Butyrate promotes the adaptation of intestinal smooth muscle cells through the yes-associated protein (YAP) pathway in a rat model of short bowel syndrome

Our previous study demonstrated that the proliferation of human intestinal smooth muscle (ISM) cells was stimulated by butyrate through the yes-associated protein (YAP) pathway in vitro, suggesting a valuable approach for intestinal adaption of short bowel syndrome (SBS). This study was conducted to confirm these findings in vivo. Three-week-old Sprague-Dawley rats were randomly divided into the following groups: Sham group (bowel transection and reanastomosis), SB W group (80% small bowel resection/water ad libitum), and SB Bu group (80% small bowel resection/50 mM sodium butyrate ad libitum). Morphological changes were determined by hematoxylin and eosin staining; the proliferation rate of ISM cells was examined by Ki67 staining, and apoptosis was determined in the TUNEL assay. Changes in the expression of YAP and its downstream genes were evaluated by quantitative-polymerase chain reaction and western blotting. Fourteen days post-operation, a significant increase in ISM thickness was observed in the SB Bu group compared to the SB W group, accompanied by enhanced proliferation of ISM cells and suppression of apoptosis. Notably, YAP expression was also significantly increased in the SB Bu group, with a 6.5-fold increase in the proportion of YAP-positive ISM cells, 2.2-fold increase in YAP mRNA expression, and 3.4-fold increase in protein expression. In conclusion, our results suggest that butyrate promotes ISM adaption through YAP in vivo, which may be a potential therapeutic approach for SBS patients.