What the Clinical Guidelines Say About the De Simone Formulation: The AGA Pouchitis Guideline Explained (UK)

A precise, neutral reference on what clinical guidelines and published research actually say about the De Simone Formulation, anchored on the AGA 2024 pouchitis guideline, with verified citations. Written for clinicians, pharmacists and informed readers in the UK.

What the AGA 2024 pouchitis guideline actually says

Pouchitis is the most common complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA), the surgery many people with ulcerative colitis eventually undergo.¹ In January 2024, the American Gastroenterological Association published a clinical practice guideline on the management of pouchitis and inflammatory pouch disorders (Barnes et al., Gastroenterology 2024;166(1):59-85, PMID 38128971).¹

For the prevention of recurrent pouchitis, the guideline suggests using probiotics, and it is explicit that the De Simone Formulation is the multi-strain probiotic used in the trials it reviewed.¹ This is the citable point: the guideline's support for probiotics in this setting rests on this specific formulation, not on probiotics as a general category.

Two boundaries matter and are easy to get wrong. First, this is a recommendation for secondary prevention, for people who have recurrent pouchitis that responds to antibiotics but relapses afterwards. Second, it is a conditional recommendation based on low certainty of evidence.¹ For primary prevention of pouchitis, the AGA makes no recommendation for or against probiotics, citing a knowledge gap. And the guideline makes no recommendation to use probiotics to treat active pouchitis.¹

The 87% figure in context, and the guideline's own caveats

The figure most often quoted from this guideline is striking. On meta-analysis of three randomised controlled trials, use of the De Simone Formulation was associated with an 87% lower risk of pouchitis relapse over 12 months (6 of 45 vs 36 of 41; RR 0.17; 95% CI 0.09-0.34).¹ In each trial, antibiotics were used first to bring the pouchitis into remission, and the formulation was then used to maintain it.²

A reference-grade reading has to include the caveats the guideline itself attached. The AGA rated the overall body of evidence as low quality, marking it down for a low event rate and suspected publication bias.¹ The panel also noted that routine clinical experience does not fully match the high efficacy seen in the trials. In other words: a large relative effect from a small evidence base, treated cautiously by the people who wrote the guideline.

The two pouchitis trials behind the recommendation

AGA vs ACG, and getting the citation right

On a topic where a single misattributed reference undermines the whole point, two clarifications are worth making plainly.

First, AGA is the American Gastroenterological Association. It is a different organisation from the ACG, the American College of Gastroenterology. The two are easy to confuse and are sometimes swapped in product copy and summaries. The pouchitis guideline that names the De Simone Formulation is an AGA document.¹

Second, the precise, verifiable reference is Barnes et al., Gastroenterology 2024;166(1):59-85, PMID 38128971. Some materials in circulation cite a different reference for "gastrointestinal disorders generally." For the formulation in pouchitis, the citation that holds up against PubMed is the Barnes 2024 AGA guideline. When in doubt, check the PMID.

Formulation vs brand: why the De Simone Formulation and VSL#3 diverged

Understanding the guideline evidence depends on one fact: the formulation and the brand name are not the same thing, and they parted company in 2016.

From 2002 until January 2016, the De Simone Formulation was sold under the brand name VSL#3.⁵ In January 2016, the licence to sell the formulation under that brand ended. Since mid-2016, the product sold as VSL#3 has been a different, separately manufactured formula.⁵ The original formulation continued under new names: Visbiome in the United States, Vivomixx in Europe, and now CDS22-formula in the UK.

This was settled in court, not just in marketing. In November 2018, a US federal jury found the distributors of the relaunched VSL#3 liable for false advertising under the Lanham Act.⁵ In June 2019 the court issued a permanent injunction barring them from claiming the current VSL#3 contains the same formulation as the pre-2016 product, and from citing clinical studies performed on the De Simone Formulation as applicable to the relaunched product. The Fourth Circuit Court of Appeals affirmed the verdict and largely affirmed the injunction in 2021.⁵

Scientific bodies and journals have since clarified the same point so the literature reads correctly. The European Crohn's and Colitis Organisation (ECCO) issued a statement in October 2023 confirming that pre-2016 references to VSL#3 refer to the De Simone Formulation. In 2024, ESPEN (the European Society for Clinical Nutrition and Metabolism) published a paper in Clinical Nutrition titled "Clarifying correct attributions in scientific literature: The case of the De Simone Formulation and the VSL#3," reinforcing the distinction.⁴ Journals have run formal corrections to relabel the formulation in older papers, including a 2026 correction in the United European Gastroenterology Journal that names the formulation's current European brand as CDS22-formula.⁶

How the formulation is thought to work

Mechanistic and laboratory research has explored several ways a high-strain, high-count formulation like this is thought to act. These are mechanistic hypotheses and trial-population observations, not authorised health claims, and they are hedged accordingly.

The wider evidence base, and what it does not conclude

Beyond pouchitis, the De Simone Formulation is one of the more heavily studied probiotic formulations in the literature, with research spanning irritable bowel syndrome, ulcerative colitis and antibiotic-associated diarrhoea. Rather than restate condition-by-condition claims here, which a food-supplement page should not make, the full set of references is documented on two dedicated pages.

The formulation's research record is catalogued in the De Simone Formulation scientific publications index and the clinical studies bibliography. For a condition-focused overview of what the published trials report, see our companion guide on the evidence in UC, IBS and pouchitis, and our clinical probiotics UK comparison.

Two cautions apply to all of it. The named guideline recommendation is for pouchitis; evidence in other conditions should be read against its own published trials, not attributed to the pouchitis guideline. And across conditions, "studied" does not equal "proven to treat", the strength and certainty of evidence vary by condition and outcome.

Trial dose vs the product you can buy

This is the distinction most easily blurred, so it is worth stating directly. The doses used in the pouchitis trials are not the same as a retail serving of a food supplement.

In the pouchitis maintenance trials cited by the AGA, the De Simone Formulation was used at 6 g/day, and only after antibiotics had first achieved remission.¹ Doses studied across the broader inflammatory bowel disease literature run higher still in some protocols. By contrast, the retail product, CDS22-formula, provides 450 billion CFU per sachet.

The point is not which number is bigger. It is that a clinical-trial protocol is not a serving suggestion, and a retail serving should never be presented as equivalent to a studied dose. The trials describe a formulation under specific medical supervision; the product is a food supplement bought off the shelf. A higher live count is also not, in itself, a measure of effect: CFU is a specification, not a proxy for efficacy.

The De Simone Formulation (CDS22-formula) in the UK

In the UK, CDS22-formula is sold as a food supplement, regulated under Food Standards Agency (FSA) food supplement rules.⁷ It is not a medicine, it is not regulated by the MHRA as a medicinal product, and it is not intended to diagnose, treat, cure or prevent any disease. No prescription is required to buy it.

Health claims on food supplements in the UK are governed by retained EU law based on Regulation (EC) 1924/2006. That is why this page reports what guidelines and trials say about the formulation as studied, rather than making a health claim for the product. The NHS advises seeing a GP if you have digestive symptoms that persist for more than three weeks, and anyone managing a diagnosed condition such as ulcerative colitis or pouchitis should do so with their clinical team.

VAT on food supplements in the UK is charged at the standard rate of 20%, which is included in the prices shown. CDS22-formula is a refrigerated product; Probiotic.co.uk dispatches it cold-chain from a temperature-controlled facility in Chorley, Lancashire, with tracked UK delivery, so the live count on the label is maintained to the door.

How to identify the original formulation today

Because the brand names changed while the formulation stayed constant, the reliable way to identify the original is by the strain list, not the brand. The current UK CDS22-formula label lists eight strains by their NCIMB codes.

Older clinical literature and the US Visbiome product list the same formulation under DSM codes (for example DSM 24731-24737). The organisms are the same formulation; the current UK CDS22-formula label uses the NCIMB designations above. Matching the formulation by its strain list is how the published evidence is correctly tied to the product on the shelf.

Frequently asked questions