Abstract
Ulcerative Colitis(UC) is a chronic intestinal inflammation affecting the intestines, yet its underlying causes remain unclear. In recent decades, the global prevalence of UC has been on the rise, leading to an increasing demand for therapeutic drugs with minimal side effects. Huan Kui Le (HKL), a traditional Chinese medicine compound, has demonstrated promising efficacy when combined with Lactobacillus acidophilus (Lac.) for UC intervention. However, the precise therapeutic mechanism of this combination remains unknown. The study focused on understanding the mechanisms of UC by examining the effects of Lac. and HKL (LH) treatment. The outcomes discovered that the disruption of gut microbiota, triggered by the activation of the NLRP3 inflammasome, plays a crucial role in UC development. This disruption exacerbates UC symptoms by causing disturbances in inflammatory cytokines and mucosal permeability. We investigated the dynamic changes following the application of this treatment using 16S rRNA sequencing, HE, WB, IHC, and ELISA. Compared with the UC group, LH treatment reduced colon pathological injury, improved colon length, and decreased IL-1 β serum levels. Furthermore, it restored the expression of TJs and preserved mucosal barrier integrity. LH treatment also mitigated colon injury by attenuating the expression of pyroptosis-related genes and proteins, such as NLRP3 and Caspase-1. Additionally, LH treatment altered the gut microbiota's microecology, characterized by a reduction in pathogenic bacteria abundance like Escherichia-shigella and an increase in beneficial bacteria abundance like Akkermansia and Erysipelatoclostridium. Overall, our findings indicate that LH therapy may be associated with intestinal barrier repair, inflammasome inhibition, and gut microbiota regulation, suggesting its potential as a UC treatment.