to date have generally been modest and inconsistent. The current study reported partial, significant relief from bloating symptoms at 4 and 8 weeks of intervention with a combination of 2 strain-specific probiotics—Lactobacillus acidophilus NCFM and Bifidobacterium animalis sp. lactis Bi-07. Another study yielded a similar, statistically significant post-intervention reduction in abdominal bloating (P=0.046) using a multispecies probiotic blend (VSL#3®), although there were no reported between-group comparisons.5
Until more general data are available, these effects on bloating must be assigned to the specific probiotic strains and doses that were employed in these studies. There is some concern among clinicians that probiotic interventions actually impart an effect on fecal microbiology, so it is noteworthy that Ringel and colleagues completed a fecal analysis of microbial DNA using qPCR. In the current study, L-NCFM was detected in the fecal DNA from only the post-intervention group. B-LBi07 was detected in all groups but at a higher concentration post-intervention (PCR primers for B-LBi07 are less specific and can amplify other related strains). Importantly, the treatment with combined L-NCFM and B-LBi07 yielded good safety and tolerability data, with no reported significant adverse events or changes in blood tests between baseline to mid-intervention and post-intervention periods.
The combination of L-NCFM and B-LBi07 probiotic strains at 1x1011 CFU BID effectively manipulates the microbiota in subjects with FBDs and may provide a clinical benefit by reducing the severity of bloating symptoms in patients diagnosed with non-constipation IBS, functional diarrhea, or functional bloating. This study further supports the argument for using multispecies probiotics as a means to manage various gastrointestinal symptoms in patients with FBDs.