Bifidobacterium infantis effectively treats IBS symptoms in adults
Design and Duration: Randomized, double-blind, placebo-controlled trial for eight weeks, preceded by a 4-week run-in period and followed by a 4-week washout period to assess symptoms post-treatment.
Participants: 75 volunteers, ages 18-73 years (average 44.3 years) who fit the Rome II criteria for irritable bowel syndrome (IBS)–diagnosis based on the presence for 12 weeks (not necessarily consecutive) during the past year of abdominal discomfort or pain and two out of three of the following symptoms: relieved with defecation, onset associated with a change in frequency of stool, and onset associated with a change in stool appearance. Symptoms that cumulatively support the diagnosis of IBS are [less than or equal to]3 bowel, movements per week; >3 bowel movements per day; hard or lumpy stools; loose or watery stools; straining during defecation; urgency; incomplete evacuation of bowels; mucus in stools; and a sensation of abdominal fullness, bloating or swelling.
Subclassification of IBS determined that 28% were diarrhea predominant, 26% constipation dominant, and 45% alternated between constipation and diarrhea. Twenty-five percent were smokers, and 88% drank alcohol. Inflammatory bowel disease (IBD) and other organic gastrointestinal diseases were ruled out, as were “significant systemic diseases.” Excluded from the study were pregnant women; people with lactose intolerance or immunodeficiency; and previous abdominal surgery, except for hernia repair and appendectomy.
Study Medication and Dosage: Volunteers were randomized to receive 1 X [10.sup.10] cfu (colony forming units) of Lactobacillus salivarius subspecies salivarius UCC4331 or Bifidobacterium infantis 35624 in a malted milk drink or placebo q.d. Probiotic species were originally isolated from the ileocolic region of an adult human; were nonpathogenic; were resistant to intestinal acid and bile; and demonstrated the ability to adhere to epithelial cells, to transiently colonize the human gastrointestinal tract, and to be metabolically active.
Outcome Measures: IBS symptoms were assessed based on volunteer diary cards, which were collected at weekly appointments. Three categories of symptoms were evaluated–abdominal pain or discomfort, bloating or distension, and bowel movement difficulty or urgency–using a 7-point ordinal scale (Likert scale*) and a 10-point visual analog scale (VAS). Changes in quality of life were determined at baseline and at the end of the treatment washout periods by a questionnaire that asked about dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual function, and relationship impact. Hematology (CBC, blood chemistry) and quantitative immunoglobulins were tested at the initial evaluation and the conclusion of the study. Stool and peripheral blood samples were collected at the time of randomization and after treatment and analyzed for fecal flora analysis and interleukin 10 (IL-10) and IL-12p40 cytokine levels, respectively.
Key Findings: The composite Likert score was significantly lower for those treated with B. infantis 35624 compared to placebo (p<0.05) during treatment and for one week after treatment stopped. Likert scores for bloating and abdominal pain were also significantly decreased in the B. infantis 35624 group compared to placebo during this time period (p<0.05). Bowel movement difficulty decreased significantly for weeks 2-6 during the treatment with B. infantis 35624 compared to placebo (p<0.05). Treatment with L. salivarius UCC4331 resulted in a significant decrease in composite Likert score after two weeks of treatment compared to placebo (p<0.05), but this significance was not maintained during rest of the study. Similarly, L. salivarius UCC4331 significantly decreased the Likert score for abdominal pain, but only at weeks 2 and 9 (p<0.05).
The composite VAS score significantly decreased in weeks 2-9 in the B. infantis 35624 group compared to placebo (p<0.05). Treatment with B. infantis 35624 resulted in significantly lower scores for bowel movement difficulty and composite Likert and composite VAS scores compared to L. salivarius UCC4331 (p[less than or equal to]0.05). Quality of life was significantly improved only for "health worry" in the B. infantis 35624 group (p=0.05).
At baseline the IL-10/IL-12 ratio was significantly different in volunteers with IBS compared to healthy controls (69[+ or -]15 vs. 176[+ or -]31 pg/mL, respectively; p=0.003). Treatment with B. infantis 35624 significantly increased the IL-10/IL-12 ratio (p=0.001), which approximated the IL-10/IL-12 levels detected in the control group at baseline (values not reported). Stool cultures were negative for the probiotics at baseline and during the washout period, but positive during the treatment phase.
Four adverse events were reported, including epistaxis, unstable angina, chest pain secondary to anxiety, and abdominal pain secondary to IBS exacerbation and constipation. The authors do not specify which group experienced these adverse events.
Practice Implications: IBS is one of the most common gastrointestinal conditions and yet effective treatment options are lacking. While probiotic therapy has been found to effectively treat diarrhea in children and adults, their use in IBS, where many patients experience either diarrhea or constipation, or both, is a relatively new area of clinical research. Previous clinical trials using probiotics have been somewhat underwhelming to date with one trial finding that use of Lactobacillus plantarum successfully treated only flatulence in IBS patients (Am J Gastroenterol, 2000; 95:1231-8). Another trial using the same organism reporting a rather remarkable response rate of 100% for the probiotic group versus 16% for a placebo group (Eur J Gastroenterol, 2001; 13:1143-7). Using probiotic cultures of human origin, this well-controlled and powered trial shows that the B. lactis culture more effectively treated all IBS symptoms (with the exception of bowel movement frequency) than either L. salivarius or placebo. Also of interest is the finding of a normalization of the ratio of pro-inflammatory cytokines–results that suggest an immunomodulating and anti-inflammatory action for the organism. Hopefully, future trials will provide an analysis of results based on the subtype of IBS. It will also be interesting to see how other well-researched human origin strains such as L. reuteri or L. GG would perform compared to this B. lactis strain.
O’Mahony L, McCarthy J, Kelly P, et al. “Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles.” Gastroenterol, 2005; 128:541-51.
By Donald Brown, ND
COPYRIGHT 2005 Original Internist, Inc.
COPYRIGHT 2007 Gale Group