Irritable bowel syndrome has been attributed to various factors such as intestinal inflammation and small intestinal bacterial overgrowth. Most previous studies on probiotics focused on one to two etiological factors. The purpose of this study was to evaluate the effect of multi-strain probiotic intake on the various causes in patients with irritable bowel syndrome.

Treatment

The subjects took the Ther-Biotic® Complete capsule®(350mg/capsule, Prothera, Inc., USA) once daily for 8 weeks.

Arm Label

Target Number of Participant

Arm Type

Arm Description

The subjects took the Ther-Biotic® Complete capsule®(350mg/capsule, Prothera, Inc., USA) once daily for 8 weeks.

Gender

Age

Description

1) Age >=19 years and <=70 years
2) Diagnosed with diarrhea-predominant IBS according to the Rome III criteria
3) Positive test results of hydrogen breath test or fecal calprotectin level
4) Patients who agreed and completed with informed consent form, and patients who can afford to conduct the study

1) intake of probiotics including Ther-Biotic® Complete
2) diagnosed gastrointestinal diseases(less than 2 years) other than diarrhea-predominant IBS, such as constipation-predominant IBS, mixed type IBS, Crohn’s disease, celiac disease, ulcerative colitis, or maligmant tumor of the colon)
3) past history of intestinal surgery such as gastrectomy or cholecystectomy (except appendectomy)
4) patients who have history of viral hepatitis(including type A, B, or C), liver cirrhosis, malignancy, chronic kidney disease, congestive heart failure and thyroid disease
5) patients who have red-flag sign, such as rectal bleeding or unintended weight loss 
6) intake of medications which affect liver function
7) history of travel to parasite-endemic countries
8) pregnant women or lactating women

Bristol stool scale

After 8 weeks of taking probiotics

gastrointestinal symptoms(questionnaire)

After 8 weeks of taking probiotics

lactulose hydrogen breath test, fecal calprotectin, fecal microbiome

After 8 weeks of taking probiotics

safety evaluation(adverse effects, laboratory test, physical examination)

After 8 weeks of taking probiotics

During the screening period, 17 subjects were enrolled, 6 were excluded, and 1 patient withdrew consent at the last follow–up, and the final study included 10 participants. The full analysis set (FAS) (n = 11) included patients randomized to treatment who received at least one dose of the assigned treatment. The per protocol set (PPS) (n = 10) included those who completed the study according to the protocol. The mean age of the patients was  47.7 ± 10.1(mean age ± standard deviation) and all patients were men. Bristol Stool Form Scale improved significantly after probiotic treatment (baseline vs. after treatment; 4.8 ± 0.6 vs 3.9 ± 0.9, P = 0.031, 4.9 ± 0.6 vs. 3.8 ± 1.0, P = 0.016, respectively). Abdominal discomfort, dyspepsia, and flatulence were significantly improved in both FAS and PPS groups (FAS group: 5.5 ± 2.4 vs 3.4 ± 1.9, P = 0.010; 5.5 ± 1.5 vs 4.0 ± 1.7, P = 0.046; 5.7 ± 2.6 vs 3.7 ± 1.8, P = 0.037; PPS group: 5.7 ± 2.5 vs 3.1 ± 1.7, P = 0.019; 5.8 ± 1.3 vs 3.8 ± 1.6, P = 0.006; 6.1 ± 3.7 vs 3.6 ± 1.9, P = 0.008, respectively). However, epigastric soreness was not significantly improved in either group. In the fecal microbial analysis, operational taxonomic units decreased statistically significantly after 8 weeks in both FAS and PPS groups (FAS group: 251.1 ± 60.7 vs 198.7 ± 63.0, P = 0.018; PPS group: 245.8 ± 61.2 vs 188.1 ± 55.1, P = 0.017). We also analyzed 34 bacterial genera associated with health benefits. We also investigated 14 genera of harmful bacteria In the FAS group, nine patients showed an increased number of beneficial bacteria (42.9 ± 16.9% vs 54.3 ± 14.6%, P = 0.020), and nine patients demonstrated a decrease in the number of harmful bacteria at the end of treatment compared with baseline (12.5 ± 13.3 % vs. 4.9 ± 3.8 %, P = 0.010). 
- No serious adverse events were reported in any patient. Furthermore, we analyzed 5 genera of lactic acid bacteria (Bifidobactrium, Lactobacillus, Lactococcus, Leuconostoc, and Weissella). The average number of lactic acid bacteria increased 4.7 times at the end of treatment compared with baseline (0.89 ± 1.0 % vs 4.2 ± 5.1 % P = 0.010). In the PPS group, nine patients showed increase in beneficial bacteria (41.2 ± 16.8 % vs 53.7 ± 15.3 %, P = 0.018), and nine patients demonstrated decreased harmful bacteria (13.0 ± 13.9 % vs 4.7 ± 4.0 %, P = 0.010). The average number of lactic acid bacteria after treatment increased 4.4-fold (1.03 ± 1.03 % vs 4.56 ± 5.16 % P = 0.010). Six out of 11 patients tested positive for lactulose hydrogen breath test at baseline and two out of six patients turned negative after 8 weeks of probiotic treatment. In both FAS and PPS groups, the average fecal calprotectin levels were not significant altered after treatment, although there was a tendency to decrease (FAS group: 323.4 ± 684.9 mg/kg vs. 180.4 ± 327.1 mg/kg, P = 0.375; PPS group: 364.4 ± 729.1 mg/kg vs. 200.9 ± 347.6 mg/kg, P = 0.375).No serious adverse events were reported in any patient. Compliance was optimal in all groups.