Saccharomyces boulardii in Crohn's disease: biologic plausibility without sufficient support for routine adjunctive use

This record contains the reproducible research release associated with the manuscript “Saccharomyces boulardii in Crohn’s disease: biologic plausibility without sufficient support for routine adjunctive use.”

This preprint presents a structured, question-centred translational evidence synthesis addressing a single clinical question: whether current evidence supports routine adjunctive use of Saccharomyces boulardii during standard Crohn’s disease treatment to improve remission outcomes. The analysis resolves a common interpretive issue in translational literature, where mechanistic plausibility is conflated with clinical efficacy despite limited and heterogeneous direct evidence.

The study integrates direct Crohn clinical reports, mechanistic literature, organism-side transcriptomic resources, public host-response datasets, and a terminal ileum disease-anchor dataset within a unified analytic framework. Evidence classes are explicitly separated (direct, derived, adjacent, and contextual) to preserve evidentiary hierarchy and prevent category error. Formal meta-analysis is not performed due to sparse and non-commensurable clinical endpoints.

Across the retained evidence base, support concentrates in barrier-related and inflammatory domains, including epithelial restitution and attenuation of NF-kappaB–linked signalling. Organism-side data reinforce strain-specific plausibility rather than generalised probiotic effects. In contrast, anti-pathobiont interpretations weaken under strict admissibility, with stronger evidence in generic pathogenic E. coli systems than in Crohn-relevant AIEC contexts.

The decisive limitation is the direct Crohn clinical record. Available studies are sparse, heterogeneous, and uneven in design. When interpreted within an appropriate endpoint hierarchy, where durable remission and relapse prevention are primary the most informative randomised maintenance trial does not demonstrate benefit and outweighs earlier smaller positive signals. Taken together, the clinical evidence supports continued investigation but does not support routine adjunctive use.

The resulting structure is coherent: mechanistic signals are present but concentrated and do not align with the clinically decisive domain of remission durability. This work demonstrates the importance of maintaining strict separation between biologic plausibility and clinical efficacy in translational synthesis.

The framework is translational in intent. It supports targeted follow-up, particularly in barrier-focused remission-support or maintenance settings, and defines the most informative next steps as direct Crohn-relevant experimental systems and strain-defined adjunctive trials with remission outcomes as the primary endpoint. In the absence of such evidence, routine adjunctive use is not supported.

This Zenodo record contains the full manuscript and associated materials corresponding to the current version of the study.