Microbiota-derived IPA protects against colitis by regulating intestinal HMGCS2-mediated ketogenesis to facilitate mucosal healing.

However, low-dose IPA (20 mg/kg) administration demonstrated marginal attenuation of disease phenotypes, showing only modest mitigation in pathological indices, mucosal barrier integrity and inflammatory markers that failed to reach statistical significance compared to vehicle-treated controls (Fig. 1g–k and Supplementary Fig. 1f, g ), suggesting that IPA mediates protection against DSS-induced colitis in a dose- and time course-dependent manner.

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