Research project led by Bailey Hanna, MS, RDN - no affiliate links, ads or sponsored products.
De Simone Formulation is an 8-strain probiotic blend, previously known as VSL#3 and sold by VSL Pharmaceuticals before June 2016. It is now exclusively manufactured for ExeGi Pharma and sold under the brand name, Visbiome.
Seven studies have been conducted on this probiotic formulation in IBS populations. (1)(2)(3)(4)(5)(6)(7) One study was excluded from analysis due to confounding dietary interventions during probiotic treatment. (7) The remaining six placebo-controlled trials, despite variations in design, evidence quality, and IBS subtypes, were all conducted on small IBS populations.
Overall, the studies showed consistent neutral or insignificant effects compared to placebo on bowel habits, constipation, diarrhea, and mental health parameters. However, potential benefits were observed in symptoms of distention/bloating, gas/flatulence, global IBS symptoms, abdominal pain/discomfort, and quality of life.
Key Takeaway:
This probiotic has shown potential benefits for IBS symptoms related to distention/bloating, flatulence, global IBS symptoms, abdominal pain, discomfort, and quality of life. It does not appear to significantly impact bowel habits, constipation, diarrhea, or mental health parameters in IBS based on current evidence.
Dosing:
Adolescents and Adults (ages 12 +)
Trial Duration
References:
Evaluate products based on whether they transparently disclose all ingredients and their amounts, exclusively use probiotics tested in randomized placebo-controlled trials in IBS populations, and contain studied doses.
This probiotic has higher quality studies in IBS populations supporting it. View our evidence evaluation framework to learn how we assess the quality of studies.
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A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome
Aliment Pharmacol Ther 2003;17:895–904
ADULTS
A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating
Neurogastroenterol Motil 2005;17(5):687–96
VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled,double-blind, crossover study
J Pediatr Gastroenterol Nutr 2010;51(1):24–30
CHILDREN 4-18 years
Gut microbiota is not modified by Randomized, Double-blind, Placebo-controlled Trial of VSL#3 in Diarrhea-predominant Irritable Bowel Syndrome
Probiotics Antimicrob Proteins. 2011 Mar;3(1):1-7
Melatonin Regulation as a Possible Mechanism for Probiotic (VSL#3) in Irritable Bowel Syndrome: A Randomized Double-Blinded Placebo Study
Dig Dis Sci 60, 186–194 (2015)
ADULTS 20-76 years
Randomized, Double-Blind Placebo-Controlled Trial to Assess the Effect of Probiotics on Irritable Bowel Syndrome in Veterans With Gulf War Illness
Fed Pract. 2022 Oct;39(10):410-417
There was no post-treatment between group statistically significant differences for urgency(p=0.6)
No data
There were no post-treatment between group statistically significant differences for bowel function (e.g., stool frequency (p=0.45), stool consistency (p=0.30), ease of passage (p=0.15), aggregate score (p=0.51)
There was no post-treatment between group statistically significant differences for the overall symptom score (p=0.37)
There was no post-treatment between group statistically significant differences for pain (p=0.6)
Additionally, reductions in gastrointestinal (GI) discomfort were also statistically significant compared to placebo (*p < 0.01 from visits 2 to 4), with a Cohen’s d of 2.5.
The comparison between the two groups using ancova indicated a borderline statistically significant improvement with VSL#3 treatment for abdominal bloating (p=0.09).
Abdominal bloating was reduced (p=0.046) in the VSL#3 group [mean post- minus pre-treatment score, − 13.7; 95% confidence interval (CI), − 2.5 to − 24.9], but not in the placebo group (P= 0.54) (mean post- minus pre-treatment score, − 1.7; 95% CI, 7.1 to − 10.4)
There was no post-treatment between group statistically significant differences for flatulence (p=0.51)
At baseline, the VSL#3-treated patients tended to have higher symptom scores (abdominal pain, bloating, flatulence and faecal urgency) than those in the placebo group; therefore, baseline scores were incorporated as covariates to compare the post-treatment symptoms between the two groups using ancova.
There were no statistically significant differences throughout the treatment period between groups for urgency (p=0.32)
See bowel habits cell regarding ease of passage and incomplete evacuation
There were no statistically significant differences throughout the treatment period between groups for “ease of passage,” number of stools per week, stool form, or for incomplete evacuation.
There were no statistically significant differences throughout the treatment period between groups for pain (p=0.22)
The proportion of the two groups who reached the threshold of 50% weeks with satisfactory relief, thus fulfilling the a priori set criterion for responders for abdominal bloating was 46% (11 of 24) for the VSL# 3 group vs 33% (8 of 24) for the placebo group (Fisher’s exact test, P = 0.27).
Treatment with VSL# 3 was associated with reduced flatulence over the entire treatment period (placebo 39.5 ± 2.6 vs VSL# 3 29.7 ± 2.6, p = 0.011);
Similarly, during the first 4 weeks of treatment, flatulence scores were reduced (placebo 40.1 ± 2.5 vs VSL# 3 30.8 ± 2.5, p= 0.014).
Colonic transit was reduced with VSL# 3 relative to placebo (colon geometric center 2.27 ± 0.20 vs 2.83 ± 0.19, (p=0.05 respectively; the clinical relevance of this change was unclear given the mixed bowel habits present in the study population and the lack of significant differences in other bowel habit symptoms like stool form, frequency, or ease of passage.
Stool frequency — After an improvement of approximately 0.5 points for both groups at the end of the 2 weeks run-in phase, the subsequent decline of the score was as follows.
At the completion of the 6 weeks receiving VSL#3 the score was reduced by 1.05 ± 0.6 (P < 0.001), from 2.3 ± 0.5 to 1.25 ± 0. 3. While receiving placebo, the patients went from 2.2 ± 0.5 to 1.3 ± 0.4, a decline of 0.9 ± 0.3 (P < 0.001). In this case, the difference between these 2 changes did not reach statistical significance (P = 0.06).
A subset analysis of the 3 subtypes of IBS could not be conducted given the small number for each category. However, the overall highest prevalence of responders was found in the group of patients presenting diarrhea-predominant IBS (14/20 patients responded to VSL#3; 3 of these also responded to placebo; of the 6 nonresponders, 1 responded to placebo
For subjective global assessment: 44 of the 59 patients responded to VSL#3; 2 of the 15 nonresponders did respond to placebo. Of the 44 who responded to VSL#3, 17 did not respond to placebo.
The changes from baseline were already statistically significant (P < 0.05) at week 2 on the probiotic, and remained such at weeks 4 (P < 0.01) and 6 (P < 0.001), whereas they were only significant at weeks 4 (P < 0.05) and 6 (P < 0.05) while taking placebo.
The comparison between the magnitude of the change in score between study start and end of treatment seen after VSL#3 and that seen after placebo was statistically significant (P < 0.05) in favor of the probiotic.
The decline in the score for abdominal pain/discomfort was better when taking the probiotic than when taking placebo. From baseline to week 6, the patients taking VSL#3 reported a decline in score of 1.0 ± 0.2 (P < 0.001) compared with a decline of 0.5 ± 0.2 while taking placebo (P < 0.05).
The difference between these 2 changes was significant at P < 0.05. In terms of responders, 40 of the 59 patients responded to VSL#3 and 19 did not; none of these responded to the placebo. Of the 40 who responded to VSL#3, 20 did not respond to placebo.
For bloating and gassiness: the 6 weeks of study period resulted in a further reduction of the score by 1.35 ± 0.4 (P < 0.001) to a final 1.05 ± 0.3 in the group receiving VSL#3, while the score only declined by 0.5 ± 0.2 (P < 0.01) to a final 1.6 ± 0.2 after 6 weeks receiving placebo.
Again, the difference between these 2 changes was significant at P < 0.05. For this symptom, 42 of the 59 patients responded to VSL#3 and 17 did not; only 1 of them responded instead to the placebo. Of the 42 that responded to VSL#3, 16 responded also to placebo.
See cell for bloating
Caregivers assessment on family life disruption: An initial improvement with a score reduction of 0.8 points was reported at the end of the 2-week run-in phase. Subsequently, a further significant decline of 0.9 ± 0.2 points (P < 0.001) was seen at the end of the 6 weeks on VSL#3, although a nonsignificant reduction of 0.51 ± 0.3 points was reported at the end of the 6 weeks on placebo.
For this parameter, the difference between these 2 changes in favor of the probiotic was significant at P < 0.01.
There was no statistically significant between group difference for GSRS-IBS diarrhea subscale scores
There was no statistically significant between group difference for GSRS-IBS constipation subscale scores
There was no statistically significant between group difference for GSRS-IBS global subscale scores
GSRS-IBS pain subscale scores decreased significantly over the treatment period in both groups, but there was no difference between the groups in the degree of change
There was no statistically significant between group difference for GSRS-IBS bloating subscale scores
Significant decreases in scores were also observed in the combined groups for 3 of 7 QOL statements and the overall QOL score, with no differences between the groups.
There was a significant between group difference for GSRS-IBS satiety subscale scores There were no differences noted at baseline or with probiotic consumption at the Phylum, Class, Order, Family or Genus levels regarding microbiome composition.
There were no significant changes in bowel habit satisfaction scores on the IBS-SSS. There were no significant changes in strool type or frequency of defecation scores on the IBS-SSS.
There were no significant changes in total IBS-SSS scores compared to placebo in the overall population, though there were significant changes in male participants randomized to the VSL#3 group and to participants with a normal circadian rhythm in the VSL#3 group.
There was no significant change in abdominal pain intensity scores on the IBS-SSS before or after treatment between the probiotic and placebo group. There was a significant difference in abdominal pain duration in the VSL#3 group compared to placebo both before and after treatment (p <0.05).
Among patients who were treated with VSL#3 for 6 weeks, rectal distension pressure threshold that was required to induce the pain sensations was significantly increased from 38.38 (3.02) to 42.47 (3.25) mm Hg (p<0.05). Moreover, the increase in the distension pressure threshold of pain sensation was marginally correlated with the reduction of pain duration (r = 0.45, p = 0.052).
A increasing trend in the mean pain tolerance threshold was observed in VSL#3 treated groups [from 41.98 (2.53) to 45.87 (3.26) mmHg], which correlated with an improvement in the abdominal pain scores (r = 0.51, p = 0.02).
There was a significant difference in abdominal distention intensity in the VSL#3 group compared to placebo both before and after treatment (p <0.05).
Changes in psychological parameters as shown in total anxiety, total depression scores and Perceived Stress Scale 10 Item scores, as well as changes in sleep quality parameters after treatment in the VSL#3 group were similar to those in the placebo group.
There were no significant changes in quality of life scores on the IBS-SSS
In the present study, no detectable changes of either morning or night salivary melatonin were found among IBS patients grouped by treatment of VSL#3 or placebo. However, when patients were sub-grouped by gender within each treatment arm, a significant increase of the morning melatonin (from 5.43 to 9.74 pg/ml) was observed in male patients but not females with post-treatment of VSL#3 (p = 0.03).
Moreover, the increase of their morning melatonin was marginally correlated with the increase of satisfaction in bowel habits among males treated with VSL#3 (r = 0.61, p = 0.058). Interestingly, although there was no significant difference in change of IBS symptoms between males and females in each treatment group; VSL#3 treated males significantly reduced their IBS severity scores in contrast to placebo treated males, which was not observed in female patients.
Notably among patients with normal salivary baseline diurnal melatonin level, VSL#3 showed significantly superior therapy outcome than placebo in a number of the IBS symptoms, namely, pain days, satisfaction in bowel habits, quality of life as well as total IBS symptoms severity scores.
There were also differences between the two treatment groups in baseline psychological scores and baseline sleep disturbance scores (as illustrated in Table 1). As a result, subjects in the placebo arm had more psychological disturbance and worse sleep scores. IBS patients assigned to receive placebo happened to have a higher anxiety with the mean value suggesting a borderline abnormality.
There was a greater mean (SEM) improvement of diarrhea severity in the probiotic group compared with the placebo group: 18 (6), a 31% improvement, vs 6 (5), a 13% improvement, respectively; however, the difference was not statistically significance (P = .13)
There was no statistically significant differences in constipation scores between groups (p=0.29).
There was a greater mean (SEM) improvement in satisfaction of bowel habits in the probiotic group compared with the placebo group: 16 (7), a 35% improvement vs 4 (9), an 8% worsening; this also was not statistically significant (P = .09). There was no statistically significant differences in stool frequency (p=0.76) or stool consistency (p=0.78) between groups.
There was no statistically significant differences in bowel symptom total scores between groups (p=0.13).
There was no statistically significant differences in abdominal pain scores between groups (p=0.75).
There was no statistically significant differences in bloating scores between groups (p=0.74).
There was no difference in the change in “IBS interfering with life” or IBS-QOL before and after treatment in either group.
There was no improvement in any of the symptoms of GWI (all P ≥ .06). There was no significant change in symptoms for the PTSD scale between groups (p=0.77)