Targeting duodenum to reverse MASLD

Yu JW et al. (World J Gastroenterol. 2025;31:105188. DOI: 10.3748/wjg.v31.i16.105188) used male Sprague-Dawley rats fed a high-fat diet for 8 weeks to recapitulate metabolic dysfunction-associated steatotic liver disease (MASLD) experimentally. MASLD rats were randomized to receive either the duodenal mucosal ablation (DMA) using irreversible electroporation (IRE) during laparotomy or sham DMA. Data have shown that DMA was associated with duodenal thickening compared to the control group, crypts were narrower and shallower crypts and villi slimmer than sham DMA group. Moreover, the DMA group exhibited improved liver histology compared to the sham group though accompanied by inconsistent variations in blood lipid values and statistically non-significant variations in surrogate indices of MASLD. Thirdly, DMA rats had lower serum concentrations of gut hormones with crucial metabolic functions, lower lipopolysaccharide serum level, increased duodenal expression and immunofluorescence staining intensity of gut hormones expression, and higher expression of zonula occludens-1 and claudin than sham-rats. The study by Yu, et al. has innovative findings and is properly designed to illustrate the pathomechanisms underlying improved MASLD histology after DMA with IRE. However, this paper also has some methodological limitations that prompt additional studies in animal models and, ideally, in humans to be conducted as soon as safety and feasibility are demonstrated.