Octreotide attenuates experimental severe acute pancreatitis through inhibiting pyroptosis and modulating intestinal homeostasis

Severe acute pancreatitis (SAP) is a common clinical condition characterized by acute abdominal symptoms. Octreotide (OCT) is a commonly prescribed treatment for acute pancreatitis (AP). Recent research shows that pyroptosis and intestinal homeostasis significantly contribute to the progression of AP. However, it remains unclear whether OCT treats SAP through modulating pyroptosis and intestinal microbiota. Our study aimed to investigate and validate the potential therapeutic effects of OCT on SAP and underlying mechanisms. The inhibition of pyroptosis in mice using disulfiram was investigated to elucidate the role of pyroptosis in AP. Molecular biology experiments confirmed that OCT effectively inhibited the expression of pyroptosis-related markers. Additionally, the composition, abundance, and functionality of the intestinal microbiota were analyzed using 16S rRNA sequencing, while short-chain fatty acids (SCFAs) were quantified by targeted metabolomics. Our study demonstrated that the administration of OCT significantly mitigated the severity of SAP in a dose-dependent manner. Furthermore, the inhibition of pyroptosis in mice attenuated SAP, thereby highlighting the critical role of pyroptosis in this condition. OCT administration was observed to suppress the expression of key pyroptosis markers. Additionally, there was a notable reduction in intestinal permeability and bacterial translocation. OCT reverses gut dysbiosis caused by SAP, increasing beneficial bacteria while inhibiting pathogenic strains. Furthermore, OCT administration enhanced the levels of SCFAs, including propanoic acid, acetic acid, and butyric acid. Our findings indicate OCT has the potential to alleviate SAP by suppressing pyroptosis and restoring intestinal homeostasis.