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De Simone Formulation (8-strain high-dose probiotic blend)
An 8-strain blend dosed in the hundreds of billions to trillions of CFU per day — roughly 45 to 7,000 times a typical 1-10 billion CFU consumer probiotic — with the largest effect size in the probiotic literature for one narrow use: maintaining remission in chronic pouchitis after ulcerative colitis surgery. It is null for IBS and Crohn's — and since 2016 the brand name no longer reliably identifies the formulation that was studied.
What the evidence says
Most VSL#3 / Visbiome studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2000–2020 with a typical study size of 119 participants.
Based on 14 studies · 5 meta-analyses · 8 RCTs · 685 total participants
Confidence
High confidenceBy outcome
For chronic pouchitis the effect size is among the largest in any probiotic literature and is seen in two trials, but those two trials share senior authorship with the same Bologna group so they are not independent replications, and Cochrane grades the evidence low certainty on just 76 pooled participants — and the blend is null for IBS and Crohn's, with the brand-versus-formulation split leaving today's product identity unresolved.
1 trial ongoing or recruiting · none completed on ClinicalTrials.gov
Registered trials show research momentum for VSL#3 / Visbiome, not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Sep 2026
Our research database did not respond in time, so the studies and count above cover only our curated set. This refreshes automatically.
This is an 8-strain blend (four Lactobacillus, three Bifidobacterium, one Streptococcus thermophilus) dosed at 450 billion to 7.2 trillion CFU per day across the trials — orders of magnitude above a typical consumer probiotic.
For chronic pouchitis, an inflammatory complication after ulcerative colitis surgery, the effect size is among the largest in any probiotic literature: 85% maintained remission at 9-12 months versus 3% on placebo, pooled as a relative risk over 20. A separate trial found 85% versus 6% remission at one year.
It also cuts first-onset pouchitis after surgery. For inducing remission in mild-to-moderate active ulcerative colitis, three separate meta-analyses find a benefit for this blend.
Note the file's own cited meta-analysis (Shen 2014) also found probiotics AS A CLASS significantly increase remission in active UC (RR 1.51, P=0.01), so this is not a case of the blend succeeding where the class fails.
Beyond that the record turns negative: the dedicated IBS meta-analysis of 5 RCTs is flatly null on pain, bloating, stool consistency and quality of life; the Crohn's post-operative trial missed its primary endpoint; and a hepatic encephalopathy trial also missed its primary endpoint, with only secondary hospitalisation outcomes reaching significance.
Two important caveats. First, even the pouchitis evidence is graded LOW certainty by Cochrane, resting on two trials totalling 76 participants. Second, and critical for shoppers: in 2016 the formulation was licensed to Visbiome, and published sources have since decoupled the trial evidence from the brand name.
Cochrane's 2019 review reports every result under the name 'De Simone Formulation' rather than VSL#3, and a clinical guideline issued a formal published erratum stating that its recommendation referred only to the product used in the cited literature, now known generically as the De Simone Formulation.
All the trial evidence predates that split.
Faecal lactobacilli, bifidobacteria and S. thermophilus rose significantly from baseline only in the treated group, and returned toward baseline once treatment stopped — so the effect requires continued dosing.
Gut biopsies in the post-operative Crohn's trial showed reduced mucosal inflammatory cytokine levels versus placebo — a real biological effect that nonetheless did not translate into the clinical endpoint.
In intestinal cell monolayers the formulation accelerated wound closure and blocked oxidative injury, with the result differing between products sold under the same brand name. Laboratory work only, and not among the studies cited on this page. Note the result differed between products sold under the same brand name.
How VSL#3 / Visbiome works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
The population where benefit is strongest and best established. Use under gastroenterology supervision.
One small positive trial (n=29) with weight-based dosing and no related adverse events. Promising but unreplicated; specialist supervision only.
Standard live-probiotic caution applies; no product-specific case data exists either way.
No data — no trial enrolled pregnant women. Untested rather than shown safe.
In the pouchitis trials antibiotics were used first to induce remission, with the probiotic started afterward for maintenance. No drug interaction was reported in any trial.
Tip: Reported in 1 of 40 participants in the Cochrane pouchitis analysis; overall adverse-event rates matched placebo
VSL#3 / Visbiome has an evidence score of 6.5/10 — moderate evidence based on 20 indexed studies, including 5 meta-analyses. An 8-strain blend dosed in the hundreds of billions to trillions of CFU per day — roughly 45 to 7,000 times a typical 1-10 billion CFU consumer probiotic — with the largest effect size in the probiotic literature for one narrow use: maintaining remission in chronic pouchitis after ulcerative colitis surgery. It is null for IBS and Crohn's — and since 2016 the brand name no longer reliably identifies the formulation that was studied. Representative study: PMID 31785173.
The commonly studied dose of VSL#3 / Visbiome is Prevention and maintenance are DIFFERENT doses and are often conflated. Preventing the first onset of acute pouchitis used 900 billion CFU/day (1 sachet). Maintaining remission in established chronic or refractory pouchitis — where the effect size is largest — used 6 g/day, which at 5 x 10^11 viable bacteria per gram is about 3 trillion CFU/day, in both maintenance trials. As a ulcerative colitis add-on, 3.6 trillion CFU daily; the active-UC induction trial went highest at 3.6 trillion CFU TWICE daily (7.2 trillion/day), and the paediatric trial lowest at 450 billion/day weight-based. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
Timing is flexible for VSL#3 / Visbiome — consistent daily use matters more than the time of day. No trial specified meal timing.
VSL#3 / Visbiome is generally well-tolerated and considered safe for most healthy adults at recommended doses. Reported side effects are uncommon and include abdominal cramps, vomiting or diarrhoea. Use caution if any of these apply to you: Severe immunocompromise or immunosuppression (class-level precaution for live probiotics); Critical illness or indwelling central venous catheter.
Probiotics
Likely helpsLive microorganisms where strain selection determines outcome — Lactobacillus and Bifidobacterium strains best studied for gut, immune, and mood.
Saccharomyces Boulardii
Likely helpsAntibiotic-resistant probiotic yeast that supports digestive regularity and gut flora during travel and antibiotic use.
B. lactis (BB-12 / HN019)
Mostly mechanism / observationalThe most-replicated probiotic effect on gut transit — it measurably speeds things up and adds roughly one bowel movement a week in people who are already low. But it is not a constipation cure: the two largest, best-designed trials both missed their primary endpoints, and the honest effect is hours off transit time, not a fix.
L. reuteri DSM 17938
Mostly mechanism / observationalThe best-evidenced probiotic for infant colic — but specifically in breastfed babies, where an individual-participant meta-analysis found a number-needed-to-treat of 2.6. In formula-fed infants the benefit disappears, and the largest single trial actually favoured placebo. Adult claims mostly belong to different L. reuteri strains entirely.
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Reviewed by Dr. Baher Al Hakim · Last reviewed July 2026 · evidence from 14 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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