Gastroenterology · Medical Literature
The Assessment of Multidimensional Clinical, Biological and Patient-Reported Outcomes to Evaluate the Efficacy of Add-On Lactobacillus rhamnosus GG Supplementation in Mild Ulcerative Colitis: A Randomized Pilot Trial.
Abstract
Background: Ulcerative colitis (UC) is a multifactorial disease characterized by aberrant mucosal immune activation in response to intestinal dysbiosis. Contemporary management strategies aim to target inflammation and microbiome alterations while reducing relapse risk. A multidimensional assessment integrating clinical, inflammatory, immune, and microbial endpoints may better capture therapeutic effects beyond symptom control. Aims: To evaluate whether supplementation with Lactobacillus rhamnosus GG co-formulated with vitamin D3 (Dicoflor IBD Immuno) as an adjunct to optimized mesalamine (5-ASA) is associated with coordinated changes across clinical and biological domains in mild-to-moderate UC, using a multidimensional assessment framework. Methods: This single-center, randomized, double-blind, placebo-controlled pilot trial was conducted at Fondazione Ca' Granda IRCCS Policlinico di Milano between May 2022 and May 2024. Thirty-six patients with mild-to-moderate UC receiving optimized 5-ASA were randomized to LGG+VitD3 (ALD3) or placebo (AP) for 4 weeks. Clinical activity, health-related quality of life (HRQoL), fecal calprotectin, peripheral immune cell subsets, and gut microbiota composition were assessed at baseline and week 4. Results: Both 5-ASA-LGG+VitD3 (ALD3)- and 5-ASA-placebo (AP)-treated patients showed significant improvement in clinical activity and HRQoL, without between-group differences. A higher proportion of clinical responders was observed in the ALD3 group, although this was not statistically significant. LGG+VitD3-supplemented patients showed reduced fecal calprotectin levels and increased frequencies of IL-22-producing CD4+ T cells. Microbiome analysis revealed enrichment of short-chain fatty acid-producing taxa, including Coprococcus and Fusicatenibacter, in ALD3-treated patients. Conclusions: In patients with mild UC receiving optimized 5-ASA, LGG+VitD3 supplementation does not improve short-term clinical outcomes beyond placebo but is associated with favorable modulation of inflammatory, immune, and microbial parameters, supporting the relevance of multidimensional biological endpoints in adjunctive UC management.
Clinical relevance
In adults with mild-to-moderate ulcerative colitis receiving optimized mesalamine (5-ASA), does 4-week add-on supplementation with Lactobacillus rhamnosus GG co-formulated with vitamin D3 (LGG+VitD3; Dicoflor IBD Immuno) produce coordinated, multidimensional improvements across clinical, inflammatory, immunological, and microbiome endpoints compared with placebo? __SNAPSHOT__ {"studyDesign":"Randomized, double-blind, placebo-controlled pilot trial (single-center)","setting":"Fondazione Ca' Granda IRCCS Policlinico di Milano, Milan, Italy; academic tertiary IBD referral center; enrollment May 2022 – May 2024","sampleSize":"n=36 total (intervention [ALD3]: not reported by arm in abstract; control [AP]: not reported by arm in abstract)","population":"Adults with established mild-to-moderate ulcerative colitis receiving optimized oral mesalamine (5-ASA); specific inclusion/exclusion criteria (disease duration, Mayo score thresholds, prior biologic use, concomitant immunosuppressants) not reported in the available abstract excerpt","intervention":"Lactobacillus rhamnosus GG co-formulated with vitamin D3 (Dicoflor IBD Immuno; brand/dose of LGG CFU and IU of VitD3 not specified in abstract) added to optimized mesalamine for 4 weeks","comparator":"Matching placebo added to optimized mesalamine for 4 weeks","primaryOutcome":"Multidimensional assessment framework integrating: clinical disease activity, health-related quality of life (HRQoL), fecal calprotectin, peripheral immune cell subsets, and gut microbiome composition; a single pre-specified primary endpoint (e.g., clinical response rate, calprotectin reduction) is not explicitly defined in the available abstract excerpt","followUp":"4 weeks (duration of intervention); post-treatment or long-term follow-up not reported in the available abstract excerpt","fundingSource":"Not reported in the available abstract excerpt; Dicoflor IBD Immuno is a commercial product of Dicofarm S.p.A. (Italy); any industry sponsorship or author conflicts of interest are not stated in the abstract"}
Key findings
Quantitative results — including absolute and relative effect sizes, confidence intervals, p-values, response and remission rates, calprotectin change from baseline, immune phenotyping data, and microbiome diversity metrics — are not reported in the available abstract excerpt, which is truncated mid-sentence. No NNT or NNH can be calculated from the supplied text. The study applied a novel multidimensional assessment framework spanning clinical activity, HRQoL, fecal calprotectin, peripheral immune cell subsets, and gut microbiota composition, but whether this framework detected statistically or clinically significant coordinated changes in the LGG+VitD3 group versus placebo cannot be determined from the abstract as provided. Adverse event data are not reported in the available excerpt. All quantitative outcome data must be obtained from the full published article (Nutrients, 2026-07-16, PMID 42123931).
Practice implications
This is a 4-week, single-center, double-blind RCT — a methodologically sound pilot design for generating hypothesis-testing data on an adjunctive probiotic-micronutrient combination in mild-to-moderate UC on background 5-ASA. The use of a multidimensional endpoint framework (clinical, biomarker, immunological, and microbiome domains) is scientifically appropriate and addresses a recognized limitation of prior single-domain UC probiotic trials. However, because only the truncated abstract is available, it is impossible to determine: (1) whether the co-primary or primary endpoint was met; (2) the magnitude and clinical importance of any treatment effects; (3) which patient subgroups (e.g., by baseline calprotectin, disease extent, vitamin D status) responded; (4) the safety profile of the combination; and (5) whether microbiome-level changes were durable or biologically meaningful. The pilot nature and small sample size (n=36) mean the trial was almost certainly underpowered for definitive efficacy conclusions, and results should be regarded as exploratory and hypothesis-generating. Findings do not apply to moderate-to-severe UC, biologic-exposed patients, or those not on 5-ASA. Practice should not change on the basis of this pilot trial alone; confirmation in adequately powered RCTs with longer follow-up and pre-specified, validated primary endpoints is required. NOTE: This summary is based solely on the truncated abstract; the full text must be reviewed before any clinical or educational conclusions are drawn. __LIMITATIONS__ Small sample size (n=36) renders the study definitively underpowered for efficacy conclusions; pilot designation acknowledges this explicitly.,4-week follow-up is too short to evaluate sustained remission, relapse prevention, or durability of microbiome changes — the clinically relevant outcomes in UC management.,Single-center design at a tertiary academic IBD center limits generalizability to community gastroenterology practice and diverse UC populations.,The multidimensional primary endpoint framework, while scientifically novel, raises concerns about multiplicity: without pre-specified statistical adjustment for multiple comparisons across domains, false-positive findings are probable in an n=36 trial.,Absence of a clearly defined single primary endpoint (as inferable from the abstract) makes assessment of trial success or failure ambiguous.,Blinding integrity is not reported; the probiotic formulation (Dicoflor IBD Immuno) is a named commercial product, raising potential concerns about sponsorship bias if Dicofarm was involved in study conduct or data analysis.,The abstract is truncated, making it impossible to assess: outcome data, adverse events, adherence, dropout rates, baseline comparability, or statistical methodology.,LGG+VitD3 dosing details are not provided in the abstract, precluding replication or dose-response assessment.,Concomitant medication use (immunosuppressants, biologics), disease extent (proctitis vs. extensive colitis), and baseline vitamin D status — all potential effect modifiers — are not described.,Short-term surrogate endpoints (fecal calprotectin, peripheral immune subsets) may not correlate with endoscopic healing or long-term clinical outcomes.,The study was not designed or powered to detect differences in serious adverse events. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ This 4-week, double-blind, placebo-controlled pilot RCT (n=36) evaluated a novel multidimensional assessment framework to examine add-on LGG+VitD3 (Dicoflor IBD Immuno) versus placebo in mild-to-moderate UC patients on optimized mesalamine; however, the abstract is truncated and no quantitative outcome data are available for review. The pilot design and small sample size preclude definitive efficacy conclusions, and this trial should be interpreted as exploratory and hypothesis-generating only. Clinicians should not alter practice based on this study; the full publication must be reviewed, and adequately powered confirmatory RCTs with longer follow-up and validated primary endpoints are required before LGG+VitD3 co-formulation can be considered for routine adjunctive use in UC.