ArticleNPJ systems biology and applications2026
Signed, sealed, delivered: a generalizable model for living biotherapeutic dosing and metabolism.
Article in NPJ systems biology and applications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Living Biotherapeutic Products (LBPs) offer a promising therapeutic strategy for metabolic disorders rooted in gut microbiome dysfunction, yet quantitative frameworks for predicting their efficacy remain underdeveloped. We introduce the Bacterial Compartment Absorption and Transit (BCAT) model, a pharmacokinetic-pharmacodynamic framework that couples probiotic transit, endogenous microbiome metabolism, and enzymatic transformation within a unified dose-optimization setting. Building on the classical CAT model, BCAT incorporates mechanistically-derived colon compartments and treats dosing time as a control variable. We validate BCAT against clinical data for native choline metabolism and SYNB1618 probiotic trials, achieving 5% mean prediction error compared to ~30% for prior two-compartment models. Applying BCAT to trimethylaminuria (TMAU), we predict that ~10
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