Fig. 10

Putative mechanism describing how phenylbutazone induces injury in the GI tract. We propose that phenylbutazone induces oxidative injury to colonocytes which subsequently alters several cell signaling responses including ER stress and activation of the proteasome ubiquitin system. Further, this combination of host changes results in concommitant alteration of the microbiome, potentially due to lumenal redox imbalances. Obligate anaerobic bacteria, and their metabolites (e.g., butyrate), are then depleted due to their sensitivity to lumenal oxygen content. Loss of the critical SCFA butyrate then exacerbates cellular injury