Nonalcoholic fatty liver disease (NAFLD), characterized by inflammation and hepatocyte ballooning, ranks among the most prevalent liver disorders globally, affecting approximately 30 % of the population [1]. Despite its prevalence, the accurate molecular mechanisms underlying its development remain unclear, leading to treatments primarily focused on symptom relief through diet and medications. Liver inflammation is a critical factor in NAFLD progression [2]. A bidirectional relationship exists between NAFLD and type 2 diabetes mellitus (T2DM): NAFLD increases T2DM risk and complications, while T2DM exacerbates NAFLD severity and complications [3]. Individuals with obesity or T2DM face an elevated risk of developing the more severe form of NAFLD, nonalcoholic steatohepatitis (NASH), characterized by inflammation, hepatocyte injury, and advanced fibrosis. Chronic tissue inflammation is a hallmark of obesity and T2DM, observed in insulin-target tissues like adipose tissue, liver, muscle, and pancreatic islets [4]. Pyroptosis is a form of cell death triggered by proinflammatory signals and closely associated with inflammation [5]. It predominantly occurs in inflammatory cells like macrophages and can be initiated by bacterial or pathogen infection, leading to inflammasome activation and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) [6]. Caspase-1 is a key protease involved in processing the inactive precursors of IL-18 and IL-1β, linking pyroptosis to caspase-1-related cell death. Caspase-1 also cleaves and activates Gasdermin D (GSDMD) [7]. Among the NLRP group of NLR proteins, NLRP3 is a prominent member. Structurally, it comprises a C-terminal leucine-rich repeat (LRR) domain, a central NACHT domain, and an N-terminal pyrin domain (PYD) [8]. The NLRP3 inflammasome is particularly noteworthy as it responds to various stimuli, including bacteria, viruses, components of dying cells, and particulate matter. Programmed cell death variants such as pyroptosis play a crucial role in the progression of liver diseases [9]. The induction of pyroptosis is mediated by GSDMD, and its overexpression is associated with the spontaneous onset of liver damage in the absence of secondary factors, highlighting its pivotal role in NAFLD pathogenesis [10]. NF-κB facilitates the transcription of GSDMD by binding to its promoter region, thereby upregulating GSDMD expression and promoting pyroptosis [11]. Recent literature has demonstrated that activation of the NLRP3 inflammasome leads to caspase-1 activation, subsequently triggering pyroptosis in various diseases, including FLD, suggesting a connection between inflammasomes and the pathogenesis of these conditions [12]. Evidence suggests that a high-fat diet (HFD) can lead to the generation of cytoplasmic lipopolysaccharides (LPS) by gut microbiota, which can activate pyroptosis and contribute to NAFLD progression [13]. Promising results have been observed in the treatment of NAFLD with therapeutics targeting the NLRP3 inflammasome and caspase 1, indicating that targeting pyroptosis is a viable approach for managing the disease [14]. Studies have shown that deficiency in caspase-1 confers protection against HFD-induced NAFLD progression to NASH. Deficiency in caspase-11 notably reduced liver IL-1β levels, diminished plasma membrane expression of N-terminal GSDMD, induced significant changes in liver transcriptomes and mitigated hepatic monocyte/macrophage pyroptosis in HFD-induced NAFLD [13]. The gut-liver axis denotes the reciprocal relationship between the gut, including its microbiota, and the liver, stemming from interactions among dietary, genetic, and environmental factors. This interplay clarifies how disruptions in the intestinal barrier lead to the increased influx of bacteria or their byproducts into the liver, exacerbating various hepatic diseases [15]. Modulating intestinal microbiota to alter intestinal metabolites has emerged as a novel intervention strategy for NAFLD treatment. Despite relatively few studies on the alleviation of NAFLD by probiotics, there is a limited number of probiotics demonstrating efficacy in NAFLD mitigation. Recent reports have highlighted the beneficial effect of Bifidobacterium adolescentis (B. adolescentis) in alleviating NAFLD induced by HFD diets [[16], [17], [18]]. However, the precise mechanism through which this probiotic exerts its effect remains poorly understood. This study aimed to explore the impact of B. adolescentis on the expression of pyroptotic-related genes and assess liver panel and lipid profile, along with stereological indices.