Arabinoxylan and glycolysis inhibitors alleviate trimethylamine accumulation and gut barrier impairment by inhibiting the PERK pathway

regulating Tjp1/2/3, Ocln expression and downregulating Trim40), suppressing PERK pathway genes (14.1%-60.6% reduction), and lowering TMA levels. Notably, co-treatment with AX and glycolysis inhibitors (particularly the pyruvate kinase inhibitor) exerted a synergistic effect, further reducing TMA levels and Trim40 expression. We identified a PERK-TMA axis as a key player in the pathophysiology of gut barrier impairment. In this axis, glycolysis inhibitors enhanced AX-mediated restoration of the PERK pathway, with reductions in PERK-related gene expression ranging from 1.11% to 67.4% compared to the AX monotherapy group. These results characterize a regulatory chain, "metabolic stress reduction, TMA transporter inhibition, barrier recovery", which exhibits potential for reducing TMA accumulation.