Irritable bowel syndrome (IBS) affects an estimated 30–45 million United States adults (~10–15%). It is a disorder of gut-brain interaction: not life-threatening, but a major driver of disability, absenteeism, anxiety/depression and healthcare cost. This oracle estimates the causal reduction in symptom burden — the shared mediator — achievable by combining dietary, pharmacological and gut-brain therapies, using effect sizes from named trials and network meta-analyses. It is distinct from the inflammatory-bowel-disease oracle. For education, not individual medical advice.
Tick the interventions to combine. Each shows its trial effect estimate, 95% confidence interval (CI), E-value, mechanism, and citation. ★ = in the current Pareto effective set but not yet ticked.
Headline is the front-door estimate: shared symptom overlap removed via dose-response saturation; residual direct-effect overlap removed via the eigenvalue model at ρ̄.
Under monotonicity + exogeneity (E-value bounds the exogeneity assumption).
Faithful causal directed acyclic graph (DAG). Each therapy is a node; most act through the shared mediator visceral hypersensitivity / symptom severity, which drives disability, mood and healthcare use — the components of the morbidity burden Y. Tricyclics, SSRIs and gut-directed psychotherapy also act independently of gut symptoms (on anxiety and coping). Named confounders — especially placebo response — open back-door paths (adjusted). Illustrative of structure. Mediator cascade: interventions attach to the node they act on (diet / fibre → gut motility / → brain-gut), which converge on the disease state and thence the endpoint — drawing the intermediate mediators explicitly is what exposes d-separation and per-channel saturation.
Eigenvalue diagnostics for the selected interventions under an equicorrelation matrix (off-diagonal ρ̄). A large λmax relative to k signals redundancy; n_eff is the effective number of independent interventions actually contributing.
On mechanistic grounds ρ̄ ≈ 0.30 is defensible: fibre, antispasmodics, diet and secretagogues overwhelmingly share the luminal-symptom pathway, so a substantial fraction of their nominal effects overlap. Gut-brain neuromodulators and psychotherapy retain more independent (mood-mediated) effect, which is why ρ̄ is user-adjustable rather than fixed. Note the unusually large placebo response in IBS trials, which the E-value helps bound. Most of the overlap is now handled structurally by the mediator nodes (same-node substitutes saturate); ρ̄ governs only the residual correlation among direct effects.
Minimum-effective-set analysis. Set a target combined risk reduction; the model finds the smallest set of interventions — accounting for front-door mediator overlap — that reaches it, and highlights them. If the target exceeds what all interventions together can achieve, the full set is shown (never an empty one). "Apply" ticks exactly that set.
Monte Carlo propagation. Each selected intervention's log-effect is sampled from a normal distribution implied by its 95% CI; samples are combined with the same eigenvalue overlap discount. 5,000 draws.
Intervening on the selected set S with Pearl's do-operator (setting the interventions, not merely observing them). Contrast against do(∅) = no intervention.
For each intervention: "if not for this one, the combined front-door effect would be…". Isolates each intervention's marginal causal contribution after mediator-overlap removal, so shared-pathway agents are not double-credited.
| If not for… | RR without it | RR with full set | marginal RRR lost |
|---|
One-at-a-time sensitivity. Each intervention's effect is swung across its 95% confidence interval (others held at point estimate); the bar is the resulting swing in the combined front-door effect. A long bar means the combined estimate leans heavily on that single trial's precision.
Front-door (mediation) decomposition. Most IBS therapies act through one shared mediator — reduction of visceral hypersensitivity / symptom severity. Each log-effect is split into a symptom-mediated (indirect) and a symptom-independent (direct) part. Indirect parts are pooled through the mediator with dose-response saturation (symptom relief saturates — stacking a third luminal agent yields diminishing returns), removing the mediator cross-correlation; direct parts keep the residual eigenvalue correlation at ρ̄. Tricyclics, SSRIs and gut-directed psychotherapy, whose effects on mood and coping are partly symptom-independent, are therefore NOT fully discounted against the antispasmodics. Here mediated effects are pooled WITHIN each cascade node (dose-response saturation of substitutes) and composed in SERIES across nodes (d-separated channels), with the per-node reductions reported so the channel structure is visible.
| Intervention | RR | %sympt | med-frac | indirect log | direct log |
|---|
Which % of cross-correlation is appropriate? Not one number. The mediator overlap is fixed empirically by the symptom saturation (currently removing — of the summed mediated effect when interventions are stacked). Note a domain caveat: secretagogues and SSRIs favour IBS-C, while rifaximin, low-FODMAP and tricyclics favour IBS-D — subtype-specific agents only combine within a subtype. Symptom-mediated fractions are transparent, adjustable priors.
Front-door caveat (antithesis): the endpoint is symptom relief / responder status — a surrogate with no mortality translation. Because IBS trials have a 30–40% placebo response, favourable relative risks are calculated against a high bar and overstate real-world open-label benefit.
Select interventions to generate a plain-language summary.